Miracle-dz/UniFAR-FTUs huggingface dataset:
General Strategy for Decoration of Enveloped Viruses with Functionally Active Lipid-Modified Cytokines

ABSTRACT Viral particles preferentially incorporate extra- and intracellular constituents of host cell lipid rafts, a phenomenon central to pseudotyping. Based on this mechanism, we have developed a system for the predictable decoration of enveloped viruses with functionally active cytokines that circumvents the need to modify viral proteins themselves. Human interleukin-2 (hIL-2), hIL-4, human granulocyte-macrophage colony-stimulating factor (hGM-CSF), and murine IL-2 (mIL-2) were used as model cytokines and fused at their C terminus to the glycosylphosphatidylinositol (GPI) acceptor sequence of human Fcγ receptor III (CD16b). We show here that genetically modified cytokines are all well expressed on 293 producer cells. However, only molecules equipped with GPI anchors but not those linked to transmembrane/intracellular regions of type I membrane proteins are efficiently targeted to lipid rafts and consequently to virus-like particles (VLP) induced by Moloney murine leukemia virus Gag-Pol. hIL-4::GPI and hGM-CSF::GPI coexpressed on VLP were found to differentiate monocytes towards dendritic cells. Apart from myeloid-committed cell types, VLP-bound cytokines also act efficiently on lymphocytes. hIL-2::GPI strongly costimulated T-cell receptor (TCR)/CD3 dependent T-cell activation in vitro and mIL-2::GPI-coactivated antigen-specific T cells in vivo. On a molar basis, the functional activity of VLP-bound hIL-2::GPI was found to be comparable to that of soluble hIL-2. VLP decorated with hIL-2::GPI and coexpressing a TCR/CD3 ligand have an IL-2-specific activity of 5 × 104 units/mg protein. Virus particles decorated with lipid-modified cytokines might help to improve viral strains for vaccination purposes, the propagation of factor-dependent cell types, as well as gene transfer by viral systems in the future.
Serum-induced signal transduction determines the peripheral location of beta-actin mRNA within the cell

Cell motility is dependent upon the reorganization of the cellular cytoskeleton. Actin filaments form the major component of the cytoskeleton and respond rapidly to serum growth factors. We have previously shown that myoblasts sort the two cytoskeletal beta- and gamma-actin isoform mRNAs to different intracellular regions and that only beta-actin mRNA was associated with peripheral regions of cell motility (Hill, M.A. and P. Gunning. 1993. J. Cell Biol. 122: 825-832). We now show by in situ hybridization that 3T3 fibroblasts similarly sort actin isoform mRNAs and that peripheral beta-actin mRNA is regulated by serum. In the absence of serum, we could not detect beta- actin mRNA at the periphery. Addition of serum rapidly redistributed beta-actin mRNA to the periphery. gamma-actin mRNA distribution was not altered by serum addition at any time. Both proteins, as identified by immunochemistry with isoform-specific antibodies, were found in similar cellular structures. Serum-stimulated cell motility is mediated through the GTPase signal transduction pathway. We find that an RNA-binding protein, p62, that is part of this pathway, displays a localization pattern similar to beta-actin mRNA. Our results suggest a new biological mechanism which integrates signal transduction with the supply of an architectural component required for membrane remodeling. We propose that active transport of beta-actin mRNA to regions of cell motility is one possible objective of these signal transduction pathways.
Recruiting new neurons from the subventricular zone to the rat postnatal cortex: an organotypic slice culture model

The neurogenic subventricular zone (SVZ) of the lateral ventricle is a potential source for neuronal replacement in the postnatal or adult neocortex after injury. Here we present a novel model system to directly explore the cellular mechanisms of this process. In order to visualize directed migration from the SVZ towards the cortex, we transplanted green fluorescent protein‐labeled progenitor/stem cells into the SVZ of newborn rats. At 2 days after transplantation, we generated organotypic slice cultures and applied fluorescent time‐lapse imaging to explore directly the migration and integration of donor cells into the host tissue for up to 2 weeks. Our studies revealed that subventricular grafts provide a significant number of immature neurons to neocortical regions. In the cortex, immature neurons first migrate radially towards the pial surface and then differentiate into GABAergic interneurons. We conclude that our model system presents a novel and effective experimental paradigm to evaluate the recruitment of SVZ‐derived neurons into the postnatal cortex, a phenomenon that may represent a potential route for cortical repair.
Marriage Institutions and Sibling Competition: Evidence from South Asia*

