Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Ligand Interactions for Bacterial Immunoglobulin‐Binding Proteins on Human and Murine Cells of the Hematopoetic Lineage

A group of bacterial Ig‐binding surface proteins were studied: protein H and Ml are from Streptococcus pyogenes and interact with IgG, protein L is expressed by Peptostreptococcus magnus and shows affinity for Ig light chains, whereas protein LG is a chimeric construction combining the binding properties of protein L with the IgG‐binding activity of protein G from group C and G streptococci. Proteins L and H coupled to Sepharose were mitogenic for human peripheral blood lymphocytes (PBL) and mouse splenic B cells, but not when added in soluble form. Differentiation to Ig secretion was induced by protein H‐Sepharose in mouse splenic B cells but not in human PBLs. In FACS analysis FITC‐labelled protein H stained virtually all CD19+ cells in human peripheral blood as well as a majority of the CD3+ population. Protein L bound the majority of the CD19+ population, but also a fraction of the CD19−/CD3 population. Protein Ml was not mitogenic but stained the entire CD19+ population and 70% of the CD3+ population. Identical staining patterns were observed with mouse splenocytes using B220 and T‐cell receptor as lineage markers. The chimeric protein LG was a potent mitogen for mouse splenic B cells when added either coupled to Sepharose or in soluble form. In addition, protein LG induced differentiation to Ig secretion of the responding mouse splenic B cells. In FACS analysis, protein LG stained the entire CD19+ and the majority of the CD19−/CD3 lymphocyte population as well as all B220+ mouse splenocytes and a fraction of the splenic T cells. These data indicate that the bacterial proteins studied interact with surface structures of several leucocyte populations and can hence interfere with the immune system at multiple levels.
AC Loss and Other Researches with 5 m HTS Model Cables

The test facility developed in Russian Scientific R&D Cable Institute permits to perform extensive tests of heavily instrumented HTS cable models with length up to 5 m. Several HTS cables with different design have been developed and tested at this facility. The test programs included, besides usual critical current measurements, current distribution measurements among layers, joint resistance test, etc. The facility's equipment permits digital measurements of voltage and current with high accuracy and, therefore, digital ac loss analysis in model cables. In this paper we present the details of the test facility and results of tests and ac loss measurements in few 5 m model cables. ac losses in model cables made of 1 G and 2 G wires and other cable parameters are discussed and compared.
Elimination of trachoma as a public health problem in Ghana: Providing evidence through a pre-validation survey

Background In order to achieve elimination of trachoma, a country needs to demonstrate that the elimination prevalence thresholds have been achieved and then sustained for at least a two-year period. Ghana achieved the thresholds in 2008, and since 2011 has been implementing its trachoma surveillance strategy, which includes community and school screening for signs of follicular trachoma and trichiasis, in trachoma-endemic districts. In 2015–2016, the country conducted a district level population-based survey to validate elimination of trachoma as a public health problem. Methods As per WHO recommendations, a cross-sectional survey, employing a two-stage cluster random sampling methodology, was used across 18 previously trachoma endemic districts (evaluation units (EUs) in the Upper West and Northern Regions of Ghana. In each EU 24 villages were selected based on probability proportional to estimated size. A minimum of 40 households were targeted per village and all eligible residents were examined for clinical signs of trachoma, using the WHO simplified grading system. The number of trichiasis cases unknown to the health system was determined. Household environmental risk factors for trachoma were also assessed. Results Data from 45,660 individuals were examined from 11,099 households across 18 EUs, with 27,398 (60.0%) children aged 1–9 years and 16,610 (36.4%) individuals 15 years and above All EUs had shown to have maintained the WHO elimination threshold for Trachomatous inflammation-Follicular (TF) (<5.0% prevalence) in children aged 1–9 years old. The EU TF prevalence in children aged 1–9 years old ranged from between 0.09% to 1.20%. Only one EU (Yendi 0.36%; 95% CI: 0.0–1.01) failed to meet the WHO TT elimination threshold (< 0.2% prevalence in adults aged 15 and above). The EU prevalence of trichiasis (TT) unknown to the health system in adults aged ≥15 years, ranged from 0.00% to 0.36%. In this EU, the estimated TT backlog is 417 All TT patients identified in the study, as well as through on-going surveillance efforts will require further management. A total of 75.9% (95% CI 72.1–79.3, EU range 29.1–92.6) of households defecated in the open but many households had access to an improved water source 75.9% (95%CI: 71.5–79.8, EU range 47.4–90.1%), with 45.5% (95% CI 41.5–49.7%, EU range 28.4–61.8%) making a round trip of water collection < 30 minutes. Conclusion The findings from this survey indicate elimination thresholds have been maintained in Ghana in 17 of the 18 surveyed EUs. Only one EU, Yendi, did not achieve the TT elimination threshold. A scheduled house-by-house TT case search in this EU coupled with surgery to clear the backlog of cases is necessary in order for Ghana to request validation of elimination of trachoma as a public health problem.
MENTAL DETERIORATION IN EPILEPTIC CHILDREN*

