Effects of curcumin in the interaction with cardiolipin-containg lipid monolayers and bilayers.
Curcumin, a plant polyphenol extracted from the Chinese herb turmeric, has gained widespread attention in recent years because of its multifunctional properties as antioxidant, antinflammatory, antimicrobial, and anticancer agent. Effects of the molecule on mitochondrial membranes properties have also been evidenced. In this work, the interaction of curcumin with models of mitochondrial membranes composed of dimyristoylphosphatidylcholine (DMPC) or mixtures of DMPC and 4 mol% tetramyristoylcardiolipin (TMCL) has been investigated by using biophysical techniques. Spectrophotometry and fluorescence allowed to determine the association constant and the binding energy of curcumin with pure DMPC and mixed DMPC/TMCL aqueous bilayers. The molecular organization of pure DMPC and cardiolipin-containing Langmuir monolayers at the air-water interface were investigated and the morphology of the monolayers transferred into mica substrates were characterized through atomic force microscopy (AFM). It is found that curcumin associates at the polar/apolar interface of the lipid bilayers and the binding is favored in the presence of cardiolipin. At 2 mol%, curcumin is well miscible with lipid monolayers, particularly with mixed DMPC/TMCL ones, where compact terraces formation characterized by a reduction of the surface roughness is observed in the AFM topographic images. At 10 mol%, curcumin perturbs the stability of DMPC monolayers and morphologically are evident terraces surrounded by cur aggregates. In the presence of TMCL, very few curcumin aggregates and larger compact terraces are observed. The overall results indicate that cardiolipin augments the incorporation of curcumin in model membranes highlighting the mutual interplay cardiolipin-curcumin in mitochondrial membranes.


Clinical pharmacokinetics of bretylium.
Bretylium is a class III antiarrhythmic agent which is used for the management of serious and refractory ventricular tachyarrhythmias. It exhibits a complex pharmacokinetic profile which is poorly understood. The drug is poorly absorbed following oral administration, and its oral bioavailability is in the region of 18 to 23%. Peak plasma concentrations occur at 1 to 9 hours after oral ingestion, and following oral doses of 5 mg/kg average 76 ng/ml, which is 28-fold lower than those achieved after equivalent intravenous doses. Approximately 75% of a bretylium dose is absorbed within 24 hours of intramuscular administration. Peak plasma concentrations occur at 30 to 90 minutes after intramuscular administration and range from 670 to 1500 ng/ml in subjects receiving 4 mg/kg. Bretylium is negligibly bound to plasma proteins (1-6%). Although drug tissue concentrations have not been reported in humans, high values for the apparent volume of distribution suggest extensive tissue binding. In animals, bretylium is progressively taken up by the myocardium over a period of 12 hours, and at 12 hours after bolus administration, myocardial concentrations exceed plasma concentrations 6 to 12 times. It is also avidly taken up by adrenergic nerves in animals. Bretylium is almost entirely cleared by the renal route and its total body clearance is closely correlated with renal clearance. Available data suggest that bretylium exhibits a complex pharmacokinetic profile which has been described by a 3-compartment model in subjects receiving intravenous dosing. The terminal elimination half-life ranges from 7 to 11 hours following oral, intramuscular and intravenous administration, and renal clearance is about 600 ml/min after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Effective behavioral treatment of self-biting by a child with Lesch-Nyhan syndrome.
Behavior modification consisting of differential reinforcement of incompatible behavior and "punishment' was used for short periods at an early intervention center and was effective in eliminating self-biting of the arms, forearms and backs of the hands by a two-year-old with Lesch-Nyhan syndrome. No side-effects of the "punishment' component were observed. The effectiveness of the treatment was generalized to 3 1/2-hour sessions with his teacher at the early intervention center, and to the child's home. At six-month follow-up the teacher and parents indicated the continued absence of biting of the arms, forearms and back of the hands. The same treatment was applied to biting the fingers and the palms of the hands, without success.


Electrophysiological correlates of rod outer segment disc shedding in rabbit retina.
We hypothesize that the b-wave of the electroreginogram (ERG) can provide a precise, noninvasive measure of the morning rod disc shedding event. ERGs were recorded in the dark from photoentrained rabbits using a 500 nm test light. Histological examination of the pigment epithelium confirmed that an increase in large phagosome content occurred shortly after light onset. In albino rabbits the b-wave decreased in amplitude at about 30 min after the time of normal light onset. The corresponding decrease in sensitivity required to produce this change in amplitude was 0.11 log unit. No ERG effect was seen in pigmented rabbits.


Duration of venom immunotherapy: relationship to the severity of symptoms of initial insect sting anaphylaxis.
This study assessed the postulate that the adequate duration of venom immunotherapy (VIT) is related to the severity of the initial sting anaphylactic symptoms. Data were collected from patients with venom allergy who had sting anaphylaxis and subsequent positive venom skin test results, received maintenance VIT, and had field re-stings after cessation of VIT. There were 217 re-stings in 113 patients with 15 systemic reactions in 10 patients (a re-sting reaction rate of 9% per sting and 7% per patient). Re-sting reactions occurred in 1 of 25 patients with initial mild anaphylaxis (4%), 2 of 41 patients with moderate reactions (5%), and 7 of 47 patients with initial severe symptoms (15%). The results were not influenced by the duration of VIT or the interval between cessation of VIT and the re-sting. Eighteen patients who converted to negative skin test reactions had no reactions when re-stung. These results suggest a relationship between the severity of anaphylaxis and subsequent duration of VIT. Two to three years is sufficient for patients who had mild to moderate anaphylaxis. Longer duration of therapy is advisable for patients who had severe symptoms and continue to have positive venom skin test results.


Demonstration of a single antigen-antibody system in 26 patients with non-A, non-B viral hepatitis.
26 patients with viral hepatitis were selected on the basis of negative responses to serological tests for hepatitis B virus and hepatitis A virus infections. The illness was acute in 19 patients and chronic persistent in the remaining 7. Immunodiffusion tests showed a single antigen-antibody system in the sera of all 26 patients. Each patient had at least one serum sample positive for antigen or antibody. In 1 post-transfusion case, the corresponding immunological marker was found in the donor. This system was considered specific for the disease, since the markers could not be detected in sera from patients with other liver conditions or immune complex diseases, or in sera from healthy blood donors without a history of hepatitis. The antigen could be separated from contaminating serum proteins. The purified preparation showed immunological identity with all our antigen-containing sera and with samples of a study already published. These results suggest the existence of an antigen associated with non-A, non-B, viral hepatitis and probably related to an infectious agent responsible for all the cases in this study.


Detection of human cytomegalovirus in atherosclerotic carotid arteries in humans.
Atherosclerosis plays an important role in stroke. A microbiological infection has been suggested to be involved in the pathogenesis of atherosclerosis, in particular the human cytomegalovirus (HCMV). The objective of this study was to determine the association between HCMV infection and atherosclerosis of the internal carotid arteries in patients of Chinese Han ethnicity with ischemic stroke. HCMV DNA and antigen were detected in atherosclerotic internal carotid arteries from 35 patients with ischemic stroke and 20 controls from a Chinese Han ethnic population. Immunohistochemistry, in situ hybridization and polymerase chain reaction were used to detect the HCMV immediate early (IE) and late (L) antigen as well as DNA in the vascular walls. We observed that the proportion of cases that tested positive for HCMV IE but not L antigen and DNA was statistically greater in stroke patients compared with the control population. HCMV IE antigen and DNA were associated with the pathological process of atherosclerosis. The vessel wall might be the infection site of the dormant virus.


[Surgical management of acute retinal necrosis].
To investigate the effects of vitreoretinal surgery in the management of acute retinal necrosis (ARN). 17 cases (20 eyes) of ARN had undertaken the surgery, including vitreoretinal surgery for 18 eyes and scleral surgery for 2 eyes. 14 cases (21 eyes) of ARN patients hospitalized at the same period without surgery were used as controls. The follow-up was 5 months to 5 years. 15 eyes in the control group (71.4%) became phthisis bulbi. Useful vision remained in 17 eyes in the surgical group. Retinal detachment is still a severe complication of ARN, and proper vitreoretinal surgery can improve its prognosis.


Correction to: How to measure blood pressure using an arterial catheter: a systematic 5-step approach.
An amendment to this paper has been published and can be accessed via the original article.


Femtosecond symmetry breaking and coherent relaxation of methane cations via x-ray spectroscopy.
Understanding the relaxation pathways of photoexcited molecules is essential to gain atomistic-level insight into photochemistry. We performed a time-resolved study of ultrafast molecular symmetry breaking through geometric relaxation (Jahn-Teller distortion) on the methane cation. Attosecond transient absorption spectroscopy with soft x-rays at the carbon K-edge revealed that the distortion occurred within 10 ± 2 femtoseconds after few-femtosecond strong-field ionization of methane. The distortion activated coherent oscillations in the asymmetric scissoring vibrational mode of the symmetry-broken cation, which were detected in the x-ray signal. These oscillations were damped within 58 ± 13 femtoseconds because vibrational coherence was lost with the energy redistributing into lower-frequency vibrational modes. This study completely reconstructs the molecular relaxation dynamics of this prototypical example and opens avenues for exploring complex systems.


Peri-implant femoral fractures: Challenges, outcomes, and proposal of a treatment algorithm.
Non-prosthetic peri-implant fractures are challenging injuries. Multiple factors must be carefully evaluated for an adequate therapeutic strategy, such as the state of bone healing, the type of implant, the time and performed personnel of previous surgery, and the stability of fixation. The aim of this study is to propose a rationale for the treatment. The peri-implant femoral fractures (PIFFs) system, a therapeutic algorithm was developed for the management of all patients presenting a subtype A PIFF, based on the type of the original implant (extra- vs. intra-medullary), implant length and fracture location. The adequacy and reliability of the proposed algorithm and the fracture healing process were assessed at the last clinical follow-up using the Parker mobility score and radiological assessment, respectively. In addition, all complications were noticed. Continuous variables were expressed as mean and standard deviation, or median and range according to their distribution. Categorical variables were expressed as frequency and percentages. This is a retrospective case series of 33 PIFFs, and the mean post-operative Parker mobility score was (5.60 ± 2.54) points. Five patients (15.1%) achieved complete mobility without aids (9 points) and 1 (3.0%) patient was not able to walk. Two other patients (6.1%) were non-ambulatory prior to PPIF. The mean follow-up was (21.51 ± 9.12) months (range 6 - 48 months). There were 7 (21.2%) complications equally distributed between patients managed either with nailing or plating. There were no cases of nonunion or mechanical failure of the original implant. The proposed treatment algorithm shows adequate, reliable and straightforward to assist the orthopaedic trauma surgeon on the difficult decision-making process regarding the management of PIFF occurring in previously healed fractures. In addition, it may become a useful tool to optimize the use of the classification, thus potentially improving the outcomes and minimizing complications.


