Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated PPI- and WGCNA-Retrieval of Hub Gene Signatures Shared Between Barrett's Esophagus and Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is a deadly cancer with high mortality rate, especially in economically advanced countries, while Barrett's esophagus (BE) is reported to be a precursor that strongly increases the risk of EAC. Due to the complexity of these diseases, their molecular mechanisms have not been revealed clearly. This study aims to explore the gene signatures shared between BE and EAC based on integrated network analysis. We obtained EAC- and BE-associated microarray datasets GSE26886, GSE1420, GSE37200, and GSE37203 from the Gene Expression Omnibus and ArrayExpress using systematic meta-analysis. These data were accompanied by clinical data and RNAseq data from The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to explore the relationship between gene sets and clinical traits as well as to discover the key relationships behind the co-expression modules. A differentially expressed gene-based protein–protein interaction (PPI) complex was used to extract hub genes through Cytoscape plugins. As a result, 403 DEGs were excavated, comprising 236 upregulated and 167 downregulated genes, which are involved in the cell cycle and replication pathways. Forty key genes were identified using modules of MCODE, CytoHubba, and CytoNCA with different algorithms. A dark-gray module with 207 genes was identified which having a high correlation with phenotype (gender) in the WGCNA. Furthermore, five shared hub gene signatures (SHGS), namely, pre-mRNA processing factor 4 (PRPF4), serine and arginine-rich splicing factor 1 (SRSF1), heterogeneous nuclear ribonucleoprotein M (HNRNPM), DExH-Box Helicase 9 (DHX9), and origin recognition complex subunit 2 (ORC2), were identified between BE and EAC. SHGS enrichment denotes that RNA metabolism and splicosomes play a key role in esophageal cancer development and progress. We conclude that the PPI complex and WGCNA co-expression network highlight the importance of phenotypic identifying hub gene signatures for BE and EAC.
Throughput/area optimised pipelined architecture for elliptic curve crypto processor

A pipelined architecture is proposed in this work to speed up the point multiplication in elliptic curve cryptography (ECC). This is achieved, at first; by pipelining the arithmetic unit to reduce the critical path delay. Second, by reducing the number of clock cycles (latency), which is achieved through careful scheduling of computations involved in point addition and point doubling. These two factors thus, help in reducing the time for one point multiplication computation. On the other hand, the small area overhead for this design gives a higher throughput/area ratio. Consequently, the proposed architecture is synthesised on different FPGAs to compare with the state-of-the-art. The synthesis results over GF(2 m ) show that the proposed design can work up to a frequency of 369, 357 and 337 MHz when implemented for m = 163, 233 and 283 bit key lengths, respectively, on Virtex-7 FPGA. The corresponding throughput/slice figures are 42.22, 12.37 and 9.45, which outperform existing implementations.
Larger organ size caused by obesity is a mechanism for higher cancer risk

Obesity increases significantly cancer risk in various organs. Although this has been recognized for decades, the mechanism through which this happens has never been explained. Here, we show that obese people (BMI ≥30) have on average 55% (95%CI: 46%-66%), 68% (95%CI: 59%-76%), and 39% (95%CI: 29%-49%) larger kidneys, liver, and pancreas, respectively. We also find a significant linear relationship between the increase in organ volume and the increase in cancer risk (P-value<10−12). These results provide a mechanism explaining why obese individuals have higher cancer risk in several organs: the larger the organ volume the more cells at risk of becoming cancerous. These findings are important for a better understanding of the effects that obesity has on cancer risk and, more generally, for the development of better preventive strategies to limit the mortality caused by obesity.
Usability of Partially Localised Websites in Switzerland: A Study with Screen Reader Users

