Cloning and expression of a transcription factor activator protein-1 (AP-1) member identified from manila clam Venerupis philippinarum.
The transcription factor activator protein-1 (AP-1) proteins are implicated to play a major role in the regulation of numerous genes involved in the function and development of the immune system, cell differentiation, proliferation, apoptosis, etc. It can bind to promoter of its target genes in a sequence-specific manner to transactivate or repress them. In this study, the full-length cDNA of an AP-1 was identified from Venerupis philippinarum (denoted as VpAP-1) by EST analysis and RACE approaches. Phylogenetic analysis indicated that VpAP-1 had higher evolutional conservation to invertebrate than vertebrate counterparts and should be a new member of the AP-1 protein family. Spatial expression analysis found that VpAP-1 transcript was most abundantly expressed in the hemocytes and hepatopancreas, weakly expressed in the tissues of the gills, mantle and muscle. After Vibrio anguillarum challenge, the expression of VpAP-1 transcript in overall hemocyte population was up-regulated in the first 6h, and then decreased to 1.5-fold of the control group at 12h. As time progressed, a second peak of VpAP-1 expression was detected at 24h post-infection, which was 5-fold compared with that of the control group (P<0.01). After that, the expression level was sharply decreased and dropped to 0.5-fold of the control at 96h. The above results indicated that VpAP-1 was perhaps involved in the immune responses against microbe infection and might be contributed to the clearance of bacterial pathogens.


[Primary study of relationship between lumbar degenerative disease and morbidity of primary knee osteoarthritis].
To study the relationship between lumbar degenerative disease and morbidity of primary unilateral knee osteoarthritis. The clinical data of 115 unilateral knee osteoarthritis patients and 119 bilateral knee osteoarthritis patients undergoing TKR (total knee replacement) at our hospital in 2008 were retrospectively analyzed. According to clinical signs of lumbar degenerative disease and radiological changes, these patients were divided into upper/lower/whole/none lumbar degenerative disease group respectively. chi(2) test was performed to compare the difference of lumbar degenerative conditions between unilateral knee osteoarthritis and bilateral knee osteoarthritis patients. The morbidity side of lumbar intervertebral disc protrusion or nerve root canal stenosis in primary unilateral osteoarthritis patients was the same as the morbidity side of primary unilateral osteoarthritis. Lumbar degenerative disease morbidity [(34 + 20 + 15)/115 = 60%] of primary unilateral knee osteoarthritis was higher than that [(3 + 5 + 4 + 6 + 19)/119 = 31.1%] of primary bilateral knee osteoarthritis (chi(2) = 19.723, P = 0.000);Upper lumbar degenerative disease morbidity (34/115 = 29.6%)of primary unilateral knee osteoarthritis was higher than that [(3 + 5)/119 = 6.7%] of primary bilateral knee osteoarthritis, (chi(2) = 20.720, P = 0.000); lower lumbar degenerative disease morbidity (20/115 = 17.4%)of primary unilateral knee osteoarthritis was higher than that [(4 + 6)/119 = 8.4%] of primary bilateral knee osteoarthritis (chi(2) = 4.227, P = 0.040); there was no difference for whole lumbar degenerative disease morbidity between primary unilateral and bilateral knee osteoarthritis patients (chi(2) = 0.402, P = 0.526). The primary unilateral knee osteoarthritis morbidity is correlated with lumbar degenerative disease for the same elder patient. Upper lumbar degenerative disease can induce the incidence and aggravation of primary unilateral knee osteoarthritis; the flexion deformity of primary knee osteoarthritis may cause the aggravation of lower lumbar degenerative disease, even upper lumbar degenerative disease.


The acidic protein binding site is partially hidden in the free Saccharomyces cerevisiae ribosomal stalk protein P0.
The ribosomal stalk is essential for translation; however, its overall structure is poorly understood. Characterization of the region involved in the interactions between protein P0 and the 12 kDa acidic proteins P1 and P2 is fundamental to understand the assembly and function of this structure in the eukaryotic ribosome. The acidic protein content is important for the ribosome efficiency and affects the translation of specific mRNAs. By usage of a series of progressively truncated fragments of protein P0 in the two-hybrid test, a region between positions 213 and 250 was identified as the minimal protein part able to interact with the acidic proteins. Extensions at either end affect the binding capacity of the fragment either positively or negatively depending on the number of added amino acids. Deletions inside the binding region confirm its in vivo relevance since they drastically reduce the P0 interacting capacity with the 12 kDa acidic proteins, which are severely reduced in the ribosome when the truncated protein is expressed in the cell. Moreover, recombinant His-tagged P0 fragments containing the binding site and bound to Ni(2+)-NTA columns can form a complex with the P1 and P2 proteins, which is able to bind elongation factor EF2. The results indicate the existence of a region in P0 that specifically interacts with the acidic proteins. These interactions are, however, hindered by the presence of neighbor protein domains, suggesting the need for conformational changes in the complete P0 to allow the assembly of the ribosomal stalk.


Design of a continuous-wave tunable terahertz source using waveguide-phase-matched GaAs.
A novel source of continuous-wave terahertz radiation based on difference frequency generation (DFG) in GaAs crystal is proposed. Phase matching is provided using integration of appropriate optical and terahertz waveguides based on dispersive properties of GaAs. The output frequency can be tuned between 0-3.5 THz by tuning the incident wavelengths in the range of 1.5-1.6 microm.


The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants.
Mycophenolic acid (MPA), a standard immunosuppressive drug, is characterized by unexplained highly variable pharmacokinetics in transplant recipients. The primary metabolic pathway of MPA is glucuronidation; however, literature reports are inconsistent and the contribution of all human UDP-glucuronosyltransferases (UGTs) has never been systematically assessed. Sixteen heterologously expressed UGTs were studied for MPA 7-O-glucuronidation and compared with liver, kidney, and intestine microsomes. For direct measurement of MPA and mycophenolic acid 7-O-glucuronide (MPAG), we used a liquid chromatography-mass spectrometry protocol. Metabolic studies demonstrated that the glucuronidation of MPA in humans occurs mainly in the liver at variable rates, as well as in the kidney and the intestine. Kinetic data normalized for UGT expression levels point to 1A8 and 1A9 as the main UGTs, as well as to low-activity enzymes, 1A1, 1A7, and 1A10. According to their expression profiles, 1A8 and 1A9 are proposed, respectively, as the main extra-hepatic and the only hepatic enzymes involved. The effects of naturally occurring 1A8 ((*)2 and (*)3) and 1A9 ((*)2 and (*)3) variants on MPA 7-O-glucuronidation were studied and data suggest that the C(277)Y of 1A8 and the M(33)T of 1A9 may influence MPAG levels. A number of low-activity alleles were also identified in 1A1 [(*)6 (G(71)R), (*)7 (Y(486)D), (*)27 (P(229)Q), and (*)35 (L(233)R)], 1A7 [(*)3 (K(129)K(131)R(208)), (*)4 (R(208)), (*)5 (S(115)), (*)8 (K(129)K(131)D(139)R(208)), and (*)9 (S(115)K(129)K(131))], and 1A10 [(*)2 (E(139)K)]. Our study provides preliminary evidences that genetic factors, especially in the hepatic UGT1A9, may contribute to the variability of MPA pharmacokinetics observed in transplant patients.


[Effect of smoking on the microRNAs expression in pneumoconiosis patients].
To investigate the effect of smoking on the microRNAs (miRNAs) expression in pneumoconiosis patients. Real-time qPCR was used to measure the expression levels of miR-21, miR-200c, miR-16, miR-204, miR-206, miR-155, let-7g, miR-30b, and miR-192 in 36 non-smoking patients with pneumoconiosis and 38 smoking patients with pneumoconiosis, and the differences in expression levels between the two groups were evaluated by two-independent samples t-test. The expression of miR-192 in serum showed a significant difference between non-smoking and smoking pneumoconiosis patients (P < 0.05), and it decreased gradually in smoking patients with stage I and II pneumoconiosis. In the serum of all pneumoconiosis patients, the expression level of miR-16 was the highest, while the expression level of miR-204 was the lowest. Pneumoconiosis patients have differential expression of miRNAs in serum, and smoking has an effect on the miRNAs expression in pneumoconiosis patients.


Activation of the silent progesterone receptor gene by ectopic expression of estrogen receptors in a rat fibroblast cell line.
We describe the construction and characterization of a novel estrogen (E2)-responsive cell line, Rat1+ER, which ectopically expresses estrogen receptor (ER). Human ER cDNA was introduced by retrovirus-mediated gene transfer into the Rat1 cell line, which does not express functional ER endogenously. Rat1+ER cells express functional ER based on radioreceptor assays, immunoblotting, and transient transfection experiments using E2-responsive reporter plasmids. The effects of this ectopic ER expression were studied on three endogenous E2-responsive genes, prolactin (PRL), progesterone receptor (PR), and epidermal growth factor receptor (EGFR). PRL, usually expressed in the lactotrophs of the pituitary, is not expressed at all in Rat1+ER cells, with or without E2 addition, and appears to require other factors for expression. In contrast, although PR is not expressed in Rat1 cells, it is induced in Rat1+ER cells upon the addition of E2. This induction appears to occur at the transcriptional level and is insensitive to cycloheximide treatment. This is one of the few examples where the expression of one gene activates an otherwise silent gene. Another contrasting observation is that, although EGFR is basally expressed in Rat1+ER cells, the addition of E2 has no effect. Our studies paint a complicated picture of E2 regulation of endogenous genes: the activation of the PR gene may only require the presence of E2 and ER, whereas EGFR and PRL genes require factors in addition to ER for basal as well as E2-regulated expression.