Psoriasis seems often underdiagnosed in patient with axial spondyloarthritis.
Axial spondyloarthritis (axSpA) is known to be associated with several extra-skeletal manifestations (ESM), including the inflammatory skin disease psoriasis. It is important to recognize and diagnose psoriasis timely in axSpA in order to provide optimal treatment and outcome for both axSpA and psoriasis. In this observational study, all patients from the Dutch Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort included before June 2016 were sent a questionnaire with self-screening psoriasis questions including prototypical color pictures. Of the 592 questionnaires sent, 448 (75.7%) were eligible for analysis. Of these 448 respondents, 58 (13%) had a positive self-screening for psoriasis symptoms, currently or in the past. In 28 (48%) of 58 patients, psoriasis diagnosis could be verified by medical records, resulting in a psoriasis prevalence rate of 6.3%. In comparison with patients with a confirmed psoriasis diagnosis, patients reporting psoriasis symptoms without a verified diagnosis mentioned more mild than moderate-severe psoriasis symptoms (25% vs. 3%, p = 0.02), and their psoriasis lesions were less often located on the torso area (3% vs. 18%, p = 0.04), the intergluteal cleft (0% vs. 25%, p = 0.02), and legs (7% vs. 43%, p < 0.01). Of the 31 axSpA patients who reported currently active psoriasis, 74% had only mild psoriasis symptoms. Especially mild psoriasis seems often underdiagnosed in patients with axSpA using a patient questionnaire with prototypical pictures of psoriasis lesions. This questionnaire could be beneficial in tracing patients with undiagnosed psoriasis in daily clinical practice. As a next step, further validation of this questionnaire is needed.


AAV-Vectored Expression of Marburg Virus-Neutralizing Antibody MR191 Provides Complete Protection From Challenge in a Guinea Pig Model.
Although there are no approved countermeasures available to prevent or treat disease caused by Marburg virus (MARV), potently neutralizing monoclonal antibodies (mAbs) derived from B cells of human survivors have been identified. One such mAb, MR191, has been shown to provide complete protection against MARV in nonhuman primates. We previously demonstrated that prophylactic administration of an adeno-associated virus (AAV) expressing MR191 protected mice from MARV. Here, we modified the AAV-MR191 coding sequence to enhance efficacy and reevaluated protection in a guinea pig model. Remarkably, 4 different variants of AAV-MR191 provided complete protection against MARV, despite administration 90 days prior to challenge. Based on superior expression kinetics, AAV-MR191-io2, was selected for evaluation in a dose-reduction experiment. The highest dose provided 100% protection, while a lower dose provided ∼88% protection. These data confirm the efficacy of AAV-mediated expression of MR191 and support the further development of this promising MARV countermeasure.


Virus tolerance and recovery from viral induced-symptoms in plants are associated with transcriptome reprograming.
Plant recovery from viral infection is characterized by initial severe systemic symptoms which progressively decrease, leading to reduced symptoms or symptomless leaves at the apices. A key feature to plant recovery from invading nucleic acids such as viruses is the degree of the host's initial basal immunity response. We review current links between RNA silencing, recovery and tolerance, and present a model in which, in addition to regulation of resistance (R) and other defence-related genes by RNA silencing, viral infections incite perturbations of the host physiological state that trigger reprogramming of host responses to by-pass severe symptom development, leading to partial or complete recovery. Recovery, in particular in perennial hosts, may trigger tolerance or virus accommodation. We discuss evidence suggesting that plant viruses can avoid total clearance but persistently replicate at low levels, thereby modulating the host transcriptome response which minimizes fitness cost and triggers recovery from viral-symptoms. In some cases a susceptible host may fail to recover from initial viral systemic symptoms, yet, accommodates the persistent virus throughout the life span, a phenomenon herein referred to as non-recovery accommodation, which differs from tolerance in that there is no distinct recovery phase, and differs from susceptibility in that the host is not killed. Recent advances in plant recovery from virus-induced symptoms involving host transcriptome reprogramming are discussed.


Rapid evolution of wing size clines in Drosophila subobscura.
Parallel latitudinal clines across species and continents provide dramatic evidence of the efficacy of natural selection, however little is known about the dynamics involved in cline formation. For example, several drosophilids and other ectotherms increase in body and wing size at higher latitudes. Here we compare evolution in an ancestral European and a recently introduced (North America) cline in wing size and shape in Drosophila subobscura. We show that clinal variation in wing size, spanning more than 15 degrees of latitude, has evolved in less than two decades. In females from Europe and North America, the clines are statistically indistinguishable however the cline for North American males is significantly shallower than that for European males. We document that while overall patterns of wing size are similar on two continents, the European cline is obtained largely through changing the proximal portion of the wing, whereas the North American cline is largely in the distal portion. We use data from sites collected in 1986/1988 (Pegueroles et al. 1995) and our 1997 collections to compare synchronic (divergence between contemporary populations that share a common ancestor) and allochronic (changes over time within a population) estimates of the rates of evolution. We find that, for these populations, allochronically estimated evolutionary rates within a single population are over 0.02 haldanes (2800 darwins), a value similar in magnitude to the synchronic estimates from the extremes of the cline. This paper represents an expanded analysis of data partially presented in Huey et al. (2000).


Decreased expression of p27 is associated with malignant transformation and extrathyroidal extension in papillary thyroid carcinoma.
Cell cycle regulatory proteins including p16, p27, and p53 are well studied in various cancers. However, their single or concurrent roles related with the clinicopathological parameters are not clearly recognized. We analyzed the expression of p16, p27, and p53 cell cycle regulatory proteins in papillary thyroid carcinoma (PTC). To determine the prognostic significance of cell cycle regulatory proteins, 107 PTCs were examined. We analyzed the individual expression of p16, p27, and p53 and their concurrent expressions, with the relationship to various clinicopathological parameters including differentiation from benign lesions. High expression of p16 and p53 and low expression of p27 were related with the distinguishing of PTC from benign lesions. In addition, normal thyroidal tissue showed higher p27 expression than nodular hyperplasia. In relation to extrathyroidal extension (ETE), the low expression of p27 was related with the presence of ETE. The low expression of p27 and high expression of p16 and p53 may affect the development of PTC. In addition, low p27 expression is related with the existence of ETE.


Isolation of persistent left superior vena cava during atrial fibrillation ablation.
Persistent left superior vena cava is a rarely seen anomaly but it may be an arrhythmogenic source for paroxysmal atrial fibrillation. Furthermore, the complex anatomicregion between the left superior vena cava and the pulmonary veins may leads to misinterpretation of the pulmonary vein recordings during atrial fibrillation ablation. Approaches that might be helpful to overcome these problems are discussed in this case report.


Seizures and transient cognitive deterioration as sequelae of acute lithium intoxication.
Acute lithium toxicity has been reported to produce transient convulsions and permanent cognitive deficits. We report a case of a permanent seizure disorder and transient cognitive deficit as sequelae of acute severe lithium toxicity.


Interrelationship between glomerular filtration rate and renal transport of sodium and chloride during fetal life.
The maturation of the glomerular filtration rate (GFR) and the interrelationship between the GFR and the renal transport of sodium and chloride have been evaluated during the last trimester of gestation with the use of long-term experiments in fetal lambs. An increase in GFR (milliliters per minute) parallel to the increase in fetal body weight was demonstrated; however, no significant change was shown when the GFR (milliliters per minute per kilogram of fetal body weight) (1.141 +/- 0.079) was related to fetal body weight or gestational age. There was a constant increase in sodium and chloride reabsorption (microequivalents per minute) during the last third of gestation. This increase in sodium and chloride reabsorption was less than the increase in GFR (milliliters per minute) before 129 days but became higher than the rise of GFR (milliliters per minute) after 129 days of gestation.


Modulation of H-reflex and V-wave responses during dynamic balance perturbations.
Motoneuron excitability is possible to measure using H-reflex and V-wave responses. However, it is not known how the motor control is organized, how the H-reflex and V-wave responses modulate and how repeatable these are during dynamic balance perturbations. To assess the repeatability, 16 participants (8 men, 8 women) went through two, identical measurement sessions with ~ 48 h intervals, where maximal isometric plantar flexion (IMVC) and dynamic balance perturbations in horizontal, anterior-posterior direction were performed. Soleus muscle (SOL) neural modulation during balance perturbations were measured at 40, 70, 100 and 130 ms after ankle movement by using both H-reflex and V-wave methods. V-wave, which depicts the magnitude of efferent motoneuronal output (Bergmann et al. in JAMA 8:e77705, 2013), was significantly enhanced as early as 70 ms after the ankle movement. Both the ratio of M-wave-normalized V-wave (0.022-0.076, p < 0.001) and H-reflex (0.386-0.523, p < 0.001) increased significantly at the latency of 70 ms compared to the latency of 40 ms and remained at these levels at latter latencies. In addition, M-wave normalized V-wave/H-reflex ratio increased from 0.056 to 0.179 (p < 0.001). The repeatability of V-wave demonstrated moderate-to-substantial repeatability (ICC = 0.774-0.912) whereas the H-reflex was more variable showing fair-to-substantial repeatability (ICC = 0.581-0.855). As a conclusion, V-wave was enhanced already at 70 ms after the perturbation, which may indicate that increased activation of motoneurons occurred due to changes in descending drive. Since this is a short time-period for voluntary activity, some other, potentially subcortical responses might be involved for V-wave increment rather than voluntary drive. Our results addressed the usability and repeatability of V-wave method during dynamic conditions, which can be utilized in future studies.