Epileptic attacks of all sorts are common in children but probably less than a third of them are associated with serious psychological difficulties (Pond and Bidwell, 1960). Of this latter group a much smaller proportion actually deteriorate by the loss of already acquired intellectual and personality functions as the condition progresses. The concept of deterioration in epileptic adults has often been elaborated and the clinical picture is well known (Pond, 1957). Much less is known about children, and the present paper attempts to define the clinical problem as it presents and to investigate the factors apparently related to deterioration. The paper is not concerned with epileptic children who have always been of idiot or imbecile level but with those who have achieved a certain amount of intellectual progress that later is lost. Also excluded are the rare but well recognized neurological degenerations such as the lipidoses.
Defective glucocorticoid receptor signaling and keratinocyte-autonomous defects contribute to skin phenotype of mouse embryos lacking the Hsp90 co-chaperone p23

p23 is a small acidic protein with intrinsic molecular chaperone activity. It is best known as a co-chaperone of the major cytosolic molecular chaperone Hsp90. p23 binds the N-terminus of Hsp90 and stabilizes the ATP-bound and N-terminally closed Hsp90 dimer. It is in this configuration that many Hsp90 clients are most stably bound. Considering the important role of p23 in the Hsp90 cycle, it came as a surprise that it is not absolutely essential for viability in the budding yeast or for mouse development. Mice without p23 develop quite normally until birth and then all die perinatally because of immature lungs. The only other apparent phenotype of late stage embryos and newborns is a skin defect, which we have further characterized here. We found that skin differentiation is impaired, and that both apoptosis and cell proliferation are augmented in the absence of p23; the consequences are a severe thinning of the stratum corneum and reduced numbers of hair follicles. The altered differentiation, spontaneous apoptosis and proliferation are all mimicked by isolated primary keratinocytes indicating that they do require p23 functions in a cell-autonomous fashion. Since the phenotype of p23-null embryos is strikingly similar to that of embryos lacking the glucocorticoid receptor, a paradigmatic Hsp90-p23 client protein, we investigated glucocorticoid signaling. We discovered that it is impaired in vivo and for some aspects in isolated keratinocytes. Our results suggest that part of the phenotype of p23-null embryos can be explained by an impact on this particular Hsp90 client, but do not exclude that p23 by itself or in association with Hsp90 affects skin development and homeostasis through yet other pathways.
Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy 1

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high‐ and low‐risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world‐wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA‐association are present which render MS heterogeneous even in this ethnically homogeneous population.
New Insights Into Microaneurysms in the Deep Capillary Plexus Detected by Optical Coherence Tomography Angiography in Diabetic Macular Edema.

PURPOSE To study the association between the distributions of microaneurysms detected by en face optical coherence tomography angiography (OCTA) and diabetic macular edema (DME). METHODS The study design was a retrospective chart review of 27 patients (33 eyes) with DME. The eyes were scanned using OCTA (6 × 6 mm) and spectral-domain (SD) OCT macular cube. Each of the images of the capillary plexus was overlaid onto the image of the topographic map, and the densities of the microaneurysms were measured by ImageJ software. The association between the distribution of microaneurysms and macular edema was evaluated. RESULTS For microaneurysms in areas with and without edema, 77.3 ± 8.1% of these microaneurysms were located in the deep capillary plexuses (DCP). However, in areas of edema where the retinal thickness was more than 400 μm, 91.3 ± 9.1% of the microaneurysms were found in the DCP. This difference was statistically significant (P < 0.001). In the macular edema area, there was a significantly higher density of microaneurysms in the DCP compared to the superficial capillary plexuses (1.71/mm2 vs. 0.17/mm2, P < 0.001). There was also a significant correlation between the macular volume and the density of microaneurysms in the DCP in edema (r = 0.63, P < 0.001). CONCLUSIONS Our study demonstrated a high proportion of microaneurysms in the DCP, as well as a novel association between the distributions of microaneurysms detected by OCTA and DME. Results also indicated that microaneurysms located in the DCP contribute to the pathogenesis of DME.
Functional analysis of the evolutionary conserved arginine 182 residue in human glutathione S‐transferase P1‐1

