Miracle-dz/UniFAR-FTUs huggingface dataset:
C-Terminal Helical Domains of Dengue Virus Type 4 E Protein Affect the Expression/Stability of prM Protein and Conformation of prM and E Proteins

Background The envelope (E) protein of dengue virus (DENV) is the major immunogen for dengue vaccine development. At the C-terminus are two α-helices (EH1 and EH2) and two transmembrane domains (ET1 and ET2). After synthesis, E protein forms a heterodimer with the precursor membrane (prM) protein, which has been shown as a chaperone for E protein and could prevent premature fusion of E protein during maturation. Recent reports of enhancement of DENV infectivity by anti-prM monoclonal antibodies (mAbs) suggest the presence of prM protein in dengue vaccine is potentially harmful. A better understanding of prM-E interaction and its effect on recognition of E and prM proteins by different antibodies would provide important information for future design of safe and effective subunit dengue vaccines. Methodology/Principal Findings In this study, we examined a series of C-terminal truncation constructs of DENV4 prME, E and prM. In the absence of E protein, prM protein expressed poorly. In the presence of E protein, the expression of prM protein increased in a dose-dependent manner. Radioimmunoprecipitation, sucrose gradient sedimentation and pulse-chase experiments revealed ET1 and EH2 were involved in prM-E interaction and EH2 in maintaining the stability of prM protein. Dot blot assay revealed E protein affected the recognition of prM protein by an anti-prM mAb; truncation of EH2 or EH1 affected the recognition of E protein by several anti-E mAbs, which was further verified by capture ELISA. The E protein ectodomain alone can be recognized well by all anti-E mAbs tested. Conclusions/Significance A C-terminal domain (EH2) of DENV E protein can affect the expression and stability of its chaperone prM protein. These findings not only add to our understanding of the interaction between prM and E proteins, but also suggest the ectodomain of E protein alone could be a potential subunit immunogen without inducing anti-prM response.
Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition

Background The ubiquitous transcription factor Sp1 regulates the expression of a vast number of genes involved in many cellular functions ranging from differentiation to proliferation and apoptosis. Sp1 expression levels show a dramatic increase during transformation and this could play a critical role for tumour development or maintenance. Although Sp1 deregulation might be beneficial for tumour cells, its overexpression induces apoptosis of untransformed cells. Here we further characterised the functional and transcriptional responses of untransformed cells following Sp1 overexpression. Methodology and Principal Findings We made use of wild-type and DNA-binding-deficient Sp1 to demonstrate that the induction of apoptosis by Sp1 is dependent on its capacity to bind DNA. Genome-wide expression profiling identified genes involved in cancer, cell death and cell cycle as being enriched among differentially expressed genes following Sp1 overexpression. In silico search to determine the presence of Sp1 binding sites in the promoter region of modulated genes was conducted. Genes that contained Sp1 binding sites in their promoters were enriched among down-regulated genes. The endogenous sp1 gene is one of the most down-regulated suggesting a negative feedback loop induced by overexpressed Sp1. In contrast, genes containing Sp1 binding sites in their promoters were not enriched among up-regulated genes. These results suggest that the transcriptional response involves both direct Sp1-driven transcription and indirect mechanisms. Finally, we show that Sp1 overexpression led to a modified expression of G1/S transition regulatory genes such as the down-regulation of cyclin D2 and the up-regulation of cyclin G2 and cdkn2c/p18 expression. The biological significance of these modifications was confirmed by showing that the cells accumulated in the G1 phase of the cell cycle before the onset of apoptosis. Conclusion This study shows that the binding to DNA of overexpressed Sp1 induces an inhibition of cell cycle progression that precedes apoptosis and a transcriptional response targeting genes containing Sp1 binding sites in their promoter or not suggesting both direct Sp1-driven transcription and indirect mechanisms.
Feedforward Inhibition Underlies the Propagation of Cholinergically Induced Gamma Oscillations from Hippocampal CA3 to CA1

Gamma frequency (30–80 Hz) oscillations are implicated in memory processing. Such rhythmic activity can be generated intrinsically in the CA3 region of the hippocampus from where it can propagate to the CA1 area. To uncover the synaptic mechanisms underlying the intrahippocampal spread of gamma oscillations, we recorded local field potentials, as well as action potentials and synaptic currents in anatomically identified CA1 and CA3 neurons during carbachol-induced gamma oscillations in mouse hippocampal slices. The firing of the vast majority of CA1 neurons and all CA3 neurons was phase-coupled to the oscillations recorded in the stratum pyramidale of the CA1 region. The predominant synaptic input to CA1 interneurons was excitatory, and their discharge followed the firing of CA3 pyramidal cells at a latency indicative of monosynaptic connections. Correlation analysis of the input–output characteristics of the neurons and local pharmacological block of inhibition both agree with a model in which glutamatergic CA3 input controls the firing of CA1 interneurons, with local pyramidal cell activity having a minimal role. The firing of phase-coupled CA1 pyramidal cells was controlled principally by their inhibitory inputs, which dominated over excitation. Our results indicate that the synchronous firing of CA3 pyramidal cells rhythmically recruits CA1 interneurons and that this feedforward inhibition generates the oscillatory activity in CA1. These findings identify distinct synaptic mechanisms underlying the generation of gamma frequency oscillations in neighboring hippocampal subregions.
Presenting Distributive Laws

