text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
Azetidine-2-carboxylic acid (Aze) 1 is a non-protein amino acid present in sugar beets and in table beets (Beta vulgaris). It is readily misincorporated into proteins in place of proline 2 in many species, including humans, and causes numerous toxic effects as well as congenital malformations. Its role in the pathogenesis of disease in humans has remained unexplored. Sugar beet agriculture, especially in the Northern Hemisphere, has become widespread during the past 150 years, and now accounts for nearly 30% of the world's supply of sucrose. Sugar beet byproducts are also used as a dietary supplement for livestock. Therefore, this study was undertaken as an initial survey to identify Aze-containing links in the food chain. Herein, we report the presence of Aze 1 in three sugar beet byproducts that are fed to farm animals: sugar beet molasses, shredded sugar beet pulp, and pelleted sugar beet pulp. | Azetidinecarboxylic Acid |
A short synthesis of 6,6,6-trifluoro-L-acosamine 15 and 6,6,6-trifluoro-L-daunosamine 19 has been accomplished. The pyranose ring system of these carbohydrate analogues was formed by a hetero-Diels-Alder reaction of vinylogous imide 11 and ethyl vinyl ether which gave adduct 12a in 40% yield. Hydroboration gave 13 and subsequent hydrogenolytic removal of the (R)-2-phenylethyl chiral auxiliary gave ethyl 6,6,6-trifluoro-L-acosaminide 14. Acid hydrolysis furnished target 15. Glycoside 13 was N-trifluoroacetylated to give 16, the structure was confirmed by single crystal X-ray diffraction. The C-4 stereochemistry of 16 was inverted by Swern oxidation of the 4-OH group, and subsequent borohydride reduction to give 17. Hydrogenolytic removal of the auxiliary gave ethyl-6,6,6-trifluoro-L-daunosaminide 18. Acid hydrolysis provided 19. | Fluorine |
Herbs have a long history of use as galactagogues and several commercial formulations have been prepared using herbs. Several active substances such as polyphenols, flavonoids, isoflavones and terpenes are present in the herbal formulations that produce unpleasant taste and decreases consumption of the products. Furthermore, some of these active compounds are unstable when exposed to environmental conditions. In this respect, different approaches can be utilized in order to mask the taste and increase the stability of core substances such as microencapsulation. In the present study, microcapsules containing galactagogue herbs extract were developed through ionotropic gelation and Box-Behnken design was used to investigate the effects of independent variables (chitosan (CS): 1-2%, extract: 1-5% and sodium tripolyphosphate (TPP): 1-3%) on encapsulation efficiency (EE%). Following evaluation of the model, the optimum condition of encapsulation process was selected as 1.19% chitosan, 2.69% extract and 2.08% TPP with EE% of 83.054%. Microcapsules had an acceptable spherical morphology and the results of Fourier transform-infrared spectroscopy (FTIR) revealed the presence of the extract within the microcapsules. The mean diameters of CS-TPP microcapsules containing extract was 27â¯mum with polydispersity index of 0.53, indicative of polydisperse nature of the microcapsules. The in vitro release in simulated gastric fluid (SGF; pHâ¯1.2) and simulated intestinal fluid (SIF; pHâ¯7.4) were 55.19% and 85.04%, respectively during 24â¯h. The freeze-dried extract-loaded microcapsules were stable during 150â¯days of storage and have potential to be used in food matrices with neutral pH. | Galactogogues |
The glucosinolates (GSLs) is a well-defined group of plant metabolites characterized by having an S-beta-d-glucopyrano unit anomerically connected to an O-sulfated (Z)-thiohydroximate function. After enzymatic hydrolysis, the sulfated aglucone can undergo rearrangement to an isothiocyanate, or form a nitrile or other products. The number of GSLs known from plants, satisfactorily characterized by modern spectroscopic methods (NMR and MS) by mid-2018, is 88. In addition, a group of partially characterized structures with highly variable evidence counts for approximately a further 49. This means that the total number of characterized GSLs from plants is somewhere between 88 and 137. The diversity of GSLs in plants is critically reviewed here, resulting in significant discrepancies with previous reviews. In general, the well-characterized GSLs show resemblance to C-skeletons of the amino acids Ala, Val, Leu, Trp, Ile, Phe/Tyr and Met, or to homologs of Ile, Phe/Tyr or Met. Insufficiently characterized, still hypothetic GSLs include straight-chain alkyl GSLs and chain-elongated GSLs derived from Leu. Additional reports (since 2011) of insufficiently characterized GSLs are reviewed. Usually the crucial missing information is correctly interpreted NMR, which is the most effective tool for GSL identification. Hence, modern use of NMR for GSL identification is also reviewed and exemplified. Apart from isolation, GSLs may be obtained by organic synthesis, allowing isotopically labeled GSLs and any kind of side chain. Enzymatic turnover of GSLs in plants depends on a considerable number of enzymes and other protein factors and furthermore depends on GSL structure. Identification of GSLs must be presented transparently and live up to standard requirements in natural product chemistry. Unfortunately, many recent reports fail in these respects, including reports based on chromatography hyphenated to MS. In particular, the possibility of isomers and isobaric structures is frequently ignored. Recent reports are re-evaluated and interpreted as evidence of the existence of isoGSLs", i.e. non-GSL isomers of GSLs in plants. For GSL analysis, also with MS-detection, we stress the importance of using authentic standards." | Thioglycosides |
African swine fever virus (ASFV) is the causative pathogen of the recent African swine fever epidemic, with devastating impacts on economy. A recent study by Wang et al. reveals the multilayer structural details of ASFV at near-atomic resolution, which provides interesting insights about giant virus assembly and paves the way for vaccine development. | Virus Assembly |
This paper gives an overview of the model of a neutron star with non-zero strangeness constructed within the framework of the nonlinear realization of the chiral SU(3)L x SU(3)R symmetry. The emphasis is put on the physical properties of the matter of a neutron star as well as on its internal structure. The obtained solution is particularly aimed at the problem of the construction of a theoretical model of a neutron star matter with hyperons that will give high value of the maximum mass. | Stars, Celestial |
Plant defense against disease is a complex multistage system involving initial recognition of the invading pathogen, signal transduction and activation of specialized genes. An important role in pathogen deterrence belongs to so-called plant defense peptides, small polypeptide molecules that present antimicrobial properties. Using multidimensional liquid chromatography, we isolated a novel antifungal peptide named Sm-AMP-X (33 residues) from the common chickweed (Stellaria media) seeds. The peptide sequence shows no homology to any previously described proteins. The peculiar cysteine arrangement (C(1)X3C(2)XnC(3)X3C(4)), however, allocates Sm-AMP-X to the recently acknowledged alpha-hairpinin family of plant defense peptides that share the helix-loop-helix fold stabilized by two disulfide bridges C(1)-C(4) and C(2)-C(3). Sm-AMP-X exhibits high broad-spectrum activity against fungal phytopathogens. We further showed that the N- and C-terminal tail" regions of the peptide are important for both its structure and activity. The truncated variants Sm-AMP-X1 with both disulfide bonds preserved and Sm-AMP-X2 with only the internal S-S-bond left were progressively less active against fungi and presented largely disordered structure as opposed to the predominantly helical conformation of the full-length antifungal peptide. cDNA and gene cloning revealed that Sm-AMP-X is processed from a unique multimodular precursor protein that contains as many as 12 tandem repeats of alpha-hairpinin-like peptides. Structure of the sm-amp-x gene and two related pseudogenes sm-amp-x-psi1 and sm-amp-x-psi2 allows tracing the evolutionary scenario that led to generation of such a sophisticated precursor protein. Sm-AMP-X is a new promising candidate for engineering disease resistance in plants." | Stellaria |
Sixteen patients with uncomplicated hypertension were studied in a double-blind within-patient trial comparing slow release oxprenolol (SRO) with conventional oxprenolol (CO). The anti-hypertensive effect of SRO once daily was greater than that of CO once daily, although this did not reach statistical significance. CO once daily was less effective than CObd and this difference was statistically significant for lying diastolic blood pressure. After exercise testing 26 hours post-dose, blood pressure and pulse rate were marginally lower on SRO than on CO, but this difference was not significant. Blood pressure readings 24 h post-dose were lower following morning dosing than following evening dosing, although pulse rates showed the opposite trend. | Oxprenolol |
OBJECTIVES: Gestational Trophoblastic Neoplasia (GTN) is a rare group of malignant placental-related tumours requiring systemic anti-cancer treatment. Leptomeningeal disease (LMD) related to GTN is not well reported with no consensus in optimal treatment. We offer recommendations for management of these patients. METHODS: We discuss five patients with GTN who presented with features of LMD and were diagnosed with gadolinium-enhanced MRI brain, all of whom received low dose induction etoposide-cisplatin (EP) followed by either EP-etoposide, methotrexate (CNS) and actinomycin-D (EMA) or EMA(CNS)-cyclophosphamide and vincristine (CO). RESULTS: Four out of the five patients additionally received intrathecal methotrexate. Four patients had complete hCG response to first line multi-agent chemotherapy, one patient required second line paclitaxel, cisplatin alternating with paclitaxel, etoposide (TP/TE), where paclitaxel was substituted with nab-paclitaxel due to anaphylaxis, followed by hysterectomy. One of the four initial complete hCG responders relapsed in the lung requiring further systemic treatment with subsequent lobectomy. Patient reported outcomes indicate persistent neurological symptoms are mild and do not affect functionality and quality of life. CONCLUSION: With a follow-up range of 2-6 years, all five patients remain cured demonstrating excellent survival outcomes with the avoidance of whole-brain radiotherapy in all cases." | Gestational Trophoblastic Disease |
Mevalonate pathway deregulation has been observed in several diseases, including Mevalonate kinase deficiency (MKD). MKD is a hereditary auto-inflammatory disorder, due to mutations at mevalonate kinase gene (MVK), encoding mevalonate kinase (MK) enzyme. MVK mutations have been reported as associated with impairment of mevalonate pathway with consequent decrease of protein prenylation levels, defective autophagy and increase of IL-1beta secretion, followed by cell death. Since 25-hydroxycholesterol (25-HC), a metabolite of cholesterol, can suppress IL-1beta production, thus reducing inflammation, we evaluated the effect of 25-HC in an in vitro model of mevalonate pathway alteration, obtained using Lovastatin. Human glioblastoma cell line (U87-MG) was chosen to mimic, at least in part, the central nervous system impairment observed in MKD; 25-HC effects were evaluated aimed at disclosing if this compound could be considered as novel potential drug for MKD. Our results showed that 25-HC is able to reduce inflammation but it is ineffective to restore autophagy flux and to decrease apoptosis levels, both caused by lower protein prenylation; so, in spite of its anti-inflammatory action it is not useful to rescue defective prenylation/autophagy impairment-driven apoptosis in Lovastatin impaired mevalonate pathway. We hypothesize the presence in the mevalonate pathway of alternative mechanisms acting between inflammation and apoptotic autophagy impairment. | Protein Prenylation |
A longitudinal daily diary study examined how chronic perceptions of a partner's regard for oneself might affect the day-to-day relational contingencies of self-esteem. Married partners each completed a diary for 21 days, and completed measures of satisfaction twice over the year. Multilevel analyses revealed that people who chronically felt more positively regarded compensated for one day's acute self-doubts by perceiving greater acceptance and love from their partner on subsequent days. In contrast, people who chronically felt less positively regarded by their partner internalized acute experiences of rejection, feeling worse about themselves on days after they feared their partner's disaffection. Over the year, such self-esteem sensitivity to rejection predicted declines in the partner's satisfaction. | Rejection, Psychology |
Danon disease is a rare X-linked dominant genetic disorder caused by loss-of-function mutations in the lysosome-associated membrane protein 2 gene. Progression of Danon disease is unknown because of its rare incidence in a diverse ethnic population. We report longitudinal data from two patients who were diagnosed with Danon disease by a genetic test. The evaluation protocol included electrocardiographic monitoring, echocardiography, and magnetic resonance imaging. Progression of hypertrophic cardiomyopathy to dilated cardiomyopathy was observed in the first patient. He died from sudden cardiac arrest. The second patient is currently suffering from hypertrophic cardiomyopathy. Development of the hypertrophic phase progressing into the dilated phase in Danon disease may provide useful information for early identification and clinical decisions in patients with this disease." | Glycogen Storage Disease Type IIb |
We report the successful topical treatment of focal epithelial hyperplasia (Heck's disease) with interferon-beta (Fiblaferon gel). Topical treatment with interferon-beta appears to be an effective, simple, non-invasive, cheap and low-risk alternative to other invasive or surgical therapeutic modalities. | Focal Epithelial Hyperplasia |
Despite the failure of recent attempts to reform health care, strategies of managed competition remain the dominant prescription for government oversight of managed care. A number of assumptions and prescriptions in the conventional managed competition model are challenged. More specifically, externalities in the costs and benefits associated with health care and asymmetric information between providers and patients make it unlikely that a managed care system designed to be responsive to consumers will, in practice, produce socially desirable outcomes. An alternative approach for the regulation of managed care more explicitly protects the role of health care professionals as agents for their patients while defining the appropriate role of managed care as the agent for broader societal interests. This strategy of countervailing agency-" acknowledges that oversight of managed care inevitably involves value-laden choices. It is based on institutional arrangements and regulatory strategies that are intended to balance competing interests and values." | Managed Competition |