The mutational replacement of Arg182 with threonine markedly decreased the specific activities for GSH‐conjugation reaction. The kcat of R182T for GSH‐[1‐chloro‐2,4‐dinitrobenzene] conjugation reaction was about 100‐fold smaller than that of the wild type. On the other hand, the affinity for GSH of R182T was not significantly affected. The pKa of the thiol group of GSH bound in R182T was ∼0.9 pK units higher than those in the wild type, but the kcat/Km1‐chloro‐2,4‐dinitrobenzene values at high pH were not so much lower than those of the wild type. The thermostability of R182T was significantly lower than that of the wild type. Therefore, Arg182 seems to be important for the construction of the active enzyme structure.
Effects of melatonin on proliferation of cancer cell lines

Papazisis KT, Kouretas D, Geromichalos GD, Sivridis E, Tsekreli OK, Dimitriadis KA, Kortsaris A.H. Effects of melatonin on proliferation of cancer cell lines. J. Pineal Res. 1998; 25:211–218. © Munksgaard, Copenhagen
Sofosbuvir, a NS5B polymerase inhibitor in the treatment of hepatitis C: a review of its clinical potential

Treatment of chronic hepatitis C (HCV) is currently undergoing a significant change. Traditional interferon-based therapy has been limited by both efficacy and tolerability, and many direct acting antiviral (DAA) drugs are emerging. Sofosbuvir (GS-7977) is a HCV NS5B nucleotide polymerase inhibitor that has now been evaluated extensively in phase II and III interferon-free clinical trials. The focus of this review is on the clinical potential of sofosbuvir in the treatment of HCV. Sofosbuvir has a pan-genotypic effect on HCV, although viral genotype-specific differences in sustained virological response (SVR) have emerged in phase III clinical trials. Sofosbuvir has been studied both as dual therapy with ribavirin and also as triple therapy with either NS5A inhibitors or a protease inhibitor. High rates of SVR have been reported with these interferon-free combinations, particularly with genotypes 1 and 2, and the safety profile has been very favourable in both cirrhotic and noncirrhotic patients, without issues of viral resistance. Interferon-free, once-daily treatment of HCV is now becoming a reality.
Skin Manifestations in Diabetic Patients Attending a Diabetic Clinic in the Qassim Region, Saudi Arabia

Objective: To investigate the prevalence of skin manifestations in diabetic patients attending a diabetic clinic in the Qassim region, Saudi Arabia. Subjects and Methods: A prospective observational study was performed on 320 patients (174 males and 146 females) attending the diabetic clinic. A detailed dermatological examination was carried out by a consultant dermatologist and the cutaneous findings were recorded. Results: The overall prevalence of skin manifestations was 91.2%. Cutaneous lesions were seen in 12 patients (34.3%) of type 1 diabetes mellitus (DM) and 280 (98.2%) of type 2 diabetics. There was a statistically significant difference (p < 0.001) in skin manifestations between type 1 and type 2 DM patients. For those patients having diabetes of less than 5 years’ duration, the incidence of skin manifestations was 80.6%; for those having had diabetes for more than 5 years, the incidence was 98%. This difference was statistically significant (p < 0.001). The skin manifestations that had a statistically significant difference (p < 0.05) in prevalence between the 2 durational groups were gangrene, diabetic dermopathy, paresthesia, diabetic feet, diabetic bullae and fungal infections. Conclusion: Diabetics had a greater prevalence of skin manifestations in type 2 than type 1, and as the duration of diabetes increased, the likelihood of developing skin manifestations also increased. Early referral to the dermatologist may help to detect complications of the skin in diabetes at an early stage and may prevent disability caused by these complications.
MicroRNAs in central nervous system development

Abstract During early and late embryo neurodevelopment, a large number of molecules work together in a spatial and temporal manner to ensure the adequate formation of an organism. Diverse signals participate in embryo patterning and organization synchronized by time and space. Among the molecules that are expressed in a temporal and spatial manner, and that are considered essential in several developmental processes, are the microRNAs (miRNAs). In this review, we highlight some important aspects of the biogenesis and function of miRNAs as well as their participation in ectoderm commitment and their role in central nervous system (CNS) development. Instead of giving an extensive list of miRNAs involved in these processes, we only mention those miRNAs that are the most studied during the development of the CNS as well as the most likely mRNA targets for each miRNA and its protein functions.
Studies on the constituents of medicinal and related plants in Sri Lanka. II. Isolation and structures of new gamma-pyrone and related compounds from Hypericum mysorense Heyne.