Distributive laws of a monad \(\mathcal{T}\) over a functor F are categorical tools for specifying algebra-coalgebra interaction. They proved to be important for solving systems of corecursive equations, for the specification of well-behaved structural operational semantics and, more recently, also for enhancements of the bisimulation proof method. If \(\mathcal{T}\) is a free monad, then such distributive laws correspond to simple natural transformations. However, when \(\mathcal{T}\) is not free it can be rather difficult to prove the defining axioms of a distributive law. In this paper we describe how to obtain a distributive law for a monad with an equational presentation from a distributive law for the underlying free monad. We apply this result to show the equivalence between two different representations of context-free languages.
Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90

Antibodies targeting receptor-mediated entry of HCV into hepatocytes confer limited therapeutic benefits. Evidence suggests that exosomes can transfer genetic materials between cells; however, their role in HCV infection remains obscure. Here, we show that exosomes isolated from sera of chronic HCV infected patients or supernatants of J6/JFH1-HCV-infected Huh7.5 cells contained HCV RNA. These exosomes could mediate viral receptor-independent transmission of HCV to hepatocytes. Negative sense HCV RNA, indicative of replication competent viral RNA, was present in exosomes of all HCV infected treatment non-responders and some treatment-naïve individuals. Remarkably, HCV RNA was associated with Ago2, HSP90 and miR-122 in exosomes isolated from HCV-infected individuals or HCV-infected Huh7.5 cell supernatants. Exosome-loading with a miR-122 inhibitor, or inhibition of HSP90, vacuolar H+-ATPases, and proton pumps, significantly suppressed exosome-mediated HCV transmission to naïve cells. Our findings provide mechanistic evidence for HCV transmission by blood-derived exosomes and highlight potential therapeutic strategies.
Use of 16S Ribosomal DNA for Delineation of Marine Bacterioplankton Species

ABSTRACT All of the marine bacterioplankton-derived 16S ribosomal DNA sequences previously deposited in GenBank were reanalyzed to determine the number of bacterial species in the oceanic surface waters. These sequences have been entered into the database since 1990. The rate of new additions reached a peak in 1999 and subsequently leveled off, suggesting that much of the marine microbial species richness has been sampled. When the GenBank sequences were dereplicated by using 97% similarity as a cutoff, 1,117 unique ribotypes were found. Of the unique sequences, 609 came from uncultured environmental clones and 508 came from cultured bacteria. We conclude that the apparent bacterioplankton species richness is relatively low.
Self-tuned congestion control for multiprocessor networks

One-track performance in tightly-coupled multiprocessors typically, degrades rapidly beyond network saturation. Consequently, designers must keep a network below its saturation point by reducing the load on the network. Congestion control via source throttling-a common technique to reduce the network load-presents new packets from entering the network in the presence of congestion. Unfortunately, prior schemes to implement source throttling either lack vital global information about the network to make the correct decision (whether to throttle or not) or depend on specific network parameters, network topology or communication pattern. This paper presents a global-knowledge-based, self-tuned, congestion control technique that prevents saturation at high loads across different network configurations and commutation pattern. Our design is composed of two key components. First, we use global information about a network to obtain a timely estimate of network congestion. We compare this estimate to a threshold value to determine when to throttle packet injection. The second component is a self-tuning mechanism that automatically determines appropriate threshold values based on throughput feedback. A combination of these two techniques provides high performance under heavy load does not penalize performance under light load, and gracefully adapts to changes in communication patterns.
Do the BGC-I and BGC-II domains of the Aravalli Craton, Northwestern India Represent Accreted Terranes?