A usability study involving ten multilingual visually impaired users was conducted on two university websites in German. Both websites were partially localised into French, English and, one of them, into Italian, but to different degrees: the first one had been reorganised, while the second one offered a mirror structure. The main goals were to observe the interaction of multilingual screen reader users with partially localised websites and to evaluate the impact of language selection by the user and the implementation of different localisation strategies on the overall usability of the test websites. The quantitative and qualitative data collected through the tests suggest that screen reader users generally prefer to browse in their native tongue and that they are used to find a way to change the language when needed. Users who browse the localised versions encounter more usability problems that are more often related to language than users who browse the original version. Finally, neither localisation degree proved satisfactory for screen reader users
Purified Vitexin Compound 1 Inhibits UVA-Induced Cellular Senescence in Human Dermal Fibroblasts by Binding Mitogen-Activated Protein Kinase 1

Purified vitexin compound 1 (VB1), a novel lignanoid isolated from the seeds of the Chinese herb Vitex negundo, has strong antioxidant abilities and broad antitumor activities. However, little is known about its anti-photoaging effect on the skin and the underlying mechanism. Here, we demonstrated that VB1 significantly attenuates ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs), as evidenced by senescence-associated β-gal staining, MTT assays, and western blot analysis of the expression of p16 and matrix metalloproteinase-1 (MMP-1). Furthermore, mass spectrometry revealed that VB1 could directly bind to Mitogen-Activated Protein Kinase 1 (MAPK1). Molecular docking and molecular dynamics simulation methods confirmed the mass spectroscopy results and predicted six possible binding amino acids of MAPK1 that most likely interacted with VB1. Subsequent immunoprecipitation analysis, including different MAPK1 mutants, revealed that VB1 directly interacted with the residues, glutamic acid 58 (E58) and arginine 65 (R65) of MAPK1, leading to the partial reversal of UVA-induced senescence in HEK293T cells. Finally, we demonstrated that the topical application of VB1 to the skin of mice significantly reduced photoaging phenotypes in vivo. Collectively, these data demonstrated that VB1 reduces UVA-induced senescence by targeting MAPK1 and alleviates skin photoaging in mice, suggesting that VB1 may be applicable for the prevention and treatment of skin photoaging.
Tryptophan residues in TDP-43 and SOD1 mediate the cross-seeding and toxicity of SOD1

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons. Neuronal superoxide dismutase-1 (SOD1) inclusion bodies are characteristic of familial ALS with SOD1 mutations, while a hallmark of sporadic ALS is inclusions containing aggregated wild-type TAR DNA-binding protein 43 (TDP-43). Co-expression of mutant or wild-type TDP-43 with SOD1 leads to misfolding of endogenous SOD1 and aggregation of SOD1 reporter protein G85R-GFP in HEK293FT cells, and promotes synergistic axonopathy in zebrafish. This pathological interaction is dependent upon natively solvent-exposed tryptophans in SOD1 (tryptophan-32) and TDP-43 RRM1 (tryptophan-172), in concert with natively sequestered TDP-43 N-terminal domain tryptophan-68. TDP-43 RRM1 intrabodies reduce wild-type SOD1 misfolding in HEK293FT cells, via blocking tryptophan-172. Tryptophan-68 becomes antibody-accessible in aggregated TDP-43 in sporadic ALS motor neurons and cell culture. 5-fluorouridine inhibits TDP-43-induced G85R-GFP SOD1 aggregation in HEK293FT cells, and ameliorates axonopathy in zebrafish, via its interaction with SOD1 tryptophan-32. Collectively, our results establish a novel and potentially druggable tryptophan-mediated mechanism whereby two principal ALS disease effector proteins might directly interact in disease.
Density-dependent private benefit leads to bacterial mutualism

Microorganisms produce materials leaked from the cell which are beneficial for themselves and their neighbors. We modeled the situation when cells can produce different costly secretions which increase the carrying capacity of the population. Strains that lose the function of producing one or more secretions avoid the cost of production and can exhaust the producers. However, secreting substances provides a private benefit for the producers in a density-dependent way. We developed a model to examine the outcome of the selection among different type of producer strains from the non-producer strain to the partial producers, to the full producer one. We were particularly interested in circumstances under which selection maintains partners that produce complementary secreted materials thus forming an interdependent mutualistic interaction. We show that interdependent mutualism is selected under broad range of conditions if private benefit decreases with density. Selection frequently causes the coexistence of more and less generalist cooperative strains, thus cooperation and exploitation co-occur. Interdependent mutual-ism is evolved under more specific circumstances if private benefit increases with density and these general observations are valid in a well-mixed and in a structured deme model. We show that the applied population structure supports cooperation in general, which, depending on the level of private benefit and intensity of mixing helps either the specialist or the generalist cooperators.
Nonlinear effects of intrinsic dynamics on temporal encoding in a model of avian auditory cortex