Using data from South Asia, this article examines how arranged marriage cultivates rivalry among sisters. During marriage search, parents with multiple daughters reduce the reservation quality for an older daughter’s groom, rushing her marriage to allow sufficient time to marry off her younger sisters. Relative to younger brothers, younger sisters increase a girl’s marriage risk; relative to younger singleton sisters, younger twin sisters have the same effect. These effects intensify in marriage markets with lower sex ratios or greater parental involvement in marriage arrangements. In contrast, older sisters delay a girl’s marriage. Because girls leave school when they marry and face limited earning opportunities when they reach adulthood, the number of sisters has well-being consequences over the life cycle. Younger sisters cause earlier school-leaving, lower literacy, a match to a husband with less education and a less skilled occupation, and (marginally) lower adult economic status. Data from a broader set of countries indicate that these cross-sister pressures on marriage age are common throughout the developing world, although the schooling costs vary by setting. JEL Codes: J1, I25, O15.
Determinants of Commercial Bank Interest Margins and Profitability: Some International Evidence

Using bank-level data for 80 countries in the year's 1988-95, this article shows that differences in interest margins and bank profitability reflect a variety of determinants: bank characteristics, macroeconomic conditions, explicit and implicit bank taxation, deposit insurance regulation, overall financial structure, and underlying legal and institutional indicators. A larger ratio of bank assets to gross domestic product and a lower market concentration ratio lead to lower margins and profits, controlling for differences in bank activity, leverage, and the macroeconomic environment. Foreign banks have higher margins and profits than domestic banks in developing countries, while the opposite holds in industrial countries. Also, there is evidence that the corporate tax burden is fully passed onto bank customers, while higher reserve requirements are not, especially in developing countries.
Benefits of long-term beta-blockade in experimental chronic aortic regurgitation.

The objective of this study was to assess the long-term effects of beta-blockade on survival and left ventricular (LV) remodeling in rats with aortic valve regurgitation (AR). The pharmacological management of chronic AR remains controversial. No drug has been definitively proven to delay the need for valve replacement or to affect morbidity and/or mortality. Our group has reported that the adrenergic system is activated in an animal model of AR and that adrenergic blockade may help maintain normal LV function. The effects of prolonged treatment with a beta-blocker are unknown. Forty Wistar rats with severe AR were divided into 2 groups of 20 animals each and treated with metoprolol (Met, 25 mg.kg(-1). day(-1)) or left untreated for 1 yr. LV remodeling was evaluated by echocardiography. Survival was assessed by Kaplan-Meir curves. Hearts were harvested for tissue analysis. All Met-treated animals were alive after 6 mo vs. 70% of untreated animals. After 1 yr, 60% of Met-treated animals were alive vs. 35% of untreated animals (P = 0.028). All deaths, except one, were sudden. There were no differences in LV ejection fraction (all >50%) or LV dimensions. LV mass tended to be lower in the Met-treated group. There was less subendocardial fibrosis in this group, as well as lower LV filling pressures (LV end-diastolic pressure). beta-Adrenergic receptor ratio (beta(1)/beta(2)) was improved. One year of treatment with Met was well tolerated. Met improved 1-yr survival, minimized LV hypertrophy, improved LV filling pressures, decreased LV subendocardial fibrosis, and helped restore the beta-adrenergic receptor ratio.
Experimental research and finite element analysis of elastic and strength properties of fiberglass composite material

