Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypic and genotypic characterization of antibiotic Resistant Gram Negative Bacteria isolated in Tabuk City, Saudi Arabia

Antimicrobial surveillance and identifying the genetic basis of antimicrobial resistance provide important information to optimize patient care. The present study was analytical cross sectional study aimed to determine the prevalence of MDR, XDR, PDR and extended-spectrum β-lactamases genes (SHV, CTX-M and TEM) among Gram-negative bacteria isolated in Tabuk, Saudi Arabia. A total number of 386 non-duplicate Gram-negative isolate were collected. Identification and susceptibility testing were done using automation system (BD Phoenix™). The extracted DNA were subjected to multiplex polymerase chain reaction (PCR). The results showed that only 15 (3.9%) of isolates were fully susceptible, the overall prevalence of XDR, MDR, PDR was 129 (33.4%), 113 (29.3%) and 48(12.4%) respectively. High resistant rate was observed against the antibiotic agents of cephalosporins class 79.3% followed by the agents of penicillins class 69.4%. The most dominant gene was bla SHV which detected in 106/386 (27.5%) isolates followed by bla CTX-M 90/386 (23.3%). Bla CTX-M showed significant relation with all used antibiotic except ampicillin/clavulanic acid, aztreonam, cefoxtin, and meropene. The isolates which showed most frequent resistant genes were Klebsiella pneumoniae 90/124 (72.6%), A. baumanni 37/67 (55.2%), and P.mirabilis 24/44 (54.5%). These findings underscores the need for optimization of current therapies and prevention of the spread of these organisms.
The yeast eIF2 kinase Gcn2 facilitates H2O2-mediated feedback inhibition of both protein synthesis and ER oxidative folding during recombinant protein production

Recombinant protein production is a known source of oxidative stress. Knowledge of which ROS are involved or the specific growth phase in which stress occurs however remains lacking. Using modern, hypersensitive genetic H2O2-specific probes, micro-cultivation and continuous measurements in batch culture, we observed H2O2 accumulation during and following the diauxic shift in engineered Saccharomyces cerevisiae, correlating with peak α-amylase production. In agreement with previous studies supporting a role of the translation initiation factor kinase Gcn2 in the response to H2O2, we find Gcn2-dependent phosphorylation of eIF2α to increase alongside translational attenuation in strains engineered to produce large amounts of α-amylase. Gcn2 removal significantly improved α-amylase production in two previously optimized high-producing strains, but not in the wild-type. Gcn2-deficiency furthermore reduced intracellular H2O2 levels and the unfolded protein response whilst expression of antioxidants and the ER disulfide isomerase PDI1 increased. These results suggest protein synthesis and ER oxidative folding to be coupled and subject to feedback inhibition by H2O2. Importance Reactive oxygen species (ROS) accumulate during recombinant protein production both in yeast and Chinese hamster ovary cells, two of the most popular organisms used in the multi-million dollar protein production industry. Here we document increased H2O2 in the cytosol of yeast cells producing α-amylase. Since H2O2 predominantly targets the protein synthesis machinery and activates the translation initiation factor kinase Gcn2, we removed Gcn2, resulting in increased recombinant α-amylase production in two different previously engineered high-producing protein production strains. Removal of this negative feed-back loop thus represents a complementary strategy for improving recombinant protein production efforts currently used in yeast. Gcn2-deficiency also increased the expression of antioxidant genes and the ER-foldase PDI1, suggesting that protein synthesis and ER oxidative folding are linked and feed-back regulated via H2O2. Identification of additional components in this complex regulation may further improve protein production and contribute to the development of novel protein-based therapeutic strategies.
Proximity-Labeling Reveals Novel Host and Parasite Proteins at the Toxoplasma Parasitophorous Vacuole Membrane