[Uretero-fallopian fistula secondary to low anterior resection for rectal cancer].
A 71-year-old woman presented with lower abdominal pain and urinary incontinence 18 days after low anterior resection for rectal cancer. Computed tomography and magnetic resonance urography revealed right hydronephrosis, cystic mass in the right pelvic cavity and hydrometra. Positron emission tomography showed dilated right upper urinary tract communicating with dilated right fallopian tube and uterine body, and the finding was quite characteristic. Laboratory studies revealed that the serum and the fluid from hydrometra levels of creatinine were 1.06 mg/dL and 6.15 mg/dL, respectively. We diagnosed this case as uretero-fallopian fistula. Since the conservative management of uretero-fallopian fistula with ureteral stent was not accomplished, she underwent right ureteroureterostomy and adnexectomy. The intraoperative findings included dilated right ureter and fallopian tube adherent to the stenotic right ureteral segment ligated by suture during prior surgery. The histopathological findings showed endometriosis and inflammatory changes of uterine appendages. Follow-up at 3 months demonstrated resolution of the urinary incontinence and the ureteral obstruction and fistula.


Level spacing statistics of classically integrable systems: investigation along the lines of the Berry-Robnik approach.
By extending the approach of Berry and Robnik, the limiting level spacing distribution of a system consisting of infinitely many independent components is investigated. The limiting level spacing distribution is characterized by a single monotonically increasing function mu(S) of the level spacing S. Three cases are distinguished: (1) Poissonian if mu(+ infinity)=0, (2) Poissonian for large S, but possibly not for small S if 0<mu(+infinity)<1, and (3) sub-Poissonian if mu(+infinity)=1. This implies that, even when energy-level distributions of individual components are statistically independent, non-Poissonian level spacing distributions are possible.


Anti-infective drug use in relation to the risk of agranulocytosis and aplastic anemia. A report from the International Agranulocytosis and Aplastic Anemia Study.
The risks of agranulocytosis and aplastic anemia in relation to the use of anti-infective drugs were estimated in a population-based case-control study conducted in Europe and Israel. Anti-infective drug use in the 2-week period before the onset of illness was compared between 251 patients admitted to hospital with agranulocytosis and 1271 controls hospitalized for reasons judged to be unrelated to previous use of anti-infective drugs. Anti-infectives significantly associated with agranulocytosis when used for at least 3 consecutive days were trimethoprim/sulfamethoxazole (relative risk, 12; 95% confidence interval, 3.9 to 40) and macrolides (infinity). The relative risk estimate for any use of sulfonamides without trimethoprim was elevated, but not statistically significant (3.6; 0.7 to 18). These estimates took confounding by various factors, in particular the use of other drugs, into account. The estimated excess risks of agranulocytosis attributable to the use of trimethoprim/sulfamethoxazole and macrolides in a 2-week period were 1.6 and 7.1 per million, respectively. Anti-infective use during the 29- through 180-day period before hospital admission was compared between 135 patients with aplastic anemia and 1410 controls. Although relative risk point estimates were elevated for trimethoprim/sulfonamides (2.1), other sulfonamides (2.9), and beta-lactams (1.5), none was statistically significant.


Methylenetetrahydrofolate reductase polymorphisms are related to male infertility in Brazilian men.
The objective of this study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic infertile Brazilian patients with nonobstructive azoospermia (NOA) or severe oligozoospermia and fertile Brazilian men as controls to explore the possible association of these polymorphisms and male infertility. A case-control study was carried out, including 156 idiopathic infertile Brazilian patients with NOA (n=49) or severe oligozoospermia (n=107) and 233 fertile men as controls. Polymorphisms C677T and A1298C were studied by quantitative polymerase chain reaction and the results were statistically analyzed. The frequency of genotypes MTHFR 677CC, 677CT, and 677TT in idiopathic infertile men with NOA were 55.1%, 30.6%, and 14.3% (p=0.0305); 50.6%, 42.0%, and 7.5% (p=0.0006) regarding the severe oligozoospermic men; and 71.7%, 53.0%, and 5.6% in the control group. As for polymorphism A1298C, regarding the NOA group, the frequencies of the 1298AA, 1298AC, and 1298CC genotypes were 53.0%, 28.6%, and 18.4% (p=0.0132); 42.0%, 44.9%, and 13.1% (p=0.0188) among the severe oligozoospermic group; and 55.8%, 38.2%, and 6.0% (14/233) in the control group. The data suggest that MTHFR C677T and A1298C could be important genetic factors predisposing to infertility in Brazilian infertile men.


Flow cytometric detection of erythropoietic cytotoxicity in mouse bone marrow.
Erythroblast proliferation and maturation in bone marrow are the processes leading to the formation of polychromatic erythrocytes (PE) and normochromatic erythrocytes (NE), respectively. PE contain RNA but no DNA, and can therefore be distinguished both from NE (which lack both RNA and DNA) and from nucleated cells (which contain both DNA and RNA). Cytotoxic agents that induce impairment of the maturation process change the PE:NE ratio. We have developed a simple and rapid method of determining the PE:NE ratio, based on flow cytometric analysis of formaldehyde-fixed, acridine orange (AO)-stained cells. The effects of cyclophosphamide (CP), mitomycin C (MMC), and vincristine (VC) were tested and the PE:NE ratio was evaluated over 7 days of treatment. In this study we monitored the kinetics of these compounds and were able to demonstrate both a time- and a dose-dependent effect. We detected a difference between the effects of the alkylating agents tested and those induced by the spindle inhibitor tested. Flow cytometry of fixed bone marrow samples stained with AO provides more information, better and more rapid statistical analysis, than conventional microscopic methods for counting the PE:NE ratio.


Vibrational processing of a dynamic structural flight system: A multichannel spectral estimation approach.
Dynamic testing of large flight vehicles (rockets) is not only complex, but also can be very costly. These flights are infrequent and can lead to disastrous effects if something were to fail during the flight. The development of sensors coupled to internal components offers a great challenge in reducing their size, yet still maintaining their precision. Sounding rockets provide both a viable and convenient alternative to the more costly vehicular flights. Some of the major objectives are to test various types of sensors for monitoring components of high interest as well as investigating real-time processing techniques. Signal processing presents an extreme challenge in this noisy multichannel environment. The estimation and tracking of modal frequencies from vibrating structures is an important set of features that can provide information about the components under test; therefore, high resolution multichannel spectral processing is required. The application of both single channel and multichannel techniques capable of producing reliable modal frequency estimates of a vibrating structure from uncertain accelerometer measurements is discussed.


Pulmonary embolism and thrombolysis.
A meta-analysis of studies including about 2000 patients with pulmonary embolism suggests that thrombolysis slightly reduces overall mortality at one month in patients under 65 but increases the number of major bleeding events, including intracranial haemorrhage.


Medicine prices, availability, and affordability in the Shaanxi Province in China: implications for the future.
In 2009, China implemented the National Essential Medicines System (NEMS) to improve access to high-quality low-cost essential medicines. To measure the prices, availability and affordability of medicines in China following the implementation of the NEMS. 120 public hospitals and 120 private pharmacies in ten cities in Shaanxi Province, Western China. The standardized methodology developed by the World Health Organization and Health Action International was used to collect data on prices and availability of 49 medicines. Median price ratio; availability as a percentage; cost of course of treatment in days' wages of the lowest-paid government workers. In the public hospitals, originator brands (OBs) were procured at 8.89 times the international reference price, more than seven times higher than the lowest-priced generics (LPGs). Patients paid 11.83 and 1.69 times the international reference prices for OBs and generics respectively. A similar result was observed in the private pharmacies. The mean availabilities of OBs and LPGs were 7.1 and 20.0 % in the public hospitals, and 12.6 and 29.2 % in the private pharmacies. Treatment with OBs is therefore largely unaffordable, but the affordability of the LPGs is generally good. High prices and low availability of survey medicines were observed. The affordability of generics, but not OBs, is reasonable. Effective measures should be taken to reduce medicine prices and improve availability and affordability in Shaanxi Province.


A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with Experimental Lupus.
Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance in human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from nonautoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired apoptotic cell uptake by MΦ also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO) (do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4+) large peritoneal MΦ. The peritoneal exudate of pristane-treated mice contained mainly Ly6Chi inflammatory monocytes; whereas in MO-treated mice, it consisted predominantly of a novel subset of highly phagocytic MΦ resembling small peritoneal MΦ (SPM) that expressed CD138+ and the scavenger receptor Marco. Treatment with anti-Marco-neutralizing Abs and the class A scavenger receptor antagonist polyinosinic acid inhibited phagocytosis of apoptotic cells by CD138+ MΦ. CD138+ MΦ expressed IL-10R, CD206, and CCR2 but little TNF-α or CX3CR1. They also expressed high levels of activated CREB, a transcription factor implicated in generating alternatively activated MΦ. Similar cells were identified in the spleen and lung of MO-treated mice and also were induced by LPS. We conclude that highly phagocytic, CD138+ SPM-like cells with an anti-inflammatory phenotype may promote the resolution of inflammation in lupus and infectious diseases. These SPM-like cells are not restricted to the peritoneum and may help clear apoptotic cells from tissues such as the lung, helping to prevent chronic inflammation.


Human and organizational factors in reliability assessment and management of offshore structures.
Today, there is a worldwide infrastructure of offshore structure systems that include fixed, floating, and mobile platforms, pipelines, and ships. Background on current and future trends in development of comprehensive programs to help improve the quality and reliability of offshore structure systems are discussed. A combination of proactive, reactive, and interactive risk assessment and management approaches have been developed and applied. Two risk assessment and management instruments are detailed in this article: a qualitative Quality Management Assessment System (QMAS), and a quantitative System Risk Analysis System (SYRAS). Application of QMAS to produce human and organizational performance shaping factors that are used as input to SYRAS is discussed.