Basement complex of the Aravalli craton (NW India) is commonly known as the Banded Gneissic Complex (BGC). It is classified into BGC-I and BGC-II based on the basement-supracrustal relationship and metamorphic grade of their lithologies. The duality of the basement complex, BGC, has been a subject of debate amongst the workers. Many workers postulate that both the domains of the BGC irrespective of its division are Archean. However, recently, workers have shown that the basement complex occurring to the north of Nathdwara (Rajasthan), i.e. the BGC-II is Proterzoic, whereas the BGC-I occurring to the south and east of Nathdwara is largely Archean. Present work attempts to reconcile various geological attributes of both the BGC-I and the BGC-II and their corresponding lithologies to compare, assess and ascertain whether or not the two domains of the BGC are same. In this endeavour, it is observed that the domains do not bear similar geological history of genesis and evolution. To account for the geological heterogeneity and geochronological age for the corresponding lithologies of both the BGC-I and the BGC-II, it is surmised that the two domains formed and evolved independently which were later accreted and amalgamated to form a single domain.
Onion (Allium Cepa) Production in Urban and Peri-Urban Areas: Financial Performance and Importance of this Activity for Market Gardeners in Southern Benin

Food safety has always been and continues to be a major concern for all countries of the world. This concern is all the more perennial in the developing countries like Benin with a low economic level and still rudimentary and extensive agriculture. To reduce a little bit of food insufficiency, is developed urban and peri-urban agriculture based mainly on market gardening. This study focused particularly on the production of onion in southern Benin. It aims to analyze its performance, to understand the importance of this activity but also to see what are the obstacles faced by these producers. Three municipalities were investigated: Grand-Popo, Cotonou and Seme-Kpodji. A total of 60 farmers were surveyed at 20 per municipality. Quantitative and qualitative tools were combined for the analysis of data collected through individual and group interviews. A joint analysis approach was used to achieve specific objectives. It consists to combine speech analysis, participant observation with statistical tools such as the frequency distribution, the regression model and calculation of performance indicators. It follows from all of these analyzes that onion production is profitable from a financial point of view. This performance is enhanced by factors such as age, experience and membership of a producer group. Similarly, the farmers claimed for majority that onion occupies a special place in their market garden production. This production improves their socio-economic and food situations. However, the constraints that undermine the more onion production and thus constitute important producer concerns are financial, institutional, organizational, property constraints and those directly related to production. Farmers therefore, expect a little more effort from agricultural policies to improve the development of this sector.
Alcohol consumption and mammographic density in a multiethnic population

This report examined the association between alcohol intake and breast cancer risk as assessed by mammographic densities in a multiethnic population. Information for this analysis was available from 2 previous investigations: a nutritional intervention study (The Breast, Estrogens, and Nutrition Study; BEAN) with 217 premenopausal women and a nested case‐control study within The Multiethnic Cohort (MEC) with 1,250 primarily postmenopausal women. On the basis of self‐reported alcohol intake from a validated food frequency questionnaire, women were categorized into abstainers (<1 drink/month), low (<1 drink/day) and high (≥1 drink/day) alcohol consumers. On average, 3 mammograms were available per woman. Using mixed models, we calculated mean percent densities for each alcohol consumption category while adjusting for covariates. Mean alcohol intakes for women in the BEAN study and for cases and controls in the MEC study were 2.0, 2.7 and 1.8 drinks/week, respectively. Overall, the difference in densities between abstainers and the highest alcohol intake category was only 1–2% and the differences were not statistically significant. However, the difference was 3–5% for women aged 55–65 years and for breast cancer cases. In postmenopausal women without hormone replacement therapy (HRT), breast density increased by 2% for each higher alcohol intake category. Breast densities were also elevated for high alcohol consumers on estrogen‐only therapy as compared to abstainers and low consumers, whereas combined HRT use was associated with higher mammographic densities independent of alcohol use. In conclusion, despite the low alcohol intake in our population, alcohol consumers had higher percent breast densities than did abstainers. The larger difference in some subgroups suggests that women with certain characteristics may be more susceptible to the influence of alcohol on breast density than others. © 2005 Wiley‐Liss, Inc.
Na-K pump current in the Amphiuma collecting tubule