OBJECTIVE: Co-stimulatory T cell cytokines are important in the progression of RA. This study investigates the interplay between 4-1BB, a disintegrin and metalloprotease-17 (ADAM17) and galectin-9 (Gal-9) in RA. METHODS: Stimulated mononuclear cells from patients with chronic RA (n = 12) were co-incubated with tissue inhibitor of metalloproteinase, 4-1BB ligand and Gal-9. Plasma samples were examined for soluble 4-1BB (s4-1BB) in newly diagnosed, treatment-naive patients with RA (n = 97). The 28-joint DAS with CRP (28DAS-CRP), total Sharp score, erosion score and joint space narrowing were used to evaluate treatment outcome serially over a 2-year period. RESULTS: RA CD4(+) and CD8(+) synovial T cells express high levels of 4-1BB. The addition of TNF-alpha to cultured synovial mononuclear cells increased shedding of 4-1BB. 4-1BB ligand only increased TNF-alpha shedding in combination with Gal-9. RNA interference-mediated knockdown of ADAM17 or the addition of an ADAM17 inhibitor reduced the 4-1BB shedding. Shedding of 4-1BB was not influenced by Gal-9. Plasma levels of s4-1BB were increased in early RA and correlated with the number of swollen joints at baseline. After 3 months of treatment, the plasma levels of s4-1BB were equal to those of the controls. Baseline plasma levels of s4-1BB were inversely correlated with DAS28-CRP after 2 years of treatment, but not with total Sharp score, erosion score or joint space narrowing. CONCLUSION: ADAM17 induces 4-1BB shedding in RA. Gal-9 is pivotal for the function of 4-1BB and induction of TNF-alpha. Furthermore, high plasma levels of s4-1BB were associated with the number of swollen joints, but also with a low DAS28-CRP after 2 years treatment in early RA. | Matrix Metalloproteinase 17 |
The effect of DHP-218, a dihydropyridine phosphonate Ca2+ channel blocker, on atrioventricular (AV) nodal conductivity was compared with its vascular effect in dogs. In isolated, blood-perfused AV node preparations, a long-lasting increase in AV conduction time which culminated in second- or third-degree AV block at large doses occurred when DHP-218 was injected into the AV node artery, but not when injected into the artery that supplies the His-Purkinje-ventricular system. However, with DHP-218, a far longer-lasting increase in blood flow through both arteries occurred, and at smaller doses it occurred with little effect on AV conduction. In anesthetized, open-chest dogs of which heart rate was controlled at 150 beats/min, intravenous DHP-218 produced an initially rather quick and later very slowly developing and long-lasting fall in blood pressure. AV conduction time was prolonged only after the largest dose. The functional refractory period of the AV conduction system was rather shortened in all doses examined except for the largest dose. A marked increase in AV conduction time which culminated in third-degree AV block was seen in one of six dogs, only under conditions in which the heart was deprived of central neural control. These results indicate appreciable selectivity of DHP-218 for vasculature versus the AV node." | Refractory Period, Electrophysiological |
OBJECTIVE: To determine the expression of Pfg377 ortholog gene in Plasmodium vivax, and examine its correlation with mosquito infection. METHODS: Seventy clinical blood samples positive for P. vivax by microscopy, were used for the mosquito infectivity assay. Infectivity to female Anopheles dirus was determined from oocyst counts. The transcripts of Pfg377 ortholog gene of P. vivax from blood samples infective and non-infective to mosquitoes were examined using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Of 70 P. vivax positive blood samples, 50 (71.4%) samples were mosquito-infective and 20 (28.6%) were not. In infective samples, the expression level of Pfg377 ortholog gene was significantly higher than in the non-infective group (P<0.05). In infective samples, the expression level of Pfg377 ortholog gene at >/=100 copies/ml of blood cut-off point correlated with >/=10 oocysts/mosquito cut-off point of average oocyst numbers and with >/=50% cut-off point of per cent infected mosquitoes (Pearson's chi-square correlation, P=0.014 and P=0.026, respectively). CONCLUSION: The cut-off point of the expression level of Pfg377 ortholog gene could be used to predict the infectiousness of P. vivax gametocytes leading to mosquito infection and parasite transmission in the field. | Plasmodium vivax |
The delayed health effects from accidental exposure to bromine vapors in a group of six people were evaluated. During the acute exposure, they had only some respiratory symptoms and skin burns of first to second degree involving small areas. All were treated in one hospital and released within 1-4 d. Six to 8 wk later, some still had health complaints such as cough, shortness of breath, chest tightness, eye irritation, headache, dizziness, fatigue, and memory, sleep, and sexual disturbances, but no objective laboratory or clinical evidence of effects. Mechanisms that might have led to manifestations of such complaints 1-2 mo after the accident are discussed and possible ways to alleviate similar situations are suggested. | Bromine |
Nature uses a limited set of metabolites to perform all of the biochemical reactions. To increase the metabolic capabilities of biological systems, we have expanded the natural metabolic network, using a nonnatural metabolic engineering approach. The branched-chain amino acid pathways are extended to produce abiotic longer chain keto acids and alcohols by engineering the chain elongation activity of 2-isopropylmalate synthase and altering the substrate specificity of downstream enzymes through rational protein design. When introduced into Escherichia coli, this nonnatural biosynthetic pathway produces various long-chain alcohols with carbon number ranging from 5 to 8. In particular, we demonstrate the feasibility of this approach by optimizing the biosynthesis of the 6-carbon alcohol, (S)-3-methyl-1-pentanol. This work demonstrates an approach to build artificial metabolism beyond the natural metabolic network. Nonnatural metabolites such as long chain alcohols are now included in the metabolite family of living systems. | 2-Isopropylmalate Synthase |
Axillary meristems form in the axils of leaves. After an initial phase of meristematic activity during which a small axillary bud is produced, they often enter a state of suspended growth from which they may be released to form a shoot branch. This post-embryonic growth plasticity is typical of plants and allows them to adapt to changing environmental conditions. The shoot architecture of genotypically identical plants may display completely contrasting phenotypes when grown in distinct environmental niches, with one having only a primary inflorescence and many arrested axillary meristems and the other displaying higher orders of branches. In order to cease and resume growth as required, the plant must co-ordinate its intrinsic developmental programme with the responses to environmental cues. It is thought that information from the environment is integrated throughout the plant using plant hormones as long-distance signals. In the present review, we focus primarily on how two of these hormones, auxin and strigolactones, may be acting to regulate shoot branching. | Meristem |
l-Asparaginase catalyzes the hydrolysis of asparagine into aspartic acid and ammonia. The present work elaborates the isolation and identification of a novel endophytic fungal isolate producing l-glutaminase and urease-free l-asparaginase. Cell growth and enzyme production were investigated for large production. The isolated endophytic fungi were identified at molecular levels and a phylogenetic tree was constructed. The enzyme synthesis was evaluated by cultivating the isolated microorganisms in potato dextrose agar medium. Out of 27 isolated endophytes, nine were producing l-glutaminase and urease-free l-asparaginase." l-Asparaginase from Chaetomium sp. exhibited superior enzyme activity than from the other isolates. Observed optimal conditions for l-asparaginase activity were 25 min of incubation time, 0.5 mg of enzyme source, 40 degrees C of temperature, and pH 7.0. l-Asparaginase from Chaetomium sp. exhibited anticancer activity on human blood cancer (MOLT-4) cells. The current study has demonstrated the production of contaminant-free l-asparaginase enzyme from endophytic fungal species. The results showed that: (a) maximum enzyme activity was observed for l-asparaginase from Chaetomium sp., (b) concentration of glucose in the medium as a carbon source suppressed the enzyme production. Chaetomium sp. is a novel source for "l-glutaminase and urease-free l-asparaginase," which may play a major role in pharmacotherapy." | Chaetomium |
Cell recycled culture of succinic acid-producing Anaerobiospirillum succiniciproducens was anaerobically carried out using an internal membrane filter module in order to examine the physiological response of A. succiniciproducens to a high-cell-density environment. The optimal growth of A. succiniciproducens and its enhanced succinic acid productivity were observed under CO2-rich conditions, established by adding NaHCO3 and Na2CO3, in the cell recycled system. A. succiniciproducens grew up to 6.50 g-DCW/l, the highest cell concentration obtained so far, in cell recycled cultures. The cells did not change their morphology, which is known to be easily changed in unfavorable or stress environments. The maximum productivity of succinic acid was about 3.3 g/l/h, which is 3.3 times higher than those obtained in batch cultures. These results can serve as a guide for designing highly efficient cell recycled systems for succinic acid at a commercial level. | Anaerobiospirillum |
Magnetic resonance imaging (MRI) has become a valuable technology for the diagnosis and treatment of femoroacetabular impingement (FAI). This article reviews the basic pathophysiology of FAI, as well as the techniques and indications for MRI and magnetic resonance arthrography. Normal MRI anatomy of the hip and pathologic MRI anatomy associated with FAI are also discussed. Several case examples are presented demonstrating the diagnosis and treatment of FAI. | Femoracetabular Impingement |
The overall rate constants for the reactions of hydroxyl radicals (OH) with four small methyl esters, namely methyl formate (CH(3)OCHO), methyl acetate (CH(3)OC(O)CH(3)), methyl propanoate (CH(3)OC(O)C(2)H(5)), and methyl butanoate (CH(3)OC(O)C(3)H(7)), were investigated behind reflected shock waves using UV laser absorption of OH radicals near 306.69 nm. Test gas mixtures of individual methyl esters and tert-butyl hydroperoxide (TBHP), a fast source of OH at elevated temperatures, diluted in argon were shock-heated to temperatures spanning from 876 to 1371 K at pressures near 1.5 atm. The overall rate constants were determined by matching the measured OH time-histories with the computed profiles from the comprehensive chemical kinetic mechanisms of Dooley et al. (2010) and Dooley et al. (2008), which were originally developed for the oxidation of methyl formate and methyl butanoate, respectively. These measured values can be expressed in Arrhenius form as k(CH(3)OCHO+OH) = 2.56 x 10(13) exp(-2026/T) cm(3) mol(-1) s(-1), k(CH(3)OC(O)CH(3)+OH) = 3.59 x 10(13) exp(-2438/T) cm(3) mol(-1) s(-1), k(CH(3)OC(O)C(2)H(5)+OH) = 6.65 x 10(13) exp(-2539/T) cm(3) mol(-1) s(-1), and k(CH(3)OC(O)C(3)H(7)+OH) = 1.13 x 10(14) exp(-2515/T) cm(3) mol(-1) s(-1) over the temperature ranges studied. Detailed error analyses were performed to estimate the overall uncertainties of these reactions, and the estimated (2sigma) uncertainties were found to be +/-29% at 913 K and +/-18% at 1289 K for k(CH(3)OCHO+OH), +/- 29% at 930 K and +/-17% at 1299 K for k(CH(3)OC(O)CH(3)+OH), +/- 25% at 909 K and +/-17% at 1341 K for k(CH(3)OC(O)C2H(5)+OH), and +/-24% at 925 K and +/-16% at 1320 K for k(CH(3)OC(O)C(3)H(7)+OH). We believe these are the first direct high-temperature rate constant measurements for the reactions of OH with these small methyl esters. These measured rate constants were also compared with the estimated values employed in different comprehensive kinetic mechanisms. Additionally, the structure-activity relationship from Kwok and Atkinson (1995) was used to estimate these four rate constants, and the estimations from this group-additivity model are in good agreement with the measurements (within ~25%) at the present experimental conditions. | Formic Acid Esters |
It was shown that high-fat feeding of mice with cardiac-specific overexpression of peroxisome proliferator-activated receptor (PPAR) alpha but not wild type animals leads to the accumulation of ceramide (an important mediator of lipotoxicity) in the heart [Finck et al. 2003 Proc Natl Acad Sci USA]. To investigate the mechanism of this phenomenon we examined the effects of PPARalpha activation on ceramide metabolism in the myocardium. Male Wistar rats were fed either a standard chow or a high-fat diet. Each group was divided into two subgroups: control and treated with selective PPARalpha activator - WY-14643. In the rats fed on the standard diet WY-14643 did not affect the myocardial content of sphingomyelin and ceramide but reduced the content of sphinganine and sphingosine. It also inhibited the activity of neutral sphingomyelinase and increased the activity of acid sphingomyelinase, whereas the activity of ceramidases and serine palmitoyltransferase (SPT) remained stable. High-fat diet itself did not affect the content of the examined sphingolipids. However, it reduced the activity of sphingomyelinases and ceramidases having no effect on the activity of SPT. Administration of WY-14643 to this group significantly increased the content of myocardial free palmitate, ceramide, sphingomyelin and the activity of SPT. Our results demonstrated that PPARalpha activation modulates myocardial ceramide metabolism and leads to the accumulation of ceramide in the heart of the high-fat fed rats due to its increased synthesis de novo." | Galactosylgalactosylglucosylceramidase |
The expression levels of the p21(Cip1) family CDK inhibitors (CKIs), p21(Cip1), p27(Kip1) and p57(Kip2), play a pivotal role in the precise regulation of cyclin-dependent kinase (CDK) activity, which is instrumental to proper cell cycle progression. The stabilities of p21(Cip1), p27(Kip1) and p57(Kip2) are all tightly and differentially regulated by ubiquitylation and proteasome-mediated degradation during various stages of the cell cycle, either in steady state or in response to extracellular stimuli, which often elicit site-specific phosphorylation of CKIs triggering their degradation." | Cyclin-Dependent Kinase Inhibitor p57 |