Toxoplasma is an intracellular pathogen which resides and replicates inside a membrane-bound vacuole in infected cells. This vacuole is modified by both parasite and host proteins which participate in a variety of host-parasite interactions at this interface, including nutrient exchange, effector transport, and immune modulation. ABSTRACT Toxoplasma gondii is a ubiquitous, intracellular parasite that envelops its parasitophorous vacuole with a protein-laden membrane (PVM). The PVM is critical for interactions with the infected host cell, such as nutrient transport and immune defense. Only a few parasite and host proteins have so far been identified on the host-cytosolic side of the Toxoplasma PVM. We report here the use of human foreskin fibroblasts expressing the proximity-labeling enzyme miniTurbo, fused to a domain that targets it to this face of the PVM, in combination with quantitative proteomics to specifically identify proteins present at this interface. Out of numerous human and parasite proteins with candidate PVM localization, we validate three parasite proteins (TGGT1_269950 [GRA61], TGGT1_215360 [GRA62], and TGGT1_217530 [GRA63]) and four new host proteins (PDCD6IP/ALIX, PDCD6, CC2D1A, and MOSPD2) as localized to the PVM in infected human cells through immunofluorescence microscopy. These results significantly expand our knowledge of proteins present at the Toxoplasma PVM and, given that three of the validated host proteins are components of the ESCRT (endosomal sorting complexes required for transport) machinery, they further suggest that novel biology is operating at this crucial host-pathogen interface. IMPORTANCE Toxoplasma is an intracellular pathogen which resides and replicates inside a membrane-bound vacuole in infected cells. This vacuole is modified by both parasite and host proteins which participate in a variety of host-parasite interactions at this interface, including nutrient exchange, effector transport, and immune modulation. Only a small number of parasite and host proteins present at the vacuolar membrane and exposed to the host cytosol have thus far been identified. Here, we report the identification of several novel parasite and host proteins present at the vacuolar membrane using enzyme-catalyzed proximity-labeling, significantly increasing our knowledge of the molecular players present and novel biology occurring at this crucial interface.
ARGONAUTE10 is required for cell fate specification and the control of formative cell divisions in the Arabidopsis root meristem

A key question in plant biology is how oriented cell divisions are integrated with patterning mechanisms to generate organs with adequate cell type allocation. In the root vasculature, a miRNA gradient controls the abundance of HD-ZIP III transcription factors, which in turn control cell fate and spatially restrict vascular cell proliferation to specific cells. Here, we show that a functional miRNA gradient requires an opposing gradient of ARGONAUTE10, which sequesters miRNAs to protect HD-ZIP III transcripts from degradation. In the absence of ARGONAUTE10, xylem precursor cells undergo periclinal divisions that lead to continuous strands of differentiated xylem elements at ectopic positions. Notably, periclinal daughter cells maintain xylem identity even when they are located outside of the xylem axis, resulting in disrupted tissue boundaries. We further demonstrate that ARGONAUTE10 and HD-ZIP IIIs buffer cytokinin signalling to control formative cell divisions, providing a framework for integration of phytohormone and miRNA-mediated patterning.
Insights into Mus musculus Population Structure across Eurasia Revealed by Whole-Genome Analysis

For more than 100 years, house mice (Mus musculus) have been used as a key animal model in biomedical research. House mice are genetically diverse, yet their genetic background at the global level has not been fully understood. Previous studies suggested that they originated in South Asia and diverged into three major subspecies almost simultaneously, approximately 350,000–500,000 years ago; however, they have spread across the world with the migration of modern humans in prehistoric and historic times (∼10,000 years ago to present), and undergone secondary contact, which have complicated the genetic landscape of wild house mice. In this study, we sequenced the whole genomes of 98 wild house mice collected from Eurasia, particularly East Asia, Southeast Asia, and South Asia. We found that although wild house mice consist of three major genetic groups corresponding to the three major subspecies, individuals representing admixture between subspecies are much more ubiquitous than previously recognized. Furthermore, several samples showed an incongruent pattern of genealogies between mitochondrial and autosomal genomes. Using samples likely retaining the original genetic components of subspecies with least admixture, we estimated the pattern and timing of divergence among the subspecies. Our results provide critical understanding of the genetic diversity of wild house mice at the global level, which may be particularly useful for future biomedical and evolutionary research.
Nutritional redundancy in the human diet and its application in phenotype association studies

