Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster

Abstract The regulatory architecture of gene expression is known to differ substantially between sexes in Drosophila, but most studies performed so far used whole-body data and only single crosses, which may have limited their scope to detect patterns that are robust across tissues and biological replicates. Here, we use allele-specific gene expression of parental and reciprocal hybrid crosses between 6 Drosophila melanogaster inbred lines to quantify cis- and trans-regulatory variation in heads and gonads of both sexes separately across 3 replicate crosses. Our results suggest that female and male heads, as well as ovaries, have a similar regulatory architecture. On the other hand, testes display more and substantially different cis-regulatory effects, suggesting that sex differences in the regulatory architecture that have been previously observed may largely derive from testis-specific effects. We also examine the difference in cis-regulatory variation of genes across different levels of sex bias in gonads and heads. Consistent with the idea that intersex correlations constrain expression and can lead to sexual antagonism, we find more cis variation in unbiased and moderately biased genes in heads. In ovaries, reduced cis variation is observed for male-biased genes, suggesting that cis variants acting on these genes in males do not lead to changes in ovary expression. Finally, we examine the dominance patterns of gene expression and find that sex- and tissue-specific patterns of inheritance as well as trans-regulatory variation are highly variable across biological crosses, although these were performed in highly controlled experimental conditions. This highlights the importance of using various genetic backgrounds to infer generalizable patterns.
Genistein ameliorated experimentally induced gastric ulcer in rats via inhibiting gastric tissues fibrosis by modulating Wnt/β-catenin/TGF-β/PKB pathway

ABSTRACT Objectives Gastric ulcer (GU) is a prevalent chronic digestive disease affecting about 10% of the world's population leading to gastrointestinal perforation and bleeding. Genistein is a legume flavonoid with antioxidants, anti-inflammatory and antibacterial activities. Therefore, we aimed to investigate the ability of genistein to reduce experimentally induced GU in rats by affecting gastric tissue fibrosis Wnt/β-catenin/TGF-β/SMAD4 pathway. Methods Thirty rats were used. Ten rats served as control, and GU was induced in twenty rats using a single dose of indomethacin (80 mg/kg) orally. Following induction of GU, ten were treated with genistein 25 mg/kg orally. The gastric tissues were isolated to investigate markers of gastric fibrosis, Wnt, β-catenin, transforming growth factor (TGF)-β, SMAD4, and Protein kinase B (PKB). In addition, gastric sections were stained with PAS and anti-TGF-β antibodies. Results Investigation GU micro-images revealed degeneration in both surface cells and glandular epithelial cells, which was improved by genistein. In addition, treatment with genistein significantly reduced the expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB. Conclusion Besides antioxidant activity, genistein improves experimentally induced GU in rats, at least in part, via reduction of gastric tissue fibrosis as indicated by reduction in expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB.
“In Vitro” Utilization of Labelled Esterified Fatty Acids and Glyceride Glycerol from Triglyceride-Rich Lipoproteins in Rat Adipose Tissue

Triglyceride-rich lipoproteins (chylomicrons and very low density lipoproteins) were labelled "in vivo" by injecting (U-14C)-glycerol and (9-10(n)-3H)-palmitate in female rats. After purification, these lipoproteins contained most of the 3H in esterified fatty acids and the 14C in glyceride glycerol of neutral lipids. This preparation was incubated "in vitro" in the presence of either isolated adipocytes or epididymal fat pad pieces from male rats. With the incubation, a certain proportion of both 3H-esterified fatty acids and 14C-glyceride glycerol disappeared from the medium, the effect being greater when the incubations were performed with adipocytes than with fat pad pieces. Much greater radioactivity appeared in the lipids of adipocytes than in those of fat pad pieces at the end of 60 or 120 min incubation, and the incorporation of 3H being relatively greater than that of 14C. With the latter isotope, the label appeared not only in the glyceride glycerol fraction but also in the free and esterified fatty acids. Although it is known that lipoproteins lipase activity is lower in adipocytes than in fat pad pieces, our results indicate that, in the former preparation, the enzyme may be more accessible for the substrate. These data also demonstrate that glycerol released by the hydrolysis of lipoprotein glycerides may be partially incorporated into lipids by adipose tissue.
Piezo1 Mediates Vasodilation Induced by Acute Hyperglycemia in Mouse Renal Arteries and Microvessels