Cerebellar involvement in warts Hypogammaglobulinemia immunodeficiency myelokathexis patients: neuroimaging and clinical findings.
Warts Hypogammaglobulinemia Immunodeficiency Myelokathexis (WHIM) syndrome is a primary immunodeficiency characterized by recurrent bacterial infections, severe chronic neutropenia, with lymphopenia, monocytopenia and myelokathexis which is caused by heterozygous gain of functions mutations of the CXC chemokine receptor 4 (CXCR4). WHIM patients display an increased incidence of non-hematopoietic conditions, such as congenital heart disease suggesting that abnormal CXCR4 may put these patients at increased risk of congenital anomalies. Studies conducted on CXCR4 and SDF-1-deficient mice have demonstrated the role of CXCR4 signaling in neuronal cell migration and brain development. In particular, CXCR4 conditional knockout mice display abnormal cerebellar morphology and poor coordination and balance on motor testing. In order to evaluate a possible neurological involvement in WHIM syndrome subjects, we performed neurological examination, including International Cooperative Ataxia Rating Scale, cognitive and psychopathological assessment and brain Magnetic Resonance Imaging (MRI) in 6 WHIM patients (age range 8-51 years) with typical gain of functions mutations of CXCR4 (R334X or G336X). In three cases (P3, P5, P6) neurological evaluation revealed fine and global motor coordination disorders, balance disturbances, mild limb ataxia and excessive talkativeness. Brain MRI showed an abnormal orientation of the cerebellar folia involving bilaterally the gracilis and biventer lobules together with the tonsils in four subjects (P3, P4, P5, P6). The neuropsychiatric evaluation showed increased risk of internalizing and/or externalizing problems in four patients (P2, P3, P4, P6). Taken together, these observations suggest CXCR4 gain of function mutations can be associated with cerebellar malformation, mild neuromotor and psychopathological dysfunction in WHIM patients.


In vitro degradation, photo-dynamic and thermal antibacterial activities of Cu-bearing chlorophyllin-induced Ca-P coating on magnesium alloy AZ31.
Surgical failures, caused by postoperative infections of bone implants, are commonly met, which cannot be treated precisely with intravenous antibiotics. Photothermal therapy (PTT) and photodynamic therapy (PDT) have attracted widespread attention due to their non-invasive antibacterial effects on tissues and no bacterial resistance, which may be an excellent approach to solve infections related to bone implants for biodegradable magnesium alloys. Herein, a sodium copper chlorophyllin (SCC) with a porphyrin ring induced Ca-P coating was prepared on AZ31 magnesium alloy via layer-by-layer (LbL) assembly. The morphology and composition of the samples were characterized through field emission scanning electron microscope (FE-SEM) with affiliated energy dispersive spectrometer (EDS), X-ray diffractometer (XRD), and Fourier infrared spectrometer (FTIR) and X-ray photoelectron spectrometer (XPS) as well. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and hydrogen evolution experiments were employed to evaluate the corrosion behavior of the samples. Atomic absorption spectrophotometer was used to measure Cu elemental content of different immersion periods. Cytocompatibility and antibacterial performance of the coatings were probed using in vitro cytotoxicity tests (MTT assay), live/dead cell staining and plate counting method. The results showed that the obtained (Ca-P/SCC)10 coating exhibited good corrosion resistance, antimicrobial activity (especially under 808 nm irradiation) and biocompatibility. The antibacterial rates for E. coli and S. aureus were 99.9% and 99.8%, respectively; and the photothermal conversion efficiency was as high as 42.1%. Triple antibacterial mechanisms including photodynamic, photothermal reactions and copper-ions release were proposed. This coating exhibited a promising application for biodegradable magnesium alloys.


Inter-species comparison of liver and small intestinal microsomal metabolism of fluoranthene.
The magnitude of susceptibility to toxicant exposure may depend on the ability of animals to metabolize the chemicals. The present study has been undertaken to see whether any differences exist among mammals in the metabolism of fluoranthene (FLA), a polycyclic aromatic hydrocarbon (PAH) compound. Microsomes were isolated from the small intestine and liver of rat, mouse, hamster, goat, sheep, pig, dog, cow, monkey, and humans (commercially procured), and incubated with FLA. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA/metabolites by reverse-phase HPLC with fluorescence detection. The metabolism of FLA in both liver and small intestine was in the order: human > monkey > cow > goat > sheep > dog > pig > hamster > rat > mouse under conditions of the test system used. The rate of metabolism (pmol of metabolite/min/mg protein) was found to be more in liver than in intestine in all the species studied. The FLA metabolites identified were FLA 2,3-diol, trans-2,3-dihydroxy-1,10b-epoxy-1,2,3,10beta tetrahydro FLA (2,3D FLA), 3-hydroxy FLA, and 8-hydroxy FLA. The rodent microsomes produced considerably higher proportion of FLA 2,3-diol, and 2,3D FLA than did pig, dog, and humans. On the other hand, microsomes from higher mammals converted a greater proportion of FLA to 3-hydroxy FLA, the detoxification product of FLA. Overall, our results revealed a great variation among species to metabolize FLA.


Mini-review of microplastics in the atmosphere and their risks to humans.
Studies of microplastics (MPs) have highlighted their ubiquity in various environments. Recently, microplastics have been observed in atmospheric fallout collected from some cities. Although the studies are limited, some researches have shown that synthetic textiles are main source of airborne microplastics, and fibers are the dominant shape of microplastics in the atmosphere. Due to their small size, airborne microplastics can be directly inhaled posing health risks to humans, particularly to industry workers. Meteorological conditions and human activities affect the distribution and deposition of airborne microplastics. Furthermore, airborne microplastics are contributors to microplastic pollution in aquatic environments. We summarized the current knowledge and provide insights into further research to better understand airborne microplastics and their risks to human.


Mitochondrial genome datasets for the sweetpotato weevil, Cylas formicarius elegantulus (Coleoptera: Brentidae), collected in the United States.
The sweetpotato weevil, Cylas formicarius elegantulus (Summers) (Coleoptera: Brentidae), is one of the most destructive pests of sweetpotato worldwide. Genomic analyses of sweetpotato weevils can provide insights into their genetic diversity, population structure, and dispersal as well as provide information to support management strategies. Adult sweetpotato weevils were collected by various methods from Ipomoea batatas L. (sweetpotato) or I. coccinea L. (red morning glory) in the U.S. states of Georgia, Hawaii, South Carolina, and Texas. Genomic DNA was extracted from individual weevil specimens and sequenced using Illumina NovaSeq. A total of 181 GB of 150 base pair (bp) paired-end reads were generated for 40 specimens. Mitochondrial genomes were assembled for each specimen via reference mapping and annotated using Geneious Prime. Full mitochondrial genome sequences range from 17,141 to 17,152 bp with an average GC content of 21.8% and average coverage of 3307 × . A maximum likelihood phylogenetic analysis considering the mitochondrial protein coding genes is provided. Mitochondrial genomes and assembled reads are deposited in NCBI GenBank, providing 40 mitogenomes of C. formicarius elegantulus collected in the U.S.


Changes of the porous structure of activated carbons applied in a filter bed pilot operation.
The paper investigates the changes in porosity (i.e., in the accessible adsorption capacity of carbonaceous adsorbents for pollutants during filter bed maturation) of three activated carbons applied in a filter bed pilot operation. The results of this investigation may help to reduce operating costs, increase granular activated carbon bed life, maximize the useful life of biofilters, and understand the mechanism of water purification by carbon adsorbents. The analysis of the pore structure was limited to the first year of service of the beds, since this was when the largest decrease in the available pore capacity occurred. Low-temperature nitrogen adsorption isotherms were used to evaluate the structural parameters and pore size distributions (PSDs) of carbon samples (virgin (reference) and mature adsorbents for different periods of water treatment) on the basis of the Nguyen and Do (ND) method and density functional theory (DFT). These results were compared with small-angle X-ray scattering (SAXS) investigations (PSDs calculated by Glatter's indirect transformation method (ITP)). The results show that in general, the ND and ITP methods lead to almost the same qualitative distribution curve behavior. Moreover, the enthalpy of immersion in water, mercury porosimetry, densities (true and apparent), and the analysis of ash are reported and compared to explain the decrease in adsorptive capacity of the carbons investigated. On the other hand, the efficacy of TOC (total organic carbon, i.e., a quantity describing the complex matrix of organic material present in natural waters) removal and the bacteria count were analyzed to explain the role of adsorption in the elimination of contaminants from water. Finally, a mechanism of organic matter removal was suggested on the basis of the above-mentioned experimental data and compared with mechanisms reported by other authors.


Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation.
Human SNM1B/Apollo is involved in the cellular response to DNA-damage, however, its precise role is unknown. Recent reports have implicated hSNM1B in the protection of telomeres. We have found hSNM1B to interact with TRF2, a protein which functions in telomere protection and in an early response to ionizing radiation. Here we show that endogenous hSNM1B forms foci which colocalize at telomeres with TRF1 and TRF2. However, we observed that additional hSNM1B foci could be induced upon exposure to ionizing radiation (IR). In live-cell-imaging experiments, hSNM1B localized to photo-induced double-strand breaks (DSBs) within 10s post-induction. Further supporting a role for hSNM1B in the early stages of the cellular response to DSBs, we observed that autophosphorylation of ATM, as well as the phosphorylation of ATM target proteins in response to IR, was attenuated in cells depleted of hSNM1B. These observations suggest an important role for hSNM1B in the response to IR damage, a role that may be, in part, upstream of the central player in maintenance of genome integrity, ATM.


Fever of undetermined etiology after cleaning of steam turbine condensers.
Two outbreaks of a febrile syndrome marked by chills, headaches, myalgia, nausea, and malaise occurred in workers who had cleaned the steam condensers of electric power turbines. Mean incubation period was 38 hours. Twenty-two of twenty-three exposed men became ill. Clinical and environmental investigation failed to reveal the etiology of the outbreaks. The circumstances and clinical syndrome have points of similarity to fever following inhalation of metal fumes and low-grade, stained cotton dust, and to Pontiac fever.


Usefulness of the neutrophil-to-lymphocyte ratio in predicting lymph node metastasis in patients with non-small cell lung cancer.
Preoperative neutrophil-to-lymphocyte ratio (NLR) is a new hotspot for its prognostic significance in many types of cancers. In this study, a novel diagnosing model-the combination of enhanced contrast computed tomography (ECCT) and NLR (COCT-NLR) was constructed to detect the lymph nodal involvement in patients with non-small cell lung cancer (NSCLC). The clinicopathological parameters and thoracic ECCT images of 353 NSCLC patients were retrospectively reviewed. The COCT-NLR model was constructed and evaluated in detecting regional lymph nodal metastasis in patients with NSCLC. Univariate and multivariate analyses of clinicopathological parameters revealed that NLR value was independently associated with regional nodal involvement rate in patients with NSCLC (odds ratio (OR) = 4.770; 95 % confidence interval (CI), 2.487-9.146; P < 0.001). Compared with ECCT and NLR, the COCT-NLR model showed the highest efficacy in predicting nodal involvement. The sensitivity and specificity of COCT-NLR were 70.59 and 74.89 %, respectively. The COCT-NLR model is a valuable tool in detecting regional lymph node metastasis in patients with NSCLC.


