Miracle-dz/UniFAR-FTUs huggingface dataset:
A Microdomain Formed by the Extracellular Ends of the Transmembrane Domains Promotes Activation of the G Protein-Coupled α-Factor Receptor

ABSTRACT The α-factor receptor (Ste2p) that promotes mating in Saccharomyces cerevisiae is similar to other G protein-coupled receptors (GPCRs) in that it contains seven transmembrane domains. Previous studies suggested that the extracellular ends of the transmembrane domains are important for Ste2p function, so a systematic scanning mutagenesis was carried out in which 46 residues near the ends of transmembrane domains 1, 2, 3, 4, and 7 were replaced with cysteine. These mutants complement mutations constructed previously near the ends of transmembrane domains 5 and 6 to analyze all the extracellular ends. Eight new mutants created in this study were partially defective in signaling (V45C, N46C, T50C, A52C, L102C, N105C, L277C, and A281C). Treatment with 2-([biotinoyl] amino) ethyl methanethiosulfonate, a thiol-specific reagent that reacts with accessible cysteine residues but not membrane-embedded cysteines, identified a drop in the level of reactivity over a consecutive series of residues that was inferred to be the membrane boundary. An unusual prolonged zone of intermediate reactivity near the extracellular end of transmembrane domain 2 suggests that this region may adopt a special structure. Interestingly, residues implicated in ligand binding were mainly accessible, whereas residues involved in the subsequent step of promoting receptor activation were mainly inaccessible. These results define a receptor microdomain that provides an important framework for interpreting the mechanisms by which functionally important residues contribute to ligand binding and activation of Ste2p and other GPCRs.
Kidney diseases in HIV/HCV-co-infected patients

Background:Hepatitis C virus (HCV) co-infection occurs in 25% of HIV-infected persons. The impact of HIV/HCV coinfection on renal and patient outcomes is unclear. Methods:The main objective of the study is the comparison of outcomes (progression to advanced renal failure, initiation of dialysis, and death) in patients with HIV (n = 40), HCV (n = 30) or coinfection (n = 30) during the period between January 1999 and December 2007. Results:Patients were predominantly white men with a mean creatinine clearance of 50.6 ± 32.2 ml per min per 1.73 m2. Membranoproliferative glomerulonephritis (MPGN) and HIV-associated nephropathy were found in 34 and 9%, respectively. Seventeen patients needed transitory or definitive hemodialysis after 2, 2.5, and 12 months in HIV/HCV (n = 5), HIV (n = 6) and HCV (n = 6) infections, respectively. In multivariate analysis, variables found to independently predict outcome in HIV/HCV coinfected patients were younger age, a longer delay to kidney biopsy, cryoglobulinemia and MPGN. Twenty-one patients died, mostly in the HCV (n = 8) and/or HIV/HCV coinfected (n = 12) groups. The relative risk of death for HIV/HCV co-infected patients was 2.1 times more than for HCV-infected patients and 7.5 times more than for HIV-infected patients. HIV/HCV co-infection [odds ratio (OR), = 4; 95% confidence interval (CI), 1.3–12.9; P = 0.015] and MPGN (OR, 6; 95% CI, 2–18.8; P = 0.0018) were independently associated with death. Conclusion:Kidney disease is a relatively frequent complication in HIV or HCV monoinfected individuals. The impact of kidney disease on survival of HIV/HCV coinfected patients seems deleterious but remains largely unknown.
Cardiac‐Restricted Overexpression of the A2A‐Adenosine Receptor in FVB Mice Transiently Increases Contractile Performance and Rescues the Heart Failure Phenotype in Mice Overexpressing the A1‐Adenosine Receptor