Studying human dietary intake may help us identify effective measures to treat or prevent many chronic diseases whose natural histories are influenced by nutritional factors. Here, by examining five cohorts with dietary intake data collected on different time scales, we show that the food intake profile varies substantially across individuals and over time, while the nutritional intake profile appears fairly stable. We refer to this phenomenon as ‘nutritional redundancy’ and attribute it to the nested structure of the food-nutrient network. This network enables us to quantify the level of nutritional redundancy for each diet assessment of any individual. Interestingly, this nutritional redundancy measure does not strongly correlate with any classical healthy diet scores, but its performance in predicting healthy aging shows comparable strength. Moreover, after adjusting for age, we find that a high nutritional redundancy is associated with lower risks of cardiovascular disease and type 2 diabetes.
Frequent coexistence of closely related tree species on a small scale in temperate evergreen forests in Japan

Understanding how biotic interaction affects species composition and distribution is a major challenge in community ecology. In plants, negative reproductive interaction among closely related species (i.e., reproductive interference) is known to hamper the coexistence of congenic species. Since the magnitude of reproductive interference in plants depends on pollen flow distance, we hypothesized that the coexistence of congeners on a small spatial scale would be less likely to occur by chance but that such coexistence would be likely to occur on a scale larger than pollen flow distance. In the present study, we tested this hypothesis using spatially explicit woody plant survey data. Contrary to our prediction, congenic tree species often coexisted at the finest spatial scale and significant exclusive distribution was not detected. Our results suggest that cooccurrence of congenic tree species is not structured by reproductive interference, and they indicate the need for further research to explore the factors that mitigate the effects of reproductive interference.
Facilitation drives estrogen receptor positive (ER+) breast cancer growth and survival under drug pressure Authors:

Competition between different lineages of cells within a tumor has been considered in cancer evolution and progression, but positive interactions like facilitation have received far less study. We developed isogenic estrogen positive breast cancer cell lineages (CAMA-1 and MCF7) sensitive and resistant to CDK4/6 inhibition in order to investigate the mechanisms of cell interaction under selective pressure. When these sensitive and resistant lineages are grown in coculture under ribociclib treatment, sensitive cells survive and proliferate better than in monoculture despite the effects of competition. Conditioned media taken from resistant CAMA1 cells reproduces this advantage, suggesting that secretion of some factor from resistant cells underlies the effect. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were used to identify factors secreted by cell lineages. While the less active estrone metabolite was detected in medium from both lineages, highly active estradiol was only detectable in media that included resistant cells. Because sensitive cells are more dependent on estrogen signaling than resistant cells, they benefit from the increase in local estradiol, leading to facilitated growth when in coculture in the presence of ribociclib. This facilitation of sensitive cells by resistant cells is recapitulated when cells are treated with small molecule inhibitors that target estrogen signaling pathways. We developed a set of mathematical models to quantify the strength of competition and facilitation between cell lines and evaluate the effects of treatments that modify these interactions. These analyses support the conclusion that resistant cell lineages benefit sensitive lineages during therapy through the increased production and sharing of local estradiol, and themselves suffer from increased competition and suppression as a result. Our multidisciplinary approach analyzes and quantifies interactions between ER+ cancer lineages during treatment and provides the framework to evaluate these effects in patients and improve therapy.
Marker-free imaging of α-Synuclein aggregates in a rat model of Parkinson’s disease using Raman microspectroscopy