The mammalian pyruvate dehydrogenase complex (PDC) plays central and strategic roles in the control of the use of glucose-linked substrates as sources of oxidative energy or as precursors in the biosynthesis of fatty acids. The activity of this mitochondrial complex is regulated by the continuous operation of competing pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) reactions. The resulting interconversion cycle determines the fraction of active (nonphosphorylated) pyruvate dehydrogenase (E1) component. Tissue-specific and metabolic state-specific control is achieved by the selective expression and distinct regulatory properties of at least four PDK isozymes and two PDP isozymes. The PDK isoforms are members of a family of serine kinases that are not structurally related to cytoplasmic Ser/Thr/Tyr kinases. The catalytic subunits of the PDP isoforms are Mg2+-dependent members of the phosphatase 2C family that has binuclear metal-binding sites within the active site. The dihydrolipoyl acetyltransferase (E2) and the dihydrolipoyl dehydrogenase-binding protein (E3BP) are multidomain proteins that form the oligomeric core of the complex. One or more of their three lipoyl domains (two in E2) selectively bind each PDK and PDP1. These adaptive interactions predominantly influence the catalytic efficiencies and effector control of these regulatory enzymes. When fatty acids are the preferred source of acetyl-CoA and NADH, feedback inactivation of PDC is accomplished by the activity of certain kinase isoforms being stimulated upon preferentially binding a lipoyl domain containing a reductively acetylated lipoyl group. PDC activity is increased in Ca2+-sensitive tissues by elevating PDP1 activity via the Ca2+-dependent binding of PDP1 to a lipoyl domain of E2. During starvation, the irrecoverable loss of glucose carbons is restricted by minimizing PDC activity due to high kinase activity that results from the overexpression of specific kinase isoforms. Overexpression of the same PDK isoforms deleteriously hinders glucose consumption in unregulated diabetes." | Pyruvate Dehydrogenase Acetyl-Transferring Kinase |
Radiation therapy plays a critical role in the current management of cancer patients. The most common linear accelerator-based treatment device delivers photons of radiation. In an ever more precise fashion, state-of-the-art technology has recently allowed for both modulation of the radiation beam and imaging for this treatment delivery. This has resulted in better patient outcome with far fewer side effects than were achieved even a decade ago. Recently, a push has begun for proton therapy, which may have clinical advantage in select indications, although significant limitations for these devices have become apparent. In addition, currently, heavy particle therapy has been touted as a potential means to improve cancer patient outcomes. This article will highlight current benefits and drawbacks to modern radiation therapy and speculate on future tools that will likely dramatically improve radiation oncology. | Photons |
OBJECTIVE: While single-use and detachable-tip duodenoscopes have been recently developed to overcome risks of infection transmission, there are no reliable tools to objectively assess their technical performance. We evaluated the reliability and validity of a newly developed tool to assess the technical performance of reusable duodenoscopes. METHODS: An assessment tool was developed to measure duodenoscope performance based on three distinct criteria: maneuverability, mechanical/imaging characteristics and ability to perform requisite interventions. The assessment tool was tested prospectively on duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at nine academic medical centers over a 6-month period. The main outcome was reliability of the duodenoscope assessment tool, which was estimated using Cronbach's coefficient alpha (alpha). The secondary outcome was validity of the assessment tool. RESULTS: The assessment tool evaluated technical performance of reusable duodenoscopes in 1080 ERCP procedures. Indications were biliary in 92.8% and pancreatic in 7.2% procedures. The overall Cronbach's coefficient alpha for maneuverability was 0.81, assessment of mechanical/imaging characteristics was 0.92, and ability to perform requisite interventions was 0.87. On multiple linear regression analysis, prolonged procedure duration, older patient age and pancreatic interventions were significantly positively associated with higher (worse) scores. CONCLUSIONS: The newly developed assessment tool appears reliable and valid for evaluating the technical performance of duodenoscopes. Registration: ClinicalTrials.gov Identifier: NCT04004533. | Duodenoscopes |
BACKGROUND: Alstrom syndrome is a rare inherited ciliopathy with progressive multisystem involvement. Dilated cardiomyopathy is common in infancy and recurs or presents de novo in adults with high rates of premature cardiovascular death. Although Alstrom syndrome is characterised by fibrosis in solid organs such as the liver, the pathogenesis of related cardiomyopathy are not clear. To date it is not known whether diffuse interstitial myocardial fibrosis is present before the onset of heart failure symptoms or changes in conventional parameters of left ventricular function. METHODS: In this observational study, 26 patients with Alstrom syndrome (mean age 27 +/- 9 years, 65 % male, 24 h ABPM 130 +/- 14 / 77 +/- 9 mmHg) without symptomatic cardiovascular disease were recruited from a single centre and compared to matched healthy controls. All subjects underwent cardiac MRI (1.5 T) to assess ventricular function, diffuse interstitial myocardial fibrosis by measurement of extracellular volume on T1-mapping (MOLLI) and coarse replacement fibrosis using standard late gadolinium enhancement imaging. RESULTS: Global extracellular volume was increased in Alstrom syndrome with wider variation compared to controls (0.30 +/- 0.05 vs. 0.25 +/- 0.01, p < 0.05). Left ventricular long axis function and global longitudinal strain were impaired in Alstrom syndrome without change in ejection fraction, ventricular size or atrial stress (NT-proBNP) (p < 0.05). Global extracellular volume was associated with reduced peak systolic longitudinal strain (r = -0.73, p < 0.01) and strain rate (r = -0.57, p < 0.01), increased QTc interval (r = 0.49, p < 0.05) and serum triglycerides (r = 0.66, p < 0.01). Nine (35 %) patients had diffuse mid-wall late gadolinium enhancement in a non-coronary artery distribution. CONCLUSION: Diffuse interstitial myocardial fibrosis is common in Alstrom syndrome and is associated with impaired left ventricular systolic function. Serial studies are required to determine whether global extracellular volume may be an independent imaging biomarker of vulnerability to dilated cardiomyopathy and heart failure. | Alstrom Syndrome |
A linear accelerator has three independent axes that are nominally intersecting at the isocenter. Modern treatment techniques require the coincidence of these axes to lie within a 1-mm diameter sphere. A solution to verify this requirement is to wrap a film on a cylindrical surface, align the cylinder to the linac's isocenter and gantry axis, and take multiple exposures of slits, rotating either the gantry, collimator, or couch between exposures. The resulting exposure pattern is the 3D equivalent of the 2D star shot and encodes sufficient information to determine each axis' position in 3D. Moreover, this method uses a single sheet 8x10" film, a standard film scanner, and a phantom that can be readily built in-house, making a practical solution to this 3D-measurement problem." | Phantoms, Imaging |
OBJECTIVE: Alcohol-impaired driving results in thousands of deaths annually. Alcohol ignition interlocks require a negative breath test to start a vehicle's engine, and 44 states have mandated some form of interlock law for drivers convicted of driving while intoxicated (DWI). The objective of this study was to estimate the association between interlock laws and fatal impaired-driving crashes. METHODS: Differences in three interlock laws were evaluated by comparing alcohol-impaired passenger vehicle drivers involved in fatal crashes between 2001 and 2019 in the United States across state and time. State/time differences unrelated to interlock laws were controlled for by fitting a Poisson model. The exposure measure was the number of passenger vehicle drivers in fatal crashes that did not involve impaired drivers. Laws requiring interlocks for drivers convicted of DWI covered: repeat offenders, repeat offenders and high-BAC offenders, all offenders, or none. RESULTS: The number of states with all-offender interlock laws during the study period went from three in 2001 to 29 in 2019, and the number of states with any of the three laws increased from 16 to 44. All-offender laws were associated with 26% fewer drivers with 0.08+ BAC involved in fatal crashes, compared with no law. Repeat-offender laws were associated with a 9% reduction in impaired drivers, compared with no law. Repeat and high-BAC laws were associated with a 20% reduction in impaired drivers in fatal crashes, compared with no law. CONCLUSION: Laws mandating alcohol ignition interlocks, especially those covering all offenders, are an effective impaired-driving countermeasure that reduces the number of impaired drivers in fatal crashes. | Criminal Behavior |
BACKGROUND: Accumulation of advanced glycation end-products (AGEs) in skin has been associated with skin aging. Inhibition of glycation of proteins of extracellular matrix may help skin texture and appearance. The objective of the study was to demonstrate the antiglycation activity of topically applied carnosine and novel facial cream (FC) containing carnosine in human skin explants ex vivo. METHODS: Glycation was induced in human skin explants by methylglyoxal (MG) in culture media. FC containing carnosine (FC-CARN) or carnosine in aqueous solution (AQ-CARN) was applied topically on skin explants. Levels of AGEs carboxymethyl-lysine (CML) and pentosidine were determined in the epidermis and dermis of skin sections and were used to calculate antiglycation activity. RESULTS: Exposure to MG led to increases in CML and pentosidine in skin explants. Antiglycation effect for AQ-CARN was CML: -64 and -41%, pentosidine: -48 and 42% in epidermis and reticular dermis respectively. Antiglycation effect for FC-CARN was CML: -150 and -122%, pentosidine: -108 and -136%, in epidermis and reticular dermis respectively. CONCLUSION: Topically applied carnosine protects against the glycation induced by MG. Novel FC-CARN significantly reduced levels of AGEs in both epidermis and reticular dermis in human skin explants. | Skin Cream |
Samuel Taylor Coleridge suffered from a variety of bowel disorders throughout his life; though a large part of his ailment was caused by his famous opium habit, he continuously sought an organic origin, and on at least two separate occasions, in 1804 and 1831-32, he ascribed his disorders to attacks of cholera." With Asiatic cholera apparently first reaching England in late 1831, there was considerable argument among both physicians and the general public as to whether it was a distinctly new disease, or merely a severer variation of traditional English cholera, known as "cholera morbus." Coleridge took a particular interest in these discussions. In this paper, we attempt to establish the exact nature of his attacks of illness, and point to the complexities of describing and framing new diseases and bowel disorders in the early nineteenth century." | Cholera Morbus |
Monomethylmercury (MMHg) is a potent neurotoxicant that can be bioaccumulated and biomagnified through trophic levels. Human populations whose diets contain MMHg are at risk of MMHg toxicity. The gut microbiota was identified as a potential factor causing variation in MMHg absorption and body burden. However, little is known about the role of gut microbiota on Hg transformations. We conducted a series of in vitro experiments to study the effects of dietary nutrient change on Hg metabolism and the human gut microbiota using anoxic fecal slurry incubations. We used stable Hg isotope tracers to track MMHg production and degradation and characterized the microbiota using high throughput sequencing of the 16S rRNA gene. We show that the magnitude of MMHg degradation is individual dependent and rapidly responds to changes in nutrient amendments, leading to complete degradation of the MMHg present. Although the mechanism involved remains unknown, it does not appear to involve the well-known mer operon. Our data are the first to show a nutrient dependency on the ability of the simulated human gut microbiota to demethylate MMHg. This work provides much-needed insights into individual variations in Hg absorption and potential toxicity. | Peptones |
The cytokine IL-1 is critical to the pathogenesis of a variety of human conditions and diseases. Unlike most other cytokines, IL-1 is counterbalanced by two endogenous inhibitors. The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra. In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1. While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling. IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP). Additionally, IL-1R2 exists in both a membrane bound and soluble form (sIL-1R2) that has biological properties similar to both a decoy receptor and a binding protein. Thus far, IL-1R2 has been implicated in arthritis, endometriosis, organ transplantation, sepsis/sickness behavior, diabetes, atherosclerosis, autoimmune inner ear disease (AIED), Alzheimer's disease and ulcerative colitis. In this review, we will detail the functional properties of IL-1R2 and examine its role in human disease." | Receptors, Interleukin-1 Type II |
The California poppy, Eschscholzia californica, produces benzophenanthridine alkaloids (BPAs), an important class of biologically active compounds. Cell cultures of E. californica were investigated as an alternative and scalable method for producing these valuable compounds; treatment with yeast extract increased production from low levels to 23 mg/g dry weight (DW) of BPAs. A shotgun proteomic analysis of E. californica cell cultures was undertaken to explore changes in metabolism associated with enhanced BPA production. We implemented differential centrifugation and then shotgun proteomics based on nanoliquid chromatography/mass spectrometry (nano-LC-MS/MS) for peptide separation and analysis. A unigene database available for E. californica was translated and utilized for protein identification. Approximately 646 proteins (3% false discovery rate at the protein level) were identified. Differentially abundant proteins observed with elicitation included enzymes involved in (S)-adenosyl methionine (SAM) biosynthesis and BPA biosynthesis. These results demonstrate (1) the identification of proteins from a medicinal plant using shotgun proteomics combined with a well-annotated, translated unigene database and (2) the potential utility of proteomics for exploring changes in metabolism associated with enhanced secondary metabolite production. | Eschscholzia |