BRG1 Governs Nanog Transcription in Early Mouse Embryos and Embryonic Stem Cells via Antagonism of Histone H3 Lysine 9/14 Acetylation.
During mouse preimplantation development, the generation of the inner cell mass (ICM) and trophoblast lineages comprises upregulation of Nanog expression in the ICM and its silencing in the trophoblast. However, the underlying epigenetic mechanisms that differentially regulate Nanog in the first cell lineages are poorly understood. Here, we report that BRG1 (Brahma-related gene 1) cooperates with histone deacetylase 1 (HDAC1) to regulate Nanog expression. BRG1 depletion in preimplantation embryos and Cdx2-inducible embryonic stem cells (ESCs) revealed that BRG1 is necessary for Nanog silencing in the trophoblast lineage. Conversely, in undifferentiated ESCs, loss of BRG1 augmented Nanog expression. Analysis of histone H3 within the Nanog proximal enhancer revealed that H3 lysine 9/14 (H3K9/14) acetylation increased in BRG1-depleted embryos and ESCs. Biochemical studies demonstrated that HDAC1 was present in BRG1-BAF155 complexes and BRG1-HDAC1 interactions were enriched in the trophoblast lineage. HDAC1 inhibition triggered an increase in H3K9/14 acetylation and a corresponding rise in Nanog mRNA and protein, phenocopying BRG1 knockdown embryos and ESCs. Lastly, nucleosome-mapping experiments revealed that BRG1 is indispensable for nucleosome remodeling at the Nanog enhancer during trophoblast development. In summary, our data suggest that BRG1 governs Nanog expression via a dual mechanism involving histone deacetylation and nucleosome remodeling.


Difficult Wiring of a Recanalized Thrombotic Lesion in the Right Coronary Artery Analyzed with Optical Coherence Tomography.
BACKGROUND Recanalized thrombi are usually unrecognized in conventional coronary angiography. However, multiple channels have been observed in recanalized thrombotic lesions. Therefore, the wire apparently crosses the lesion in some difficult cases. We analyzed the cause of difficult wiring of a recanalized thrombotic lesion using optical coherence tomography (OCT). CASE REPORT An 87-year-old man with chest pain was admitted to our hospital. Coronary angiography showed significant stenosis of the proximal right coronary artery with irregular linear filling and haziness. Crossing of the wire for the lesion was very difficult but was achieved using a parallel wire technique. OCT clearly demonstrated multiple small channels which had ambiguous findings on angiography and intravascular ultrasound. These structures showed a honeycomb-like appearance suggests the recanalized thrombi. A drug-eluting stent was subsequently deployed to fully cover the entire lesion. CONCLUSIONS OCT is useful to evaluate the accurate tissue characteristics of a recanalized thrombotic lesion. Because recanalized thrombi have multiple small channels and since there are some cases in which a part of the channel only flows into a side branch, it is necessary to carefully monitor wiring at the time of percutaneous coronary intervention.


[The role of three-dimensional speckle tracking imaging derived parameters on predicting outcome of hypertrophic cardiomyopathy patients with MYH7 mutations].
Objective: To evaluate the cardiac functional changes in hypertrophic cardiomyopathy(HCM) patients with β-myosin heavy chain gene (MYH7) mutations by three-dimensional (3D) speckle tracking imaging(3D-STI) and conventional echocardiography modalities, and then to explore the potential predictors of adverse cardiovascular events in these patients. Methods: A consecutive series of 192 HCM patients admitted in our center from October 2014 to October 2016 were genetically screened to identify MYH7 mutations in this retrospective study. A total of 43 HCM patients with MYH7 mutations were enrolled. The patients were divided into events group(n=13) and no event group(n=30) according to the presence or absence of adverse cardiovascular events(primary and secondary endpoints). All patients were followed up to January 2019 after comprehensive evaluation of 3D-STI, two-dimensional and Doppler echocardiography. The adverse cardiovascular events were recorded. Results: The median follow up time was 1 012 (812, 1 330) days. During follow-up, 13 patients (30.2%) reached endpoints: 6 cases of the primary endpoints(2 cases of sudden cardiac death(SCD), 3 cases of survival after defibrillation, and 1 case of appropriate implantable cardioverter-defibrillator(ICD) discharge); 7 cases of the second endpoints(5 cases of heart failure hospitalization, 1 case of syncope and cardioversion due to supraventricular tachycardia, and 1 case of end-stage HCM). Patients with adverse cardiovascular events had higher prevalence of syncope and risk of SCD, enlarged left atrial volume index(LAVI) and reduced 3D left ventricular global longitudinal train (3D-GLS), as compared to those without adverse events(all P<0.05). The multivariate Cox regression analysis showed that reduced 3D-GLS(HR=0.814, 95%CI 0.663-0.999, P=0.049) was an independent predictor for adverse cardiovascular events. The cutoff value of 3D-GLS≤13.67% was linked with significantly increased risk of adverse cardiovascular events in this patient cohort(AUC=0.753, 95%CI 0.558-0.948, sensitivity 86%, specificity 69%, P<0.05). The Kaplan-Meier analysis indicated that the patients with the 3D-GLS≤ 13.67% faced higher risk of death than those with 3D-GLS>13.67%. Conclusion: 3D-GLS is useful on predicting adverse cardiovascular events in HCM patients with MYH7 mutations.


Recurring errors among recent history of psychology textbooks.
Five recurring errors in history of psychology textbooks are discussed. One involves an identical misquotation. The remaining examples involve factual and interpretational errors that more than one and usually several textbook authors made. In at least 2 cases some facts were fabricated, namely, so-called facts associated with Pavlov's mugging and Descartes's reasons for choosing the pineal gland as the locus for mind-body interaction. A fourth example involves Broca's so-called discovery of the speech center, and the fifth example involves misinterpretations of Lloyd Morgan's intentions regarding his famous canon. When an error involves misinterpretation and thus misrepresentation, I will show why the misinterpretation is untenable.


The response of a human malignant melanoma cell line to high LET radiation.
The response of a human malignant melanoma cell line in vitro to high linear energy transfer radiation was studied utilizing the neutrons produced by the reaction of 16 and 50 MeV deuterons on beryllium. The relative biological effectiveness (RBE) relative to cobalt-60 gamma radiation was determined under conditions of complete oxygenation. The data indicate that the radioresistance ascribed to malignant melanoma in vivo is not an intrinsic quality of the cell but rather may be mediated by the in vivo environment.


Proximity of the nucleotide binding domains of the P-glycoprotein multidrug transporter to the membrane surface: a resonance energy transfer study.
Very little structural information is available for P-glycoprotein (Pgp), which has been implicated in the multidrug resistance of human tumors because of its ability to act as an ATP-driven efflux pump for hydrophobic compounds. Highly purified Pgp has been labeled on two cysteine residues with the fluorescence probe NBD-Cl (7-chloro-4-nitro-2,1,3-benzoxadiazole). We show that NBD labels the same cysteine residues as MIANS [2-(4-maleimidoanilino)naphthalene-6-sulfonic acid]; they are located within the Walker A motif of the nucleotide binding domain, close to the site where ATP binds. NBD- and MIANS-labeled Pgps were reconstituted by detergent dilution into phospholipid vesicles containing increasing mole fractions of rhodamine- or NBD-labeled phosphatidylethanolamine (PE), respectively. The fluorescence of the NBD-Pgp and MIANS-Pgp donors was quenched in a concentration-dependent manner by the rhodamine-PE and NBD-PE acceptors. Using two different methods to analyze Förster resonance energy transfer, the distance of the Pgp-bound probes from the lipid-water interfacial region of the bilayer was estimated to be 31-35 A. This distance is compatible with the low-resolution structure of Pgp determined by electron microscopy, and indicates that the nucleotide binding domains lie close to the membrane surface. The experimental data fitted very well to theoretical quench curves for a single protein-bound fluor, suggesting that the two nucleotide binding domains are located equidistant from the bilayer. Following the addition of ATP to MIANS-Pgp, the NBD-PE quench curve no longer conformed to the models. These results imply that Pgp interacts differently with PE when it is in the ATP-bound form.


[Evaluation of spirometric and pulmonary haemodynamic parameters in patients with COPD].
In this study we aimed to asses the association between the spirometric test which is known to be an indicator of severity of the disease and pulmonary artery pressure, in patient chronic obstructive pulmonary disease (COPD). Study population consisted of 51 patients with COPD. Severity of the disease was graded by the criteria of European Respiratory Society; mildly obstructive 5 patients (FEV1 > 70%), moderately obstructive 10 (FEV1= 50-69%), severely obstructive 36 patients (FEV1 < 50%). Measurement of pulmonary artery pressure was performed bt microcatheterisation method. Statistical analysis was performed between two groups; group I consisted of mildly and moderately obstructive patients, and group II severely obstructive patients. Pulmonary artery pressure of the group II patients was significantly higher than that of group I patients (27 +/- 4 mmHg vs 22 +/- 1.6 mmHg, respectively p< 0.001). There were also statistically significant difference between group I and group II in respect to FEV1% (63 +/- 7 vs 28 +/- 9 respectively p< 0.001), FEV1 L (1.84 +/- 0.46 vs 0.89 +/- 0.36 respectively p< 0.001), FEV1/FVC (71 +/- 10 vs 53 +/- 11 respectively p< 0.001), FVC% (73 +/- 8 vs 47 +/- 10 respectively p< 0.001), and MMF% (38 +/- 13 vs 15 +/- 6 respectively p< 0.001). Pulmonary artery pressure and diameter of right descending pulmonary artery on chest X-ray of the patients were negatively correlated with FEV1%, FEV1 L, FVC and MMF (p< 0.001 for all). We have shown pulmonary artery pressure of the patients with COPD was negatively correlated with the spirometric parameters such as FEV1%, FEV1 L, FVC and MMF. So FEV1 < 50% can be used as an indicator of increased pulmonary artery pressure in patients with COPD.