Neurons exhibit diverse intrinsic dynamics, which govern how they integrate synaptic inputs to produce spikes. Intrinsic dynamics are often plastic during development and learning, but the effects of these changes on stimulus encoding properties are not well known. To examine this relationship, we simulated auditory responses to zebra finch song using a linear-dynamical cascade model, which combines a linear spectrotemporal receptive field with a dynamical, conductance-based neuron model, then used generalized linear models to estimate encoding properties from the resulting spike trains. We focused on the effects of a low-threshold potassium current (KLT) that is present in a subset of cells in the zebra finch caudal mesopallium and is affected by early auditory experience. We found that KLT affects both spike adaptation and the temporal filtering properties of the receptive field. Interestingly, the direction of the effects depended on the temporal modulation tuning of the linear (input) stage of the cascade model, indicating a strongly nonlinear relationship. These results suggest that small changes in intrinsic dynamics in tandem with differences in synaptic connectivity can have dramatic effects on the tuning of auditory neurons.
Deep learning for automatic segmentation of the nuclear envelope in electron microscopy data, trained with volunteer segmentations

Advancements in volume electron microscopy mean it is now possible to generate thousands of serial images at nanometre resolution overnight, yet the gold standard approach for data analysis remains manual segmentation by an expert microscopist, resulting in a critical research bottleneck. Although some machine learning approaches exist in this domain, we remain far from realizing the aspiration of a highly accurate, yet generic, automated analysis approach, with a major obstacle being lack of sufficient high‐quality ground‐truth data. To address this, we developed a novel citizen science project, Etch a Cell, to enable volunteers to manually segment the nuclear envelope (NE) of HeLa cells imaged with serial blockface scanning electron microscopy. We present our approach for aggregating multiple volunteer annotations to generate a high‐quality consensus segmentation and demonstrate that data produced exclusively by volunteers can be used to train a highly accurate machine learning algorithm for automatic segmentation of the NE, which we share here, in addition to our archived benchmark data.
Adoptive Cell Transfer of Regulatory T Cells Exacerbates Hepatic Steatosis in High-Fat High-Fructose Diet-Fed Mice

Background and Aims: Non-alcoholic steatohepatitis (NASH) is a multisystem condition, involving the liver, adipose tissue, and immune system. Regulatory T (Treg) cells are a subset of T cells that exert an immune-controlling effect. Previously, a reduction of Treg cells in the visceral adipose tissue (VAT) was shown to be associated with a more severe degree of liver disease. We aimed to correct this immune disruption through adoptive cell transfer (ACT) of Treg cells. Methods: Male 8-week-old C57BL/6J mice were fed a high-fat high-fructose diet (HFHFD) for 20 weeks. Treg cells were isolated from the spleens of healthy 8 to 10-week-old C57BL/6J mice and were adoptively transferred to HFHFD-fed mice. PBS-injected mice served as controls. Plasma ALT and lipid levels were determined. Liver and adipose tissue were assessed histologically. Cytotoxic T (Tc), Treg, T helper (Th) 1 and Th17 cells were characterized in VAT, liver, subcutaneous adipose tissue (SAT), blood, and spleen via flow cytometry. Gene expression analysis was performed in SAT and VAT of mice fed either the HFHFD or a control diet for 10–32 weeks. Results: ACT increased Treg cells in SAT, but not in any of the other tissues. Moreover, the ACT induced a decrease in Th1 cells in SAT, liver, blood, and spleen. Higher plasma ALT levels and a higher degree of steatosis were observed in ACT mice, whereas the other HFHFD-induced metabolic and histologic disruptions were unaffected. Expression analysis of genes related to Treg-cell proliferation revealed a HFHFD-induced decrease in all investigated genes in the SAT, while in the VAT the expression of these genes was largely unaffected, except for a decrease in Pparg. Conclusion: ACT of Treg cells in HFHFD-fed mice exacerbated hepatic steatosis, which was possibly related to the increase of Treg cells in the SAT and/or the general decrease in Th1 cells. Moreover, the HFHFD-induced decrease in Pparg expression appeared critical in the decrease of Treg cells at the level of the VAT and the inability to replenish the amount of Treg cells by the ACT, while the mechanism of Treg cell accumulation at the level of the SAT remained unclear.
Hemopexin as an Inhibitor of Hemolysis-Induced Complement Activation