In order to investigate the association of the protease trypsin with cinnamic acid, the interaction was characterized by using fluorescence, UV-vis absorption spectroscopy, molecular modeling and an enzymatic inhibition assay. The binding process may be outlined as follows: cinnamic acid can interact with trypsin with one binding site to form cinnamic acid-trypsin complex, resulting in inhibition of trypsin activity; the spectroscopic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being -8.95 kJ mol(-1) and 50.70 J mol(-1) K(-1), respectively. Noncovalent interactions make the main contribution to stabilize the trypsin-cinnamic acid complex; cinnamic acid can enter into the primary substrate-binding pocket and alter the environment around Trp and Tyr residues. | Trypsin |
Mycoplasma ovipneumoniae (M. ovipneumoniae) is a bacterium that specifically infects sheep and goat and causes ovine infectious pleuropneumonia. In an effort to understand the pathogen-host interaction between the M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory response using a primary air-liquid interface (ALI) epithelial culture model generated from bronchial epithelial cells of Ningxia Tan sheep (Ovis aries). The ALI culture of sheep bronchial epithelial cells showed a fully differentiated epithelium comprising distinct epithelial types, including the basal, ciliated and goblet cells. Exposure of ALI cultures to M. ovipneumoniae led to increased expression of Toll-like receptors (TLRs), and components of the myeloid differentiation factor 88 (MyD88)-dependent TLR signaling pathway, including the MyD88, TNF receptor-associated factor 6 (TRAF6), IL-1 receptor-associated kinases (IRAKs) and nuclear factor-kappa B (NF-kappaB), as well as subsequent pro-inflammatory cytokines in the epithelial cells. Of interest, infection with M. ovipneumoniae failed to induce the expression of TANK-binding kinase 1 (TBK1), TRAF3 and interferon regulatory factor 3 (IRF3), key components of the MyD88-independent signaling pathway. These results suggest that the MyD88-dependent TLR pathway may play a crucial role in sheep airway epithelial cells in response to M. ovipneumoniae infection, which also indicate that the ALI culture system may be a reliable model for investigating pathogen-host interactions between M. ovipneumoniae and airway epithelial cells. | Mycoplasma ovipneumoniae |
Nurses are expected to provide a safe haven for clients. When clients seek the services of nurses, they are vulnerable, and they expect privacy and confidentiality. Reporting acknowledged or suspected intimate partner violence (IPV) to authorities can impact nurse-client trust relationships. This article discusses the legal ramifications of reporting of IPV and their implications in a health care setting. | Mandatory Reporting |
The conditioned place preference paradigm was used to study the reinforcing properties of beta-phenylethylamine (PEA), d-amphetamine and l-amphetamine. The results confirmed that each drug produced place preferences for a distinctive environment that had previously been paired with the drug treatment. PEA proved as effective as the amphetamine isomers, although substantially less potent. This is the first report of a reinforcing effect of PEA in the rat and supplements previous evidence that PEA is self-administered intravenously in the dog. | Phenethylamines |
Stroke therapy has largely focused on preventing damage and encouraging repair outside the ischemic core, as the core is considered irreparable. Recently, several studies have suggested endogenous responses within the core are important for limiting the spread of damage and enhancing recovery, but the role of blood flow and capillary pericytes in this process is unknown. Using the Rose Bengal photothrombotic model of stroke, we illustrate blood vessels are present in the ischemic core and peri-lesional regions 2 weeks post stroke in male mice. A FITC-albumin gel cast of the vasculature revealed perfusion of these vessels, suggesting cerebral blood flow (CBF) may be partially present, without vascular leakage. The length of these vessels is significantly reduced compared to uninjured regions, but the average width is greater, suggesting they are either larger vessels that survived the initial injury, smaller vessels that have expanded in size (i.e., arteriogenesis), or that neovascularization begins with larger vessels. Concurrently, we observed an increase in platelet-derived growth factor receptor beta (PDGFRbeta, a marker of pericytes) expression within the ischemic core in two distinct patterns, one which resembles pericyte-derived fibrotic scarring at the edge of the core, and one which is vessel associated and may represent blood vessel recovery. We find little evidence for dividing cells on these intralesional blood vessels 2 weeks post stroke. Our study provides evidence flow is present in PDGFRbeta-positive vessels in the ischemic core 2 weeks post stroke. We hypothesize intralesional CBF is important for limiting injury and for encouraging endogenous repair following cerebral ischemia. | Rose Bengal |
PURPOSE: To evaluate the effect of sympathomimetic amine therapy for a life threatening autoimmune disorder. MATERIALS AND METHODS: Dextroamphetamine sulfate was used to treat edema, myalgia, and chronic fatigue associated with autoimmune hepatitis (AIH). RESULTS: Sympathomimetic amine therapy completely abrogated the symptoms associated with AIH. CONCLUSIONS: AIH should be added to the long list of chronic treatment-refractory conditions that respond quickly and effectively to treatment with sympathomimetic amines. | Dextroamphetamine |
Alzheimer's disease is a multifactorial syndrome, for which effective cures are urgently needed. Seeking for enhanced therapeutic efficacy, multitarget drugs have been increasingly sought after over the last decades. They offer the attractive prospect of tackling intricate network effects, but with the benefits of a single-molecule therapy. Herein, we highlight relevant progress in the field, focusing on acetylcholinesterase inhibition and amyloid pathways as two pivotal features in multitarget design strategies. We also discuss the intertwined relationship between selected molecular targets and give a brief glimpse into the power of multitarget agents as pharmacological probes of Alzheimer's disease molecular mechanisms. | Galantamine |
Comparative physiology has traditionally focused on the physiological responses of animals to their physicochemical environment. In recent years, awareness has increased among physiologists of the potential for behavioural factors, such as the social environment of the animal, to affect physiological condition and responses. This recognition has led to an emerging trend within the field toward using multidisciplinary approaches that incorporate both behavioural and physiological techniques. Research areas in which the integrated study of behaviour and physiology has been particularly fruitful include the physiology of the social environment, sensory physiology and behaviour, and physiological constraints on behavioural ecology. The manner in which incorporating behavioural considerations has informed the physiological data collected is discussed for each of these areas using specific examples. | Ethology |
Prokineticins are multifunctional secreted proteins that were originally identified as regulators of intestinal contraction but subsequently shown to affect vascular function, hyperalgesia, spermatogenesis, neuronal survival, circadian rhythm, nociception, feeding behaviour, immune responses, haematopoiesis and the development of the olfactory and gonadotropin-releasing hormone systems. Their role in the reproductive tract is still not fully elucidated, although they are reputed to increase microvascular permeability. Expression of prokineticins and their receptors has been reported in the ovary, uterus, placenta, testis and prostate. Their expression has also been reported in various pathologies of the reproductive tract, and future studies will highlight whether inhibition of prokineticin function in these pathologies would be a useful therapeutic target." | Vascular Endothelial Growth Factor, Endocrine-Gland-Derived |
The objective of this study was to examine the ocular hydrodynamic effects of topically and centrally administered naphazoline, alone and following pretreatment with pertussis toxin (PTX) and alpha(2)/I(1)receptor antagonists. Topically and intracisternally administered naphazoline was examined for its ability to alter intraocular pressure (IOP) of rabbits in the absence and presence of receptor antagonists (rauwolscine, efaroxan) and a G(i/o)ribosylating agent PTX. In addition, the topical effects of naphazoline on pupil diameter and aqueous humor flow rate were evaluated. Topical unilateral application of naphazoline (7.5, 25 and 75 micro g; 25 micro l) elicited an ipsilateral dose-dependent mydriasis (2, 4 and 5.5 mm) that peaked at 2 hr with a duration of up to 5 hr. The IOP decreases induced by naphazoline were bilateral and dose-dependent (3, 6 and 10 mmHg); the response peaked at 1 hr and lasted for up to 5 hr. Pretreatment with efaroxan (250 micro g) elicited significantly greater antagonism of the ocular hypotensive response to naphazoline than did rauwolscine (250 micro g) suggesting an involvement of imidazoline (I(1)) receptors. Intracisternal application of naphazoline (3.3 micro g) also produced bilateral reductions (6 mmHg) of IOP that were immediate (10 min post drug) and lasted for approximately 2 hr. In PTX-pretreated (2.5 micro g kg(-1), i.a.) rabbits, the ocular hypotensive effects of naphazoline by both routes (topically and centrally) were attenuated by 50--65%. In addition to producing ocular hypotension, topical application of naphazoline (75 micro g; 25 micro l) caused significant reduction, from 2.8 to 1.5 micro l min(-1), in aqueous humor flow. These in vivo data indicate that, regardless of route of administration, alteration of aqueous humor flow by naphazoline was induced by the activation of alpha(2)and I(1)receptors. The ocular hypotensive effects produced by central administration did not result in sedation, therefore, there is the suggestion that central alpha(2)adrenergic receptors were stimulated minimally by naphazoline. Thus, these data suggest that ocular hypotensive effects and suppression of aqueous humor flow rate by naphazoline are mediated, in part, by alpha(2)and/or central I(1)at both central (brain) and peripheral (eye) sites. Moreover, these data indicate that the receptors are linked to PTX-sensitive G((i/o))proteins. | Naphazoline |
There is growing interest in finding ways to enhance longevity and the quality of life. This paper summarizes a vast scientific literature over the past two decades that has suggested approaches to enhancing biological resilience - and particularly neurological function - via hormetic and preconditioning processes. The employment of hormesis and preconditioning has been shown to protect biological systems from many of the effects of aging, both by sustaining structural and functional integrity, and by affording relative protection against certain types of diseases. The paper confronts the challenges - and opportunities - for society when considering possible practical use of evolving evidence about the mechanisms, processes and effects of these biological phenomena. | Hormesis |
In this paper we investigate the optical forces induced by localized optical modes propagating along three parallel waveguides, of which only the central one is free to move. In this configuration, when all three waveguides are identical, the components of the optical-force acting on the free beam are decoupled along the axis of symmetry. As a result, two dimensional optomechanical control of the central waveguide, like single-mode optical trapping, can be achieved. We also study non symmetric configurations, that can be used, for example, to tailor the position of the optical trap. Unlike other techniques that rely on buckling, multi-mode excitation or radiation-pressure, single-mode optomechanical-operation should help the realization of faster and simpler on-chip positioning of a single nanobeam since most of the parameters involved can be controlled with great precision. | Micromanipulation |
Control of rodent adventitial infections in biomedical research facilities is of extreme importance in assuring both animal welfare and high-quality research results. Sixty-three U.S. institutions participated in a survey reporting the methods used to detect and control these infections and the prevalence of outbreaks from 1 January 2014 through 31 December 2015. These results were then compared with the results of 2 similar surveys published in 1998 and 2008. The results of the current survey demonstrated that the rate of viral outbreaks in mouse colonies was decreasing, particularly in barrier facilities, whereas the prevalence of parasitic outbreaks has remained constant. These results will help our profession focus its efforts in the control of adventitial rodent disease outbreaks to the areas of the greatest needs. | Rodent Diseases |
PURPOSE: Today's social support systems for parents of preterm infants tend to pay more attention to mothers than fathers. As a father also plays a critical role in caring for a preterm infant, there is a need to advance understanding of paternal concerns and needs about social supports that should better support fathers. DESIGN AND METHODS: Interviews were conducted with 18 parents of preterm infants (i.e., 10 mothers and 8 fathers) who have been discharged from the NICU to home. All interviews were audio-recorded and subsequently transcribed verbatim for analysis. RESULTS: The fathers' primary resources are healthcare professionals, their partners, and peer fathers of preterm infants. The fathers expressed various social support needs associated with informational, belonging, and emotional supports. CONCLUSIONS: It is recommended that a social support system be customized accordingly to better accommodate paternal needs. PRACTICE IMPLICATIONS: Healthcare professionals may refer to the study results in designing the educational materials for fathers of preterm infants. | Paternal Behavior |
Pleuritis or pleural effusion frequently develops in patients with pneumonia or heart failure. Most of these pleural changes regress without intrapleural intervention. The detailed mechanisms of the regression of the pleural changes in humans are not well documented. We studied the parietal pleura of nine patients with lung cancer and two patients with coronary artery disease by scanning electron microscopy (SEM). All patients had neither radiographic nor gross evidence of pleural disease but all had mixed surface alterations by SEM. Focal denudation of mesothelial cells was common. Deeper injuries exposed thick and thin interweaving collagen bundles. Patchy depositions of amorphous or crystallized fibrin covered normal and damaged pleural surfaces, frequently admixed with macrophages, red blood cells, and tissue debris. Reactive mesothelial cells appeared to proliferate over the fibrin. Our findings suggest that subclinical pleural alterations occur often in patients with pulmonary or cardiac diseases and that an intact pleural surface in those patients is restored mainly by the proliferation of reactive mesothelial cells. | Pleura |