Cloning and characterisation of mmc-1, a microfilarial-specific gene, from Brugia pahangi.
Nine differentially expressed genes were cloned from Brugia pahangi in a screen which sought to identify cDNAs that were differentially expressed between the microfilariae from the mammalian host and the mosquito vector. One gene (mmc-1), that was up-regulated in mammalian-derived microfilariae, was characterised in detail. RT-PCR analysis demonstrated that mmc-1 was specific to the microfilarial stage of the life cycle and was not transcribed by developing microfilariae in utero, but only following the release of the microfilariae from the adult female. Analysis of DNA from other filarial worms suggested that mmc-1 may be a Brugia-specific gene. Using serum samples from individuals exposed to Brugia malayi infection, it was shown that MMC-1 was specifically recognised by antibodies of the IgG3 subclass. mmc-1 has no homologues in the data bases and its function in the parasite is unknown.


The Association Between Environmental Lead Exposure and Recurrent Respiratory Infections in Children Aged 3-7 Years in Shenyang, China.
To investigate the lead exposure levels, and the effect of blood lead level (BLL) on recurrent respiratory infections in children aged 3-7 years in Shenyang. A case-control study including 78 children with recurrent respiratory infections and 141 controls was performed. Venous blood was obtained for BLL, and a questionnaire was completed. The BLL was significantly higher in children with recurrent respiratory infections than that in the control group [Median (IQR): 2.56 (1.29-6.19) vs 1.99 (0.90-5.92) µg/dL, P=0.029]. Children with BLL ≥1.95 µg/dL were more likely to be suffering from recurrent respiratory infections (OR=2.328, 95%CI=1.228-4.413) than those with BLL <1.95 µg/dL. High lead level can increase the risk of respiratory infections in preschool children.


Early follow-up of lead performance in atrioventricular sequential systems.
Recent developments in pacemaker technology led us to report our initial and follow-up assessment of atrioventricular (A-V) sequential systems in 50 consecutive patients. Primary indications for pacing were sinus node dysfunction or A-V block. Leads were introduced through the subclavian vein. Atrial J-tined leads (27 silicone, 19 urethane) were positioned in the atrial appendage or stump in 46 patients, and coronary sinus or Bisping leads were placed in 4 patients; all 50 patients had tined ventricular leads. A Medtronic 5992 generator was placed in 35 patients and an Intermedics 259-01 generator in 15. Median implantation time was 105 minutes. Complications requiring reoperation in 409 patient-months of follow-up included lead retraction (one patient), phrenic nerve stimulation (one), pseudofracture (one), and atrial lead-induced "cross talk" (one). Monthly telephone transmission confirmed atrial capture in 35 patients and loss of capture in 1; the remainder had no identifiable P wave. Ventricular capture was confirmed in all. Postimplant and follow-up checks showed good stability of lead positions. We conclude that these systems have a low incidence of problems in short-term follow-up.


Vascular access in gynecologic cancer using the Groshong right atrial catheter.
From December 1986 through July 1987, forty-one Groshong catheters were inserted in 38 patients with invasive gynecologic cancer for a cumulative total of 4170 days of patient use. (mean catheter indwelling time: 93 days; range: 3-300 days). A supraclavicular approach was used to cannulate the brachiocephalic vein in 31 patients. In 6 patients, the subclavian vein was cannulated via an infraclavicular approach, while 4 patients had the catheters placed via external jugular venous cutdown. Thirty-seven catheters were inserted at the bedside without fluoroscopy using the Seldinger technique and a peel-away catheter introducer sheath. A chest x-ray was used to confirm the right atrial position of the catheter. Major complications included two pneumothoraces, and three catheter-related cases of sepsis. A unique feature of the Groshong catheter is a pressure-sensitive two-way valve at the intravascular end, minimizing the potential for air embolism and back-bleeding. This eliminates the need for a heparin flush or external clamping, but permits blood sampling. Catheter insertion and maintenance procedures at bedside are simple, time saving, and cost effective. With the increasing use of continuous chemotherapy infusion protocols, use of vesicant drugs, hyperalimentation, and the need for outpatient therapy, we recommend early placement of the Groshong catheter in the oncology patient.


Coexistence of two competing corixid species (Heteroptera) in an archipelago of temporary rock pools.
Coexistence of Callicorixa producta and Arctocorisa carinata in an archipelago of rock pools appears to be facilitated by division of the environment on the time axis. To test this, a hypothesis is built on r-K theory. As A. carinata is twice the size of C. producta it is expected that the former species is more K-selected living in more permanent pools where food resources are limiting and competition strong. The smaller C. producta is expected to prefer newly refilled pools with abundant food, and thus to be more r-selected. Gathered test data on 17 life history and population ecological features agree with the prediction. It is also shown that the both rock-pool corixids are more r-selected than other species of the family.


In vitro Anticancer Activities of Some Triterpene Glycosides from Holothurians of Cucumariidae, Stichopodidae, Psolidae, Holothuriidae and Synaptidae families.
Triterpene glycosides isolated from holothurians are natural products known to possess cytotoxic properties against cancer cells. However, their anticancer prophylactic activity has not been studied sufficiently. The anticancer prophylactic; cytotoxic, and pro-apoptotic properties of 18 triterpene glycosides, as well as their effects on the transcriptional activities of activator protein-I (AP-1) and nuclear factor-KB (NF-KB), were examined using methods that included EGF-induced JB6 C141 P' cell transformation in soft agar, flow cytometry, MTS assessment of cell viability, and a luciferase activity assay. The compounds inhibited EGF-induced neoplastic JB6 C141 P' cell transformation in soft agar and caused apoptosis and necrosis of human HL-60 and THP-I leukemia cells. AP- and NF-KB were involved in the cellular response to the treatment by the compounds. Conclusion: glycosides isolated from holothurians of Cucumariidae, Stichopodidae, Psolidae, Holothuriidae and Synaptidae families have potential for development as new antitumor agents and as instruments to study AP-I and NF-kB.


Induction of autoimmune diabetes in non-obese diabetic mice requires interleukin-21-dependent activation of autoreactive CD8⁺ T cells.
Non-obese diabetic (NOD) mice lacking interleukin (IL)-21 or IL-21 receptor do not develop autoimmune type 1 diabetes (T1D). We have shown recently that IL-21 may promote activation of autoreactive CD8(+) T cells by increasing their antigen responsiveness. To investigate the role of IL-21 in activating diabetogenic CD8(+) T cells in the NOD mouse, we generated IL-21-deficient NOD mice expressing the highly pathogenic major histocompatibility complex (MHC) class-I-restricted 8.3 transgenic T cell receptor (TCR). IL-21 deficiency protected 8.3-NOD mice completely from T1D. CD8(+) T cells from the 8.3-NOD.Il21(-/-) mice showed decreased antigen-induced proliferation but displayed robust antigen-specific cytolytic activity and production of effector cytokines. IL-21-deficient 8.3 T cells underwent efficient homeostatic proliferation, and previous antigen stimulation enabled these cells to cause diabetes in NOD.Scid recipients. The 8.3 T cells that developed in an IL-21-deficient environment showed impaired antigen-specific proliferation in vivo even in IL-21-sufficient mice. These cells also showed impaired IL-2 production and Il2 gene transcription following antigen stimulation. However, IL-2 addition failed to reverse their impaired proliferation completely. These findings indicate that IL-21 is required for efficient initial activation of autoreactive CD8(+) T cells but is dispensable for the activated cells to develop effector functions and cause disease. Hence, therapeutic targeting of IL-21 in T1D may inhibit activation of naive autoreactive CD8(+) T cells, but may have to be combined with other strategies to inhibit already activated cells.


Establishment of an adrenocortical carcinoma xenograft with normotensive hyperaldosteronism in vivo.
We established a xenograft line of human adrenocortical carcinoma (ADR-1), and analyzed the hyperaldosteronism induced by the xenograft in vivo. Adrenocortical carcinoma specimens from a 25-year-old woman were subcutaneously inoculated into nude mice (BALB/c-nu/nu) followed by serial passages in vivo. ADR-1 retained the histopathological features (trabecular and sinusoid nests) seen in the primary carcinoma. The patient showed hyperaldosteronism (serum aldosterone >4000 pg/ml) and hypokalemia (serum K 2.1 mEq/l), but did not show hypertension. The nude rat (F344-rnu/rnu) bearing ADR-1 showed hyperaldosteronism (serum aldosterone 3320+/-1420 pg/ml; control 191+/-130 pg/ml) and hypokalemia (serum K 3.4+/-0.4 mEq/l; control 5.2+/-1.0 mEq/l) in vivo, and hypertension was not obvious. ADR-1 was shown immunohistochemically to retain production of human-specific corticosteroid synthetase. The xenograft ADR-1 will be useful to elucidate the regulatory mechanism of normotensive hyperaldosteronism.


Gene expression during development of Myxococcus xanthus. Analysis of the genes for protein S.
Protein S is an abundant spore coat protein produced during fruiting body formation (development) of the bacterium Myxococcus xanthus. We have cloned the DNA which codes for protein S and have found that this DNA hybridizes to three protein S RNA species from developmental cells but does not hybridize to RNA from vegetative cells. The half-life of protein S RNA was found to be unusually long, about 38 minutes, which, at least in part, accounts for the high level of protein S synthesis observed during development. Hybridization of restriction fragments from cloned M. xanthus DNA to the developmental RNAs enabled us to show that M. xanthus has two directly repeated genes for protein S (gene 1 and gene 2) which are separated by about 10(3) base-pairs on the bacterial chromosome. To study the expression of the protein S genes in M. xanthus, eight M. xanthus strains were isolated with Tn5 insertions at various positions in the DNA which codes for protein S. The strains which contained insertions in gene 1 or between gene 1 and gene 2 synthesized all three protein S RNA species and exhibited normal levels of protein S on spores. In contrast, M. xanthus strains exhibited normal levels of protein S on spores. In contrast, M. xanthus strains with insertions in gene 2 had no detectable protein S on spores and lacked protein S RNA. Thus, gene 2 is responsible for most if not all of the production of protein S during M. xanthus development. M. xanthus strains containing insertions in gene 1, gene 2 or both genes, were found to aggregate and sporulate normally even though strains bearing insertions in gene 2 contained no detectable protein S. We examined the expression of gene 1 in more detail by constructing a fusion between the lacZ gene of Escherichia coli and the N-terminal portion of protein S gene 1 of M. xanthus. The expression of beta-galactosidase activity in an M. xanthus strain containing the gene fusion was shown to be under developmental control. This result suggests that gene 1 is also expressed during development although apparently at a much lower level than gene 2.


