Miracle-dz/UniFAR-FTUs huggingface dataset:
Preneoplastic proliferative changes induced by experimental blastocystosis

Background: Studying the pathogenic potential of Blastocystis spp. by in vitro and in vivo experimental studies led to suspicions concerning its role in development of cancer colon. Still, this hypothesis remains under investigations. Objective: To investigate the pathology induced in the gut of mice inoculated with Blastocystis spp. isolates derived from patients with and without colorectal carcinoma (CRC). Subjects and Methods: Seven Blastocystis spp. isolates were derived from patients with CRC, six from non-CRC patients with symptomatic blastocystosis and six from non-CRC asymptomatic Blastocystis spp. carriers. Isolates were used to induce experimental blastocystosis in three groups of three-weeks-old BALB-c mice: GI was inoculated by CRC isolates; GII by symptomatic non-CRC isolates; and GIII by non-CRC asymptomatic isolates. Always, one clinical isolate was used to infect one mouse. Each group contained one negative control mouse inoculated with parasite-free culture medium, kept under the same conditions. Results: Histopathological examination of sections of intestine of all inoculated mice in the three groups showed positive infection with parasites seen only in the cecum and colon, no parasites were seen in the small intestine. Inflammatory cells infiltrations were detected in mice of the three groups with varying degrees. Vacuolar forms of Blastocystis spp. were seen infiltrating the submucosa in sections from mice in GI (4 mice) and GII (2 mice) but not in GIII. The significant difference in the pathologic changes induced in the intestine of mice in the three groups was observed being more severe with polypoid formation in mice in GI (4 mice) than in GII (1 mouse). Conclusion: Blastocystis spp. isolates associating CRC differ in their proliferative and invasive pathogenic capabilities than symptomatic isolates. Asymptomatic Blastocystis spp. are non-invasive organisms causing only mild inflammatory response in the large intestine of experimentally infected animals
DeepMAsED: Evaluating the quality of metagenomic assemblies

Motivation/background Methodological advances in metagenome assembly are rapidly increasing in the number of published metagenome assemblies. However, identifying misassemblies is challenging due to a lack of closely related reference genomes that can act as pseudo ground truth. Existing reference-free methods are no longer maintained, can make strong assumptions that may not hold across a diversity of research projects, and have not been validated on large scale metagenome assemblies. Results We present DeepMAsED, a deep learning approach for identifying misassembled contigs without the need for reference genomes. Moreover, we provide an in silico pipeline for generating large-scale, realistic metagenome assemblies for comprehensive model training and testing. DeepMAsED accuracy substantially exceeds the state-of-the-art when applied to large and complex metagenome assemblies. Our model estimates close to a 5% contig misassembly rate in two recent large-scale metagenome assembly publications. Conclusions DeepMAsED accurately identifies misassemblies in metagenome-assembled contigs from a broad diversity of bacteria and archaea without the need for reference genomes or strong modelling assumptions. Running DeepMAsED is straight-forward, as well as is model re-training with our dataset generation pipeline. Therefore, DeepMAsED is a flexible misassembly classifier that can be applied to a wide range of metagenome assembly projects. Availability DeepMAsED is available from GitHub at https://github.com/leylabmpi/DeepMAsED.
Structural basis for osmotic regulation of the DNA binding properties of H-NS proteins

H-NS proteins act as osmotic sensors translating changes in osmolarity into altered DNA binding properties, thus, regulating enterobacterial genome organization and genes transcription. The molecular mechanism underlying the switching process and its conservation among H-NS family members remains elusive. Here, we focus on the H-NS family protein MvaT from P. aeruginosa and demonstrate experimentally that its protomer exists in two different conformations, corresponding to two different functional states. In the half-opened state (dominant at low salt) the protein forms filaments along DNA, in the fully opened state (dominant at high salt) the protein bridges DNA. This switching is a direct effect of ionic strengths on electrostatic interactions between the appositively charged DNA binding and N-terminal domains of MvaT. The asymmetric charge distribution and intramolecular interactions are conserved among the H-NS family of proteins. Therefore, our study establishes a general paradigm for the molecular mechanistic basis of the osmosensitivity of H-NS proteins.
Homeostatic Recovery of Embryonic Spinal Activity Initiated by Compensatory Changes in Resting Membrane Potential