A hallmark of Parkinson’s disease (PD) is the formation of Lewy bodies in the brain. Lewy bodies are rich in the aggregated form of misfolded α-Synuclein (α-Syn). The brain from PD patients can only be analysed after post-mortem, limiting the diagnosis of PD to the manifestation of motor symptoms. In PD patients and animal models phosphorylated α-Syn was detected in the gut, thus, raising the hypothesizes that early-stage PD could be diagnosed based on colon tissues biopsies. Non-invasive marker-free technologies represent an ideal method to potentially detect aggregated α-Syn in vivo. Raman microspectroscopy has been established for the detection of molecular changes such as alterations of protein structures. Here, the olfactory bulb in the brain and the muscularis mucosae of colon tissue sections of a human BAC-SNCA transgenic (TG) rat model was analysed using Raman imaging and microspectroscopy. Raman images from TG and WT rats were investigated using spectral, principal component and true component analysis. Spectral components indicated protein aggregates (spheroidal oligomers) in TG rat brain and colon tissues even at a young age but not in WT. In summary, we have demonstrated that Raman imaging is capable to detect α-Syn aggregates in colon tissues of a PD rat model and making it a promising tool for future use in PD pathology.
Factors affecting bacterial community dynamics and volatile metabolite profiles of Thai traditional salt fermented fish

Bacterial diversity of the Thai traditional salt fermented fish with roasted rice bran (Pla-ra) was investigated using classical and molecular approaches. Bacterial population of Pla-ra ranged from 102–106 in solid-state (SSF) and 106–109 CFU/g in submerged (SMF) fermentation types. Halanaerobium spp. and Lentibacillus spp. were the main genera particularly detected when rRNA analysis was applied. Tetragenococcus halophillus were dominant during the final stage in sea salt-recipe samples while Bacillus spp. were found in those rock salt recipes. In contrast, cultural plating demonstrated that Bacillus spp. , generally B. amyloliquefaciens, were the dominant genera. In addition, B. pumilus, B. autrophaeus, B.subtilis and B. velezensis shown some relations with rock salt-recipe samples. The main volatile metabolites in all samples were butanoic acid and its derivatives. Key factors affected bacterial profiles and volatile compounds of salt fermented fish were type of salt, addition of roasted rice bran, and fermenting conditions.
The ability of Pseudomonas aeruginosa to adopt a Small Colony Variant (SCV) phenotype is conserved, and not restricted to clinical isolates

A subpopulation of Small Colony Variants (SCVs) is a frequently observed feature of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) lungs biofilms. SCVs have almost exclusively been reported from infected hosts, essentially CF individuals or, by extension, from laboratory cultivation of strains originated from infected hosts. We previously reported the identification of P. aeruginosa SCVs emerging from a non-clinical strain and displaying features shared with clinical SCVs. In the present work, we investigated the ability of 22 P. aeruginosa isolates from various environmental origins to, under laboratory culture conditions, spontaneously adopt a SCV-like smaller alternative morphotype distinguishable from the ancestral parent strain. Unexpectedly, we found that all the P. aeruginosa strains tested have the ability to adopt a SCV morphotype, regardless of their origin. Based on the phenotypes already described for SCVs, the SCV-like morphotypes obtained were clustered in two groups displaying various phenotypic profiles, including one characteristic of already described SCVs. We conclude that the ability to switch to a SCV phenotype is a conserved feature in Pseudomonas aeruginosa. IMPORTANCE P. aeruginosa is an opportunistic pathogen that thrives in many environments. It is significant public health concern, notably because it is the most prevalent pathogen found in the lungs of people with cystic fibrosis (CF). In infected hosts, its persistence is believed to be related to the emergence of an alternative small colony variant (SCV) phenotype. By reporting the distribution of P. aeruginosa SCVs in various non-clinical environments, this work contributes to understanding a conserved adaptation mechanism used by P. aeruginosa to rapidly adapt in all environments. Counteraction of this strategy could prevent P. aeruginosa persistent infection in the future.
Cortico-subcortical β burst dynamics underlying movement cancellation in humans