The epithelial sodium channel (ENaC) plays an essential role in transepithelial sodium reabsorption in the renal connecting tubule and collecting duct. Therefore, controlling ENaC activity is an important regulatory event in electrolyte and extracellular volume homeostasis, and thus in the control of blood pressure. Many independent signaling pathways converge on ENaC, although the most important for its physiological role is the enhancement of channel activity by the steroid hormone aldosterone. In this review, we briefly summarize current knowledge about ENaC regulation and the different chemical compounds available to directly or indirectly modify channel function. In addition, current and possible clinical uses of ENaC and aldosterone antagonists are highlighted." | Epithelial Sodium Channel Agonists |
This set of experiments was designed to evaluate the effects of thiabendazole (TBZ), a relatively nontoxic thiazole derivative, on the delayed hypersensitivity response of normal mice, tumor-bearing mice, and mice immunosuppressed by radiation and chemotherapy. Normal mice treated with a single intraperitoneal injection (20 mg. per kilogram) of TBZ given on the day of challenge with 2,4 dinitrochlorobenzene (DNCB) had 41 percent greater swelling of the injected foot pad than did control animals. This increased immune reactivity could be transferred with spleen cells from TBZ-treated animals as well as with macrophages incubated in vitro with TBZ. Mice given sublethal radiation (450 r) had almost complete restoration of the delayed hypersensitivity response (90 percent of control) when treated with TBZ. The immunosuppressive effects of Adriamycin also could be reversed in a similar fashion. It is likely that the immune function of more than one population of spleen cells is amplified by TBZ treatment. The observed effects strongly suggest that thiabendazole may have a role as an adjunct in cancer therapy. | Thiabendazole |
In this essay, I have elaborated on the ideas and experiments that have guided my research career. First, I present my early research history and my involvement in determining the neurobiological basis of the consolidation process based primarily on the consolidation paradigm. Based on a series of experiments and a new interest in cognitive psychology, I then developed a cognitive and neurobiologically based model of memory. This model represents a comprehensive view of memory organization based on multiple processes and multiple forms of memory representation and is based on the neurobiology of a multiple attribute, multiple process, tripartite system model of memory. I present some detailed evidence in terms of the neural foundations, specific attributes, and processes of operation for the event-based, knowledge-based, and rule-based memory systems. In addition, I present a set of experiments to demonstrate that there might be parallel processing of mnemonic information in rats and humans. Finally, I recognize that ideas can be generated by reading the extant literature, interaction with colleagues at meetings, and exchange of ideas with students to design and execute hopefully meaningful experiments. | Memory |
The ability of a biological system to drive the formation of a microstructure as complex and ordered as the molluscan shell is of immense interest to the fields of nanotechnology and biomedicine. Although recent studies have greatly expanded our knowledge of the genes involved in shell formation, the mechanism by which matrix proteins are regulated and directed to the appropriate region of the shell, a process critical for microstructure control, is still obscure. The formation of microstructure-specific compartments within the extrapallial cavity may be the outcome of precise regulation of the vesicle trafficking of shell components within secretory cells at the mineralization front and/or the overall organization and morphology of the mantle itself. Here, we investigate the ultrastructure of the mantle of the gastropod Haliotis asinina as current models put forward to describe molluscan shell formation are primarily based on observations from bivalves despite crystallographic and molecular studies indicating large differences between molluscan classes. We find that the H. asinina mantle is structurally complex and comprised of novel cells packed with a diversity of vesicle types consistent with a complex system to control the secretion of the shell matrix and associated factors. | Gastropoda |
Matrix metalloproteinases (MMPs) play an important role in many physiological and pathological processes. To assay the activities of MMPs is important in diagnosis and therapy of the MMPs associated diseases, such as neoplastic, rheumatic and cardiovascular diseases. Several assay systems have been developed, which include bioassay, zymography assay, immunoassay, fluorimetric assay, radio isotopic assay, phage-displayed assay, multiple-enzyme/multiple-reagent assay and activity-based profiling assay. The principle, application, advantage and disadvantage of these assays have been reviewed in this article. | Protease Inhibitors |
Radiation dermatitis, limited to the irradiated site, is the most common cutaneous adverse reaction due to radiotherapy. There are scattered reports of erythema multiforme-like rash, Stevens-Johnson syndrome, and toxic epidermal necrolysis associated with radiotherapy. Some of these reports include cases without remarkable drug history, which suggests rashes induced by radiotherapy. The lack of a large cohort study, however, makes it difficult to ascertain the time course, severity, and outcome of the cases. We aimed to evaluate the potential association between radiotherapy and erythema multiforme-like rash in a larger sample of patients. We examined the records of patients at our institute who received radiotherapy and developed a rash from 2010 to 2021. We present 30 patients with erythema multiforme-like rash, which arose during or after radiotherapy. We describe the background, details of radiotherapy, and clinical course of the patients including the cutaneous and extracutaneous symptoms. Radiotherapy was the most likely cause of rash, and in most cases, the rash was relieved by conservative management and radiation could be continued. When erythema multiforme-like rash arises in patients under cancer treatment, radiotherapy should be considered a potential trigger. | Erythema Multiforme |
The ferritin-like DNA-binding protein from starved cells (Dps) family proteins are present in a number of pathogenic bacteria. Dps in the enterohepatic pathogen, Helicobacter hepaticus is characterized and a H. hepaticus dps mutant was generated by insertional mutagenesis. While the wild type H. hepaticus cells were able to survive in an atmosphere containing up to 6.0% O2, the dps mutant failed to grow in 3.0% O2, and it was also more sensitive to oxidative reagents like H2O2, cumene hydroperoxide and t-butyl hydroperoxide. Upon air exposure, the dps- cells had more damaged DNA than the wild type; they became coccoid or lysed and they contained approximately 6-fold higher amount of 8-oxoguanine (8-oxoG) DNA lesions than wild type cells. Purified H. hepaticus Dps was shown to be able to bind both iron and DNA. The iron-loaded form of Dps protein had much greater DNA binding ability than the native Dps or the iron-free Dps. | Helicobacter hepaticus |
Increased environmental awareness is slowly driving the industry to develop alternatives to chemical routes for synthesis. Lipase catalysed synthesis is one such alternative route that is environmentally more acceptable. In this study, immobilized Candida antarctica lipase (Lipozyme 435) was used for the esterification of ricinoleic acid and isopropyl alcohol. Molecular sieves were used to remove the water formed during esterification to drive the reaction in forward direction. The optimal conditions observed were 40 degrees C temperature, 4% enzyme concentration, 1:1 acid: alcohol ratio and 4 hours time interval. Under the described conditions, the reusability of lipase was tested and it was found that above 80% esterification was observed for over three cycles. | Ricinoleic Acids |
OBJECTIVE: To evaluate the association between mean echogenicity of the puborectalis muscle, measured using transperineal ultrasonography, in women during their first pregnancy and the subsequent mode of delivery. METHODS: This is a secondary analysis of a prospective observational study on the association between stress urinary incontinence and levator muscle avulsion after delivery of a first pregnancy. In this study, 280 nulliparous women with singleton pregnancies were examined with transperineal ultrasound examination at 12 and 36 weeks of gestation. Patients were recruited from an obstetrics practice associated with the university medical center in Utrecht, the Netherlands. Mean echogenicity of the puborectalis muscle values were measured at rest, in pelvic floor muscle contraction, and during the Valsalva maneuver. The subsequent mode of delivery was classified into five categories: spontaneous vaginal delivery, instrumental vaginal delivery, elective cesarean delivery, cesarean delivery resulting from nonreassuring fetal status, and cesarean delivery resulting from failure to progress. Mean echogenicity of the puborectalis muscle values according to mode of delivery were compared by analysis of variance and Tukey's post hoc test. RESULTS: Of the 254 women included, 157 had spontaneous vaginal delivery, 47 underwent cesarean delivery (11 elective, 36 emergency), and 45 had vacuum operative vaginal delivery; in five patient files, the mode of delivery was not recorded. Of the analyzed women, those who delivered by cesarean because of failure to progress had a significantly lower mean echogenicity of the puborectalis muscle in pelvic floor contraction at 12 weeks of gestation (mean echogenicity of 116+/-14) than women who had spontaneous vaginal delivery (132+/-21; Tukey's post hoc test, P=.03), instrumental vaginal delivery (138+/-21; P=.004), and cesarean delivery resulting from nonreassuring fetal status (139+/-20; P=.02). CONCLUSION: Lower mean echogenicity of the puborectalis muscle values in pelvic floor contraction during the first pregnancy at 12 weeks of gestation is associated with subsequent cesarean delivery as a result of failure to progress. | Pelvic Floor |
1. Eye positions of monkeys were tracked while low-current electrical stimulation was delivered to area PG of the posterior parietal cortex. Stimulation was delivered while monkeys were in darkness, while they were in a dimly illuminated room, or while they actively fixated on small lamps to receive a liquid reward. 2. Resulting eye movements fell into one of three categories, depending roughly on the area stimulated. Stimulation of caudal regions generally resulted in saccades that were of approximately equivalent amplitudes and directions. When more rostral areas were stimulated, saccades were generally produced that directed the eyes toward roughly the same position in the head. Distributed throughout all regions were sites for which elicited saccades did not fall clearly into either of these coordinate bases. Stimulation of lateral areas produced low-velocity eye movements that were directed ipsilaterally from the stimulated hemisphere. 3. Stimulation made while monkeys fixated on target lamps produced saccades with more variability and less amplitude than those produced while monkeys were in darkness. Low-velocity eye movements could only be elicited while monkeys were in darkness. 4. Craniocentric saccades typically brought the eyes to within a 10-20 degrees area, and saccades could not be produced when the initial eye position was near this area. Craniocentric saccades were always greater than 5 degrees in amplitude. 5. It is concluded that area PG is organized into at least two zones that differ in the way by which they code saccades. A caudal region codes saccades in a way similar to that found in the frontal cortex and superior colliculus of primates. A rostral region codes saccades in a craniocentric manner, although it is restricted only to gross redirection of gaze without the accuracy monkeys are capable of using in directing their eyes. | Cerebral Peduncle |
Administration of unithiol to animals with endotoxin shock promotes deposition of catecholamines in chromaffin cells of the adrenals, blocks their secretion to the bloodstream and prevents the development of injuries to the cortical substance of the gland. Administration of unithiol for endotoxemia prevents damage to intracellular organelles of cardiomyocytes. However, insignificant disorders of the contractile apparatus of the cells and histohematic barriers are maintained. The capacity of unithiol to prevent the progress of destructive alterations in the heart and adrenals permits recommending it for use in combined treatment of septic conditions. | Unithiol |
We have previously identified species-specific DNA fragments, referred to as MS2/28 and Mm14, of Mycoplasma synoviae and Mycoplasma meleagridis, respectively. In the present study, we extended our analysis of the MS2/28 fragment that was found to encode a species-specific antigenic site, and we demonstrated the specificity of the Mycoplasma gallisepticum hemagglutinin protein encoded by pMGA1.2 (a member of the vlhA gene family). Then, we combined the Escherichia coli-expressed products of MS2/28, Mm14, and pMGA1.2, to develop a recombinant antigen-based enzyme-linked immunosorbent assay (recELISA), for the simultaneous and specific detection of antibodies to the three aforementioned major avian mycoplasma species. For comparative purposes, a novel in-house crude antigen capture ELISA (capELISA) was developed in parallel. In the latter protocol, the microtiter wells were enriched in species-specific antigens by capturing sonicated crude antigens on coated rabbit polyclonal antibodies that had been extensively adsorbed with the whole antigen of the heterologous species. With regard to rapid serum agglutination, both ELISA tests were highly specific, and they showed a significant correlation when field sera from naturally infected birds were tested. recELISA proved to be highly specific because absorbance values, with the heterologous species, were significantly lower (P < 0.001) than those obtained with capELISA. Given its cost-effectiveness and simplicity, the recombinant antigen-based ELISA seems to represent a valid tool for the specific screening of the three major avian mycoplasma species. recELISA will be particularly useful with regard to trade control because a large number of samples from various fields could be rapidly processed. | Mycoplasma meleagridis |