When baseline activity in a neuronal network is modified by external challenges, a set of mechanisms is prompted to homeostatically restore activity levels. These homeostatic mechanisms are thought to be profoundly important in the maturation of the network. We have previously shown that 2-day blockade of either excitatory GABAergic or glutamatergic transmission in the living embryo transiently blocks the movements generated by spontaneous network activity (SNA) in the spinal cord. However, by 2 hours of persistent receptor blockade embryonic movements begin to recover, and by 12 hours we observe a complete homeostatic recovery in vivo. Compensatory changes in voltage-gated conductances in motoneurons were observed by 12 hours of blockade, but not changes in synaptic strength. It was unclear whether changes in voltage-gated conductances were observed by 2 hours of blockade when the recovery actually begins. Further, compensatory changes in voltage-gated conductances were not observed following glutamatergic blockade where embryonic movements were blocked but then recovered in a similar manner to GABAergic blockade. In this study, we discover a mechanism for homeostatic recovery in these first hours of neurotransmitter receptor blockade. In the first 6 hours of GABAergic or glutamatergic blockade there was a clear depolarization of resting membrane potential in both motoneurons and interneurons. These changes reduced action potential threshold and were mainly observed in the continued presence of the antagonist. Therefore, it appears that fast changes in resting membrane potential represent a key fast homeostatic mechanism for the maintenance of network activity in the living embryonic nervous system. Significance Homeostatic plasticity represents a set of mechanisms that act to recover cellular or network activity following a challenge to that activity and is thought to be critical for the developmental construction of the nervous system. The chick embryo afforded us the opportunity to observe in a living developing system the timing of the homeostatic recovery of network activity following 2 distinct perturbations. Because of this advantage, we have identified a novel homeostatic mechanism that actually occurs as the network recovers and is therefore likely to contribute to nervous system homeostasis. We found that a depolarization of the resting membrane potential in the first hour of the perturbations enhances excitability and supports the recovery of embryonic spinal network activity.
The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed macrophages into potent bactericidal phagocytes. We found that 1,495 genes were differentially expressed in M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of genes involved in metabolism, lysosome biogenesis and activation. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including nitric oxide production, phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB (TFEB), involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections.
FedDCT: Federated Learning of Large Convolutional Neural Networks on Resource Constrained Devices using Divide and Co-Training

—In Federated Learning (FL), the size of local models matters. On the one hand, it is logical to use large-capacity neural networks in pursuit of high performance. On the other hand, deep convolutional neural networks (CNNs) are exceedingly parameter-hungry, which makes memory a signiﬁcant bottleneck when training large-scale CNNs on hardware-constrained devices such as smartphones or wearables sensors. Current state-of-the-art (SOTA) FL approaches either only test their convergence properties on tiny CNNs with inferior accuracy or assume clients have the adequate processing power to train large models, which remains a formidable obstacle in actual practice. To overcome these issues, we introduce FedDCT, a novel distributed learning paradigm that enables the usage of large, high performance CNNs on resource-limited edge devices. As opposed to traditional FL approaches, which require each client to train the full-size neural network independently during each training round, the proposed FedDCT allows a cluster of several clients to collaboratively train a large deep learning model by dividing it into an ensemble of several small sub-models and train them on multiple devices in parallel while maintaining privacy. In this co-training process, clients from the same cluster can also learn from each other, further improving their ensemble performance. In the aggregation stage, the server takes a weighted average of all the ensemble models trained by all the clusters. FedDCT reduces the memory requirements and allows low-end devices to participate in FL. We empirically conduct extensive experiments on standardized datasets, including CIFAR-10, CIFAR-100, and two real-world medical datasets HAM10000 and VAIPE. Experimental results show that FedDCT outperforms a set of current SOTA FL methods with interesting convergence behaviors. Furthermore, compared to other existing approaches, FedDCT achieves higher accuracy and substantially reduces the number of communication rounds (with 4 − 8 times fewer memory requirements) to achieve
Reconstructing Sparse Multiplex Networks with Application to Covert Networks

Network structure provides critical information for understanding the dynamic behavior of complex systems. However, the complete structure of real-world networks is often unavailable, thus it is crucially important to develop approaches to infer a more complete structure of networks. In this paper, we integrate the configuration model for generating random networks into an Expectation–Maximization–Aggregation (EMA) framework to reconstruct the complete structure of multiplex networks. We validate the proposed EMA framework against the Expectation–Maximization (EM) framework and random model on several real-world multiplex networks, including both covert and overt ones. It is found that the EMA framework generally achieves the best predictive accuracy compared to the EM framework and the random model. As the number of layers increases, the performance improvement of EMA over EM decreases. The inferred multiplex networks can be leveraged to inform the decision-making on monitoring covert networks as well as allocating limited resources for collecting additional information to improve reconstruction accuracy. For law enforcement agencies, the inferred complete network structure can be used to develop more effective strategies for covert network interdiction.
Health survey of two subspecies of bent-winged bats: southern bent-winged bat (Miniopterus orianae bassanii) and eastern bent-winged bat (Miniopterus orianae oceanensis)