Dominant neuroanatomical models hold that humans regulate their movements via loop-like cortico-subcortical networks, including the subthalamic nucleus (STN), thalamus, and sensorimotor cortices (SMC). Inhibitory commands across these networks are purportedly sent via transient, burst-like signals in the β frequency (15-29Hz). However, since human depth-recording studies are typically limited to one recording site, direct evidence for this proposition is hitherto lacking. Here, we present simultaneous multi-site depth-recordings from SMC and either STN or thalamus in humans performing the stop-signal task. In line with their purported function as inhibitory signals, subcortical β-bursts were increased on successful stop-trials and were followed within 50ms by increased β-bursting over SMC. Moreover, between-site comparisons (including in a patient with simultaneous recordings from all three sites) confirmed that β-bursts in STN precede thalamic β-bursts. This provides first empirical evidence for the role of β-bursts in conveying inhibitory commands along long-proposed cortico-subcortical networks underlying movement regulation in humans.
Huntingtin CAG expansion impairs germ layer patterning in synthetic human 2D gastruloids through polarity defects

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG repeats in the Huntingtin gene (HTT). While HD has been shown to have a developmental component, how early during human embryogenesis the HTT-CAG expansion can cause embryonic defects remains unknown. Here, we demonstrate a specific and highly reproducible CAG length-dependent phenotypic signature in a synthetic model for human gastrulation derived from human embryonic stem cells (hESCs). Specifically, we observed a reduction in the extension of the ectodermal compartment that is associated with enhanced ACTIVIN signaling. Surprisingly, rather than a cell-autonomous effect, tracking the dynamics of TGFβ signaling demonstrated that HTT-CAG expansion perturbs the spatial restriction of ACTIVIN response. This is due to defects in the apicobasal polarization in the context of the polarized epithelium of the gastruloid, leading to ectopic subcellular localization of TGFβ receptors. This work refines the earliest developmental window for the prodromal phase of HD to the first two weeks of human development as modeled by our gastruloids.
The impacts of hydropower on freshwater macroinvertebrate richness: A global meta-analysis

Hydroelectric dams and their reservoirs have been suggested to affect freshwater biodiversity. However, studies investigating the consequences of hydroelectric dams and reservoirs on macroinvertebrate richness have reached opposite conclusions. We carried out a meta-analysis devised to elucidate the effects of hydropower dams and their reservoirs on macroinvertebrates richness while accounting for the potential role played by moderators such as biomes, impact types, study designs, sampling seasons and gears. We used a random and mixed effect model, combined with robust variance estimation, to conduct the meta-analysis on 72 pairs of observations (i.e., impacted versus reference) extracted from 17 studies (more than one observation per study). We observed a large range of effect sizes, from very negative to very positive impacts of hydropower. However, according to this meta-analysis, hydropower dams and their reservoirs did not have an overall clear, directional and statistically significant effect on macroinvertebrate richness. We tried to account for the large variability in effect sizes using moderators, but none of the moderators included in the meta-analysis had statistically significant effect. This suggests that some other moderators, which were unavailable for the 17 studies included in this meta-analysis, might be important (e.g., temperature, granulometry, wave disturbance and macrophytes) and that macroinvertebrate richness may be driven by local, smaller scale processes. As new studies become available, it would be interesting to keep enriching this meta-analysis, as well as collecting local habitat variables, to see if we could finally draw statistically significant conclusions about the impacts of hydropower on macroinvertebrate richness.
Effect of using a physical assistance device for movements involving trunk bending

Exoskeletons are a solution to physically relieve workers while allowing them to control the execution of their tasks and assist them (Baltrusch et al.2018). The study investigated in the search for elements able to quantify the action of a physical assistance device (PAD) on the human body for movements responsible for pathologies recognized as occupational diseases. The evaluation of a PAD allows to determine in which framework the exoskeleton can be useful for the realization of the movement. It is specified that a relevant way to insert exoskeletons in a company by always implementing a study or analysis beforehand to ensure its good integration. The objective of the study is to perform several tasks with and without the Posture Harness (HAPO) in order to analyze the kinematics of the movements and the electrical activity of erector muscles of the spine involved in carrying a load at work to understand its effects on the human body.