The influence of (central) auditory processing disorder in speech sound disorders.
Considering the importance of auditory information for the acquisition and organization of phonological rules, the assessment of (central) auditory processing contributes to both the diagnosis and targeting of speech therapy in children with speech sound disorders. To study phonological measures and (central) auditory processing of children with speech sound disorder. Clinical and experimental study, with 21 subjects with speech sound disorder aged between 7.0 and 9.11 years, divided into two groups according to their (central) auditory processing disorder. The assessment comprised tests of phonology, speech inconsistency, and metalinguistic abilities. The group with (central) auditory processing disorder demonstrated greater severity of speech sound disorder. The cutoff value obtained for the process density index was the one that best characterized the occurrence of phonological processes for children above 7 years of age. The comparison among the tests evaluated between the two groups showed differences in some phonological and metalinguistic abilities. Children with an index value above 0.54 demonstrated strong tendencies towards presenting a (central) auditory processing disorder, and this measure was effective to indicate the need for evaluation in children with speech sound disorder.


Comparison of recurrence rate and risk factors in patients with focal adenomyosis with and without medical treatment after conservative surgery.
To compare the recurrence rate and risk factors between conservative surgery followed by medical treatments and conservative surgery-only in patients with focal adenomyosis. This retrospective study was conducted in a single teaching hospital from May 2011 to October 2016. All eligible patients were identified into three groups: surgery-only group, surgery combined with gonadotropin-releasing hormone agonist (GnRHa), and a levonorgestrel-releasing intrauterine system (LNG-IUS) group. The recurrence rate and risk factors were compared among groups using Kaplan-Meier and Cox proportional hazards analyses. Receiver operating characteristic (ROC) curve analysis was applied to determine a cut-off value for identifying recurrence-related risk factors. A total of 249 postoperative patients with adenomyosis were included in the final analysis with a mean of 41 months of follow up. The recurrence rate at the long-term follow up was significantly lower in intervention groups than in the surgery-only group (P = 0.011). The Cox proportional hazards and ROC analyses showed that a menstrual cycle longer than 26 days (P = 0.026), diameter of lesions <6 cm (P = 0.030), and combination treatment using GnRHa (P = 0.039) or LNG-IUS (P = 0.007) were protective against relapse. The risk of recurrence was lower in patients with anterior (P = 0.034) or fundus (P = 0.038) adenomyosis. Postoperative therapy using GnRHa or LNG-IUS decreases the long-term relapse rate in women undergoing conservative surgery.


Variability in absolute apparent diffusion coefficient values across different platforms may be substantial: a multivendor, multi-institutional comparison study.
To determine whether and to what degree absolute apparent diffusion coefficient (ADC) values vary between different imagers, vendors, field strengths, and intraimager conditions. Informed consent and institutional review board approval were obtained. Diffusion-weighted (DW) images with nearly identical parameters were obtained at 1.5 and 3.0 T from 12 healthy volunteers at seven institutions by using 10 magnetic resonance (MR) imagers provided by four different vendors. ADC maps were generated from isotropic DW maps, and images with a b value of 0 sec/mm(2) were generated by using in-house software. The mean pixel values for the brain tissues were calculated for evaluating the differences among coil systems, imagers, vendors, and magnetic field strengths. The absolute ADC values of gray and white matter from the same vendor varied substantially: 4%-9% at 1.5 and 3.0 T. With the exception of one vendor, the intervendor variability at 1.5 T was as high as 7%. Moreover, there was substantial intraimager variability, up to 8%, depending on the coil systems in certain imagers. There is significant variability in ADC values depending on the coil systems, imagers, vendors, and field strengths used for MR imaging. The relative ADC values may be more suitable than absolute ADC values for evaluating diffusion abnormalities in patients enrolled in multicenter acute ischemic stroke trials.


Efficacy and tolerance of oral ivermectin in scabies.
The aim of this open-label study was to investigate the therapeutic effect and adverse reactions of oral ivermectin in scabies patients. There is much confusion over reports of efficacy, adverse reactions and relapses after oral treatment of scabies with ivermectin. Nineteen patients, ten otherwise healthy outpatients with scabies, and nine inpatients with scabies and another skin disease (dermatomyositis, 3; pemphigus, 2; bullous pemphigoid, 1; pyoderma, 1; HIV, 1; Behçet's disease, 1) were treated with an oral dose of 0.2 mg/kg ivermectin (1% water solution) on days 1 and 8. The presence of live mites and ova in the patient's skin was investigated before, during and after the treatment. None of the 19 patients with scabies had evidence of scabies after the second dose of ivermectin. In seven patients we noted the enhancement of pruritus 24-72 h after the first administration of ivermectin. In three patients the skin manifestation, vesicle-pustular rash increased between the second and the fourth day. The advantages of oral ivermectin treatment in scabies patients are: high therapeutic efficacy against Sarcoptes scabiei, good tolerance and influence of the drug on the whole skin surface and on clinical symptoms. The administration of the drug is easy and quick.


Cucumber mosaic virus-associated RNA 5. XI. Comparison of 14 CARNA 5 variants relates ability to induce tomato necrosis to a conserved nucleotide sequence.
Seven CARNA 5 (Cucumber mosaic virus-Associated RNA 5) variants were obtained from an Indonesian cucumber mosaic virus isolate (designated CMV-In) by serial passage of this virus in squash, Chenopodium quinoa, tobacco, and tomato. Bioassays of the isolated CARNA 5 variants for their capability to induce lethal necrosis in tomato allowed categorization of the CARNA 5 variants as either necrogenic or nonnecrogenic. Comparison of the CARNA 5 sequences with sequences previously published shows that in general CMV satellites display a high degree of nucleotide sequence conservation. Except for two sharply defined domains of variability, the sequences of the necrogenic CARNA 5s are essentially conserved, whereas those of the nonnecrogenic CARNA 5s possess at least nine additional hypervariable domains. In eight positions of the CARNA 5 sequences all necrogenic variants differ uniquely from those that are nonnecrogenic. All CMV satellites compared in this work possess open reading frames (ORFs), with equivalent initiation codons, capable of encoding polypeptides of significant lengths. Two equivalent or identical ORFs were found only in the necrogenic CARNA 5s, whereas a variable-length ORF was found in the sequences of all the CARNA 5 variants compared. These findings constitute a basis for experiments aimed at determining the biological significance, if any, of these ORFs.


Appetite sensations and eating behaviors to complete fasting in obese and non-obese individuals.
To investigate the response of appetite sensations and eating behaviors to fasting in obese and non-obese individuals. Prospective study on inpatients enrolled in weight loss program including fasting at the obesity clinic, an oriental medical center in Seoul, Korea. For seven obese (body mass index BMI> or =30) and 11 non-obese (BMI<30) patients, the modified visual analog scale (VAS) was administered three times per day throughout 9 days of complete fasting. Three-Factor Eating Questionnaire (TEEQ) was administered before and 18 days after the complete fasting period. After treatment, average weight losses were 7.4 kg (3.0 BMI) for the obese group and 6.7 kg (2.6 BMI) for the non-obese. TFEQ scales did not differ by weight status at both before and after treatments. Eighteen days after the fasting, an increase of restraint of eating was found only for the non-obese. There was a decrease of disinhibition of eating regardless of weight status. During fasting, desire to eat, hunger and prospective consumption decreased for the non-obese, while these appetite sensations tended to increase slightly for the obese. BMI, independent of dieting status, appeared to be related to appetite sensations except for satiety during fasting, but not before and 18 days after fasting.


Elimination of Mycoplasma orale from the human hepatoma cell line, PLC/PRF/5.
We have tried without success to eliminate M. orale from a human hepatoma line, PLC/PRF/5, using five different methods. We report here the successful elimination of the contamination by a modification of the technique of Marcus et al. [1] using 5-bromodeoxy-uridine (BrdU) instead of 5-bromo-uracil (5-BrUra) and light. We believe that this method may prove useful when rare and valuable cell lines carry the more common mycoplasma contaminant M. orale.


Binding of fluorescein isothiocyanate conjugated lectins to rat spermatogenic cells in tissue sections. Enhancement of lectin fluorescence obtained by fixation in Bouin's fluid.
The testes from three months old Sprague-Dawley rats were fixed in Bouin's fluid or neutral buffered 10% formalin, embedded in paraffin, sectioned and after deparaffination stained with the following fluorescein isothiocyanate coupled lectins: PNA, WGA, Con A, RCA, SBA, DBA and UEA. The results show that there are considerable differences in the staining pattern of various spermatogenic cells between different lectins. The fixation in Bouin's fluid enhanced the staining of all the lectins compared to formalin fixation in which only a weak staining could be seen in the acrosomes of spermatids after WGA or PNA staining. PNA and WGA stained specifically the acrosome of the developing spermatids, which was seen from the beginning of the acrosome formation and lasted up to late spermiogenesis. However, the staining with PNA decreased in the late spermatids whereas the intensity of the staining remained unchanged with WGA. Con A did not stain the acrosome but stained unspecifically the cytoplasm of all spermatogenic cells. RCA stained faintly the acrosome throughout the spermatid differentiation. DBA and UEA stained specifically the chromosomes of B spermatogonia. DBA also faintly stained the cell membranes of early spermatids. SBA did not show any specific staining of the spermatogenic cells. Based on this it is suggested that the carbohydrates and glycoproteins which are known to be present in the acrosome are formed already in the beginning of the acrosome formation. The decrease in the PNA staining in late spermatids possibly reflects the fact that the receptor molecules are not synthesized in late spermatids but are formed in earlier developmental stages and are thereafter preserved in the acrosome.(ABSTRACT TRUNCATED AT 250 WORDS)


MicroRNA roles in beta-catenin pathway.
β-catenin, a key factor in the Wnt signaling pathway, has essential functions in the regulation of cell growth and differentiation. Aberrant β-catenin signaling has been linked to various disease pathologies, including an important role in tumorigenesis. Here, we review the regulation of the Wnt signaling pathway as it relates to β-catenin signaling in tumorigenesis, with particular focus on the role of microRNAs. Finally, we discuss the potential of β-catenin targeted therapeutics for cancer treatment.


Direct microscopical versus cultural method in screening for candidiasis among non gravid nigerian women.
The incidence of candidiasis in 125 symptomless, non-gravid women in Ile-Ife State Hospital, Ile-Ife, Oyo-State of Nigeria was determined by either microscopic observation or cultural methods. Among the three techniques investigated, the cultural method had the highest recovery rate with 60% of the cultures from 125 patients positive. Statistical analysis of the data (X2) demonstrated a significant difference between the recovery rates at the P less than 0.01 level. The implications of these findings were discussed in the text.