Hemopexin is the main plasmatic scavenger of cell-free heme, released in the context of intravascular hemolysis or major cell injury. Heme is indispensable for the oxygen transport by hemoglobin but when released outside of the erythrocytes it becomes a danger-associated molecular pattern, contributing to tissue injury. One of the mechanisms of pro-inflammatory action of heme is to activate the innate immune complement cascade. Therefore, we hypothesized that injection of hemopexin will prevent hemolysis-induced complement activation. Human plasma-derived hemopexin is compatible with the heme clearance machinery of the mice. 100 or 500 mg/kg of hemopexin was injected in C57Bl/6 mice before treatment with phenylhydrazine (inducer of erythrocytes lysis) or with PBS as a control. Blood was taken at different timepoints to determine the pharmacokinetic of injected hemopexin in presence and absence of hemolysis. Complement activation was determined in plasma, by the C3 cleavage (western blot) and in the kidneys (immunofluorescence). Kidney injury was evaluated by urea and creatinine in plasma and renal NGAL and HO-1 gene expression were measured. The pharmacokinetic properties of hemopexin (mass spectrometry) in the hemolytic mice were affected by the target-mediated drug disposition phenomenon due to the high affinity of binding of hemopexin to heme. Hemolysis induced complement overactivation and signs of mild renal dysfunction at 6 h, which were prevented by hemopexin, except for the NGAL upregulation. The heme-degrading capacity of the kidney, measured by the HO-1 expression, was not affected by the treatment. These results encourage further studies of hemopexin as a therapeutic agent in models of diseases with heme overload.
Residence Time Analysis of RNA Polymerase Transcription Dynamics: A Bayesian Sticky HMM Approach

The time spent by a single RNA polymerase (RNAP) at specific locations along the DNA, termed “residence time”, reports on the initiation, elongation and termination stages of transcription. At the single molecule level, this information can be obtained from dual ultra-stable optical trapping experiments, revealing a transcriptional elongation of RNAP interspersed with residence times of variable duration. Successfully discriminating between long and short residence times was used by previous approaches to learn about RNAP’s transcription elongation dynamics. Here, we propose an approach based on the Bayesian sticky hidden Markov models that treats all residence times, for an E. Coli RNAP, on an equal footing without a priori discriminating between long and short residence times. In addition, our method has two additional advantages, we provide: full distributions around key point statistics; and directly treat the sequence-dependence of RNAP’s elongation rate. By applying our approach to experimental data, we find: no emergent separation between long and short residence times warranted by the data; force dependent average residence time transcription elongation dynamics; limited effects of GreB on average backtracking durations and counts; and a slight drop in the average residence time as a function of applied force in RNaseA’s presence. STATEMENT OF SIGNIFICANCE Much of what we know about RNA Polymerase, and its associated transcription factors, relies on successfully discriminating between what are believed to be short and long residence times in the data. This is achieved by applying pause-detection algorithms to trace analysis. Here we propose a new method relying on Bayesian sticky hidden Markov models to interpret time traces provided by dual optical trapping experiments associated with transcription elongation of RNAP. Our method does not discriminate between short and long residence times from the offset in the analysis. It allows for DNA site-dependent transition probabilities of RNAP to neighboring sites (thereby accounting for chemical variability in site to site transitions) and does not demand any time trace pre-processing (such as denoising).
Erythrocyte CD55 facilitates the internalization of Plasmodium falciparum parasites