BACKGROUND: Acute hyperglycemia is a risk factor for developing acute kidney injury and poor renal outcome in critically ill patients, whereby the role of renal vasculature remains unclear. We hypothesize that hyperglycemia-associated hyperosmolarity facilitates vasodilation through Piezo1-mediated eNOS (endothelial NO synthase) activation. METHODS: Vasoreactivity was analyzed using wire myography in isolated mouse mesenteric arteries and renal interlobar, and using microvascular perfusion in renal afferent arterioles and efferent arterioles, and vasa recta. Immunofluorescence and Western blot were used for molecular analyses of isolated mouse blood vessels and human umbilical vein endothelial cells. RESULTS: Pretreatment with hyperglycemia (44 mmol/L glucose; 4 hours) increased acetylcholine-induced relaxation in interlobar arteries and mesenteric arteries, which was prevented by eNOS inhibition using Nω-nitro-L-arginine methylester hydrochloride. Hyperosmotic mannitol solution had a similar effect. Hyperglycemia induced an immediate, Nω-nitro-L-arginine methylester hydrochloride–inhibitable dilation in afferent arterioles, efferent arterioles, and vasa recta, whereby stronger dilation in afferent arterioles compared to efferent arterioles. Hyperglycemia also increased glomerular filtration rate in mice. In human umbilical vein endothelial cells, hyperglycemia, and the Piezo1 activator Yoda-1 increased levels of Piezo1 protein, p-CaMKII (phosphorylated Ca2+/Calmodulin-dependent protein kinase type II), Akt (protein kinase B), and p-eNOS (phosphorylated eNOS). The hyperglycemia effect could be prevented by inhibiting Piezo1 using GsMTx4 (Grammostola spatulata mechanotoxin 4) and CaMKII using KN93 (N-[2-[[[3-(4-Chlorophenyl)-2-propenyl]-methylamino]-methyl]-phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphonamide). Furthermore, in arteries and microvessels, inhibition of Piezo1 using GsMTx4 prevented the hyperglycemia –effect, while Yoda-1 caused relaxation and dilation, respectively. CONCLUSIONS: Results reveal that Piezo1 mediates renal vasodilation induced by hyperosmolarity in acute hyperglycemia. This mechanism may contribute to the pathogenesis of renal damage by acute hyperglycemia.
Is functional electrical stimulation effective in improving walking in adults with lower limb impairment due to an upper motor neuron lesion? An umbrella review.

PURPOSE To conduct an umbrella review of systematic reviews on functional electrical stimulation (FES) to improve walking in adults with an upper motor neuron lesion. METHODS Five electronic databases were searched, focusing on the effect of FES on walking. The methodological quality of reviews was evaluated using AMSTAR2 and certainty of evidence was established through the GRADE approach. RESULTS The methodological quality of the 24 eligible reviews (stroke, n = 16; spinal cord injury (SCI), n = 5; multiple sclerosis (MS); n = 2; mixed population, n = 1) ranged from critically low to high. Stroke reviews concluded that FES improved walking speed through an orthotic (immediate) effect and had a therapeutic benefit (i.e., over time) compared to usual care (low certainty evidence). There was low-to-moderate certainty evidence that FES was no better or worse than an Ankle Foot Orthosis regarding walking speed post 6 months. MS reviews concluded that FES had an orthotic but no therapeutic effect on walking. SCI reviews concluded that FES with or without treadmill training improved speed but combined with an orthosis was no better than orthosis alone. FES may improve quality of life and reduce falls in MS and stroke populations. CONCLUSION FES has orthotic and therapeutic benefits. Certainty of evidence was low-to-moderate, mostly due to high risk of bias, low sample sizes, and wide variation in outcome measures. Future trials must be of higher quality, use agreed outcome measures, including measures other than walking speed, and examine the effects of FES for adults with cerebral palsy, traumatic and acquired brain injury, and Parkinson's disease.
How to choose an appropriate transfer function in designing a simplest ANN to solve specific problems