Modulation of human natural killer cell function by cytokines and rheumatic disease.
The activity of natural killer (NK) cells can be modified by a number of factors that either increase or suppress cytotoxicity. We have investigated in detail the cytokine induced killing of a NK resistant renal carcinoma cell line Cur by human NK cells. Preincubation of peripheral blood mononuclear cells with interferon alpha (IFN alpha), interleukin 2 (Il-2), interleukin 1 (Il-1) and tumor necrosis factor alpha greatly increased the rate and magnitude of Cur killing. Positively selected CD16 (+) cells were found to respond to cytokine stimulation and to mediate Cur killing. The effects of Il-2 and IFNa could be upregulated by costimulation of effector cells with Il-1 or TNF alpha. It was shown that TNF alpha induced Il-2 receptor expression on CD16(+) cells alone and even more in combination with Il-2. Studies of NK cell function in various rheumatic diseases revealed reduced NK cytotoxicity in peripheral blood and synovial fluid (SF), both in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). By contrast, normal NK function was found in patients with ankylosing spondylitis (AS) and psoriatic arthritis. A discordance with regard to the percentage of Leu 7 positive mononuclear cells and NK function in peripheral blood and SF was demonstrated. Minimal expression of Leu 7 positive cells and cytotoxicity was present in synovial membranes. NK function in rheumatic disease was largely independent of drug therapy. Natural killer (NK) cells are a subset of lymphocytes that mediate spontaneous cytotoxicity against certain tumor and virus infected cells without any known prior sensitation.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of extracellular redox enzyme concentrations in response to exercise in humans.
Redox enzymes modulate intracellular redox balance and are secreted in response to cellular oxidative stress, potentially modulating systemic inflammation. Both aerobic and resistance exercise are known to cause acute systemic oxidative stress and inflammation; however, how redox enzyme concentrations alter in extracellular fluids following bouts of either type of exercise is unknown. Recreationally active men (n = 26, mean ± SD: age 28 ± 8 yr) took part in either: 1) two separate energy-matched cycling bouts: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE) or 2) an eccentric-based resistance exercise protocol (RES). Alterations in plasma (study 1) and serum (study 2) peroxiredoxin (PRDX)-2, PRDX-4, superoxide dismutase-3 (SOD3), thioredoxin (TRX-1), TRX-reductase and interleukin (IL)-6 were assessed before and at various timepoints after exercise. There was a significant increase in SOD3 (+1.5 ng/mL) and PRDX-4 (+5.9 ng/mL) concentration following HIIE only, peaking at 30- and 60-min post-exercise respectively. TRX-R decreased immediately and 60 min following HIIE (-7.3 ng/mL) and MOD (-8.6 ng/mL), respectively. In non-resistance trained men, no significant changes in redox enzyme concentrations were observed up to 48 h following RES, despite significant muscle damage. IL-6 concentration increased in response to all trials, however there was no significant relationship between absolute or exercise-induced changes in redox enzyme concentrations. These results collectively suggest that HIIE, but not MOD or RES increase the extracellular concentration of PRDX-4 and SOD3. Exercise-induced changes in redox enzyme concentrations do not appear to directly relate to systemic changes in IL-6 concentration.NEW & NOTEWORTHY Two studies were conducted to characterize changes in redox enzyme concentrations after single bouts of exercise to investigate the emerging association between extracellular redox enzymes and inflammation. We provide evidence that SOD3 and PRDX-4 concentration increased following high-intensity aerobic but not eccentric-based resistance exercise. Changes were not associated with IL-6. The results provide a platform to investigate the utility of SOD3 and PRDX-4 as biomarkers of oxidative stress following exercise.


Dispersion of heavy metals (metalloids) in soils from 800-year-old pollution (Mont-Lozère, France).
Numerous palaeo metallurgical sites (n = 70) characterized by slag presenting a homogeneous typology have been reported on the Mont-Lozère Massif (Southern France). These activities took place in the medieval period. The silicated slag matrix comprises mainly Pb (25%), Sb (0.4%), and several thousand parts per million of As, Cu, and Zn. Soil samples were collected in and around two sites, to understand the dispersion mechanism affecting the slag tailings through use of metal concentrations and lead isotopic compositions. The majority of polluted soil samples show high enrichment factors (EF) for Pb and Sb, slightly lower EFs for Cu, and much lower EFs for As and Zn. We show that this "old" metal pollution was physically dispersed, through erosion of workshop soils and slag tailings, in a restricted area (ca. 200 m down slope form the site). There is no evidence for massive leaching of slag metals by soil waters, except for Zn. Thus, the pollution is mainly due to the metal-making process, i.e., smoke-fallout, pieces of ore, the crackling of smelting ore outside the oven during reduction, and charcoal, etc. The lead isotopic compositions of the soils define a binary mixing trend between local granite or background soil and slag (which represent the workshop soil). Simple mass balance equations using either Pb isotopes or Pb concentrations suggest that between 40 and 100% of the total Pb in soils comes from the Medieval workshop pollution, leaving any later pollution negligible. The large number of sites on the Mont-Lozère means this medieval pollution is significant and poses a real environmental risk.


Tapered stems one-third proximally coated have higher complication rates than cylindrical two-third coated stems in patients with high hip dislocation undergoing total hip arthroplasty with step-cut shortening osteotomy.
The results of cementless stems in total hip arthroplasty (THA) done because of congenital dislocation with step-cut osteotomy is not well known, particularly the influence of the design and the role of extent of porous coating. Therefore we performed a retrospective study to evaluate the mid to long-term results THA performed with a single type acetabular component and different geometry and fixation type stems with ceramic bearings in the setting of step-cut subtrochanteric osteotomy in high hip dislocated (HHD) patients. We asked if the stem type affect the outcomes in terms of (1) intra and postoperative complication rates (2) radiographic outcomes (3) prosthesis survival in step-cut subtrochanteric shortening osteotomy. The type of the stem, whether cylindrical or tapered does not affect the outcome if the femoral canal fit and fill is obtained and the step-cut femoral shortening osteotomy is primarily fixed. Forty-five hips in 35 patients with a mean follow up of 10 years (range, 7-14 years) were evaluated. The single type cementless cup was placed at the level of the true acetabulum, a step-cut shortening femoral osteotomy was performed and reconstruction was performed with two different types of tapered stem in twenty-two hips (Synergy™ and Image™ proximally coated, Smith and Nephew, Menphis, TN, USA) and one type of cylindrical stem (Echelon™ with 2/3 coated, Smith and Nephew, Menphis, TN, USA) in twenty-three hips. Harris hip scores (HHS) and a University of California Los Angeles (UCLA) activity scores were calculated for all patients and successive X-rays were evaluated regarding component loosening and osteolysis, along with complications related to bearing, step-cut osteotomy and stem types. Forty-one hips (91%) had good and excellent clinical outcome according to HHS. The mean UCLA activity scores improved from 3.2±0.6 points (range, 2-4) preoperatively to 6.3 points±0.5 (range, 5-7) at the latest follow-up. The mean femoral shortening was 36±10mm (range, 20-65mm). Four (9%) dislocations were observed. There were five (11%) intra-operative femoral fractures and three (7%) cases of non-union, which were observed in tapered stems. Cylindrical stems had superior neutral alignment primarily. With any stem revision as the end point, cylindrical stems had a higher survival rate (100%) than all tapered stems (82%; 95% confident interval [CI] 77-97%) at ten years. With any revision as the end point, the 10-year survival rate for acetabular component (Reflection-Ceramic Interfit) and for femoral components were 98% (95% CI, 85-99%) and 91% (95% CI, 78-97%), respectively. There were more implant related complications in HHD patients undergoing THA when tapered stems with 1/3 proximal coating were used to reconstruct a step cut osteotomized femur, compared to cylindrical stems 2/3 coated. IV, retrospective study.


Inhibition of NO biosynthesis, but not elevated blood pressure, reduces angiogenesis in rat models of secondary hypertension.
Arterial hypertension (AH) is characterized by reduced nitric oxide (NO) biosynthesis, vasoconstriction, and reduced microvascular density. In this study we asked whether AH also reduces the number of microvessels by impairing angiogenesis. AH was induced in Dahl salt-sensitive rats (DSS) with a salt diet and in Wistar-Kyoto rats by inhibiting NO formation with Nomega-nitro-L-arginine (NNA). Three weeks after induction of AH, two wound chambers containing collagen I (Vitrogen) were sutured into the mesenteric cavity of each animal. After additional 14 days, wound chamber neovascularization and the extent of vascularized connective tissue ingrowth were quantified. In NNA-induced AH, the number of newly formed vessels and the ingrowth of vascularized connective tissue into the wound chamber decreased as compared to controls. However, the number of newly formed vessels and the ingrowth of vascularized connective tissue did not change with increasing blood pressure in salt-fed DSS rats as compared to those fed a normal diet. Inhibition of NO biosynthesis, but not necessarily elevating blood pressure, reduces angiogenesis. Microvascular rarefaction in AH may be partially due to reduced angiogenesis because of impaired NO biosynthesis.


[Mechanisms of intestinal absorption of nutrients].
The nutrient uptake from the intestinal lumen into the distributing blood circulation is mediated by the epithelial cell of the small intestine. The transfer process through this distinctly polar cell consists of three partial events: entrance of substances through the brush-border membrane, traversal of a metabolic active intracellular space and exit through the baso-lateral membrane. The fundamental transfer mechanisms--simple diffusion, facilitated diffusion, antiport and symport systems, electroneutral and electrogenic processes--are described. The significance of nutrient metabolization for transport processes is discussed: proton secretion by the epithelial cell coupled to the glucose and lactate metabolization is quoted as an illustration. The "acid microclimate" resulting from this proton secretion on the mucosal surface has a significant influence on weak-electrolyte absorption. This effect was clearly demonstrated for in vitro uptake of nicotinic acid into the intestinal tissue. It can be assumed that--similar to the role of a Na+-gradient--the proton gradient on the surface of absorptive epithelia is highly significant as a driving force of nutrient absorption.


[Small intestinal cavernous hemangioma causing chronic hemorrhage: a case report].
Small intestinal hemangioma is a rare condition that can be divided histologically into capillary, cavernous or mixed types, among which the cavernous type is the most common. Here we report a case of small intestinal cavernous hemangioma with chronic hemorrhage in 44-year-old man. The patient complained of weakness and dizziness for 2 years that aggravated 1 month before admission accompanied by intermittent melena. Laboratory tests suggest severe anemia, and computed tomography, gastroscopy and colonoscopy all revealed signs of anemia. Capsule endoscopy detected small intestinal erosions, bleeding lesions and prominent neoplasms. An exploratory laparotomy was performed, in which the segment of the jejunum with lesions was resected. Pathological examination of the resected jejunum identified the neoplasm as cavernous hemangioma of the small intestine, which was the cause of severe anemia.