Neutral constituents of Hypericum mysorense HEYNE, collected in Sri Lanka, were examined. Hyperenone-A, mysorenone-A, and compound-C (methyl phenacyl 1, 1-dimethylprop-2-enyl-malonate) were isolated and their structures were determined on the basis of chemical and spectroscopic evidence. Four known xanthones were also isolated and identified.
More Pensioners, Less Income Inequality?

As is the case in most developed countries, the population of New Zealand is ageing numerically and structurally. Population ageing can have important effects on the distribution of personal income within and between urban areas. The age structure of the population may affect the distribution of income through the life-cycle profile of earnings but also through the spatial-temporal distribution of income within the various age groups. By decomposing New Zealand census data from 1986 to 2013 by age and urban area, this chapter examines the effects of population ageing on spatial-temporal changes in the distribution of personal income to better understand urban area-level income inequality (measured by the Mean Log Deviation index). We focus explicitly on differences between metropolitan and non-metropolitan urban areas. New Zealand has experienced a significant increase in income inequality over the last few decades, but population ageing has slightly dampened this trend. Because metropolitan areas are ageing slower, the inequality-reducing effect of ageing has been less in these areas. However, this urban-size differential-ageing effect on inequality growth has been relatively small compared with the faster growth in intra-age group inequality in the metropolitan areas.
Sustained-release microspheres of amifostine for improved radio-protection, patient compliance, and reduced side effects

Abstract A biweekly administration of sustained-release microsphere dosage form of amifostine, a radioprotective drug used in radiotherapy, was performed to examine the feasibility to minimize injection frequency and blood concentration-associated side effects. Model animal trials indicated that this subcutaneously injecting microspheres, 50–100 μm in diameter, achieved bi-weekly prolonged radio-protective efficacy and, at the same time, significantly reduced skin irritation than the solution form of amifostine given by the same administration route. In addition, the hypertension associated with blood concentration of amifostine was not observed in the drug-treated rats. The animals given the amifostine microspheres and amifostine showed significantly differences in white blood cell, red blood cell, hematocrit, hemoglobin and spleen tissue histopathology after exposed under a cobalt-60 γ-radiation at a dose rate of 1.0 Gy/min for 6 min. The in vitro release profile of amifostine from the micropsheres showed a minor initial burst (less than 20% of total drug loading in the first day of administration), consisting with the side effects observations. The results suggest that amifostine encapsulated in sustained-release microspheres may be an ideal dosage form for prolonged radio-protective efficacy and improved patient compliance.
CASK localizes to nuclei in developing skeletal muscle and motor neuron culture models and is agrin‐independent

Membrane‐associated guanylate kinases (MAGUKs) are cytoplasmic multi‐domain proteins that serve as scaffold proteins at cell junctions and synapses. Calmodulin‐associated serine/threonine kinase (CASK) stabilizes the integrity of synapses in the brain. Additionally, CASK is capable of acting as a transcriptional co‐activator and localizes to neuronal nuclei in the developing brain. We have recently described CASK localization to both the pre‐ and post‐synaptic membranes of the neuromuscular junction (NMJ), where it forms a complex with discs large (Dlg). CASK also localizes to some, but not all nuclei in adult mouse skeletal muscle. To begin to dissect the roles of CASK in the cellular components of the NMJ, we investigated the localization of CASK during differentiation in cell culture models of skeletal muscle and motor neurons. We demonstrate that CASK localizes to the nucleus in undifferentiated myoblasts, but is pre‐dominantly in the cytoplasm in differentiated myotubes of the C2C12 myogenic cell line. We also show nuclear localization of both CASK and Dlg in a motor neuron‐neuroblastoma hybrid cell line, MN‐1, suggesting a role for CASK and Dlg in nuclei of neurons in the peripheral nervous system. Finally, we demonstrate that CASK and Dlg do not co‐cluster with acetylcholine receptors in C2C12 myotubes in response to agrin or laminin treatment, suggesting a novel mechanism of recruitment to the NMJ that is independent of acetylcholine receptor and utrophin complexes. These studies delineate important developmental characteristics of CASK and Dlg, and suggest dual roles for these proteins in both the skeletal muscle and motor neuron components of the NMJ. © 2005 Wiley‐Liss, Inc.
Joint research towards a better radiation protection—highlights of the Fifth MELODI Workshop

MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future.