Australian bent-winged bats are small, cave-roosting, insectivorous bats. There are two subspecies: the southern bent-winged bat (Miniopterus orianae bassanii) which occurs only in south-western Victoria and south-eastern South Australia, and the eastern bent-winged bat (M. orianae oceanensis) which is more common and widespread, being distributed along the east coast of Australia. In the last 50 years, the population of southern bent-winged bats has declined to the point where the subspecies was listed as critically endangered in 2007. The cause of the population decline is not clear. This project compared the health status of both bent-winged bat subspecies to investigate the role that disease may have on the southern bentwinged bat population decline. Morphometric data was gathered for the two subspecies. Southern bent-winged bats were heavier, but forearm length was not significantly different. This suggests that southern bentwinged bats may require more energy to fly and forage than eastern bent-winged bats. Oral swabs were tested by PCR for adenoviruses, coronaviruses, filoviruses, henipaviruses, herpesviruses and lyssaviruses. Six novel herpesviruses (five betaherpesviruses and one gammaherpesvirus) were identified, with the greatest infection prevalence occurring in Victorian southern bent-winged bats. No other viruses were detected. Both bat subspecies and their environment were sampled for Pseudogymnoascus destructans, the fungus that causes white nose syndrome, which has killed millions of bats in North America. All results were negative. Bats and their environment were sampled for
Antibiotics resistance patterns of Panton-Valentine leukocidin-positive methicillin-resistant staphylococci isolated from clinical samples in Abidjan, Cte dIvoire

Methicillin-resistant staphylococci have emerged as significant pathogens which cause various infections and its multidrug resistance is a major concern. This study aimed to determine the prevalence of Panton-Valentine leukocidin (PVL) gene and antibiotic resistance patterns of staphylococci isolated from clinical infections in Abidjan. A total of 35 staphylococci strains was obtained from 35 clinical samples (pus, blood, pleural fluid, sputum, wound, and urine), then, characterized by polymerase chain reaction (PCR) to differentiate S. aureus from coagulase-negative staphylococci (CNS) and to detect the presence of PVL genes (LukS). The antimicrobial susceptibility was performed using disk diffusion method and the phenotype of resistance to macrolides-lincosamides-streptogramin B (MLSB) was detected. Out of 35 strains, 80% (28/35) were methicillin-resistant Staphylococcus aureus (MRSA) and 20% (7/35) were methicillin-resistant CNS (MR-CNS). S. aureus were isolated from 75% of outpatient samples and 84.2% of inpatient samples. However, CNS were isolated from 25% of outpatient samples and 15.8% of inpatient samples. LukS were detected in 68.6% of strains (20 MRSA and 4 MR-CNS) and both inpatients and outpatients. The highest resistance rates were observed for penicillin (100%), cefoxitin (100%), ciprofloxacin (66%), tobramycin (66%), tetracyclin (66%), sulphamethoxazole-trimethoprim (63%), erythromycin (60%), kanamycin (57%) and gentamicin (54%). In addition, S. aureus strains were subdivided into five antibiotics resistance phenotypes: 57.1% belonged to phenotype 1 (Methicillin-resistant and susceptible to Kanamycin-Tobramycin-Gentamicin) followed by 25% of phenotype 4 (Resistant to Methicillin-Kanamycin-Tobramycin-Gentamicin), 7.1% of phenotype 2 (MR with constitutive MLSB), 7.1% of phenotype 5 (MR and resistant to Kanamycin-Tobramycin-Gentamicin with inducible MLSB) and 3.6% of phenotype 3 (MR with inducible MLSB). CNS strains were grouped in three phenotypes (1, 4 and 5). 100% of LukS positive MRSA were multi-drug resistant, with 45% of strains resistant to 6 or more antibiotics. The high level of multi-drug resistance of clinical PVL positive staphylococci with inducible MLSB, suggest increasing the monitoring of these pathogens in Cote d’Ivoire. Key words: Methicillin-resistant Staphylococcus aureus (MRSA), Panton-Valentine Leukocidin, inducible MLSB, multi-drug resistance.
Pharmacological or genetic targeting of Transient Receptor Potential (TRP) channels can disrupt the planarian escape response