Classical description in a quantum spirit of the prototype four-atom reaction OH + D2.
Classical mechanics is the only practical way to simulate internuclear motion in many complex systems that are important for biology, materials science, and technology. It is therefore important to test classical dynamics on simpler systems. The OH + H(2) or OH + D(2) system is the prototype four-body chemical reaction for fundamental studies of this nature, and high-resolution experiments have been reported by Davis and co-workers. Here we use those experiments to test state-resolved quasi-classical trajectory calculations in a quantum spirit, and find good agreement with experiment. Our simulations correctly predict that the newly formed oxygen-deuterium bond in the HOD product is preferentially excited to the vibrational state v = 2, and they yield a state-resolved product translational energy distribution. Of special interest is that the triple (angle-velocity) differential cross section shows the same state-resolved structure associated with the product vibrational states that were analyzed. This level of accuracy has previously been achieved only for triatomic systems, and these new simulations demonstrate that the quasi-classical method with quantum corrections may represent a reasonable alternative to quantum scattering approaches for the description of polyatomic reaction dynamics.


SPECIATION BY REINFORCEMENT OF PREMATING ISOLATION.
The generation of premating isolation given partial or complete postzygotic isolation between populations is termed reinforcement or, in the case of complete isolation, reproductive character displacement. In this study we use computer simulations and a multilocus genetic model to reevaluate the theory of reinforcement. We consider the evolution of female preferences for a male secondary sexual trait. If the populations differ in mean female preference, there is direct selection on the preference for further divergence, which may be augmented by a correlated response to sexual selection on males. Two factors prevent divergence. First, if postzygotic isolation is not complete, gene flow can prevent divergence and lead to a hybrid swarm. This is the usual outcome whenever the average number of breeding adult offspring produced by a hybrid mating is sufficient to replace the parents. Second, one or the other population may become extinct because of the large number of hybrid matings it is involved in. The likelihood of extinction is lowered if population growth rates are high, if hybrids are inviable rather than infertile, or under some conditions when allopatric populations provide immigrants into the contact zone. Provided hybrid fitness is sufficiently low, there is a wide range of genetic and ecological conditions under which reinforcement rather easily occurs, and also a range under which it may occur because of stochastic effects on both the inheritance parameters and the population sizes.


Targeting a c-MYC G-quadruplex DNA with a fragment library.
We report here on the screening of a fragment library against a G-quadruplex element in the human c-MYC promoter. The ten fragment hits had significant concordance between a biophysical assay, in silico modelling and c-MYC expression inhibition, highlighting the feasibility of applying a fragment-based approach to the targeting of a quadruplex nucleic acid.


Comparing the response rates for superiority, noninferiority and equivalence testing with multiple-to-one matched binary data.
Paired and multiple-to-one matched data have often been collected in clinical trials and epidemiological safety studies. When the response is binary, the sample size and power are determined by the discordant pairs or matched sets. Fixed sample size determination in assessing response rate difference of superiority, noninferiority, and equivalence tests of paired binary data has been discussed by Lu and Bean (1995)Nam (1997), and Liu et al. (2002). We extend the results of Lu and Bean (1995)Nam (1997), and Liu et al. (2002) to more general cases of multiple-to-one matched binary data. We further examine two issues regarding such tests. First, we examine the issue of simultaneous test and two-stage test for both superiority and noninferiority/equivalence hypotheses. Although, as discussed in Nam (1997) and Liu et al. (2002), the standard errors restricted to null hypothesis are different between superiority and noninferiority test, the monotonic property of the two tests makes the simultaneous testing and switching between the hypotheses valid. Second, in practice, the joint distribution of matched responses is often unknown, and thus determining the sample size using only the background information of the control group could be inefficient. Furthermore, for noninferiority or equivalence tests, the sample sizes are often determined using the unrealistic alternative hypothesis that the response rates of both treatments are identical. We propose to use a two-stage adaptive design strategy for sample size reestimation that uses the interim information to improve the efficiency.


Symmetrical Catalytically Active Colloids Collectively Induce Convective Flow.
Although much attention has focused on self-motile asymmetrical catalytically active "Janus" colloids as a route to enable new fluidic transport applications, the motion of symmetrical catalytically active colloids is less investigated. This is despite isotropically active colloids being more accessible and commonly used as supports for heterogeneous catalysis. Here, we addressed this by systematically investigating the motion of platinum-coated colloids capable of isotropically decomposing hydrogen peroxide. We observed the onset of collective convective flow as the colloidal volume fraction increased above a threshold. The ballistic velocities induced by the collective flow were quantified by particle tracking and were found to increase with the volume fraction. We also determined the associated increase in the Péclet number as evidence of the potential to use convection as a simple method to enhance mass transport rates. By determining the persistence lengths, we were able to correlate the magnitude of convective flow with the overall catalytic activity per unit volume. This suggests that the mechanism for the collective flow is driven by chemical activity-induced local density differences. Finally, we discussed these results in the context of potential new fluidic applications and highlighted the role that activity-induced convection may play in experiments designed to investigate self-motile catalytic systems.


[Arthrographis kalrae--an uncommon causative agent of onychomycosis].
At a routine examination, multiple colonies of hyphomycetes of uncommon morphology were isolated from two patients with clinically suspected mycosis of the big toes (and confirmed microscopically by the presence of fragmented/thin hyphae). Based on the detailed study of the morphological and physiological characteristics of the cultures, the isolates were identified as Arthrographis kalrae. To our knowledge, this is the first isolation of the thermally dimorphic keratinolytic fungus to be reported in Slovakia.


Job satisfaction and creativity at work among occupational therapy practitioners: A mixed-methods study.
Creativity is essential to the work of occupational therapy practitioners. Nonetheless, little is known about the way it influences their work satisfaction. This study explores several internal and external factors related to organizational, personal, and socio-relational sources of creativity. Our main hypothesis was that occupational therapy practitioners are more satisfied when creative. A mixed-methods study included a qualitative (n = 22) and a quantitative (n = 250) phase. Data were gathered using focus group interviews and an online survey, where a novel assessment instrument -the Creativity in Occupational Therapy Questionnaire -was administered. The synthesis of the results revealed that factors connected with the client, the practitioner's personal characteristics, the work environment, relationships with colleagues and relationships with superiors all influenced the creativity of occupational therapy practitioners, in negative or positive ways. Professional autonomy and a supportive work environment were found to be important for the creativity of occupational therapy practitioners. Creativity at work had a statistically significant influence on work satisfaction of occupational therapy practitioners (B = 0.575, t = 6.267, p < 0.01). The results demonstrate the importance of creativity for job satisfaction of occupational therapy practitioners and suggest a dynamic reciprocal relationship between different factors and circumstances that should be considered when fostering creativity at work.


Type I Interferon in Children with Viral or Bacterial Infections.
Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. clinicaltrials.gov (NCT03163628).


A new three-dimensional exponential material model of the coronary arterial wall to include shear stress due to torsion.
The biomechanical milieu of the coronary arteries is unique in that they experience mechanical deformations of twisting, bending, and stretching due to their tethering to the epicardial surface. Spatial variations in stresses caused by these deformations could account for the heterogeneity of atherosclerotic plaques within the coronary tree. The goal of this work was to utilize previously reported shear moduli to calculate a shear strain parameter for a Fung-type exponential model of the arterial wall and determine if this single constant can account for the observed behavior of arterial segments under torsion. A Fung-type exponential strain-energy function was adapted to include a torsional shear strain term. The material parameter for this term was determined from previously published data describing the relationship between shear modulus and circumferential stress and longitudinal stretch ratio. Values for the shear strain parameter were determined for three geometries representing the mean porcine left anterior descending coronary artery dimensions plus or minus one standard deviation. Finite element simulation of triaxial biomechanical testing was then used to validate the model. The mean value calculated for the shear strain parameter was 0.0759+/-0.0009 (N=3 geometries). In silico triaxial experiments demonstrated that the shear modulus is directly proportional to the applied pressure at a constant longitudinal stretch ratio and to the stretch ratio at a constant pressure. Shear moduli determined from these simulations showed excellent agreement to shear moduli reported in literature. Previously published models describing the torsional shear behavior of porcine coronary arteries require a total of six independent constants. We have reduced that description into a single parameter in a Fung-type exponential strain-energy model. This model will aid in the estimation of wall stress distributions of vascular segments undergoing torsion, as such information could provide insight into the role of mechanical stimuli in the localization of atherosclerotic plaque formation.


Potentiation of concentric force and acceleration only occurs early during the stretch-shortening cycle.
The purpose of this study was to determine where stretch-shortening cycle (SSC) potentiation of force, power, velocity, and acceleration occurs across the concentric phase of ballistic leg presses. Second, we examined the influence of late eccentric phase force and length of the amortization phase on potentiated concentric phase performance variables. Twenty-one male runners (age: 31.9 ± 4.7 years) performed SSC and concentric-only (CO) ballistic leg press throws. Potentiations of concentric actions were calculated as the difference between SSC and CO contractions. An analysis splitting the concentric range of motion (ROM) into 6 equal time intervals determined force and acceleration were potentiated (p < 0.05) only during the first one-sixth time interval of concentric motion, whereas velocity and power were potentiated (p < 0.05) at all time intervals over the entire concentric motion with the exception of power over the last one-sixth time interval. A more precise analysis examining 20-millisecond time intervals across the first 200 milliseconds of concentric motion determined force was potentiated only over the first 140 milliseconds and acceleration only over the first 160 milliseconds. Eccentric force measured during the last 100 milliseconds of eccentric motion was related to potentiated force during the initial 200 milliseconds of concentric motion (r = 0.44, p < 0.05) and potentiated mean power across the full concentric ROM (r = 0.62, p < 0.01). Results indicate that in contrast to power and velocity, potentiation of force and acceleration occurs only early during the concentric phase of SSC ballistic leg presses. Correlational findings imply late eccentric phase force is important for generating force and power during the concentric phase of the SSC and thus training focusing on enhancing late phase eccentric force appears important for developing explosive force and power during SSC movements.