This work is devoted to the research of the strength and elastic properties of the laminated fiberglass composite. Experiments were performed on tension and compression of specimens with different orientation of the reinforcement in relation to the loading direction. The predictions of three different failure criteria (Hill criterion, Tsai-Wu criterion, Zakharov criterion) were compared to experimental results. The strength and elastic properties of the composite separate components have been also researched with the aim to perfom finite element simulation of composite failure process. The elastic moduli of the composite are determined by means of the method of the finite element homogenization.
Serotonin Promotes the Differentiation of Glutamate Neurons in Organotypic Slice Cultures of the Developing Cerebral Cortex

The monoamines serotonin (5-HT), noradrenaline (NA), and dopamine (DA), which are present in the developing brain apparently before they assume their neurotransmitter functions, are regarded as strong candidates for a role in the maturation of the cerebral cortex. Here we sought to investigate their effects on the generation and differentiation of cortical cell types. Slice cultures, prepared from the cortices of embryonic day (E) 14, E16, and E19 rat fetuses, were kept in defined medium or in defined medium plus 5-HT for 7 d. E16 cortices were also exposed to NA or DA for the same period. At the end of this period, the proportions of the neuronal [glutamate (Glu)-, GABA-, calbindin-, calretinin-labeled], glial (GFAP), and neuroepithelial (nestin) cell types were estimated for all conditions. We found that in E16 cultures, application of 5-HT, but not of NA or DA, significantly increased the proportion of Glu-containing neurons without affecting the overall neuronal population or the proportions of any other cell types. A similar effect was observed in co-cultures of E16 cortex with slices through the midbrain raphe nuclei of E19 rats. The total amount of cortical Glu, as measured with HPLC, was also increased in these co-cultures. To investigate whether the effect of 5-HT was the result of changes in cell proliferation, we exposed slices to bromodeoxyuridine (BrdU) and found that the proportion of BrdU-labeled cells was similar in the 5-HT-treated and control slices. These results indicate that 5-HT promotes the differentiation of cortical Glu-containing neurons without affecting neuroepithelial cell proliferation.
Recent Age-and Gender-Specific Trends in Mortality during Stroke Hospitalization in the United States

Background Advancements in diagnosis and treatment have resulted in better clinical outcomes after stroke; however, the influence of age and gender on recent trends in death during stroke hospitalization has not been specifically investigated. We assessed the impact of age and gender on nationwide patterns of in-hospital mortality after stroke. Methods Data were obtained from all US states that contributed to the Nationwide Inpatient Sample. All patients admitted to hospitals between 1997 and 1998 (n = 1 351 293) and 2005 and 2006 (n = 1 202 449), with a discharge diagnosis of stroke (identified by the International Classification of Diseases, Ninth Revision procedure codes), were included. Time trends for in-hospital mortality after stroke were evaluated by gender and age group based on 10-year age increments (<55, 55–64, 65–74, 75–84, >84) using multivariable logistic regression. Results Between 1997 and 2006, in-hospital mortality rates decreased across time in all sub-groups (all P < 0·01), except in men > 84 years. In unadjusted analysis, men aged > 84 years in 1997–1998 had poorer mortality outcomes than similarly aged women (odds ratio 0·93, 95% confidence interval = 0·88–0·98). This disparity worsened by 2005–2006 (odds ratio 0·88, 95% confidence interval = 0·84–0·93). After adjusting for confounders, compared with similarly aged women, the mortality outcomes among men aged >84 years were poorer in 1997–1998 (odds ratio 0·97, 95% confidence interval = 0·92–1·02) and were poorer in 2005–2006 (odds ratio 0·92, 95% confidence interval = 0·87–0·96), P = 0·04, for gender × time trend. Conclusions Over the last decade, in-hospital mortality rates after stroke in the United States have declined for every age/gender group, except men aged > 84 years. Given the rapidly ageing US population, avenues for boosting in-hospital survival among very elderly men with stroke need to be explored.
Agonist‐induced changes in cell membrane capacitance and conductance in dialysed pancreatic acinar cells of rats.