Branched-chain amino acid supplementation suppresses the detraining-induced reduction of mitochondrial content in mouse skeletal muscle.
Exercise training enhances oxidative capacity whereas detraining reduces mitochondrial content in skeletal muscle. The strategy to suppress the detraining-induced reduction of mitochondrial content has not been fully elucidated. As previous studies reported that branched-chain amino acid (BCAA) ingestion increased mitochondrial content in skeletal muscle, we evaluated whether BCAA supplementation could suppress the detraining-induced reduction of mitochondrial content. Six-week-old male Institute of Cancer Research (ICR) mice were randomly divided into four groups as follows: control (Con), endurance training (Tr), detraining (DeTr), and detraining with BCAA supplementation (DeTr + BCAA). Mice in Tr, DeTr, and DeTr + BCAA performed treadmill running exercises [20-30 m/min, 60 min, 5 times/week, 4 weeks]. Then, mice in DeTr and DeTr + BCAA were administered with water or BCAA [0.6 mg/g of body weight, twice daily] for 2 weeks of detraining. In whole skeletal muscle, mitochondrial enzyme activities and protein content were decreased after 2 weeks of detraining, but the reduction was suppressed by BCAA supplementation. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein content, a master regulator of mitochondrial biogenesis, was decreased by detraining irrespective of BCAA ingestion. Regarding mitochondrial degradation, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), a mitophagy-related protein, was significantly higher in the Tr group than in the DeTr + BCAA group, but not different from in the DeTr group. With respect to mitochondrial quality, BCAA ingestion did not affect oxygen consumption rate (OCR) and reactive oxygen species (ROS) production in isolated mitochondria. Our findings suggest that BCAA ingestion suppresses the detraining-induced reduction of mitochondrial content partly through inhibiting mitophagy.


Children Immunization App (CImA), Low-Cost Digital Solution for Supporting Syrian Refugees in Zaatari Camp in Jordan - General Description.
Mobile applications (apps) can improve health outcomes. In this study, we have described an app developed for documenting the history of vaccination among Syrian children in one of the largest refugees' camps in the Middle East region. This app includes health education information and automated reminders for parents, using a visual tool for parents with low literacy level. We have emphasized on the usability and technical concerns and have described the interdependency of technical and human considerations for such health app solution in a marginalized context.


AC-3933, a benzodiazepine partial inverse agonist, improves memory performance in MK-801-induced amnesia mouse model.
AC-3933, a novel benzodiazepine receptor partial inverse agonist, is a drug candidate for cognitive disorders including Alzheimer's disease. We have previously reported that AC-3933 enhances acetylcholine release in the rat hippocampus and ameliorates scopolamine-induced memory impairment and age-related cognitive decline in both rats and mice. In this study, we further evaluated the procognitive effect of AC-3933 on memory impairment induced by MK-801, an N-methyl-d-aspartate receptor antagonist, in mice. Unlike the acetylcholinesterase inhibitor donepezil and the benzodiazepine receptor inverse agonist FG-7142, oral administration of AC-3933 significantly ameliorated MK-801-induced memory impairment in the Y-maze test and in the object location test. Interestingly, the procognitive effects of AC-3933 on MK-801-induced memory impairment were not affected by the benzodiazepine receptor antagonist flumazenil, although this was not the case for the beneficial effects of AC-3933 on scopolamine-induced memory deficit. Moreover, the onset of AC-3933 ameliorating effect on scopolamine- or MK-801-induced memory impairment was different in the Y-maze test. Taken together, these results indicate that AC-3933 improves memory deficits caused by both cholinergic and glutamatergic hypofunction and suggest that the ameliorating effect of AC-3933 on MK-801-induced memory impairment is mediated by a mechanism other than inverse activation of the benzodiazepine receptor.


Through regulation of the SIRT1 pathway plant sterol ester of α-linolenic acid inhibits pyroptosis thereby attenuating the development of NASH in mice.
Increasing evidence demonstrated that pyroptosis and subsequent inflammation played an important role in the pathological process of non-alcoholic steatohepatitis (NASH). Plant sterol ester of α-linolenic acid (PS-ALA) was beneficial for non-alcoholic fatty liver disease, but the underlying mechanisms are still not fully understood. This study aims to investigate whether PS-ALA can protect against proptosis via regulating SIRT1. Thirty male C57BL/6J mice were fed a normal diet, a high-fat and high-cholesterol diet (HFCD), or a HFCD supplemented with either 1.3%ALA, 2%PS, or 3.3% PS-ALA for 24 weeks. Hepatocytes were treated with oleic acid and cholesterol (OA/Cho) with or without PS-ALA. We found that PS-ALA ameliorated NASH in HFCD-fed mice. In addition, PS-ALA decreased the expression of NLRP3 and ASC and reduced the co-localization of NLRP3 and cleave-Caspase-1. Also, PS-ALA protected against pyroptosis as evidenced by decreased co-localization of GSDMD and propidium iodide (PI) positive cells. Mechanistically, we revealed that the inhibitory action of PS-ALA on the pyroptosis was mediated by SIRT1. This was demonstrated by the fact that silencing SIRT1 with small interfering RNA or inhibition of SIRT1 with its inhibitor abolished the inhibition effect of PS-ALA on the expression of NLRP3 and GSDMD cleavage. Collectively, the data from the present study reveals a novel mechanism that PS-ALA inhibits pyroptosis and it triggered inflammation via stimulating SIRT1, which provides new insights into the beneficial effect of PS-ALA on NASH.


A new species of larval Dasitrombium Zhang, 1994 (Acari: Prostigmata: Neothrombiidae) parasitic on grasshoppers from Nicaragua.
A new species of larval neothrombids, Dasitrombium clarissae (Acari: Prostigmata: Neothrombiidae), parasitic on grasshoppers from Nicaragua is described. Larvae have the following diagnostic features: Ta I 110-114, Ti I 48-52, Ta II 102-106, Ti II 44-48, Ip 1020-1054, ratio L/W 1.29-1.40, and the presence on genu I of only two solenidia.


Effects of maternal corticosterone and stress on behavioral and hormonal indices of formalin pain in male and female offspring of different ages.
In previous studies, we showed for the first time that prenatal stress in rats produces long-term alterations of formalin-induced pain behavior that are dependent on age and sex, and we demonstrated an important role of the serotonergic system in mechanisms of prenatal stress (Butkevich, I.P. and Vershinina, E.A., 2001; Butkevich, I.P. and Vershinina, E.A., 2003; Butkevich, I.P., Mikhailenko, V.A., Vershinina, E.A., Khozhai, L.I., Grigorev, I.P., Otellin, V.A., 2005; Butkevich, I.P., Mikhailenko, V.A., Khozhai, L.I., Otellin, V.A., 2006). In the present study, we focus on the influence of the maternal corticosterone milieu and its role in the effects of stress during pregnancy on formalin-induced pain and the corticosterone response to it in male and female offspring of different ages. For this purpose, we used adrenalectomy (AD) in female rats 3-4 weeks before mating (as distinct from AD typically performed at the beginning of pregnancy). Since AD is considered a reliable method to treat hypercortisolism, researches on the effects of long-term AD in dams on the systems responsible for adaptive behavior in offspring are important (such studies are not described in the literature). The results demonstrate that the differences in the corticosterone response to injection of formalin and saline are obvious in 90-day-old (adult) female offspring but masked in 25-day-old ones. AD promoted the corticosterone response to formalin-induced pain but not to injection of saline in prenatally non-stressed female offspring of both ages. Prenatal stress canceled the differences in corticosterone response to injection of formalin and saline in 25-day-old offspring of AD dams and in adult offspring of sham-operated (SH) dams but caused similar differences in adult offspring of AD dams. Sex differences were found in basal corticosterone levels in AD prenatally stressed rats of both age groups, with a higher level in females, and in the corticosterone response to formalin-induced pain in the adult rats of all groups investigated, with higher corticosterone levels in females. In regard to pain behavior, AD induced significant changes in flexing+shaking in prenatally non-stressed adult offspring and canceled the differences in this behavior between non-stressed and stressed 25-day-old offspring. There were sex differences in pain behavior of the adult rats: greater flexing+shaking in AD non-stressed males but in SH non-stressed females; greater licking in prenatally-stressed AD and SH females. These results indicate that the long-term influences of maternal corticosterone on formalin-induced pain and the corticosterone response to it are determined by the sex and age of the offspring and suggest that other mechanisms, including serotonergic ones revealed in our previous studies, are involved in the effects of prenatal stress on inflammatory pain behavior.


Meningeal and choroid plexus cells--novel drug targets for CNS disorders.
The meninges and choroid plexus perform many functions in the developing and adult human central nervous system (CNS) and are composed of a number of different cell types. In this article I focus on meningeal and choroid plexus cells as targets for the development of drugs to treat a range of traumatic, ischemic and chronic brain disorders. Meningeal cells are involved in cortical development (and their dysfunction may be involved in cortical dysplasia), fibrotic scar formation after traumatic brain injuries (TBI), brain inflammation following infections, and neurodegenerative disorders such as Multiple Sclerosis (MS) and Alzheimer's disease (AD) and other brain disorders. The choroid plexus regulates the composition of the cerebrospinal fluid (CSF) as well as brain entry of inflammatory cells under basal conditions and after injuries. The meninges and choroid plexus also link peripheral inflammation (occurring in the metabolic syndrome and after infections) to CNS inflammation which may contribute to the development and progression of a range of CNS neurological and psychiatric disorders. They respond to cytokines generated systemically and secrete cytokines and chemokines that have powerful effects on the brain. The meninges may also provide a stem cell niche in the adult brain which could be harnessed for brain repair. Targeting meningeal and choroid plexus cells with therapeutic agents may provide novel therapies for a range of human brain disorders.


Pilot study of secondary prevention of posttraumatic stress disorder with propranolol.
Preclinical considerations suggest that treatment with a beta-adrenergic blocker following an acute psychologically traumatic event may reduce subsequent posttraumatic stress disorder (PTSD) symptoms. This pilot study addressed this hypothesis. Patients were randomized to begin, within 6 hours of the event, a 10-day course of double-blind propranolol (n = 18) versus placebo (n = 23) 40 mg four times daily. The mean (SD) 1-month Clinician-Administered PTSD Scale (CAPS) score of 11 propranolol completers was 27.6 (15.7), with one outlier 5.2 SDs above the others' mean, and of 20 placebo completers, 35.5 (21.5), t = 1.1, df = 29, p =.15. Two propranolol patients' scores fell above, and nine below, the placebo group's median, p =.03 (sign test). Zero of eight propranolol, but six of 14 placebo, patients were physiologic responders during script-driven imagery of the traumatic event when tested 3 months afterward, p =.04 (all p values one-tailed). These pilot results suggest that acute, posttrauma propranolol may have a preventive effect on subsequent PTSD.