Self-directed learning and student selected goals in nurse education.
This paper is a consideration of the philosophy of, and research into, general education. It examines some of the approaches to education and a small part of the research into discovery learning, self-directed study and student-selected goals of learning. Proposals are made for a single module of nurse training for admission to the register of general nurses which incorporate the philosophy and research-based ideals of self-directed learning. Finally, problems which may be anticipated in its implementation are discussed but no firm conclusions are drawn until these can be based on fact rather than conjecture.


The informational roles and psychological health of members of 10 oncology multidisciplinary teams in the UK.
We report here the different roles undertaken by the members of 10 multidisciplinary cancer teams in conveying information to patients during their care. Team members completed an Informational Roles Questionnaire measuring an individual's perception of their major role and that of their colleagues in giving information to patients. They also completed two standard psychological health measures, the General Health Questionnaire and Maslach Burnout Inventory. The information giving roles of the surgeon, oncologist, radiologist and clinical nurse specialist were well recognised by their colleagues; however, other team members' roles were more ambiguous and less well understood. The clinical nurse specialist provided the broadest information coverage for patients. Few professional groups regularly informed patients about clinical trials and family history and the clinical nurse specialist was often the only person to deal with patients' sexual well being, consequently these areas are likely to receive poor coverage. Probable psychiatric morbidity (GHQ> or =4) in teams ranged from 5 to 27%. High levels of emotional exhaustion were particularly apparent in team leaders and nurses and feelings of low levels of personal accomplishment were prevalent in the histopathologists and radiologists. Putative benefits to patients and healthcare professionals from multidisciplinary team working may not be realised without investment in team training.


Locus coeruleus neuronal activity determines proclivity to consume alcohol in a selectively-bred line of rats that readily consumes alcohol.
Sprague-Dawley rats selectively-bred for susceptibility to stress in our laboratory (Susceptible, or SUS rats) voluntarily consume large amounts of alcohol, and amounts that have, as shown here, pharmacological effects, which normal rats will not do. In this paper, we explore neural events in the brain that underlie this propensity to readily consume alcohol. Activity of locus coeruleus neurons (LC), the major noradrenergic cell body concentration in the brain, influences firing of ventral tegmentum dopaminergic cell bodies of the mesocorticolimbic system (VTA-DA neurons), which mediate rewarding aspects of alcohol. We tested the hypothesis that in SUS rats alcohol potently suppresses LC activity to markedly diminish LC-mediated inhibition of VTA-DA neurons, which permits alcohol to greatly increase VTA-DA activity and rewarding aspects of alcohol. Electrophysiological single-unit recording of LC and VTA-DA activity showed that in SUS rats alcohol decreased LC burst firing much more than in normal rats and as a result markedly increased VTA-DA activity in SUS rats while having no such effect in normal rats. Consistent with this, in a behavioral test for reward using conditioned place preference (CPP), SUS rats showed alcohol, given by intraperitoneal (i.p.) injection, to be rewarding. Next, manipulation of LC activity by microinfusion of drugs into the LC region of SUS rats showed that (a) decreasing LC activity increased alcohol intake and increasing LC activity decreased alcohol intake in accord with the formulation described above, and (b) increasing LC activity blocked both the rewarding effect of alcohol in the CPP test and the usual alcohol-induced increase in VTA-DA single-unit activity seen in SUS rats. An important ancillary finding in the CPP test was that an increase in LC activity was rewarding by itself, while a decrease in LC activity was aversive; consequently, effects of LC manipulations on alcohol-related reward in the CPP test were perhaps even larger than evident in the test. Finally, when increased LC activity was associated with (i.e., conditioned to) i.p. alcohol, subsequent alcohol consumption by SUS rats was markedly reduced, indicating that SUS rats consume large amounts of alcohol because of rewarding physiological consequences requiring increased VTA-DA activity. The findings reported here are consistent with the view that the influence of alcohol on LC activity leading to changes in VTA-DA activity strongly affects alcohol-mediated reward, and may well be the basis of the proclivity of SUS rats to avidly consume alcohol.


The relation between venous reserve capacity and low plasma volume.
Prepregnant low plasma volume (LPV) is associated with subsequent gestational hypertensive disease. It is unknown to what extent an LPV affects the venous reserve capacity (VRC). We tested the hypothesis that LPV reduces the VRC, as indicated by presyncope or altered cardiovascular changes in response to head-up tilt. In 52 nonpregnant women with a history of preeclampsia or recurrent miscarriage, the authors assessed plasma volume, stroke volume, and cardiac output and determined blood pressure, heart rate, and autonomic responses to stepwise inflicted head-up tilt. 12 participants had LPV, which related to presyncope when compared with subjects with normal plasma volume (NPV). Women with LPV without presyncope demonstrated a circulatory response comparable to NPV women at the expense of consistently higher heart rate. LPV decreases the capacity to cope with head-up tilt without affecting the response pattern, suggesting reduced VRC.


[New methods of transfection of mammalian cells].
New methods of transfection of mammalian cells are discussed in the review. The principles of each method and frequency of genetic transformation are pointed out as well as their perspectives. The retrovirus constructions are noteworthy, because of the progress attained in their creation.


Bioactive oligopeptides in dermatology: Part II.
Peptides are central to the regulation and modulation of the chemical reactions and biological responses that occur in nature. Many physiological processes are affected by the interactions of these peptides, including cell proliferation and migration, inflammation, melanogenesis, angiogenesis and innate immunity. Thus, biologically active peptides offer a great potential medically and therapeutically. Moreover, the ability to generate synthetic peptides with attention to specifically modulating their pharmacokinetics and properties for increased potency, delivery and stability has spurred much interest in this rapidly growing field of research. In this review, we focus on the therapeutic uses of bioactive peptides as antimicrobials and effectors of neurotransmitter release. We also highlight the advantages and challenges associated with this new technology and discuss methods for improving oligopeptide transdermal delivery.


The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver.
Canalicular secretion of bile salts is a vital function of the vertebrate liver, yet the molecular identity of the involved ATP-dependent carrier protein has not been elucidated. We cloned the full-length cDNA of the sister of P-glycoprotein (spgp; Mr approximately 160,000) of rat liver and demonstrated that it functions as an ATP-dependent bile salt transporter in cRNA injected Xenopus laevis oocytes and in vesicles isolated from transfected Sf9 cells. The latter demonstrated a 5-fold stimulation of ATP-dependent taurocholate transport as compared with controls. This spgp-mediated taurocholate transport was stimulated solely by ATP, was inhibited by vanadate, and exhibited saturability with increasing concentrations of taurocholate (Km approximately 5 microM). Furthermore, spgp-mediated transport rates of various bile salts followed the same order of magnitude as ATP-dependent transport in canalicular rat liver plasma membrane vesicles, i.e. taurochenodeoxycholate > tauroursodeoxycholate = taurocholate > glycocholate = cholate. Tissue distribution assessed by Northern blotting revealed predominant, if not exclusive, expression of spgp in the liver, where it was further localized to the canalicular microvilli and to subcanalicular vesicles of the hepatocytes by in situ immunofluorescence and immunogold labeling studies. These results indicate that the sister of P-glycoprotein is the major canalicular bile salt export pump of mammalian liver.


Use, usability, and impact of a card-based conversation tool to support communication about end-of-life preferences in residential elder care - a qualitative study of staff experiences.
Proactive conversations about individual preferences between residents, relatives, and staff can support person-centred, value-concordant end-of-life (EOL) care. Nevertheless, prevalence of such conversations is still low in residential care homes (RCHs), often relating to staff's perceived lack of skills and confidence. Using tools may help staff to facilitate EOL conversations. While many EOL-specific tools are script-based and focus on identifying and documenting treatment priorities, the DöBra card tool is developed to stimulate reflection and conversation about EOL care values and preferences. In this study, we explore staff's experiences of use, usability, and perceived impact of the DöBra cards in supporting discussion about EOL care in RCH settings. This qualitative study was based on data from two participatory action research processes in which RCH staff tested and evaluated use of DöBra cards in EOL conversations. Data comprise 6 interviews and 8 group meetings with a total of 13 participants from 7 facilities. Qualitative content analysis was performed to identify key concepts in relation to use, usability, and impact of the DöBra cards in RCH practice. Based on participants' experiences of using the DöBra cards as an EOL conversation tool in RCHs, we identified three main categories in relation to its usefulness. Outcomes of using the cards (1) included the outlining of content of conversations and supporting connection and development of rapport. Perceived impact (2) related to enabling openings for future communication and aligning care goals between stakeholders. Use and usability of the cards (3) were influenced by supporting and limiting factors on the personal and contextual level. This study demonstrates how the DöBra cards was found to be useful by staff for facilitating conversations about EOL values, influencing both the content of discussion and interactions between those present. The tool encouraged reflection and interaction, which staff perceived as potentially helpful in building preparedness for future care-decision making. The combination of providing a shared framework and being adaptable in use appeared to be key features for the DöBra cards usability in the RCH setting.


Reversible Deactivation of Motor Cortex Reveals Functional Connectivity with Posterior Parietal Cortex in the Prosimian Galago (Otolemur garnettii).
We examined the functional macrocircuitry of frontoparietal networks in the neocortex of prosimian primates (Otolemur garnettii) using a microfluidic thermal regulator to reversibly deactivate selected regions of motor cortex (M1). During deactivation of either forelimb or mouth/face movement domains within M1, we used long-train intracortical microstimulation techniques to evoke movements from the rostral division of posterior parietal cortex (PPCr). We found that deactivation of M1 movement domains in most instances abolished movements evoked in PPCr. The most common effect of deactivating M1 was to abolish evoked movements in a homotopic domain in PPCr. For example, deactivating M1 forelimb lift domains resulted in loss of evoked movement in forelimb domains in PPCr. However, at some sites, we also observed heterotopic effects; deactivating a specific domain in M1 (e.g., forelimb lift) resulted in loss of evoked movement in a different movement domain in PPCr (e.g., hand-to-mouth or eye-blink). At most sites examined in PPCr, rewarming M1 resulted in a reestablishment of the baseline movement at the same amplitude as that observed before cooling. However, at some sites, reactivation did not result in a return to baseline movement or to the full amplitude of the baseline movement. We discuss our findings in the context of frontoparietal circuits and how they may subserve a repertoire of ecologically relevant behaviors. The posterior parietal cortex (PPC) of primates integrates sensory information used to guide movements. Different modules within PPC and motor cortex (M1) appear to control various motor behaviors (e.g., reaching, defense, and feeding). How these modules work together may vary across species and may explain differences in dexterity and even the capacity for tool use. We investigated the functional connectivity of these modules in galagos, a prosimian primate with relatively simple frontoparietal circuitry. By deactivating a reaching module in M1, we interfered with the function of similar PPC modules and occasionally unrelated PPC modules as well (e.g., eye blink). This circuitry in galagos, therefore, is more complex than in nonprimates, indicating that it has been altered with the expansion of primate PPC.