There is strong evidence supporting the hypothesis of an electrogenic Na-K pump in the basolateral membrane of several epithelia. Thermodynamic considerations and results in nonepithelial cells indicate that the current carried by the pump could be voltage dependent. In order to measure the pump current and to determine its voltage dependence in a tight epithelium, we have used the isolated perfused collecting tubule of Amphiuma and developed a technique for clamping the basolateral membrane potential (Vbl) through transepithelial current injection. The transcellular current was calculated by subtracting the paracellular current (calculated from the transepithelial conductance measured in the presence of luminal amiloride) from the total transepithelial current. Basolateral membrane current-voltage (I-V) curves were obtained in conditions where the ratio of the pump current to the total basolateral membrane current had been maximized by loading the cells with Na+ (exposure to low-K+ bath), and by blocking the basolateral K+ conductance with barium. The pump current was defined as the difference of the current across the basolateral membrane measured before and 10-15 s after the addition of strophanthidin (20 microM) to the bath solution. With a bath solution containing 3 mM K+, the pump current was nearly constant in the Vbl range of -20 to -80 mV (52 +/- 5 microA.cm-2 at -60 mV) but showed a marked voltage dependence at higher negative Vbl (pump current decreased to 5 +/- 9 microA.cm-2 at -180 mV). In a 1.0 mM K bath, the shape of the pump I-V curve was similar but the amplitude of the current was decreased (24 +/- 4 microA.cm-2 at -60 mV). In a 0.1 mM K bath, the pump current was not significantly different from 0. Our results indicate that the basolateral Na-K pump generates a current which depends on the extracellular potassium concentration. With physiological peritubular concentration of K+ and in the physiological range of potential, the pump activity, measured as the pump-generated current, was independent of the membrane potential.
Influence of Superparameterization and a Higher‐Order Turbulence Closure on Rainfall Bias Over Amazonia in Community Atmosphere Model Version 5

We evaluate the Community Atmosphere Model Version 5 (CAM5) with a higher‐order turbulence closure scheme, named Cloud Layers Unified By Binomials (CLUBB), and a Multiscale Modeling Framework, referred to as the “superparameterization” (SP) with two different microphysics configurations to investigate their influences on rainfall simulations over southern Amazonia. The two different microphysics configurations in SP are the one‐moment cloud microphysics without aerosol treatment (SP1) and two‐moment cloud microphysics coupled with aerosol treatment (SP2). Results show that both SP2 and CLUBB effectively reduce the low biases of rainfall, mainly during the wet season, and reduce low biases of humidity in the lower troposphere with further reduced shallow clouds and increased surface solar flux. These changes increase moist static energy in the lower atmosphere and contribute to stronger convection and more rainfall. SP2 appears to realistically capture the observed increase of relative humidity prior to deep convection, and it significantly increases rainfall in the afternoon; CLUBB significantly delays the afternoon peak rainfall and produces more precipitation in the early morning, due to more gradual transition between shallow and deep convection. In CAM5 and CAM5 with CLUBB, occurrence of more deep convection appears to be a result of stronger heating rather than higher relative humidity.
Chronic asymptomatic inflammation of the prostate type IV and carcinoma of the prostate: Is there a correlation?

Abstract Objective. The aim of this study was to detect possible correlations between chronic asymptomatic inflammation of the prostate type IV and prostate cancer in patients undergoing radical prostatectomy (RPE). Material and methods. Between January and December 2010, 57 RPE specimens were prospectively evaluated with regard to histological signs of chronic inflammation. This RPE group was compared to specimens of 82 men undergoing transurethral resection of the prostate (TURP) or transvesical enucleation (TVE) of a benign prostate (BPH group). To characterize inflammatory changes, inflammatory “hot spots” were defined according to the histological criteria of Irani et al. (J Urol 1997;157:1301–3). Total prostate-specific antigen (PSA), cholesterol, triglycerides, uric acid, International Prostate Symptom Score and body mass index (BMI) were evaluated preoperatively and were correlated to the histological findings. Results. Chronic inflammation was verified in 43.86% of the RPE group, compared to 70.74% of the BPH group (p < 0.001). Multivariate analysis found a significant correlation between older patients and the inflammation score (p < 0.03) and prostate volume (p < 0.03). There was no difference in the PSA values between the inflammation and non-inflammation groups: mean PSA was 5.7 vs 6.1 ng/ml in the RPE group (p < 0.89), and 2.8 vs 2.9 ng/ml in the BPH group (p < 0.94). Gleason score distribution (5–9) and tumour stage (TNM) were similar in the inflammation and non-inflammation groups (p < 0.99, p < 0.21). Conclusions.No significant correlation between chronic prostatic inflammation and carcinoma of the prostate was detected. Contrary to expectations, a significantly higher score of inflammatory changes was found in BPH patients; also, total PSA levels were lower in the inflammation group.
Sorting within the regulated secretory pathway occurs in the trans- Golgi network

Bioactive peptides cleaved from the egg-laying hormone precursor in the bag cell neurons of Aplysia are sorted into distinct dense core vesicle classes (DCVs). Bag cell prohormone processing can be divided into two stages, an initial cleavage occurring in a late Golgi compartment, which is not blocked by monensin, and later cleavages that occur within DCVs and are blocked by monensin. Prohormone intermediates are sorted in the trans-Golgi network. The large soma-specific DCVs turn over, while the small DCVs are transported to processes for regulated release. Thus, protein trafficking differentially regulates the levels and localization of multiple biologically active peptides derived from a common prohormone.