In the heart, adenosine binds to pharmacologically distinct G‐protein‐coupled receptors (A1‐R, A2A‐R, and A3‐R). While the role of A1‐and A3‐Rs in the heart has been clarifed, the effect of genetically manipulating the A2A‐R has not been defned. Thus, we created mice overexpressing a cardiac‐restricted A2A‐R transgene. Mice with both low (Lo) and high (Hi) levels of A2A‐R overexpression demonstrated an increase in cardiac contractility at 12 weeks. These changes were associated with a signifcantly higher systolic but not diastolic [Ca2+]i, higher maximal contraction amplitudes, and a signifcantly enhanced sarcoplasmic reticulum Ca2+ uptake activity. At 20 weeks, the effects of A2A‐R overexpression on cardiac contractility diminished. The positive effects elicited by A2A‐R overexpression differ from the heart failure phenotype we observed with A1‐R overexpresson. Interestingly, coexpression of A2A‐R TGHi, but not A2A‐R TGLo, enhanced survival, prevented the development of left ventricular dysfunction and heart failure, and improved Ca2+ handling in mice overexpressing the A1‐R. These results suggest that adenosine‐mediated signaling in the heart requires a balance between A1‐ and A2A‐Rs—a fnding that may have important implications for the ongoing clinical evaluation of adenosine receptor subtype‐specifc agonists and antagonists for the treatment of cardiovascular diseases.
Estimation of the Determinants of Credit Demand by Farmers and Supply by Rural Banks in Ghana's Uppe

Credit is a strategic empowerment tool that has the potential to change the life of a person, family or community from a situation of abject poverty to a more dignified life. It can transform self-image, unlock potential and boost the productivity and well-being of the poor and vulnerable, especially farmers. This paper estimates the determinants of credit demand by farmers and supply by Rural Banks in the Upper East Region of Ghana. Semi-structured questionnaire complimented by key informant interviews and focus group discussions were used in gathering data from 250 farmers in 5 districts of Upper East Region. The logit model was used to estimate the determinants of credit demand by farmers and the Tobit model used to estimate the determinants of credit supply by Rural Banks. The findings showed that age of farmers, gender and political affiliations among others are the main determinants of credit demand by farmers. Type of crop grown, farm size and the amount of savings made are some determinants of credit supply by the Rural Banks. It is concluded that demand for credit by farmers and supply of it by Rural Banks in Ghana‟s Upper East Region are determined by socio-economic and politico-cultural factors. It is recommended that government; the Bank of Ghana and the Rural Banks themselves should develop strategies that aim at enhancing the positive determinants of credit demand and supply and mitigating the negative ones to ensure credit widening and deepening among farmers.
Leaf damage in a mangrove swamp at Sepetiba Bay, Rio de Janeiro, Brazil

Leaf damage to Rhizophora mangle L. , Avicennia schaueriana Stapf. & Leechman, and Laguncularia racemosa L. was studied in a two hectare mangrove swamp site in Sepetiba Bay. Seventeen arthropod morphospecies were identified as being responsible for the damage, and their species diversity was highest on A. schaueriana, followed by R. mangle and L. racemosa. Damage in terms of relative area was greatest in L. racemosa. Almost 9% of mangrove canopy leaf area demonstrated some damage. Loss of leaf area to herbivory was 12.1%, 8.3% and 6.2% in L. racemosa, A. schaueriana and R. mangle respectively. L. racemosa and A. schaueriana showed high percentages of leaf-margin damage in terms of the total damaged leaf area (82.2% and 56.3% respectively), while the most important type of damage in R. mangle was necrosis, representing 58.1% of the total damaged leaf area.
Dynamic Modeling and Simulation of JNK and P38 Kinase Cascades With Feedbacks and Crosstalks

All cells receive and respond to signals from their environment, whether they live freely or are part of a tissue. Feedback loops are one among the interactions in signal-transduction cascades, in which the information from the downstream components is sent back to the upstream components of the system. Crosstalks between signal-transduction cascades are able to combine the information's received and processed to trigger the appropriate response. To understand how signaling networks make decisions, the dynamic interactions of proteins in the signal-transduction cascades are important rather than just creating static maps of pathways. Based on reaction kinetics, we have developed mathematical models to predict and analyze the impacts of the feedback loops in JNK cascades and the crosstalks between JNK and P38 kinase cascades. Feedback loops in JNK cascades and crosstalks between JNK and P38 kinase cascades plays the complementary roles in making the impacts on the activation of JNK and P38 kinases. JNK and P38 kinase cascades with feedbacks and crosstalks is a robust system.
Selection of nonnucleoside reverse transcriptase inhibitor-associated mutations in HIV-1 subtype C: evidence of etravirine cross-resistance