Construction of a scale to measure load, power, and margin in life.
The development of an instrument to measure load, power, and margin in life (MIL) is described. Validity was established through factor analysis and the know-groups approach to construct validity. Stability was tested through a test-retest reliability, and Cronbach alpha reliability coefficients were obtained to test for internal consistency. Subjects consisted of 146 adult men and women volunteers for testing Form 1, later revised to Form 2. Form 2 was given to 103 volunteers; of these 66 were repeaters from the Form 1 testing; 37 were new subjects. Item analyses were performed and used to reduce the original 211 items to 94 for Form 3 of the scale.


"Little rapes," specious claims, and moral hubris: a reply to Korn, Huelsman, Reed, and Aiello.
Because they failed to include our informed consent, guided imagery scenarios, and debriefing, the relevance of Koren, Huelsman, Reed, and Aiello's (1992) data remains unknown. The design of their Study 1 did not test the greater objectivity of role taking over involved participation. The design of their Study 2 did not demonstrate the effects of demand characteristics. The older "personal acquaintances" were not at higher risk of rape as they claimed. Properly gathered data from the University of Connecticut's laboratory demonstrated that participants regarded the guided imagining of rape to be personally and scientifically beneficial, educating them about the crime and the experience of the rape victim. Prior research had demonstrated that exposure to rape stimuli in combination with debriefing had an educational effect on the decreased endorsement of rape myths. Previously published ethical principles for balancing the rights of scientists, subjects, and society explicate our ethical stance. Informed consent precludes the occurrence of wrongful harms. This poorly designed and poorly reasoned "ethical" critique was unfounded; yet, it might produce a chilling effect on both the use of guided imagery and freedom of inquiry into politically sensitive topics.


Outcomes after lobectomy and pneumonectomy in lungcancer patients aged 70 years or older.
For the early stage of nonsmall-cell lung cancer, surgical resection provides the best survival, but the surgical risk generally increases with age because of the increased prevalence of comorbidities, especially cardiovascular disorders. The aim of this study was to compare survival and mortality rates of two groups with different ages, younger and older than 70 years, who went curative resection for nonsmall-cell lung cancer. We analyzed the patients who underwent curative lung cancer surgery in the Department of Thoracic Surgery of Gaziantep University Research Hospital between January 1997 and November 2014. Patients were divided into 2 groups according to their ages. A total of 497 patients were included in data analysis (381 were under 70 years old and 116 of them were ≥70 years old). The older group showed a 1.4-fold increased risk of mortality hazard ratio when the probability of survival was analyzed by histological type, lymph node involvement, disease stage, and age. There was no distinct increase in 30-day mortality rates of patients with nonsmall-cell lung cancer who were ≥70 years old, but the hazard rate for long-term survival was higher in the older group. Curative pulmonary resections due to lung cancer should be carefully performed in septuagenarians.


Fe adsorption on hematite (α-Fe2O3) (0001) and magnetite (Fe3O4) (111) surfaces.
The structure and electronic properties of different terminations of hematite (0001) and magnetite (111) surfaces upon submonolayer Fe adsorption were studied using the spin-polarized density functional theory (DFT) including the Hubbard correction term U (DFT+U). On both oxides the Fe atoms were adsorbed on the most stable iron and oxygen terminated surfaces. The results show that Fe atoms bind strongly both to hematite and magnetite surfaces, however, the binding is distinctly stronger at the oxygen than at the iron terminated surfaces. For both oxides and surface terminations the binding energy of the Fe decreases with increasing coverage, which indicates substantial repulsive interactions between Fe adatoms. On the hematite surface, the most stable sites for Fe adsorption are bulk continuation sites which result in formation of the Fe-rich terminations. On the magnetite surface, the bulk continuation site is favored only for Fe adsorption on the oxygen terminated surface while on the iron terminated one Fe adsorbs in a position closer to the surface iron layer. Submonolayer coverages of Fe modify substantially the surface electronic structure of the oxides and, depending on the termination, can change its character from half-metallic to insulating one, and vice versa.


Clinicopathological and prognostic significance of PD-L1 in oral cancer: A preliminary retrospective immunohistochemistry study.
To evaluate the relation between PD-L1 expression in oral cavity squamous cell carcinomas and clinicopathological features as well as survival outcomes. A retrospective immunohistochemical study was carried out on 55 archived tumours from 55 patients. Tumours were stained for PD-L1 and scored by the proportion of tumour cells with positive membranous staining. PD-L1 scores were compared to the patient's clinicopathological characteristics for any significant associations. Kaplan-Meier curves were constructed for PD-L1 positive and negative tumours to investigate any advantage to survival. Positive PD-L1 staining was found in 58% of tumours and was significantly more likely in non-smokers, non-drinkers and in tongue squamous cell carcinomas. Increased PD-L1 was also associated with increased lymphocyte infiltration as well as PD-L1 staining in lymphocytes and the epithelium adjacent to tumour invasion. No survival benefit was seen from PD-L1 expression in tumour cells. PD-L1 expression is more common in non-smokers and non-drinkers, and its presence in the adjacent non-tumour epithelium suggests it may be involved in early oncogenesis.


Minimal intervention dentistry (MI) for South Africa.
The intention of Minimal Intervention Dentistry (MI) is to preserve as much tooth tissue as possible and to offer less threatening care to fearful patients. MI is based on a new understanding of cariology and the therapeutic value of biomimetic materials such as Glass lonomers. It has particular relevance to a new caries classification and employs treatment concepts such as selective caries removal and sealed restorations. The MI approach is appropriate for the vast majority of the population in South Africa; it addresses the public fear of dental treatment. It can be an effective private practice builder and is thus applicable to private and public services.


Giant supratentorial neurenteric cyst.
Intracranial neurenteric cysts are rare congenital lesions that may be mistaken for other cystic neoplastic and nonneoplastic lesions. A 35 years old right handed man presented with a one year history of progressive left hemiparesis, headache, personality changes and seizures. Clinical examination revealed a confused patient with left hemiparesis (power 4/5 in both left upper and lower limbs), upper motor neuron type signs in left half of the body (up going plantar reflex and exaggerated deep tendon reflexes at 3+), left facial weakness of upper motor neuron type. CT scan head with contrast revealed a non-enhancing spherical cystic lesion in the frontotemporoparietal region with minimal to moderate mass effect. The cyst was removed using a combination of hydrodissection and excision. Recovery was complete with no evidence of recurrence or residual disease at 3 months.


Phenotypic spectrum in recessive STING-associated vasculopathy with onset in infancy: Four novel cases and analysis of previously reported cases.
Gain-of-function variants in the stimulator of interferon response cGAMP interactor 1 (STING1) gene cause STING-Associated Vasculopathy with onset in Infancy (SAVI). Previously, only heterozygous and mostly de novo STING1 variants have been reported to cause SAVI. Interestingly, one variant that only leads to SAVI when homozygous, namely c.841C>T p.(Arg281Trp), has recently been described. However, there are no entries in public databases regarding an autosomal recessive pattern of inheritance. Here, we report four additional unrelated SAVI patients carrying c.841C>T in homozygous state. All patients had interstitial lung disease and displayed typical interferon activation patterns. Only one child displayed cutaneous vasculitis, while three other patients presented with a relatively mild SAVI phenotype. Steroid and baricitinib treatment had a mitigating effect on the disease phenotype in two cases, but failed to halt disease progression. Heterozygous c.841C>T carriers in our analysis were healthy and showed normal interferon activation. Literature review identified eight additional cases with autosomal recessive SAVI caused by c.841C>T homozygosity. In summary, we present four novel and eight historic cases of autosomal recessive SAVI. We provide comprehensive clinical data and show treatment regimens and clinical responses. To date, SAVI has been listed as an exclusively autosomal dominant inherited trait in relevant databases. With this report, we aim to raise awareness for autosomal recessive inheritance in this rare, severe disease which may aid in early diagnosis and development of optimized treatment strategies.


A method to estimate the absolute ultrasonic nonlinearity parameter from relative measurements.
The ultrasonic nonlinearity parameter (β) is determined from the particle displacement amplitudes of the fundamental and second-order harmonic components in an ultrasonic wave propagated through a material. This parameter is generally referred to as the absolute parameter. However, measuring the second harmonic component is especially difficult because its amplitude is usually much smaller than those of signals in typical ultrasonic measurements. For this reason, most studies use the relative parameter determined using the measured electric signal amplitudes of the fundamental and second harmonic ultrasonic waves. However, in many occasions, the absolute parameter is needed for a quantitative assessment of material degradation. This study proposes a method to estimate the absolute parameter from a measured relative parameter along with a proportionality constant between normalized absolute and relative parameters. This method is based on the observed fact that the ratio of between normalized relative and absolute parameters is identical after compensating proportionality constant. The method was experimentally validated for Al6061-T6 alloy specimens heat-treated for different aging times. The parameter determined through the proposed method were compared with the absolute parameters which were measured separately. The results show that these two parameters were close to each other within the measurement errors.