How to irmrporate certain constraints known a prion into the transfer function to redure thenumber of hidden units of an MFNN in solving some specific probems is disussed. The N-bit parity andsymmetrical problems are used as examples and the derivation of the transfer function based on the a privriknowledge of the input patterns is given. It is shown that by use of the method proposed, only onc hiddenunit is needed in solving the parity and symmetry test problems.
Regionalization of the antiviral response in the gastrointestinal tract to provide spatially controlled host/pathogen interactions

ABSTRACT As the largest mucosal surface, the gastrointestinal (GI) tract plays a key role in protecting the host against pathogen infections. It is a first line of defense against enteric viruses and must act to control infection while remaining tolerant to the high commensal bacteria load found within the GI tract. The GI tract can be divided into six main sections (stomach, duodenum, jejunum, ileum, colon, and rectum), and enteric pathogens have evolved to infect distinct parts of the GI tract. The intestinal epithelial cells (IECs) lining the GI tract are immune competent and can counteract these infections through their intrinsic immune response. Type I and type III interferons (IFNs) are antiviral cytokines that play a key role in protecting IECs against viruses with the type III IFN being the most important. Recent work has shown that IECs derived from the different sections of the GI tract display a unique expression of pattern recognition receptors used to fight pathogen infections. Additionally, it was also shown that these cells show a section-specific response to enteric viruses. This mini-review will discuss the molecular strategies used by IECs to detect and combat enteric viruses highlighting the differences existing along the entero-caudal axis of the GI tract. We will provide a perspective on how these spatially controlled mechanisms may influence virus tropism and discuss how the intestinal micro-environment may further shape the response of IECs to virus infections.
Torsion of bars with regular polygonal sections

In this article, the study of the torsion of cylindrical bars using large singular finite elements method leads to the resolution of the system of linear equations using MATLAB software. Particularly, the numerical solution of the problem of beams with regular section shows clearly the precision of the method depending upon the choice of different collocation points and gives in many cases, the exact solution with a relatively short computation time. The case of bars with regular polygonal section treated numerically, illustrates the precision of the method. If the number of sides is more than five, we always observe an exponential decrease in the total error with the number of coefficients preserved under field, this one reaching a minimal value for each polygon and starts increasing beyond this value. When the number of sides becomes larger, the solution tends towards the one of the circle that is known.
Native and compactly folded in-solution conformers of pepsin are revealed and distinguished by mass spectrometric ITEM-TWO analyses of gas-phase pepstatin A – pepsin complex binding strength differences