Prevalence of etravirine genotypic resistance was assessed among 92 HIV-1C-infected patients failing nevirapine and efavirenz-based regimens from a cohort of 552 Indian patients. Overall, prevalence of etravirine cross-resistance identified using the Tibotec Weighted Score was 41% (31.5% intermediately-resistant and 9.8% fully-resistant). The most frequently described nonnucleoside reverse transcriptase inhibitor-associated mutations included Y181 (35.9%), K101 (20.7%), G190 (17.4%), and V108 (15.2%). The resistant group demonstrated higher viral load (P = 0.01) and longer duration of antiretroviral treatment (P = 0.03) compared with the susceptible group.
Cytological diagnosis of metastatic glioblastoma in the pleural effusion of a lung transplant patient

The extracranial metastasis of glioblastoma is a rare event. We report the case of a patient who developed metastatic glioblastoma in pleural effusion 15 months after lung transplant, with emphasis on differential diagnosis based on cytological material. In our case, tumor cells had pleomorphic nuclei, prominent nucleoli, and fine vesicular chromatin. Some were arranged in a poorly formed pseudo‐glandular architecture, mimicking a poorly differentiated adenocarcinoma. The cytological diagnosis of metastatic glioblastoma is difficult and depends critically on clinical history and suspicion, particularly in the transplant setting. Review of the literature indicates that transmission/metastasis of intracranial malignancy occurs rarely following organ transplantation, with some debate on the suitability for transplant of organs from affected donors. Although the situation is uncommon, this report of the cytological findings of extracranial glioblastoma may extend our current knowledge and provide additional differential diagnostic information for this entity. Diagn. Cytopathol. 2014;42:619–623. © 2013 Wiley Periodicals, Inc.
Dynamics of recurrent viral infection

In chronic viral infection, low levels of viral replication and infectious particle production are maintained over long periods, punctuated by brief bursts of high viral production and release. We apply well-established principles of modelling virus dynamics to the study of chronic viral infection, demonstrating that a model which incorporates the distinct contributions of cytotoxic T lymphocytes (CTLs) and antibodies exhibits long periods of quiescence followed by brief bursts of viral production. This suggests that for recurrent viral infections, no special mechanism or exogenous trigger is necessary to provoke an episode of reactivation; rather, the system may naturally cycle through recurrent episodes at intervals which can be many years long. We also find that exogenous factors which cause small fluctuations in the natural course of the infection can trigger a recurrent episode. Our model predicts that longer periods between recurrences are associated with more severe viral episodes. Four factors move the system towards less frequent, more severe episodes: decreased viral infectivity, decreased CTL efficacy, decreased memory T cell response and increased antibody efficacy.
Speckle Interferometry at SOAR in 2020

The results of speckle interferometric observations at the 4.1 m Southern Astrophysical Research Telescope in 2020, as well as earlier unpublished data, are given, totaling 1735 measurements of 1288 resolved pairs and nonresolutions of 1177 targets. We resolved for the first time 59 new pairs or subsystems in known binaries, mostly among nearby dwarf stars. This work continues our long-term speckle program. Its main goal is to monitor orbital motion of close binaries, including members of high-order hierarchies and Hipparcos pairs in the solar neighborhood. We also report observations of 892 members of young moving groups and associations, where we resolved 103 new pairs.
Temptations of the Flesh

TO READ ALINA REYES’S LE BOUCHER is to penetrate into a world of meat, following the incision of the knife described in the first sentences of the text: “ La lame s’enfonça en douceur dans le muscle, puis le parcourut en souplesse d ’un bout à l’autre. Le geste était parfaitement maîtrisé. La tranche tomba en fléchissant mollement sur le billot. ” 1 Le Boucher is a trenchant first novel, an erotic fable whose in­ itial hero will be raw meat itself, meat animated only by the stroke of the knife: “ La viande noire luisait, ravivée par l’attouchement du couteau” (9). Meat is primordial in the world that Reyes creates. It will generate and mediate all other considerations in the text, particularly the relation of the narrator, a young woman working as a cashier in a butcher shop, and the butcher to whom she is drawn. The erotic tension in the story arises in meat, and it is nourished thereby. Meat is the force that attracts the narrator and the butcher; it is the locus upon which they correspond. I should like to examine that correspondence, in order to offer a car­ nivorous reading of Le Boucher. Early on in the novel, the narrator explicitly inscribes her relation with the butcher within the framework of the game: “ Comme chaque fois que nous étions tous les deux seuls, le boucher et moi, le jeu revenait, notre jeu, notre invention précieuse pour anéantir le monde” (17). 2 Although most erotic texts are, I think, significantly playful,3 it is rare that the ludic contract be as overt as it is in this case. As the terms of that contract become clear, a recreational space appears, one where the game the narrator announces will be played out, progressively, upon three levels. The first of these is located firmly in the stuff that furnishes the materiality of both the butcher shop and the novel, meat. This game in­ volves the projection of desire upon dead flesh, and the consequent animation of the latter as the mediator of the living flesh of narrator and butcher. Thus, the meats in the shop window strike the narrator as living jewels. The skinned rabbits, slit open to reveal their livers, are images of a double nakedness; they are described as exhibitionists. The chicken’s rump is fantastic, compared by the narrator to a false nose on a clown’s
Competing dwarf males: sexual selection in an orb‐weaving spider