A Multichannel Fluorescent Array Sensor for Discrimination of Different Types of Drug-Induced Kidney Injury.
The differences in urinary proteins could provide a novel opportunity to distinguish the different types of drug-induced kidney injury (DIKI). In this research, Au nanoparticles-polyethyleneimine (AuNPs-PEI) and the three fluorophore-labeled proteins (FLPs) have been constructed as a multichannel fluorescent array sensor via electrostatic interaction, which was used to detect the subtle changes in urine collected from the pathological state of DIKI. Once the urine from different types of DIKI was introduced, the binding equilibrium between AuNPs-PEI and FLPs would be broken due to the competitive binding of urinary protein, and the corresponding fluorescence response pattern would be generated. Depending on the different fluorescence response patterns, the different types of DIKI were successfully identified by principal component analysis (PCA) and linear discriminant analysis (LDA). Accordingly, the strategy was expected to be a powerful technique for evaluating the potential unclear mechanisms of nephrotoxic drugs, which would provide a promising method for screening potential renal-protective drugs.


Effects of perfluorooctane sulfonate (PFOS) on cognitive behavior and autophagy of male mice.
Perfluorooctane sulfonate (PFOS), an emerging environmental pollutant, is reported to cause neurotoxicity in animals and humans, but its underlying mechanisms are still unclear. We used in vivo models to investigate the effects of PFOS on cognition-related behaviors and related mechanisms. After 45 days of intragastric administration of PFOS (2 mg/kg or 8 mg/kg) in 7-week-old C57BL/6 mice, muscle strength, cognitive function and anxiety-like behavior were evaluated by a series of behavioral tests. The underling mechanisms of PFOS on impaired behaviors were evaluated by HE/Nissl staining, electron microscopy observation and western blot analysis. The results indicated that PFOS-exposed mice exhibited significant cognitive impairment, anxiety, neuronal degeneration and the abnormities of synaptic ultrastructure in the cortex and hippocampus. Western blot analysis indicated that PFOS exposure increased microtubule-associated protein light chain 3 (LC3) and decreased p62 protein levels, which may be associated with activation of autophagy leading to neuron damage. In summary, our results suggest that chronic exposure to PFOS adversely affects cognitive-related behavior in mice. These findings provide new mechanistic insights into PFOS-induced neurotoxicity.


[Ingrown toenail].
Three patients, men aged 58, 79 and 78 years, with onychocryptosis in their right, left and right hallux respectively, were treated by partial nail extraction and phenolisation of the nail bed. The wound did not heal and the symptoms worsened. The ankle-brachial index was < 0.9, which is an indication of peripheral arterial disease. This was confirmed by ultrasonography, CT and magnetic resonance angiography (MRA). In the first patient, endovascular arterial dilatation did not result in enough circulation and hallux amputation was needed. The second patient recovered after a femorofibular bypass, and the third one after a femoropopliteal bypass. Treatment of ingrown toenails might result in major complications, if a patient suffers from known or unknown peripheral arterial disease. If an ingrown toenail needs surgical treatment, efforts should be made to determine whether the patient suffers from peripheral arterial disease. This can be done by interviewing the patient, physical examination and measuring the ankle-brachial index. For diabetic patients the ankle-brachial index is not reliable; therefore toe pressure waves should be measured before surgical treatment. If signs of peripheral arterial disease are detected, the patient should be referred to the vascular surgeon before surgical treatment of the ingrown toenail.


Proteome Analysis of Hordein-Null Barley Lines Reveals Storage Protein Synthesis and Compensation Mechanisms.
Hordeins are the major barley seed storage proteins and are elicitors of celiac disease. Attempts to reduce the hordein level in barley have been made; however, the resultant pleiotropic effects are less understood. Here, data-independent acquisition mass spectrometry was used to measure proteome-wide abundance differences between wild-type and single hordein-null barley lines. Using comparative quantitative proteomics, we detected proteome-wide changes (∼59%) as a result of the specific reduction in hordein proteins. The comparative analysis and functional annotation revealed an increase in non-gluten storage proteins, such as globulins and lipid transfer proteins, and proteins rich in essential amino acids in the null lines. This study yields an informative molecular portrait of the hordein-null lines and the underlying mechanisms of storage protein biosynthesis. This study indicates the extent to which protein content can be manipulated without biological consequence, and we envision its wide-scale application for studying modified crops.


Norwalk virus infection and disease is associated with ABO histo-blood group type.
Some people are resistant to Norwalk virus (NV) infection; however, the factor(s) responsible for resistance or susceptibility to NV infection has not been identified. This study investigated the relationship between a person's ABO histo-blood group type and the risk of NV infection and symptomatic disease after clinical challenge. ABO phenotypes were identified by using serum samples from volunteers who participated in an NV challenge study (n=51). Individuals with an O phenotype were more likely to be infected with NV (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.3-103), whereas persons with a B histo-blood group antigen had decreased risk of infection (OR, 0.096; 95% CI, 0.16-0.56) and symptomatic disease (OR, 0; 95% CI, 0-0.999). This is the first report demonstrating an association between a genetic factor and the risk of NV infection and symptomatic disease.


The Ethics of Introducing GMOs into sub-Saharan Africa: Considerations from the sub-Saharan African Theory of Ubuntu.
A growing number of countries in sub-Saharan Africa are considering legalizing the growth of genetically modified organisms (GMOs). Furthermore, several projects are underway to develop transgenic crops tailored to the region. Given the contentious nature of GMOs and prevalent anti-GMO sentiments in Africa, a robust ethical analysis examining the concerns arising from the development, adoption, and regulation of GMOs in sub-Saharan Africa is warranted. To date, ethical analyses of GMOs in the global context have drawn predominantly on Western philosophy, dealing with Africa primarily on a material level. Yet, a growing number of scholars are articulating and engaging with ethical theories that draw upon sub-Saharan African value systems. One such theory, Ubuntu, is a well-studied sub-Saharan African communitarian morality. I propose that a robust ethical analysis of Africa's agricultural future necessitates engaging with African moral theory. I articulate how Ubuntu may lead to a novel and constructive understanding of the ethical considerations for introducing GMOs into sub-Saharan Africa. However, rather than reaching a definitive prescription, which would require significant engagement with local communities, I consider some of Ubuntu's broader implications for conceptualizing risk and engaging with local communities when evaluating GMOs. I conclude by reflecting on the implications of using local moral theory in bioethics by considering how one might negotiate between universalism and particularism in the global context. Rather than advocating for a form of ethical relativism, I suggest that local moral theories shed light on salient ethical considerations that are otherwise overlooked.


Application of SPR imaging sensor for detection of individual living cell reactions and clinical diagnosis of type I allergy.
A technique to visualize living cell activation in a real time manner without any labeling is required in the fields of life sciences and medicine. We have reported that surface plasmon resonance (SPR) sensors detect large changes of refractive index (RI) with living cells, such as mast cells, human basophils and lymphocytes. However conventional SPR sensors detect only an average change of RI with thousands of cells at detectable area on a sensor chip. Therefore, we developed an SPR imaging (SPRI) sensor with a CMOS camera and an objective lens in order to visualize RI of individual living cells and their changes upon stimuli. The SPRI sensor we developed could detect reactions of individual rat basophilic leukemia (RBL-2H3) cells and mouse keratinocyte cells in response to specific or nonspecific stimuli. Moreover, the sensor could detect the reactions of individual human basophils isolated from patients in response to antigens (allergens). Thus the technique can visualize the effect of various stimuli, inhibitors and/or conditions on cell reactions as change of intracellular RI distribution at single cell levels. Establishment of the technique to rapidly isolate cells from patient blood should enable us to utilize SPRI system as a high throughput screening system in clinical diagnosis, such as type I hypersensitivity and drug hypersensitivity, and as a tool to reveal novel phenomena in evanescent fields around plasma membranes.


Copper-catalysed dehydrogenative self-coupling/cyclization of 5-aminopyrazoles: synthesis and photophysical study of pyridazines.
An interesting self-coupling/cyclization of 5-aminopyrazoles is revealed, which provides a variety of pyridazine cores in reasonable yields. In this reaction, C(sp2)-C(sp2) and N-N bond formation occurs simultaneously in one reaction vessel. The photophysical properties of the synthesized compounds were also studied and some of them exhibited fluorescence properties with good quantum yields. A radical mediated reaction mechanism is proposed with the help of control experiments.


A Simple Blood Vessel Imaging Protocol for Live Zebrafish Larva.
Zebrafish larva is a simple model system to study blood vessel development because of its excellent optical properties. Current methods to study blood vessels in zebrafish involve utilizing either blood vessel-specific transgenic lines or specialized techniques such as microangiography and video capillaroscopy. In this study, we have developed a simple protocol using ImageJ to observe the blood vessels of live zebrafish larva at different developmental stages, namely 1- to 4-day postfertilization (dpf). To validate this protocol, we treated 1 dpf zebrafish embryos with 100 μM quercetin, and analyzed the impaired development of subintestinal vein in the quercetin-treated 3 dpf larvae.


An insertion-deletion polymorphism in the interferon regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases.
The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to be associated with systemic lupus erythematosus and rheumatoid arthritis. We studied whether the IRF5 gene is also associated with inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Twelve polymorphisms in the IRF5 gene were genotyped in a cohort of 1007 IBD patients (748 CD and 254 UC) and 241 controls from Wallonia, Belgium. The same polymorphisms were genotyped in a confirmatory cohort of 311 controls and 687 IBD patients (488 CD and 192 UC) from Leuven, Belgium. A strong signal of association [P = 1.9 x 10(-5), odds ratio (OR) 1.81 (1.37-2.39)] with IBD was observed for a 5 bp indel (CGGGG) polymorphism in the promoter region of the IRF5 gene. The association was detectable also in CD patients (P = 6.8 x 10(-4)) and was particularly strong among the UC patients [P = 5.3 x 10(-8), OR = 2.42 (1.76-3.34)]. The association of the CGGGG indel was confirmed in the second cohort [P = 3.2 x 10(-5), OR = 1.59 (1.28-1.98)]. The insertion of one CGGGG unit is predicted to create an additional binding site for the transcription factor SP1. Using an electrophoretic mobility shift assay, we show allele-specific differences in protein binding to this repetitive DNA-stretch, which suggest a potential function role for the CGGGG indel.