Pepsin, because of its optimal activity at low acidic pH, has gained importance in mass spectrometric proteome research as a readily available and easy-to-handle protease. Pepsin has also been study object of protein higher-order structure analyses, but questions about how to best investigate pepsin in-solution conformers still remain. We first determined dependencies of pepsin ion charge structures on solvent pH which indicated the in-solution existence of (a) natively folded pepsin (N) which by nanoESI-MS analysis gave rise to a narrow charge state distribution with an 11-fold protonated most intense ion signal, (b) unfolded pepsin (U) with a rather broad ion charge state distribution whose highest ion signal carried 25 protons, and (c) a compactly folded pepsin conformer (C) with a narrow charge structure and a 12-fold protonated ion signal in the center of its charge state envelope. Because pepsin is a protease, unfolded pepsin became its own substrate in solution at pH 6.6 since at this pH some portion of pepsin maintained a compact/native fold which displayed enzymatic activity. Subsequent mass spectrometric ITEM-TWO analyses of pepstatin A – pepsin complex dissociation reactions in the gas phase confirmed a very strong binding of pepstatin A by natively folded pepsin (N). ITEM-TWO further revealed the existence of two compactly folded in-solution pepsin conformers (Ca and Cb) which also were able to bind pepstatin A. Binding strengths of the respective compactly folded pepsin conformer-containing complexes could be determined and apparent gas phase complex dissociation constants and reaction enthalpies differentiated these from each other and from the pepstatin A – pepsin complex which had been formed from natively folded pepsin. Thus, ITEM-TWO turned out to be well suited to pinpoint in-solution pepsin conformers by interrogating quantitative traits of pepstatin A – pepsin complexes in the gas phase.
Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability

Objectives: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on antibody effector function and durability. Design: RV306 was a randomized, double-blind late boosting of the RV144 prime-boost regimen in HIV-uninfected Thai adults (NCT01931358). This analysis included study participants who received the RV144 vaccine regimen and received no additional boost (group 1) or were boosted with ALVAC-HIV and AIDSVAX (group 2) or only AIDSVAX alone (group 3) 24 weeks after completing the RV144 series. Methods: Plasma samples from RV306 study participants were used to measure antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent cellular cytotoxicity (ADCC), trogocystosis, and gp120-specifc IgG subclasses. Results: Additional boosting increased the magnitude of all Fc-mediated effector functions 2 weeks following the additional boost compared with 2 weeks after completing the RV144 regimen. However, only trogocytosis remained higher 24–26 weeks after the last vaccination for the study participants receiving an additional boost compared with those that did not receive an additional boost. The additional boost increased IgG1 and IgG4 but decreased IgG3 gp-120 specific antibodies compared with 2 weeks after completing the RV144 regimen. Conclusion: Additional boosting of RV144 improved the magnitude but not the durability of some Fc-mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable.
A feature and conjunction visual search immersive virtual reality serious game for measuring spatial and distractor inhibition attention using response time and action kinematics

ABSTRACT Background Treisman (1980) proposed that visual-spatial attention to targets presented with distractors involves parallel and serial cognition. When the target is different from distractors by a single feature, the number of distractors does not influence search speed (parallel). However, when the target is different from the distractor by a conjunction of features, increased numbers of distractors increase task difficulty (serial). Here, we developed a serious game in immersive virtual reality (IVR) for evaluating spatial and distractor inhibition attention. Methods We tested 60 healthy participants. They performed the serious game in which they had to find a target mole wearing a red miner’s helmet. In the single feature parallel conditions, the distractor moles wore blue (miner’s or horned) helmets, and in the conjunction feature serial conditions, the distractor moles wore blue miner’s helmets or red horned helmets. There were 11–17–23 distractors. Responses were made with the dominant hand by hitting the target with a virtual hammer. We measured mean response time (RT), mean velocity (MV) and coefficient of variance of speed (CV). Results Participants were significantly slower (RT and MV) and showed greater CV when responding to targets in conjunction compared to single feature search tasks. Further, participants were slower (RT and MV) and showed greater CV when the number of distractors increased. A significant interaction between search tasks and distractors showed that RT and CV only increased with distractor number for the conjunction search tasks. MV decreased with distractor number for both single and conjunction tasks, with a stronger decrease for conjunction relative to single feature search. Conclusion The results replicated previous findings, providing support for the use of immersive virtual reality technology for the simultaneous evaluation of spatial and distractor inhibition attention using complex 3D objects.
Feature-Weighted K-Nearest Neighbor Algorithm with SVM