OBJECTIVE: Fibromyalgia is a chronic disorder with a very complex symptomatology. Although generalized severe pain is considered to be the cardinal symptom of the disease, many other associated symptoms, especially non-restorative sleep, chronic fatigue, anxiety, and depressive symptoms also play a relevant role in the degree of disability characteristic of the disease. Ozone therapy, which is used to treat a wide range of diseases and seems to be particularly useful in the treatment of many chronic diseases, is thought to act by exerting a mild, transient, and controlled oxidative stress that promotes an up-regulation of the antioxidant system and a modulation of the immune system. According to these mechanisms of action, it was hypothesized that ozone therapy could be useful in fibromyalgia management, where the employed therapies are very often ineffective. PATIENTS AND METHODS: Sixty-five patients with fibromyalgia, according to the definition of the American College of Rheumatology (Arthritis Rheum 1990; 33: 160-172), were treated at the MEDE Clinic (Sacile, Pordenone, Italy) from February 2016 to October 2018. Females were 55 and males were 10; age ranged from 30 to 72 years, and the time from fibromyalgia diagnosis ranged from 0.5 to 33 years. Treatment was made by autohemotransfusion in 55 patients and by ozone rectal insufflations in 10 patients, according to SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, twice a week for one month and then twice a month as maintenance therapy. RESULTS: We found a significative improvement (>50% of symptoms) in 45 patients (70%). No patient reported important side effects. In conclusion, at our knowledge, this is the largest study of patients with fibromyalgia treated with ozone therapy reported in the literature and it demonstrates that the ozone therapy is an effective treatment for fibromyalgia patients without significant side effects. CONCLUSIONS: At the moment, ozone therapy seems a treatment that, also because without any side effect, is possible to be proposed to patients with fibromyalgia that are not obtaining adequate results from other available treatments and it can be considered as complementary/integrative medicine. | Ozone |
PURPOSE: We investigated the prevalence of deletions in the azoospermic factor (AZF) region of chromosome Yq11 in Chinese men with infertility due to idiopathic azoospermia or severe oligozoospermia. The DAZ gene cluster was also examined for mutations. METHODS: Sixty-eight men with azoospermia or severe oligozoospermia taking part in an intracytoplasmic sperm injection program were recruited. Four loci specific for AZFa, AZFb, and AZFc were amplified from genomic DNA via polymerase chain reaction to determine whether deletions were present in the AZF region. Direct DNA sequencing of amplified products was also performed to look for mutations or polymorphism from exon 2 to exon 6 of the DAZ gene cluster. RESULTS: Six (9%) of the 68 patients had AZF deletions. None had mutations in exons 2 to 6 of DAZ. CONCLUSIONS: The prevalence of AZF deletions in our study was similar to those in Western reports, as was the lack of DAZ mutations." | Deleted in Azoospermia 1 Protein |
Acetyl-l-carnitine (ALC) facilitates the entry and exit of fatty acids from mitochondria and plays an essential role in energy metabolism. Although ALC is known to exert neuroprotective effects in multiple neurological diseases, its effects on spinal cord injury (SCI)-induced mitochondrial impairments and apoptosis remain unclear. In this study, we aimed to evaluate the putative effects of ALC on mitochondrial dysfunction and apoptosis induced by SCI in a rodent model. Our results indicate that SCI elicits dynamic alternations in the expression of mitochondria-related proteins. Transmission electron microscopy analysis showed that ALC administration abrogated key ultrastructural abnormalities in mitochondria at 24h after SCI by maintaining mitochondrial length, reducing the number of damaged mitochondria, and reversing mitochondrial score (P<0.05 compared with SCI group). In addition, ALC administration maintained the mitochondrial membrane potential and mitochondrial Na(+)-K(+)-ATPase activity following SCI (P<0.05 compared with SCI group). ALC administration reversed the downregulation of mitofusin 1 (Mfn1), Mfn2, Bcl-2, and the upregulation of dynamin-related protein 1 (Drp1), mitochondrial fission 1 (Fis1), Bcl-2-associated X protein (Bax) and cytosol cytochrome c (cyto-CytC) induced by SCI (P<0.05 compared with SCI group). Finally ALC administration greatly reduced the percentage of apoptotic cells compared with the SCI group (P<0.01). In conclusion, our findings demonstrated that ALC ameliorated SCI-induced mitochondrial structural alternations, mitochondrial dysfunction, and apoptosis. | Acetylcarnitine |
OBJECTIVE: To compare magnetization transfer changes in new brain MRI lesions identified during monthly imaging in patients with multiple sclerosis (MS) randomized to treatment with 250 mug subcutaneous interferon-beta-1b (IFN-beta-1b) every other day or daily 20 mg glatiramer acetate (GA) in a post hoc study using data from the Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI (BECOME) trial. METHODS: T1-weighted images acquired with and without fat saturation pulses in the BECOME study were evaluated and found to exhibit magnetization transfer ratio (MTR) effects, and were used to compute MTR images (FSMTR). Forty-three participants who had the required imaging and new lesions, from the 75 originally randomized into the BECOME study, were included in this post hoc analysis and evaluated longitudinally during treatment to determine FSMTRDrop, an experimental measure of the completeness of FSMTR recovery in new lesions. Two sets of new brain MRI lesions were defined, one based on the appearance of gadolinium contrast enhancement (Gd lesions) and the other based on FSMTR decreases (DeltaFSMTR lesions). RESULTS: A total of 887 Gd lesions were identified in 43 participants (19 GA, 24 IFN-beta-1b) and 321 DeltaFSMTR lesions in 32 participants (16 GA, 16 IFN-beta-1b). Participants randomized to GA exhibited greater average postlesion FSMTR recovery than did those randomized to IFN-beta-1b in both Gd (p < 0.0001) and DeltaFSMTR (p < 0.0001) lesions. CONCLUSIONS: New brain lesions that developed during treatment with GA exhibited evidence of greater FSMTR recovery than during treatment with IFN-beta-1b. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that MTR recovery in patients with MS with new MRI brain lesions is greater with GA than with IFN-beta-1b. | Interferon beta-1b |
Non-classic or late-onset congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence is approximately 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess. The purpose of this review is to provide current information regarding the pathophysiology, molecular genetics, and management of this common disorder. The treatment of NCAH needs to be directed towards the symptoms. For affected children, goals of treatment include normal linear growth velocity, normal rate of skeletal maturation, "on-time" puberty. For affected adolescent and adult women, goals of treatment include regular menstrual cycles, prevention or progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations." | Steroid Metabolism, Inborn Errors |
Facial neuropathy, or seventh cranial neuropathy, is the most common cranial neuropathy. The anatomy of the facial nerve is rather complex for a cranial nerve, with a long intracranial course, in which the nerve takes three bends (or genu). Electrodiagnosis can be helpful in prognosis, but not before several days. Imaging is rarely indicated in Bell's palsy, but is often abnormal nonetheless, and can be very useful in other causes of facial neuropathy. The clinical presentation is of unilateral facial weakness of upper and lower face, hyperacusis, dysgeusia, and disordered lacrimation and salivation. Many different disease processes can result in facial neuropathy, but 70% of cases are idiopathic, or as it is best known, Bell's palsy. Ramsay Hunt syndrome, defined as facial neuropathy with herpes zoster oticus, is another common cause. Steroids given acutely are beneficial in improving outcome in Bell's palsy, and antiviral therapy seems helpful in more severe cases. Antiviral therapy is definitely helpful in Ramsay Hunt disease when given within 3 days of onset. Antibiotics are helpful in Lyme facial neuropathy, which has a very good prognosis. | Herpes Zoster Oticus |
PURPOSE: To compare the popularity of pneumatic retinopexy (PR) in 1997 with its popularity in 1990 among retinal specialists. METHODS: In 1997, a survey was mailed to the 1994-1995 members of the Retina or Vitreous Societies who lived in the United States or Canada, asking how they would manage a hypothetical retinal detachment. The choices were limited to PR, segmental scleral buckling, scleral bucking with encircling, primary vitrectomy, and Lincoff balloon. The results of the survey were compared with those previously reported by a similar survey in 1990. RESULTS: The majority (55%) of respondents selected PR, which is a twofold increase over those who preferred it in 1990 (odds ratio 2.08; 95% confidence interval 1.53, 2.85). The popularity of PR was inversely proportional to the length of time the respondents had been in practice. If the eye with the hypothetical detachment had pseudophakia, only 30% of respondents selected PR. If the eye had additional tears, vitreous hemorrhage, or lattice degeneration, only about one-sixth preferred PR. CONCLUSION: Pneumatic retinopexy was much more popular in 1997 than it was in 1990. Its popularity continues to be influenced by the age of the surgeon and by the complexity of the detachment. | Pseudophakia |
In the present work are reported investigations on the formation and chemical nature of the chorion of Ascidia malaca oocytes. The ultrastructural observations have shown that both follicle cells and test cells play a key role on chorion formation. At the beginning of vitellogenesis (stage I), chorion is formed by a single fibrogranular layer. During vitellogenesis (stage II), the chorion becomes, at first, bi-layered and successively presents three layers. The outer layer (ofl) is composed of a thin and irregular network of short fibrils. The central layer (cdl) is also made by a fibrillar component which is very compact to form an electron-dense layer. The inner layer (ifl) has a larger size compared to that of outer and central layer and it is composed by a matrix containing little and scattered globular electron-dense granules and several fibrils oriented in all directions. At the end of vitellogenesis beneath the three-layered chorion a large perivitelline space will be formed. In this space are found the test cells. Cytochemical investigations performed at light microscopy (toluidine blue) and electron microscopy (PA-TCH-SP) have shown in Ascidia malaca chorion the presence of substances with a polysaccharidic nature that are probably conjugated as glycoprotein and/or proteoglycans. | Chorion |
The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally and functionally related. Their actions have been shown to be mediated by three different receptor subtypes: PAC1-R, which has exclusive affinity for PACAP, and VPAC1-R and VPAC2-R, which have equal affinity for PACAP and VIP. We recently showed that PACAP38 induces lipolysis in rat adipocytes, and in the present study we examined whether VIP has similar effects and which of the three receptors mediates this PACAP/VIP action. We showed by RT-PCR that all three receptor subtypes are present in rat adipocytes. We demonstrated that VIP (1-100 nm), like PACAP38, stimulates lipolysis in isolated adipocytes, as determined by glycerol release. By a pharmacological approach, using antagonists and agonists specific for the receptor subtypes, we elucidated the mechanisms by which PACAP38 and VIP mediate their lipolytic effects. We found that antagonists of PAC1-R [PACAP(6-38)] and VPAC1-R (PG97-269) did not affect lipolysis induced by 0.1-100 nm PACAP38 or VIP, and that a VPAC1-R agonist [K15, R16, L27VIP(1-7)GRF(8-27)] did not affect lipolysis at 1-1000 nm. However, two different VPAC2-R agonists [Hexa-VIP(1-28) and Ro25-1553] clearly mimicked the lipolytic effect of PACAP38 and VIP. In addition, the VPAC2-R antagonist PG99-465 (100 nm) caused right-shifted dose-response curves of PACAP38- and VIP-induced lipolysis. These results therefore provide evidence that all three PACAP/VIP receptor subtypes are expressed in primary rat adipocytes, but that the VPAC2-R subtype is responsible for mediating the lipolytic effects induced by PACAP38 and VIP." | Receptors, Vasoactive Intestinal Polypeptide, Type I |
Co-processing of APIs, the practice of creating multi-component APIs directly in chemical processing facilities used to make drug substance, is gaining increased attention with a view to streamlining manufacturing, improving supply chain robustness and accessing enhanced product attributes in terms of stability and bioavailability. Direct co-precipitation of amorphous solid dispersions (ASDs) at the final step of chemical processing is one such example of co-processing. The purpose of this work was to investigate the application of different advanced solvent-based processing techniques - direct co-precipitation (CP) and the benchmark well-established spray-drying (SD) process - to the production of ASDs comprised of a drug with a high T(g) (hydrochlorothiazide, HCTZ) or a low T(g) (simvastatin, SIM) molecularly dispersed in a PVP/VA 64 or Soluplus(R) matrix. ASDs of the same composition were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD), modulated differential scanning calorimetry (mDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). Both methods produced ASDs that were PXRD amorphous, with some differences, depending on the process used, in glass transition temperature and particle size distribution. Irrespective of manufacturing method used, all ASDs remained PXRD amorphous when subjected to high relative humidity conditions (75% RH, 25 degrees C) for four weeks, although changes in the colour and physical characteristics were observed on storage for spray-dried systems with SIM and PVP/VA 64 copolymer. The particle morphology differed for co-precipitated compared to spray dried systems, with powder generated by the former process being comprised of more irregularly shaped particles of larger particle size when compared to the equivalent spray-dried systems which may enable more streamlined drug product processes to be used for CP materials. These differences may have implications in downstream drug product processing. A limitation identified when applying the solvent/anti-solvent co-precipitation method to SIM was the high antisolvent to solvent ratios required to effect the precipitation process. Thus, while similar outcomes may arise for both co-precipitation and spray drying processes in terms of ASD critical quality attributes, practical implications of applying the co-precipitation method and downstream processability of the resulting ASDs should be considered when choosing one solvent-based ASD production process over another. | Spray Drying |