Hypotheses for the adaptive significance of extreme female‐biased sexual size dimorphism (SSD) generally assume that in dimorphic species males rarely interfere with each other. Here we provide the first multivariate examination of sexual selection because of male–male competition over access to females in a species with ‘dwarf’ males, the orb‐weaving spider Argiope aurantia. Male A. aurantia typically try to mate opportunistically during the female's final moult when she is defenceless. We show that, contrary to previous hypotheses, the local operational sex ratio (males per female on the web) is male‐biased most of the season. Both interference and scramble competition occur during opportunistic mating, the former leading to significant selection for large male body size. Male condition and leg length had no effect on mating success independent of size. We discuss these findings in the context of the evolution of extreme female‐biased SSD in this clade.
Baseline ICIQ‐UI score, body mass index, age, average birth weight, and perineometry duration as promising predictors of the short‐term efficacy of Er:YAG laser treatment in stress urinary incontinent women: A prospective cohort study

A growing body of evidence indicates that a non‐invasive erbium yttrium‐aluminum‐garnet (Er:YAG) laser may be an effective and highly tolerable treatment for stress urinary incontinence (SUI) in women. The primary objective was to identify pre‐intervention predictors of short‐term Er:YAG outcomes. The secondary objective was to identify patient segments with the best Er:YAG laser treatment short‐term outcomes.
Prevalence of Transsexualism in the Netherlands

On the basis of the records of subjects undergoing cross-gender hormonal treatment at the only gender treatment centre in the Netherlands, the prevalence of transsexualism was assessed over the years 1976–1986. In 1980, the prevalence was 1:45 000 for male-to-female and 1:200 000 for female-to-male transsexuals. In 1986 the prevalence for male-to-female transsexuals was 1:18 000, and for female-to-male transsexuals, 1:54 000. The increased prevalence is apparently due to a lower threshold for applying for medical treatment rather than to a true increase in the prevalence. Nevertheless, the calculated prevalence is higher than hitherto recorded. The ratio of male-to-female compared with female-to-male transsexuals was found to remain constant at 3:1.
Ionic currents through the membrane of the mammalian oocyte and their comparison with those in the tunicate and sea urchin.