Invasion of human erythrocytes by the malaria parasite Plasmodium falciparum is a multi-step process. Previously, a forward genetic screen for P. falciparum host factors identified erythrocyte CD55 as essential for invasion, but its specific role and how it interfaces with the other factors that mediate this complex process are unknown. Using CRISPR-Cas9 editing, antibody-based inhibition, and live cell imaging, here we show that CD55 is specifically required for parasite internalization. Pre-invasion kinetics, erythrocyte deformability, and echinocytosis were not influenced by CD55, but entry was inhibited when CD55 was blocked or absent. Visualization of parasites attached to CD55-null erythrocytes point to a role for CD55 in progression of the moving junction. Our findings demonstrate that CD55 acts after discharge of the parasite’s rhoptry organelles, and plays a unique role relative to all other invasion receptors. As the requirement for CD55 is strain-transcendent, these results suggest that CD55 or its interacting partners may hold potential as therapeutic targets for malaria.
Multi-image Super Resolution of Remotely Sensed Images using Residual Feature Attention Deep Neural Networks

Convolutional Neural Networks (CNNs) consistently proved state-of-the-art results in image Super-resolution (SR), representing an exceptional opportunity for the remote sensing field to extract further information and knowledge from captured data. However, most of the works published in the literature focused on the Single-image Super-resolution problem so far. At present, satellite-based remote sensing platforms offer huge data availability with high temporal resolution and low spatial resolution. In this context, the presented research proposes a novel residual attention model (RAMS) that efficiently tackles the Multi-image Super-resolution task, simultaneously exploiting spatial and temporal correlations to combine multiple images. We introduce the mechanism of visual feature attention with 3D convolutions in order to obtain an aware data fusion and information extraction of the multiple low-resolution images, transcending limitations of the local region of convolutional operations. Moreover, having multiple inputs with the same scene, our representation learning network makes extensive use of nestled residual connections to let flow redundant low-frequency signals and focus the computation on more important high-frequency components. Extensive experimentation and evaluations against other available solutions, either for Single or Multi-image Super-resolution, demonstrated that the proposed deep learning-based solution can be considered state-of-the-art for Multi-image Super-resolution for remote sensing applications.
Widespread non-apoptotic activation of Drosophila Caspase-2/9 limits JNK signaling, macrophage proliferation, and growth of wound-like tumors

Resistance to apoptosis due to caspase deregulation is considered one of the main hallmarks of cancer. However, the discovery of novel non-apoptotic caspase functions has revealed unknown intricacies about the interplay between these enzymes and tumor progression. To investigate this biological problem, we capitalized on a Drosophila tumor model highly relevant for humans that relies on the concomitant upregulation of EGFR and the JAK/STAT signaling pathway. Our results indicate that widespread non-apoptotic activation of initiator caspases limits JNK signaling and facilitates cell fate commitment in these tumors, thus preventing the overgrowth and exacerbation of malignant features. Intriguingly, these caspase functions are strongly linked to the ability of these enzymes to control the recruitment and subsequent proliferation in situ of macrophage-like cells on the tumor. These findings assign novel tumor-suppressor activities to caspases independent of apoptosis, while providing highly relevant molecular details to understanding their diverse contribution during tumor progression.
Early-season Air Temperature Affects Phenolic Production in ‘Early Black’ Cranberry Fruit

Anecdotal information has linked cool air temperatures before harvest with increased phenolic production in cranberry; however, there is little information avail- able on the effect of temperature on phenolic production in cranberry fruit. The objective of this study was to determine the effect of air temperature throughout the growing season on the concentration of total anthocyanins, total flavonols, and total phenolics at harvest in fruit from seven 'Early Black' bogs in southeastern Massachusetts. Contrary to the anecdotal information available, correlations of temperature to fruit composition indicated that warmer temperatures early in the season (around bloom and fruit set) had the most positive impact on total anthocyanins and total flavonols. Total phenolic con- centration in the harvested fruit was impacted by air temperature in the preharvest period; however, that relationship was positive.