Alternaria is a cosmopolitan fungal genus that includes saprophytic, endophytic and pathogenic species, widely distributed in soil and organic matter in decomposition. Plant pathogenic species affect cereals, vegetables and fruit crops in the field and during storage. Alternaria spp. contamination is responsible for some of the world's most devastating plant diseases, causing serious reduction of crop yields and considerable economic losses. Alternaria species produce more than 70 secondary metabolites which are toxic to plants, and some of these phytotoxins have been chemically characterised and reported to act as mycotoxins to humans and animals. Exposure to Alternaria spp. toxins has been linked to a variety of adverse effects on human and animal health, including genotoxic, mutagenic, carcinogenic and cytotoxic effects. Alternaria spp. mycotoxins have been isolated from fruits (apple, pear, melon, apricot, grapes, raisins, strawberry, olive, citrus fruits and dried figs), vegetables (tomato, pepper and carrot) and tubers (potato), as well as from several processed foodstuffs manufactured with damaged raw materials (juices, preserves, sauces, etc.). Moreover, Alternaria spp. are frequently associated with allergic reactions in sensitized individuals. | Alternariosis |
In this issue of Immunity, Ghisletti et al. (2010) examined lipopolysaccharide (LPS)-induced binding of the p300 transcription coactivator to identify inducible enhancers throughout the genome of mouse macrophages, thereby revealing common features of enhancers that contribute to the LPS response and a critical role for PU.1 in enhancer marking. | E1A-Associated p300 Protein |
When faced with vaccine hesitancy, public health authorities are looking for effective strategies to address this issue. In this paper, the findings of 15 published literature reviews or meta-analysis that have examined the effectiveness of different interventions to reduce vaccine hesitancy and/or to enhance vaccine acceptance are presented and discussed. From the literature, there is no strong evidence to recommend any specific intervention to address vaccine hesitancy/refusal. The reviewed studies included interventions with diverse content and approaches that were implemented in different settings and targeted various populations. Few interventions were directly targeted to vaccine hesitant individuals. Given the paucity of information on effective strategies to address vaccine hesitancy, when interventions are implemented, planning a rigorous evaluation of their impact on vaccine hesitancy/vaccine acceptance will be essential. | Attitude |
Subarachnoid hemorrhage (SAH) was produced in cats by transorbital rupture of the right middle cerebral artery (MCA). In untreated cats, widespread proliferative angiopathy occurred in both MCA's by 16 days after SAH. In cats that received systemic heparin, the pathological events following SAH were clearly reduced in the ruptured artery, and were not present in the contralateral left MCA. Platelets are known to adhere to the subintimal surface of cerebral arteries after SAH. The authors suggest that platelet-derived growth factor released from the intimal platelet carpet following SAH may be the stimulus for the development of proliferative angiopathy, and that this platelet factor is inhibited by heparin. | Cerebral Arteries |
The difficulty of defining the three so-called components of << an-esthesia >> is emphasized: hypnosis, absence of movement, and adequacy of anti-nociception (intraoperative << analgesia >>). Data obtained from anesthetized animals or humans delineate the activation of cardiac and vasomotor sympathetic reflex (somato-sympathetic reflex) and the cardiac parasympathetic deactivation observed following somatic stimuli. Sympathetic activation and parasympathetic deactivation are used as monitors to address the adequacy of intraoperative anti-nociception. Finally, intraoperative nociception through the administration of nonopioid analgesics vs. opioid analgesics is considered to achieve minimal postoperative side effects. | Pain Perception |
Malaria remains one of the most prominent and dangerous tropical diseases. While artemisinin and analogs have been used as first-line drugs for the past decades, due to the high mutational rate and rapid adaptation to the environment of the parasite, it remains urgent to develop new antimalarials. The pyrimidine biosynthesis pathway plays an important role in cell growth and proliferation. Unlike human host cells, the malarial parasite lacks a functional pyrimidine salvage pathway, meaning that RNA and DNA synthesis is highly dependent on the de novo synthesis pathway. Thus, direct or indirect blockage of the pyrimidine biosynthesis pathway can be lethal to the parasite. Aspartate transcarbamoylase (ATCase), catalyzes the second step of the pyrimidine biosynthesis pathway, the condensation of L-aspartate and carbamoyl phosphate to form N-carbamoyl aspartate and inorganic phosphate, and has been demonstrated to be a promising target both for anti-malaria and anti-cancer drug development. This is highlighted by the discovery that at least one of the targets of Torin2 - a potent, yet unselective, antimalarial - is the activity of the parasite transcarbamoylase. Additionally, the recent discovery of an allosteric pocket of the human homology raises the intriguing possibility of species selective ATCase inhibitors. We recently exploited the available crystal structures of the malarial aspartate transcarbamoylase to perform a fragment-based screening to identify hits. In this review, we summarize studies on the structure of Plasmodium falciparum ATCase by focusing on an allosteric pocket that supports the catalytic mechanisms. | Multifunctional Enzymes |
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus causing a high fatality rate of up to 30%. To date, the receptor mediating SFTSV entry remained uncharacterized, hindering the understanding of disease pathogenesis. Here, C-C motif chemokine receptor 2 (CCR2) was identified as a host receptor for SFTSV based on a genome-wide CRISPR-Cas9 screen. Knockout of CCR2 substantially reduced viral binding and infection. CCR2 enhanced SFTSV binding through direct binding to SFTSV glycoprotein N (Gn), which is mediated by its N-terminal extracellular domain. Depletion of CCR2 in C57BL/6J mouse model attenuated SFTSV replication and pathogenesis. The peripheral blood primary monocytes from elderly individuals or subjects with underlying diabetes mellitus showed higher CCR2 surface expression and supported stronger binding and replication of SFTSV. Together, these data indicate that CCR2 is a host entry receptor for SFTSV infection and a novel target for developing anti-SFTSV therapeutics. | Receptors, CCR2 |
Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at high frequency in uterine fibroids (UFs) and breast fibroepithelial tumors as well as recurrently, albeit less frequently, in malignant uterine leimyosarcomas, chronic lymphocytic leukemias, and colorectal cancers. Previously, we reported that UF-linked mutations in MED12 disrupt its ability to activate cyclin C (CycC)-dependent kinase 8 (CDK8) in Mediator, implicating impaired Mediator-associated CDK8 activity in the molecular pathogenesis of these clinically significant lesions. Notably, the CDK8 paralog CDK19 is also expressed in myometrium, and both CDK8 and CDK19 assemble into Mediator in a mutually exclusive manner, suggesting that CDK19 activity may also be germane to the pathogenesis of MED12 mutation-induced UFs. However, whether and how UF-linked mutations in MED12 affect CDK19 activation is unknown. Herein, we show that MED12 allosterically activates CDK19 and that UF-linked exon 2 mutations in MED12 disrupt its CDK19 stimulatory activity. Furthermore, we find that within the Mediator kinase module, MED13 directly binds to the MED12 C terminus, thereby suppressing an apparent UF mutation-induced conformational change in MED12 that otherwise disrupts its association with CycC-CDK8/19. Thus, in the presence of MED13, mutant MED12 can bind, but cannot activate, CycC-CDK8/19. These findings indicate that MED12 binding is necessary but not sufficient for CycC-CDK8/19 activation and reveal an additional step in the MED12-dependent activation process, one critically dependent on MED12 residues altered by UF-linked exon 2 mutations. These findings confirm that UF-linked mutations in MED12 disrupt composite Mediator-associated kinase activity and identify CDK8/19 as prospective therapeutic targets in UFs. | Cyclin C |
Specific and highly sensitive colourimetric and fluorometric substrate mixtures have been prepared for the measurement of pullulanase and limit-dextrinase activity and assays employing these substrates have been developed. These mixtures comprise thermostable alpha- and beta-glucosidases and either 4,6-O-benzylidene-2-chloro-4-nitrophenyl-beta-maltotriosyl (1-6) alpha-maltotrioside (BzCNPG3G3, 1) as a colourimetric substrate or 4,6-O-benzylidene-4-methylumbelliferyl-beta-maltotriosyl (1-6) alpha-maltotrioside (BzMUG3G3, 2) as a fluorometric substrate. Hydrolysis of substrates 1 and 2 by exo-acting enzymes such as amyloglucosidase, beta-amylase and alpha-glucosidase is prevented by the presence of the 4,6-O-benzylidene group on the non-reducing end D-glucosyl residue. The substrates are not hydrolysed by any alpha-amylases studied, (including those from Aspergillus niger and porcine pancreas) and are resistant to hydrolysis by Pseudomonas sp. isoamylase. On hydrolysis by pullulanase, the 2-chloro-4-nitrophenyl-beta-maltotrioside (3) or 4-methylumbelliferyl-beta-maltotrioside (4) liberated is immediately hydrolysed to D-glucose and 2-chloro-4-nitrophenol or 4-methylumbelliferone. The reaction is terminated by the addition of a weak alkaline solution leading to the formation of phenolate ions in solution whose concentration can be determined using either spectrophotometric or fluorometric analysis. The assay procedure is simple to use, specific, accurate, robust and readily adapted to automation. | Glycoside Hydrolases |
eLife is publishing a special issue on aging, geroscience and longevity to mark the rapid progress made in this field over the past decade, both in terms of mechanistic understanding and translational approaches that are poised to have clinical impact on age-related diseases. | Geroscience |
The aim of this study was to investigate the effect of A771726, the active metabolite of leflunomide, (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad against the infection with Junin virus (JUNV), agent of Argentine hemorrhagic fever (AHF). The treatment with non-cytotoxic concentrations of A771726 of Vero and A549 cells infected with JUNV inhibited virus replication in a dose-dependent manner, as determined by virus yield reduction assay. The antiviral effectiveness of A771726 was not importantly affected by the multiplicity of infection and the virus strain. Moreover, the combination of A771726 and ribavirin had a significantly more potent antiviral activity than each single drug treatment. Mechanistic studies showed that the main action of A771726 is exerted before 6 h of JUNV infection. Accordingly, inhibition of viral RNA synthesis was detected in treated infected cells by real time RT-PCR. The exogenous addition of uridine or orotic acid produced a partial reversal of the inhibitory effect of A771726 on infective virus production whereas a total reversion was detected on JUNV RNA synthesis, probably by restoration of the enzymatic activity of dihydroorotate dehydrogenase (DHODH) and the intracellular pyrimidine pools. In conclusion, these results suggest that the antiviral target would be viral RNA synthesis through pyrimidine depletion, but any other effect of the compound on JUNV infection cannot be excluded. This study opens the possibility of the therapeutic application of a wide spectrum host-targeted compound alone or in combination with ribavirin to combat AHF as well as other human pathogenic arenaviruses. | Junin virus |
Dendrimer-mediated delivery of bioactive is a successful and widely explored concept. This paper desribes comparative data pertaining to generation dependent cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut report reportsthe drug targeting and antciancer potential of different dendrimer generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were synthesized and loaded with Melphalan. Results from loading, hemolysis, hematologic, cytotoxicty and flow cytometry assay depicted that as the generation of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is increased exponentionally. However, others parameters, i.e. loading, sustained release behavior, and targeting efficacy increased negligibly. Kaplan-Meier survival curves clearly depicted comparable therapeutic potential of PPI4M with PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to be preferable nanocarrier for anticancer drug delivery owing to analogous anticancer potential. The outcomes of the investigation evidently projects 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery benefit as well as superior biocompatibility. Thus, much against the common belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers no benefit over 4.0G. | Polypropylenes |
Acromegaly may be a rare condition and difficult to diagnose. This patient's story highlights the importance of inquisitive questioning in cases with no obvious diagnosis. | Bone Diseases, Endocrine |
Nitric oxide (NO) is a gaseous, radical molecule that plays a role in various physiological processes. Previously, we reported that transduction of murine colon cancer cells (MC38) with herpes simplex virus thymidine kinase (HSV-tk) gene resulted in a significant over-expression of cyclooxygenase-2 (COX-2) and activation of NF-kB pathway. In this study we show that TNFalpha, but not LPS, was significantly able to stimulate the production of NO in HSV-tk transduced 9L glioblastoma cell lines, mediated by the up-regulation of iNOS transcript and iNOS protein. The TNFalpha-induced up-regulation of iNOS expression was mediated by MAPK and NF-kappaB signaling pathways as revealed by using selective pharmaceutical inhibitors. A culture liquid extract of the edible and medicinal mushroom Marasmius oreades that was previously shown to inhibit iNOS expression in MCF-7 was utilized to prepare fractions and evaluate their ability to affect TNFalpha-induced iNOS expression in HSV tk transduced 9L cell lines. While most of the tested fractions were shown to inhibit TNFalpha-induced iNOS expression, they targeted different signaling pathways in a selective fashion. Here, we report that fraction SiSiF1 interfered with IKBalpha phosphorylation and consequently interfered with NF-kappaB activation pathway. SiSiF1 showed minimal interference with the phosphorylation of p38 and JNK proteins. In contrast, fraction SiSiF3 selectively inhibited the phosphorylation of p38 and fractions SiSiF4 and SiSiF5 selectively inhibited the phosphorylation of JNK with no observed effect against IKBalpha and p38 phosphorylation. Our data illustrate the complexity of iNOS regulation in HSV tk transduced 9L cell lines and also the richness of natural products with bioactive substances that may act synergistically through different signaling pathways to affect iNOS gene expression. | Marasmius |