[Preliminary data on activation of the enzyme of the metabolism of phospholipid bases in various areas of the brain].
The scope of this work was to study the effect of imydazole on base-exchange enzymic system in selected cerebral areas. We have previously demonstrated that imydazole was an activator of phosphatidylserine synthesis in slices of caudate nucleus. This effect lacked in the omogenate we had supposed that this activation by imydazole was not directed on base-exchange enzymic system, but was induced by decrease of cellular cyclic nucleotides amount. Therefore we have investigated the effect of dibutirril-AMPciclic in selected cerebral areas. In addition it was useful to state if activation by imydazole was area-specific or not.


Flexible Adipose-Vascular Tissue Assembly Using Combinational 3D Printing for Volume-Stable Soft Tissue Reconstruction.
A new concept, assembling cell-laden tissue modules, is for the first time proposed for soft tissue engineering. Adipose-vascular tissue modules composed of a synthetic polymer-based substructure and customized bioinks using planar 3D cell printing are engineered. Such tissue modules are systematically assembled into a synthetic polymer-based module holder fabricated with rotational 3D printing, resulting in the development of a flexible and volumetric tissue assembly. Whereas most of the previous studies about the construction of adipose tissue are limited to hypoxia, poor vascularization, rapid resorption, and mismatch in mechanical properties, it is aimed to realize the construction of nonhypoxic, flexible, and volume-stable tissue assembly in this study. The significance of engineered tissue assembly is proven through various in vitro and in vivo evaluations. In particular, stable volume and remarkable neovascularization/adipogenesis are observed in the implanted assembly over four weeks. Interestingly, the size of newly formed lipid droplets and the remodeled morphology in the assembly are comparable to those in native adipose tissue. As far as it is known, this work is a first report suggesting a cell printing-based tissue assembly for functional reconstruction of soft tissue.


Structure of the monomeric actin-myosin head complex as revealed by X-ray solution scattering.
In order to study the structure of a complex of monomeric actin and myosin head (S1) in the presence of nucleotide, non-polymerizable G-actin was prepared by the reaction of G-actin with m-maleimidobenzoic acid N-hydroxysuccinimide ester (MBS) and diazonium(1H)tetrazole (DHT). Although singly-modified MBS-actin forms a 2:1 complex with S1, doubly-modified DHT/MBS-G-actin forms a 1:1 complex with a dissociation constant of approximately 10(-6) M and can activate Mg-ATPase of S1 by 2-fold. Using a synchrotron X-ray source, we have measured X-ray solution scattering from reversible acto-S1 complexes obtained by mixing rabbit skeletal S1 and DHT/MBS-G-actin in the absence of nucleotide or in the presence of MgADP. The Guinier plots of the scattering intensity showed straight lines indicating no large aggregates and gave the radii of gyration of the complexes to be 49 and 46 A in the absence and presence of ADP, respectively. The analysis of the scattering curves showed that a monomeric actin binds to a tip of S1, and that the complex undergoes substantial rearrangement resulting in a more compact structure when it binds ADP.


Serum angiopoietin-2 level as a novel biomarker in atopic dermatitis.
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Angiopoietin is an intrinsic mediator induced by T helper 2 cytokines and has been reported it to play a critical role in the pathogenesis of AD. To determine the relationship between circulating angiopoietin-2 (Ang-2) in AD patients and to determine its correlation with the severity and chronicity of the disease. The present study included 38 AD patients and 38 healthy controls, age- and sex-matched. We collected 3 mm of venous blood from each subject. Enzyme-linked immunosorbent assay (ELISA) determined serum angiopoietin. We determined the correlation between serum Ang-2 level, duration of disease, severity, type of atopy, and scoring atopic dermatitis (SCORAD) score. There were highly significant differences between patients and controls with regard to serum Ang-2 levels (P < 0.001). There were significant differences between severe AD patients with serum Ang-2 levels with an increasing level of degree severity (P < 0.001). There were significant differences in serum Ang-2 levels among widespread type (P < 0.03). There was a positive significant correlation between Ang-2 levels and both duration and SCORAD score of the patient group. Serum Ang-2 levels may correlate with disease severity, chronicity in patients with AD, and serve as a potential biomarker of the disease severity.


Spirotetramat resistance adaption analysis of Aphis gossypii Glover by transcriptomic survey.
A resistant strain of the cotton aphid (SR) developed 441.26-fold and 11.97-fold resistance to spirotetramat for adult aphids and nymphs, respectively, compared with the susceptible (SS) strain. Solexa sequencing technology was employed to identify differentially expressed genes (DEGs) in the spirotetramat-resistant cotton aphid. Respective totals of 22,430,522 and 21,317,732 clean reads were obtained from SR and SS cDNA libraries and assembled into 35,222 non-redundant (Nr) consensus sequences. A total of 14,913, 9,220, 7,922, 4,314 and 4,686 sequences were annotated using Nr, Swiss-Prot, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG), respectively. Compared with the SS strain, the SR strain had 1287 significantly changed unigenes, of which 130 genes were up-regulated and 1157 genes were down-regulated (P ≤ 0.001). Among these genes, 440 unigenes were annotated, consisting of 114 up-regulated and 326 down-regulated genes. The expression levels of heat shock protein 70 (Hsp70) and UDP-glucuronosyltransferase were significantly up-regulated in the SR strain compared to the SS strain. The genes encoding cuticle proteins, salivary glue protein, fibroin heavy chain, energy ATP synthase, and cytochrome c oxidase were dramatically decreased. Among the DEGs, cytochrome P450 6A2 (c20965.graph_c0) was the only P450 gene up-regulated in the SR strain. The expression levels of 10 DEGs were confirmed by real-time qPCR, and the trends in gene expression observed by qPCR matched those of the Solexa expression profiles. The acetyl-CoA carboxylase (ACC) genes in the SR and SS libraries both contain four single nucleotide polymorphisms (SNPs), with three common SNPs: 1227 (C/T), 1811 (A/T: F/Y) and 3759 (C/T); however, 7540 (A/T) and 108 (G/A) occurred solely in the SS and SR strains, respectively.


Effect of multidose intracorporeal injection and audiovisual sexual stimulation in vasculogenic impotence.
Erections are inhibited by sympathetic stimulation. Anxiety or psychologic inhibition may produce abnormal response during impotence workup. The use of intracorporeal alpha blockers (phentolamine) and audiovisual sexual stimulation (AVSS) has been used to decrease sympathetic outflow and enhance erectile response. Thirty-three patients with suspected vasculogenic impotence were studied. They underwent pulsed Doppler ultrasound (PDUS) with multiple doses of tri-mix (mix of papaverine, phentolamine, and prostaglandin E1). AVSS was applied after maximal response to tri-mix. Seventeen patients (51.5%) responded to multidose with grade IV or V erection. When AVSS was started, 5 more patients responded, and 7 upgraded to grade V with overall response of 40 percent. AVSS can augment the in-office response to pharmacologic testing above that obtained by "maximal" pharmacologic dosing, thereby increasing the sensitivity and specificity of the test.


Generating demand for and use of evaluation evidence in government health ministries: lessons from a pilot programme in Uganda and Zambia.
The Demand-Driven Evaluations for Decisions (3DE) programme was piloted in Zambia and Uganda in 2012-2015. It aimed to answer evaluative questions raised by policymakers in Ministries of Health, rapidly and with limited resources. The aim of our evaluation was to assess whether the 3DE model was successful in supporting and increasing evidence-based policymaking, building capacity and changing behaviour of Ministry staff. Using mixed methods, we compared the ex-ante theory of change with what had happened in practice, why and with what results (intended and unintended), including a qualitative assessment of 3DE's contribution. Data sources included a structured quality assessment of the five impact evaluations produced, 46 key informant interviews at national and international levels, structured extraction from 170 programme documents, a wider literature review of relevant topics, and a political economy analysis conducted in Zambia. We found that 3DE had a very limited contribution to changing evidence-based policymaking, capacity and behaviour in both countries as a result of having a number of aspirations not all compatible with one another. Co-developing evaluation questions was more time-consuming than anticipated, Ministry evidence needs did not fit neatly into questions suitable for impact evaluations and constricted timeframes for undertaking trials did not necessarily produce the most effective results and value for money. The evaluation recommended a focusing of objectives and a more strategic approach to strengthening evaluative demand and capacity. Lessons emerge that are likely to apply in other low- and middle-income settings, such as the importance of supporting evaluative thinking and capacity within wider institutions, of understanding the political economy of evidence use and its uptake, and of allowing for some flexibility in terms of programme targets. Fixating on one type of evidence is unhelpful in the context of institutions like ministries of health, which require a wide range of evidence to plan and deliver programmes. In addition, having success tied to indicators, such as number of 'policy decisions made', provides potentially perverse incentives and neglects arguably more important aspects such as incremental programmatic adjustments and improved implementation.


Coherent ac spin current transmission across an antiferromagnetic CoO insulator.
The recent discovery of spin current transmission through antiferromagnetic insulating materials opens up vast opportunities for fundamental physics and spintronics applications. The question currently surrounding this topic is: whether and how could THz antiferromagnetic magnons mediate a GHz spin current? This mismatch of frequencies becomes particularly critical for the case of coherent ac spin current, raising the fundamental question of whether a GHz ac spin current can ever keep its coherence inside an antiferromagnetic insulator and so drive the spin precession of another ferromagnet layer coherently? Utilizing element- and time-resolved x-ray pump-probe measurements on Py/Ag/CoO/Ag/Fe75Co25/MgO(001) heterostructures, here we demonstrate that a coherent GHz ac spin current pumped by the Py ferromagnetic resonance can transmit coherently across an antiferromagnetic CoO insulating layer to drive a coherent spin precession of the Fe75Co25 layer. Further measurement results favor thermal magnons rather than evanescent spin waves as the mediator of the coherent ac spin current in CoO.


[RBC and T lymphocyte subsets in patients with bladder carcinoma: immunological study].
To study immune function of erythrocytes and the correlation with the change of T lymphocyte subsets in the patients with bladder cancer. The red blood cell C(3)b receptor rate (C(3)bRR), immune complex rate (ICR) and four kinds of tumor erythrocyte rosette tests were determined in 34 cases of bladder transitional epithelial carcinoma. The subsets of T lymphocyte were also determined by using flow cytometry (FCM). 30 non-carcinoma patients that well-matched in age and 20 healthy men were determined for comparison. The C(3)bRR, four kinds of tumor erythrocyte rosette rate, CD3, CD4 and CD4/CD8 ratio were lower in the bladder transitional epithelial carcinoma group than those of the control group. Meanwhile, ICR and CD8 were significantly elevated (P < 0.01). There was differentiation between G1 patients and G2 patients (P < 0.05). A positive correlation between C3bRR and the radio of CD4/CD8 was noted in the bladder transitional cell carcinoma group. Patients with bladder transitional cell carcinoma show lower erythrocyte function and disorder of T lymphocyte subsets. There is a close relationship between red cell immune function and T lymphocyte subsets. The cellular immune function (including the red cell immune function) in patients with poorly differentiated cells is lower.