1. Single acinar cells enzymatically isolated from the rat pancreas were subjected to tight‐seal whole‐cell recordings. Changes in cell membrane capacitance and conductance were simultaneously recorded using a phase‐sensitive detection method. 2. Acetylcholine (ACh, 0.05‐0.5 microM) and cholecystokinin octapeptide (CCK‐8, 10‐50 pM) concomitantly induced transient increases in cell membrane current, capacitance and conductance only when cytosolic Ca2+ was weakly chelated by EGTA (70 microM). These responses were prolonged when the cells were dialysed with a solution containing GTP gamma S (a stable analogue of GTP, 50‐100 microM), whereas they were inhibited by dialysing with that containing GDP beta S (a stable analogue of GDP). These results suggest that a type of guanine‐nucleotide‐binding protein (G‐protein) could be involved in ACh‐ or CCK‐receptor signalling. 3. The ACh‐ or CCK‐induced responses (with or without GTP gamma S in the cytosol) were all abolished when a high dose of EGTA (1‐2 mM) was injected into the acinar cells. In addition, A23187, a calcium ionophore, induced sustained responses when the cytosolic Ca2+ was weakly buffered by 70 microM‐EGTA. These results suggest that the secretagogues regulate the changes in cell membrane capacitance and conductance via an increase and decrease of cytosolic Ca2+ concentration. 4. Oscillatory changes in cell membrane conductance and capacitance were consistently observed even without applying secretagogues when the cells were dialysed with a solution containing GTP gamma S (50‐100 microM) and cytosolic free Ca2+ ions weakly buffered at about 10(‐6) M with a low dose of EGTA and CaCl2. 5. The peak amplitude of changes in cell membrane capacitance induced by ACh or CCK‐8, with or without GTP gamma S in the cytosol, varied between 200 and 1000 fF, thereby suggesting that 20‐100 zymogen granules can fuse with the luminal cell membrane in response to these agonists in rat exocrine pancreatic acinar cells.
Growth Hormone Deficiency, Short Stature, and Juvenile Rheumatoid Arthritis in a Patient with Autoimmune Polyglandular Syndrome Type 1: Case Report and Brief Review of the Literature

Autoimmune polyglandular syndromes (APSs) include a cluster of autoimmune and nonautoimmune conditions which have been classified into subtypes. APSs type 1 is characterized by at least two of the following: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and autoimmune Addison's disease (AD). We report the chronological history of a female patient who presented with features most consistent with APS type 1, along with growth hormone deficiency and juvenile rheumatoid arthritis (JRA). In terms of her autoimmune diagnoses, she first presented with JRA at three years of age, then hypocalcemia and hypoparathyroidism at five years of age, type 1 diabetes (DM 1) at age eleven years, adrenal insufficiency at age fourteen years, recurrent mucocutaneous candidiasis as a teenager, growth hormone deficiency at age fourteen years leading to significant short stature, primary amenorrhoea, and hypogonadism, and finally alopecia at age twenty-six years. In addition to this, she has suffered other nonautoimmune medical problems including a Tetralogy of Fallot with a surgical repair at age six years. On review of the medical literature, we found no other previously reported case with this unique combination of medical problems.
Microstructure and Crack Propagation of Electrically Conductive SiC Based Composites

The work deals with the observation of microstructure and crack propagation from macro-indentation in a set of newly developed materials. Complex composites based on SiC matrix with 30, 40 and 50 wt. % of additives (Ti and NbC) were hot pressed at 1960 oC in air atmosphere under 30 MPa pressure for 1.5 hour. The microstructure and chemical composition were studied by SEM equipped with EDX analyzer. Hardness of the composites was evaluated by means of classic Vickers macro-indentation and fracture toughness was determined by the Anstis method. Indentation cracks were observed and their propagation was analyzed. The electrical conductivity as function of volume fraction of additives was determined.
A qualitative exploration of the major challenges facing pharmacovigilance in Saudi Arabia