1. The action potential and the membrane current of the mouse oocyte were analysed by current‐clamp and voltage‐clamp techniques and they were compared with those of other animal oocytes. 2. The matured and unfertilized oocyte of the mouse in standard medium with 6 mM‐K showed the resting potential of ‐23‐1+/‐2‐9 mV. The resting potential was relatively large in the medium with 20 mM‐Ca or 10 mM‐Mn, being ‐35‐7+/‐2‐6 mV and further increased to ‐46‐9+/‐4‐8 mV with replacement of Na in the medium by choline. 3. At the cessation of large hyperpolarization below ‐90 mV in standard medium, a regenerative potential was often elicited in the form of an off‐response. The off‐response depended upon the external concentration of Ca. In 20 mM‐Ca medium it was constantly observed with hyperpolarization below ‐60 mV. Its critical level was ‐40 mV and its overshoot was +15 mV. 4. The time and potential‐dependent inward current was observed both in standard and 20 mM‐Ca media under voltage‐clamp condition. In 20 mM‐Ca medium the inward current was observed by depolarization beyond ‐40 mV and showed its maximum at ‐15 mV. It was greatly reduced by replacing the external Ca with Mn but retained by substituting Sr or Ba for Ca. The selectivity ratios among these alkali earth cations were Ca:Sr:Ba=1‐0:1‐4:0‐7. 5. The current‐voltage relation in Ca and Na‐deficient and 10 mM‐Mn medium was linear from ‐200 to +25 mV. The hyperpolarization below ‐200 mV revealed an inward‐going rectification. The depolarization above +50 mV under voltage‐clamp condition induced the outward surge current with activation and inactivation processes. 6. In contrast to the mouse oocyte, the matured and unfertilized oocyte of the sea urchin showed a large resting potential of ‐70 mV in 30 Ca ASW and the depolarization beyond ‐40 mV elicited an action potential with an overshoot of 20 mV. The action potential showed a notch in the rising phase and lasted about 1 to 2 sec. 7. Under the voltage‐clamp condition both Ca inward current and the outward surge current were observed in the sea urchin oocyte membrane just as in the mouse oocyte membrane. 8. The selectivity ratios among alkali earth cations, Ca:Sr:Ba, for 'Ca channels' of the oocyte membranes were 1‐0:1‐4:0‐7 in the mouse, 1‐0:1‐7:1‐1 in the tunicate and 1‐0:0‐7:0‐5 in the sea urchin. When the current density through Ca channels are revised in terms of the respective critical levels for Ca channels, the revised selectivity sequences become Ca greater than Sr greater than Ba, being common to all three species.
Morphology and posthatching ontogeny of the autopodial skeleton of Bolitoglossa nicefori (Caudata: Plethodontidae)

Webbed foot morphology is a highly homoplastic character in species of Bolitoglossa and has been assumed to be pedomorphic. This study examines the morphology and posthatching ontogeny of the autopodial skeleton of Bolitoglossa nicefori and compares the descriptive and morphometric results with other species of the genus. We show that the autopodial morphology of B. nicefori coincides with the generalized pattern of the genus; webbed foot morphology is produced by pedomorphosis that affect the phalange length of the digits, resulting in a synchronized growth of digits (length and ossification rates) and the fleshy web. Although the webbed foot morphology of B. nicefori might be explained by the pervasive pedomorphic developmental trend observed in the genus, the large degree of variation encountered in the morphology of the distal phalanges indicates that the pedomorphic processes acting in this species are neither a simple truncation of the autopodial developmental program during early posthatching development nor a global process acting over the whole body plan. Instead, this morphological pattern is probably a result of the modular nature of limb development. J. Morphol. , 2010. © 2010 Wiley‐Liss, Inc.
Polymorphism of Amyloid Fibrils In Vivo.

Polymorphism is a wide-spread feature of amyloid-like fibrils formed in vitro, but it has so far remained unclear whether the fibrils formed within a patient are also affected by this phenomenon. In this study we show that the amyloid fibrils within a diseased individual can vary considerably in their three-dimensional architecture. We demonstrate this heterogeneity with amyloid fibrils deposited within different organs, formed from sequentially non-homologous polypeptide chains and affecting human or animals. Irrespective of amyloid type or source, we found in vivo fibrils to be polymorphic. These data imply that the chemical principles of fibril assembly that lead to such polymorphism are fundamentally conserved in vivo and in vitro.
Kv1.2 mediates heterosynaptic modulation of direct cortical synaptic inputs in CA3 pyramidal cells

We investigated the cellular mechanisms underlying mossy fibre‐induced heterosynaptic long‐term potentiation of perforant path (PP) inputs to CA3 pyramidal cells. Here we show that this heterosynaptic potentiation is mediated by downregulation of Kv1.2 channels. The downregulation of Kv1.2 preferentially enhanced PP‐evoked EPSPs which occur at distal apical dendrites. Such enhancement of PP‐EPSPs required activation of dendritic Na+ channels, and its threshold was lowered by downregulation of Kv1.2. Our results may provide new insights into the long‐standing question of how mossy fibre inputs constrain the CA3 network to sparsely represent direct cortical inputs.
Extracranial vertebral artery dissection after trauma: A 5‐year review

The early diagnosis of vertebral artery dissection remains a formidable task. Angiography is the gold standard for diagnosis but, recently, duplex scanning has been used as a non‐invasive screening study1,2. The overall prognosis of such dissection is good, but stenosis or thrombosis of the extracranial vertebral artery can result in brainstem or spinal cord infarction.