In response to noxious stimuli, planarians cease their typical ciliary gliding and exhibit an oscillatory type of locomotion called scrunching. We have previously characterized the biomechanics of scrunching and shown that it is induced by specific stimuli, such as amputation, noxious heat, and extreme pH. Because these specific inducers are known to activate Transient Receptor Potential (TRP) channels in other systems, we hypothesized that TRP channels control scrunching. We found that chemicals known to activate TRPA1 (allyl isothiocyanate (AITC) and hydrogen peroxide) and TRPV (capsaicin and anandamide) in other systems induce scrunching in the planarian species Dugesia japonica and, except for anandamide, in Schmidtea mediterranea. To confirm that these responses were specific to either TRPA1 or TRPV, respectively, we tried to block scrunching using selective TRPA1 or TRPV antagonists and RNA interference (RNAi) mediated knockdown. Unexpectedly, co-treatment with a mammalian TRPA1 antagonist, HC-030031, enhanced AITC-induced scrunching by decreasing the latency time, suggesting an agonistic relationship in planarians. We further confirmed that TRPA1 in both species is necessary for AITC-induced scrunching using RNAi. Conversely, while co-treatment of a mammalian TRPV antagonist, SB-366791, also enhanced capsaicin-induced reactions in D. japonica, combined knockdown of two previously identified D. japonica TRPV genes (DjTRPVa and DjTRPVb) did not inhibit capsaicin-induced scrunching. Surprisingly, RNAi of either DjTRPAa or DjTRPVa/DjTRPVb disrupted scrunching induced by the endocannabinoid and TRPV agonist, anandamide. Overall, our results show that although scrunching induction can involve different initial pathways for sensing stimuli, this behavior’s signature dynamical features are independent of the inducer, implying that scrunching is a stereotypical planarian escape behavior in response to various noxious stimuli that converge on a single downstream pathway. Understanding which aspects of nociception are conserved or not across different organisms can provide insight into the underlying regulatory mechanisms to better understand pain sensation.
PeSA: A Software Tool for Peptide Specificity Analysis

The discovery of molecular interactions is crucial towards a better understanding of complex biological functions. Particularly protein-protein interactions (i.e., PPIs), which are responsible for a variety of cellular functions from epigenetic modifications to enzyme-substrate specificity, have been studied extensively over the past decades. Position-specific scoring matrices (PSSM) in particular are used extensively to help determine interaction specificity or candidate interaction motifs. However, not all studies successfully report their results as a candidate interaction motif. In many cases, this is the result of a lack of analysis tools for simple analysis and motif generation. Peptide Specificity Analyst (PeSA) is developed with the goal of filling this gap and providing an analysis software to aid peptide array analysis and subsequent motif generation. PeSA utilizes two models of motif creation: (1) frequency-based using a peptide list, and (2) weight-based using a quantified matrix. The ability to generate motifs effortlessly will make analyzing, interpreting and sharing peptide specificity study results in a simple and straightforward process. GRAPHICAL ABSTRACT HIGHLIGHTS Biological motifs are widely used representations for peptide specificity analysis. PeSA populates a list of peptides matching a set threshold from a quantified matrix. Frequency-based motif using a peptide list to spot residue patterns. Use of quantified matrices to create weight-based motifs using residue positions.
Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin

Background Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models. Method Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur. Results Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas. Conclusion The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.
A Microbial Fermentation Mixture Primes for Resistance Against Powdery Mildew in Wheat

Since many fungal pathogens develop resistance to fungicides, novel and low-cost alternative methods to improve plant health and fitness need to be developed. An approach to improve productivity in crops is to stimulate the plant’s own defence mechanisms via priming. Therefore, we investigated if a fermentation-based elicitor could prime plant defences against powdery mildew in wheat by inducing the expression of endogenous defence-related genes. Wheat seedlings were spray-treated with a fermentation-based elicitor 8 days prior to inoculation with powdery mildew. Disease assays showed a significantly reduced number of powdery mildew pustules were formed on wheat treated with the mixed elicitor. In vitro sensitivity assays tested the ability of powdery mildew conidia to germinate on agar amended with the fermentation-based product and concluded that fungal germination and differentiation were also inhibited. Tissue samples were taken at time points pertaining to different developmental stages of powdery mildew infection. Significantly higher expression of PR genes (PR1, PR4, PR5, and PR9) was observed in the microbial fermentation mixture-treated plants compared with untreated plants. These genes are often associated with the elicitation of plant defence responses to specific biotrophic pathogens, such as powdery mildew, suggesting an elicitor-mediated response in the wheat plants tested. The product components were assessed, and the components were found to act synergistically in the microbial fermentation mixture. Therefore, this fermentation-based elicitor provides an effective method for powdery mildew control.