As a nonparametric approach, K_Nearest Neighbor (K_NN) algorithm is very efficient and easily to be realized. The k_NN algorithm has been successfully used in classification, regression and pattern recognition. Two aspects, the weight of samples and the weight of features, must be paid attention to when applying K_NN to solve problems. SVM (support vector machine) to quantify the weight of features was used and FWKNN (feature_weighted K_nearest neighbor algorithm with SVM) was proposed. Experiments on artificial and natural datasets FWKNN was proposed showed that, in most cases, FWKNN improve the accuracy of classification.
Human Metapneumovirus Reinfection in Aged Mice Recapitulates Increased Disease Severity in Elderly Humans Infected with Human Metapneumovirus

Abstract Human metapneumovirus (HMPV) is a leading cause of respiratory infection in adults >65 y. Nearly all children worldwide are seropositive for HMPV by age 5 y, but reinfections occur throughout life, and there is no licensed vaccine. Recurrent HMPV infection is mild and self-resolving in immunocompetent individuals. However, elderly individuals develop severe respiratory disease on HMPV reinfection that leads to a high risk for morbidity and mortality. In this study, we developed a mouse model to mirror HMPV reinfection in elderly humans. C57BL/6J mice were infected with HMPV at 6–7 wk old, aged in-house, and rechallenged with high-dose virus at 70 wk. Aged rechallenged mice had profound weight loss similar to primary infected mice, increased lung histopathology, and accumulated cytotoxic CD8+CD44+CD62L−CD69+CD103+ memory cells despite having undetectable lung virus titer. When aged mice 14 mo postinfection (p.i.) or young mice 5 wk p.i. were restimulated with HMPV cognate Ag to mimic epitope vaccination, aged mice had an impaired CD8+ memory response. Convalescent serum transfer from young naive or 5 wk p.i. mice into aged mice on day of infection did not protect. Aged mice vaccinated with UV-inactivated HMPV also exhibited diminished protection and poor CD8+ memory response compared with young mice. These results suggest aged individuals with HMPV reinfection have a dysregulated CD8+ memory T cell response that fails to protect and exacerbates disease. Moreover, aged mice exhibited a poor memory response to either epitope peptide or UV-inactivated vaccination, suggesting that aged CD8+ T cell dysfunction presents a barrier to effective vaccination strategies.
Use-dependent facilitation of electrical transmission involves changes to postysnaptic K+ current.

Activity-dependent modulation of electrical transmission typically involves Ca2+ influx acting directly on gap junctions or initiating Ca2+-dependent pathways that in turn modulate coupling. We now describe short-term use-dependent facilitation of electrical transmission between bag cell neurons from the hermaphroditic snail, Aplysia californica, that is instead mediated by changes in postsynaptic responsiveness. Bag cell neurons secrete reproductive hormone during a synchronous afterdischarge of action potentials coordinated by electrical coupling. Here, recordings from pairs of coupled bag cell neurons in culture showed that non-junctional currents influence electrical transmission in a dynamic manner. Under dual whole-cell voltage-clamp, junctional current was linear and largely voltage-independent, while in current-clamp, the coupling coefficient was similar regardless of the extent of presynaptic hyperpolarization. Moreover, a train-stimulus of action potential-like waveforms, in a voltage-clamped presynaptic neuron, elicited electrotonic potentials, in a current-clamped postsynaptic neuron, that facilitated over time when delivered at a frequency approximating the afterdischarge. Junctional current remained constant over the train-stimulus, as did postsynaptic voltage-gated Ca2+ current. However, postsynaptic voltage-gated K+ current underwent cumulative inactivation, suggesting that K+ current run-down facilitates the electrotonic potential by boosting the response to successive junctional currents. Accordingly, preventing run-down by blocking postsynaptic K+ channels occluded facilitation. Finally, stimulation of bursts in coupled pairs resulted in synchronous firing, where active neurons could recruit silent partners through short-term use-dependent facilitation. Thus, potentiation of electrical transmission may promote synchrony in bag cell neurons and, by extension, reproductive function.