Hippocampal phosphoinositide turnover is altered by hippocampal sympathetic ingrowth and cholinergic denervation.
Cholinergic denervation of the hippocampus, by medial septal (MS) lesions, results in an unusual neuronal rearrangement in which peripheral sympathetic nerves, which originate from the superior cervical ganglia, grow into the hippocampal formation. To assess the functional significance of hippocampal sympathetic ingrowth (HSI), hydrolysis of phosphoinositides was examined in three groups: control, MS lesions + sham ganglionectomy (HSI group); and MS lesions + ganglionectomy (MSGx; no ingrowth). Four months after surgery, both norepinephrine (NE) and carbachol were found to produce a dose-dependent increase in the hydrolysis of hippocampal phosphoinositides in all groups. However, the presence of HSI, when compared to control and MSGx groups, significantly enhanced the turnover of phosphoinositides when stimulated by carbachol, but not NE. In further studies, the time course of this effect was studied. One week after surgery, carbachol-stimulated phosphoinositide turnover was equivalent among all groups; by 2 weeks, phosphoinositide turnover was enhanced in the HSI and MSGx group; by 4 weeks, PI turnover was markedly diminished in the MSGx group when compared to both the HSI and control groups, which were equivalent to each other. To ensure that the ganglionectomy alone did not alter phosphoinositide turnover, a ganglionectomy-alone group was studied at the 4-week time point. In this group, phosphoinositide turnover was equivalent to controls, suggesting no influence of the superior cervical ganglia on this response. In all groups, atropine inhibited carbachol-stimulated phosphoinositide turnover. These results suggest that both cholinergic denervation (i.e., MSGx group) and HSI produce marked functional alterations in hippocampal metabolic activity.


Shotgun proteomics of Xanthobacter autotrophicus Py2 reveals proteins specific to growth on propylene.
Coenzyme M (CoM, 2-mercaptoethanesulfonate), once thought to be exclusively produced by methanogens, is now known to be the central cofactor in the metabolism of short-chain alkenes by a variety of aerobic bacteria. There is little evidence to suggest how, and under what conditions, CoM is biosynthesized by these organisms. A shotgun proteomics approach was used to investigate CoM-dependent propylene metabolism in the Gram-negative bacterium Xanthobacter autotrophicus Py2. Cells were grown on either glucose or propylene, and the soluble proteomes were analyzed. An average of 395 proteins was identified from glucose-grown replicates, with an average of 419 identified from propylene-grown replicates. A number of linear megaplasmid (pXAUT01)-encoded proteins were found to be specifically produced by growth on propylene. These included all known to be crucial to propylene metabolism, in addition to an aldehyde dehydrogenase, a DNA-binding protein, and five putative CoM biosynthetic enzymes. This work has provided fresh insight into bacterial alkene metabolism and has generated new targets for future studies in X. autotrophicus Py2 and related CoM-dependent alkene-oxidizing bacteria.


Zinc alters fibrin ultrastructure.
Turbidimetric studies indicate that Zn(II) accelerates fibrin gelation [decreases clotting time (CT)] and increases maximal fibrin clot turbidity. For any given level of fibrinogen (0.2-2.6 mg/ml), the relative fibrin turbidity of thrombin-induced clots increases with Zn(II) in a concentration dependent manner. Zinc-associated turbidity increases are also observed in the presence of 2 mM (Ca(II). With citrate, similar turbidity increases are observed, though at higher cation levels. Thus, turbidimetry indicates that the gel formed with Zn(II) is coarser, or has thicker fibre strands. SEM micrographs confirm that fibre thickness ranges from 260 A to 2600 A, when Zn(II) levels range from 0-50 uM. With citrate, TEM micrographs reveal a more than 20 X fold increase in fibre diameter (100 A- greater than 2000 A) with higher Zn(II) (less than 1 mM) levels. Based on a fibrin monomer cross-section of approximately 60 A, the electron micrographs indicate that depending on the Zn(II) levels, fibrin strands are composed of between 2 to 40 monomeric fibrin molecules. Thus, at physiologically relevant levels, Zn(II) can drastically modulate fibrin ultrastructure.


Interleukin-17 stimulates chemokine (interleukin-8 and monocyte chemoattractant protein-1) secretion in human pancreatic periacinar myofibroblasts.
Interleukin (IL)-17 is a newly identified T-cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion in human pancreatic periacinar myofibroblasts. The secretion of IL-8 and monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression. Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity, and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding activity. In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The combination of IL-17 with IFN-gamma further enhances chemokine secretion. These findings indicate a linkage between T-cell-mediated immunity and inflammatory responses in the pancreas.


Radiosensitivity and recovery of mouse L cells during the cell cycle.
Mouse fibroblasts, subline L-929 F were synchronized by mitotic detachment. The synchronized cell cultures were irradiated with 200 kVp X-rays at different time after mitosis, and age response functions and dose effect curves were determined using the colony test. The cell age in the mitotic cycle was obtained from a computer analysis of flow cytometric DNA histograms. Both intrinsic radiosensitivity 1/D0 and extrapolation number n were found to vary during the cell cycle. The D0 has a maximum value of 176 +/- 1 rad in the middle of G1 phase and minimum of 71 +/- 1 rad at the S/G2 transition, while the extrapolation number is rather constant from the beginning of G1 phase (1.9 +/- 0.1) to the middle of S phase (2.3 +/- 0.1) and reaches a steep maximum of 9.3 +/- 1.1 at S/G2 transition. The values of n in the various phases of cell cycle are compared with the respective values of the recovery factor gamma determined after fractionated irradiation. --Cell survival after a single dose of 616 rad has minima for irradiation at G1/S transition and in early G2 phase; the survival in early G2 being about 40 times smaller than in early G1 phase. Implications for a cell cycle specific therapy are discussed.


Wnt/β-Catenin Target Genes in Colon Cancer Metastasis: The Special Case of L1CAM.
Cell adhesion to neighboring cells is a fundamental biological process in multicellular organisms that is required for tissue morphogenesis. A tight coordination between cell-cell adhesion, signaling, and gene expression is a characteristic feature of normal tissues. Changes, and often disruption of this coordination, are common during invasive and metastatic cancer development. The Wnt/β-catenin signaling pathway is an excellent model for studying the role of adhesion-mediated signaling in colorectal cancer (CRC) invasion and metastasis, because β-catenin has a dual role in the cell; it is a major adhesion linker of cadherin transmembrane receptors to the cytoskeleton and, in addition, it is also a key transducer of Wnt signaling to the nucleus, where it acts as a co-transcriptional activator of Wnt target genes. Hyperactivation of Wnt/β-catenin signaling is a common feature in the majority of CRC patients. We found that the neural cell adhesion receptor L1CAM (L1) is a target gene of β-catenin signaling and is induced in carcinoma cells of CRC patients, where it plays an important role in CRC metastasis. In this review, we will discuss studies on β-catenin target genes activated during CRC development (in particular, L1), the signaling pathways affected by L1, and the role of downstream target genes activated by L1 overexpression, especially those that are also part of the intestinal stem cell gene signature. As intestinal stem cells are highly regulated by Wnt signaling and are believed to also play major roles in CRC progression, unravelling the mechanisms underlying the regulation of these genes will shed light on both normal intestinal homeostasis and the development of invasive and metastatic CRC.


Clinicopathological heterogeneity between primary and metastatic sites of gastroenteropancreatic neuroendocrine neoplasm.
Chromogranin A (CgA), synaptophysin (Syn) and the Ki-67 index play significant roles in diagnosis or the evaluation of the proliferative activity of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, little is known about whether these biological markers change during tumor metastasis and whether such changes have effect on prognosis. We analyzed 35 specimens of both primary and metastatic tumor from 779 patients who had been diagnosed as GEP-NENs at Wuhan Union Hospital from August 2011 to October 2019. The heterogeneity of CgA, Syn and Ki-67 index was evaluated by immunohistochemical analysis. Among these 779 patients, the three most common sites of NENs in the digestive tract were the pancreas, rectum and stomach. Metastases were found in 311 (39.9%) patients. Among the 35 patients with both primary and metastatic pathological specimens, differences in the Ki-67 level were detected in 54.3% of the patients, while 37.1% showed a difference in CgA and only 11.4% showed a difference in Syn. Importantly, due to the difference in the Ki-67 index between primary and metastatic lesions, the WHO grade was changed in 8.6% of the patients. In addition, a Kaplan-Meier survival analysis showed that patients with Ki-67 index variation had a shorter overall survival (p = 0.0346), while neither Syn variation nor CgA variation was related to patient survival (p = 0.7194, p = 0.4829). Our data indicate that primary and metastatic sites of GEP-NENs may exhibit pathological heterogeneity. Ki-67 index variation is closely related to the poor prognosis of patients with tumor metastasis, but neither Syn variation nor CgA variation is related to patient prognosis. Therefore, clinicopathologic evaluation of the primary tumor and metastatic sites could be helpful for predicting the prognosis.


Description of the first full-length HIV type 1 subtype F1 strain in Argentina: implications for the origin and dispersion of this subtype in South America.
HIV-1 subtype F1 in South America is mainly found as part of diverse BF1 recombinant forms and only five full-length "pure" F1 strains from Brazil were characterized to date. In the present study we describe the first near full-length sequence of a nonrecombinant F1 HIV-1 strain from Argentina, and explore the epidemiological history of this subtype in South America. Three separate phylogenetic analyses were carried out: with all available F1 full-length sequences, with concatenated F1 sequences contained in F1 and BF1 strains, and with partial F1 env sequences derived from worldwide strains. All analyses were consistent in showing a local origin of the newly reported Argentine subtype F1 strain, and a common ancestry of the South American subtype F1 sequences, present either in pure or recombinant genomes. By coalescent analysis, the onset date of the HIV-1 subtype F1 epidemic in South America was estimated to be around the late 1970s. The results indicate for the first time that nonrecombinant F1 HIV-1 strains are present in Argentina, and suggest that the subtype F1 epidemic in South America was initiated by the introduction of a very small group of genetically related viruses during late 1970s.