Objectives: To explore the challenges facing pharmacovigilance in Saudi Arabia and formulate recommendations to improve it from the perspective of healthcare professionals in Saudi Arabia. Methods: This was a qualitative study of 4 focus group discussions with pharmacists, physicians, and academicians held under the auspices of the King Saud University School of Pharmacy and the Center for Medicine in the Public Interest, Riyadh, Saudi Arabia. A total of 29 eligible healthcare professionals were invited to participate in the discussion. The predefined themes of the study were the current practice and major challenges facing pharmacovigilance in regulatory bodies, hospitals, the community, and academia, as well as recommendations to improve pharmacovigilance practice. Result: Of the 29 participants invited, 27 attended the discussion. Challenges facing regulatory bodies included complicated adverse drug reactions (ADR) reporting forms, lack of feedback on ADRs submitted to the Saudi Food and Drug Authority, lack of decisions from the local authority to withdraw medications, and lack of data on pharmacovigilance. The challenges to pharmacovigilance in hospitals included the lack of knowledge of the significance of ADR reporting, workload, blaming culture, and lack of collaboration between regulatory bodies and hospitals. However, challenges facing pharmaceutical industries included the lack of drug manufacturers in Saudi Arabia and lack of interest in pharmacovigilance. Recommendations to improve pharmacovigilance included the need for communication, stronger regulatory requirements, the need for research, the need for unified ADRs reporting, and continuous education and training. Conclusion: The study has identified the challenges facing pharmacovigilance in Saudi Arabia and made certain recommendations to overcome them. These recommendations might be helpful for regulatory bodies to enhance spontaneous reporting and promote pharmacovigilance.
Glucose Ingestion Causes GLUT4 Translocation in Human Skeletal Muscle

In humans, ingestion of carbohydrates causes an increase in blood glucose concentration, pancreatic insulin release, and increased glucose disposal into skeletal muscle. The underlying molecular mechanism for the increase in glucose disposal in human skeletal muscle after carbohydrate ingestion is not known. We determined whether glucose ingestion increases glucose uptake in human skeletal muscle by increasing the number of glucose transporter proteins at the cell surface and/or by increasing the activity of the glucose transporter proteins in the plasma membrane. Under local anesthesia, ∼1 g of vastus lateralis muscle was obtained from six healthy subjects before and 60 min after ingestion of a 75-g glucose load. Plasma membranes were isolated from the skeletal muscle and used to measure GLUT4 and GLUT1 content and glucose transport in plasma membrane vesicles. Glucose ingestion increased the plasma membrane content of GLUT4 per gram muscle (3,524 ± 729 vs. 4,473 ± 952 arbitrary units for basal and 60 min, respectively; P < 0.005). Transporter-mediated glucose transport into plasma membrane vesicles was also significantly increased (130 ± 11 vs. 224 ± 38 pmol · mg−1 · s−1; P < 0.017), whereas the calculated ratio of glucose transport to GLUT4, an indication of transporter functional activity, was not significantly increased 60 min after glucose ingestion (2.3 ± 0.4 vs. 3.0 ± 0.5 pmol · GLUT4 arbitrary units−1 · s−1; P < 0.17). These results demonstrate that oral ingestion of glucose increases the rate of glucose transport across the plasma membrane and causes GLUT4 translocation in human skeletal muscle. These findings suggest that under physiological conditions the translocation of GLUT4 is an important mechanism for the stimulation of glucose uptake in human skeletal muscle.
Randomized Double-Blind Trial of Darbepoetin Alfa in Patients With Symptomatic Heart Failure and Anemia

Background— Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF. Methods and Results— Patients (N=319) with symptomatic HF, left ventricular ejection fraction ≤40%, and hemoglobin ≥9.0 g/dL and ≤12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0±1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 [−0.2, 1.0] g/dL; P<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0±1.0 g/dL during the study and experienced a hemoglobin increase of ≥1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa–treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; P=0.10). Occurrences of adverse events were similar in both treatment groups. Conclusions— In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical benefits. Darbepoetin alfa treatment was well tolerated and effectively raised hemoglobin. A trend of lower risk of morbidity and mortality was observed.