Catheter infection is a major complication of continuous ambulatory peritoneal dialysis (CAPD) therapy for end-stage renal disease. Catheter exist-site infections were treated with a new surgical technique consisting of dissection and removal of the existing catheter in the subcutaneous layer, insertion of a catheter connector and new catheter piece, and creation of a new subcutaneous tunnel. The new surgery can be performed on an outpatient basis and allows for the continuation of CAPD, thereby avoiding the cost associated with inpatient admission and interim hemodialysis." | Peritoneal Dialysis, Continuous Ambulatory |
Steroid 21-hydroxylase deficiency congenital adrenal hyperplasia is the most common cause of genital ambiguity in females at birth. Inhibited formation of cortisol causes increase in the release of ACTH in turn leading to overproduction of adrenal androgens. This predisposes the affected female fetus to prenatal development of genital ambiguity. A large number of patients also have aldosterone insufficiency which manifests after birth in form of inability to conserve sodium and to excrete potassium which can lead to adrenal shock and neonatal death, if left untreated. Prenatal diagnosis is possible using several methods like steroid assay of amniotic fluid and, HLA typing. Recently with advancement more accurate direct molecular genetic techniques have been utilized on chorionic villus samples in first trimester of pregnancy. Prenatal treatment is also possible and pregnancies can be managed by administering dexamethasone to the mother as soon as pregnancy is diagnosed. This suppresses fetal androgen production in genetic females preventing virilization and leading to normal development. Prenatal diagnosis and treatment are highly desirable in families with a positive family history towards birth of a child without features of the disease." | Adrenal Hyperplasia, Congenital |
Anesthetics, commonly used in preclinical and fundamental scientific research, have a depressive influence on the metabolic, neuronal, and vascular functions of the brain and can adversely influence neurophysiological results. The use of awake animals for research studies is advantageous but poses the major challenge of keeping the animals calm and stationary to minimize motion artifacts throughout data acquisition. Awake imaging in smaller-sized rodents (e.g., mice) is very common but remains scant in rats as rats are bigger, stronger, and have a greater tendency to oppose movement restraints and head fixation over the long durations required for imaging. A new model of neuroimaging of awake, head-fixed rats using customized hand-sewn slings, 3D-printed head implants, head caps, and a headframe is described. The results acquired following a single trial of single-whisker stimulation suggest an increase in the intensity of the evoked functional response. The acquisition of the evoked functional response from awake, head-fixed rats is faster than that from anesthetized rats, reliable, reproducible, and can be used for repeated longitudinal studies. | Wakefulness |
Viscum album L. (Mistletoe) is one of the most famous plants in many countries utilized for several purposes. The current study aimed to describe chemical profiles and biological activities of homogenizer-assisted extract (HAE) and ultrasound-assisted extract (UAE)) of V. album parts (leaf, fruits, and seeds). Antioxidant (radical scavenging, reducing power, metal chelation, and phosphomolybdenum assays) and enzyme inhibitory properties (cholinesterases, amylase, glucosidase, and tyrosinase) were selected for biological evaluation. Chemical profiles were studied by HPLC-MS/MS and 32 compounds were identified in the extracts; caffeoylquinic acids and its derivatives, dimethylated flavonoids were the most significant compounds. Generally, the leaf extracts exhibited the best antioxidant and enzyme inhibitory effects in our tests. Multivariate analysis was performed to obtain more information for these data, then strong correlations between total bioactive compounds and tested parameters were observed. The present findings encourage us to further investigate V. album as a potential candidate for pharmaceutical and nutraceutical applications. PRACTICAL APPLICATIONS: Viscum album L. commonly called European mistletoe is a woody perennial shrub growing on coniferous trees with lathery leaves, small flowers, and white berries. It belongs to the Santalaceae R. Br. family from Europe and western/southern Asia. Traditional medicine recognizes mistletoe as a folk remedy to manage inflammation, hypertension, ulcers, and other diseases due to the presence of different bioactive compounds, among them mistletoe lectins and viscotoxins. Recent studies documented the possible therapeutic applications of Viscum extracts in association with cancer's therapy leading to improvements in health and patient's quality of life. Thus, this work gives novel data regarding the phytochemical characterizations and antioxidant/enzymatic inhibitor activities of different types of extracts from seeds, leaves, and fruits of Viscum L. obtained by homogenizer-assisted and ultrasound-assisted techniques, in order to increase the data set of potential applications in medicine. | Viscum |
The adenine nucleotide translocase (ANT) is a key component in maintaining cellular energy homeostasis, and has also been implicated in formation of the mitochondrial permeability transition pore. Human ANT-3 was cloned from a human heart cDNA library and expressed as a histidine-tagged fusion protein in the mitochondria of the Trichoplusia ni. cell line. Overexpression resulted in a concomitant decrease in the endogenous ANT content, allowing for the characterization of binding of known ANT ligands to the human protein. Binding affinities for bongkrekic acid (BKA), ADP, and atractyloside (ATR) were measured in mitochondria from the human ANT-3 expressing cell line, and compared to similar preparations from bovine heart mitochondria by use of a novel radioiodinated derivative of ATR. Binding to ANT-3 by the high affinity inhibitors BKA and ATR, as well as the lower affinity natural ligand ADP, was similar to that measured in bovine heart mitochondria, and to that previously reported for mammalian heart mitochondria. Characterizations such as these of human ANT isoforms may lead to drug development for enhanced mitochondrial function and cellular viability." | Adenine Nucleotide Translocator 3 |
Manganese (Mn), an element found in many foods, is an important and essential nutrient for proper health and maintenance. It is toxic in high doses, however, and exposure to excessive levels can result in the onset of a neurological disorder similar to, but distinct from, Parkinson's disease. Historically, Mn neurotoxicity was most commonly associated with various occupations, such as Mn mining, welding and steel production. More recently, increases in both blood and brain Mn levels have been observed in persons with liver disease or those receiving prolonged parenteral nutrition. Additionally, rodent data suggest that iron deficiency and anemia may be risk factors for Mn neurotoxicity. Clinically, brain Mn accumulation can be monitored in vivo using non-invasive magnetic resonance imaging (MRI) due to the paramagnetic nature of this element. Indeed, MRI has been used in a variety of settings to evaluate the brain Mn deposition in various populations. This review focuses on the use of MRI technology in studies related specifically to Mn neurotoxicity. Thus, we will examine reports using MRI to confirm brain Mn accumulation in human populations, and conclude with data from non-human primate and rodent models of Mn neurotoxicity. | Manganese Poisoning |
BACKGROUND/OBJECTIVES: In Guatemala, population-wide vitamin A fortification of table sugar has been operating for two decades. The objective of this study was to estimate the adequacy of vitamin A intakes in pregnant and lactating women from low-income, urban and rural communities. SUBJECTS/METHODS: One or two previous-day dietary recalls were collected in a convenience sample of 234 pregnant and lactating women in the Western Highlands of Guatemala. Estimated daily intakes and main sources of total vitamin A, provitamin A and preformed vitamin A were calculated. Total intakes, adjusted for day-to-day variation, were examined in relation to estimated average requirements (EAR). RESULTS: Median estimated 1-day total vitamin A intake was 1177 mug retinol activity equivalents (RAE) (interquartile range (IQR) 832-1782) in the urban site and 567 mug RAE (IQR 441-737) in the rural site. Women not meeting their status-specific vitamin A requirement were 3.5 times more common in the rural communities (31%) than in the urban confines (9%). In the urban area, 26 women (21%) had preformed vitamin A intakes above 1500 mug on the day of data collection. Preformed vitamin A accounted for a median of 83.9% and 60.9% of the daily total vitamin A intake in the urban and rural sites, respectively. Sugar was the principal source of vitamin A, contributing 512 mug RAE (IQR 343-749) in the urban site and 256 mug RAE (IQR 189-363 mug) in the rural area. CONCLUSIONS: The vitamin A contribution from fortified sugar can be a determinant of reaching adequacy; nevertheless, a significant proportion of pregnant and lactating women do not meet the EAR, especially in the rural setting. | Dietary Sucrose |
T cell receptor (TCR) recognition of peptides presented by major histocompatibility complex (MHC) molecules is a fundamental process in the adaptive immune system. An understanding of this recognition process at the molecular level is crucial for TCR based therapeutics and vaccine design. The broad nature of TCR diversity and cross-reactivity presents a challenge for traditional structural resolution. Computational modelling of TCR-pMHC complexes offers an efficient alternative. This study compares the ability of four general-purpose docking platforms (ClusPro, LightDock, ZDOCK and HADDOCK) to make use of varying levels of binding interface information for accurate TCR-pMHC modelling. Each platform was tested on an expanded benchmark set of 44 TCR-pMHC docking cases. In general, HADDOCK is shown to be the best performer. Docking strategy guidance is provided to obtain the best models for each platform for future research. The TCR-pMHC docking cases used in this study can be downloaded from https://github.com/innate2adaptive/ExpandedBenchmark. | Histocompatibility Antigens |
A proteolytic enzyme, hydrolyzing N-benzoyl-D,L-arginine-p-nitro-anilide (BAPAase), has been isolated from the buckwheat seeds (Fagopyrum esculentum). The enzyme was purified 400-fold and was homogeneous according to isoelectrofocusing and disc electrophoresis in polyacrylamide gel. The molecular weight of the BAPAase was determined to be 65000 by gel-chromatography and 70000 by polyacrylamide gel electrophoresis. The sedimentation coefficient of the BAPAase was found to be 4.3 S, the isoelectric point--pH 4.5. The enzyme split peptide, esteric and amide bonds formed by carboxyl groups of lysine and arginine in synthetic substrates. The enzyme did not hydrolyse fibrinogen, did not activate chimotrypsinogen, weakly hydrolyzed histones and casein and strongly--protamine. The BAPAase did not hydrolyse albumins and globulins from the buckwheat seeds, and weakly hydrolyzed glutelins. The study of the products of the hydrolysis of salmine and sturine by BAPAase showed that the enzyme split internal peptide bonds in these substrates, and, thus, it is an endopeptidase. | Salmine |
The intensity of a stimulus has been found to have a distinct impact upon response processes (e.g., response speed, response force, & response selection). For instance, reaction times are faster to bright than to dim stimuli (e.g., Kohfeld, 1971). In the present study, we investigated the possible influence of stimulus intensity on binding processes. According to binding theories, stimulus and response features are integrated together in short-lived memory traces, called event files (Hommel, 1998). Any re-encounter with one of these integrated features leads to the automatic retrieval of the previously constructed event file and thus of the response. Thereby bindings between stimuli (relevant and irrelevant) and responses have a direct impact on behavior. In the present experiment, we presented distractors with increasing stimulus intensity and found that intensity did exert an influence on binding processes. However, our results suggest that distractor intensity per se has no direct influence on the binding effect (the more intense a distractor is, the larger the binding effect), but that distractor intensity has an indirect effect on binding via grouping due to similarity between target and distractor intensity. | Darkness |
Data from a 20-week trial comparing insulin detemir and neutral protamine Hagedorn (NPH) insulin in insulin-naive people with type 2 diabetes were analyzed using willingness-to-pay (WTP) data, a proxy for patient preference. The advantages of insulin detemir relative to NPH insulin with respect to a lower hypoglycemia rate and less weight gain were associated with a value of euro27.87 per month. | Insulin, Long-Acting |
A series of salicylanilides (1a-h) bearing varied substituents at the 3'- or 4'-position of the anilino moiety (substituent = p-OCH3, p-CH3, m-CH3, H, p-Cl, m-Cl, p-CO2CH3, and p-CN) were synthesized. In acetonitrile all of the substituted salicylanilides 1a-h predominantly adopt the closed-ring" conformation facilitated by a strong intramolecular OH...O=C hydrogen bond. In the presence of H2PO4-, the conformation of 1a-h was found to be modulated by the substituent. With our proposed proton-transfer fluorescence probing method, we were able to show that the conformation of 1a-f bearing a not highly electron-withdrawing substituent was switched to the "open-ring" form by H2PO4-, whereas 1h bearing a highly electron-withdrawing substituent, p-CN, remained in the "closed-ring" conformation. The significance of these findings for understanding, from a molecular structural point of view, the mechanism of salicylanilide-based inhibitors for inhibiting the protein tyrosine kinase epidermal growth factor receptor was discussed." | Salicylanilides |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.