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Mashup Score: 0Niche-aware metagenomic screening for enzyme methioninase illuminates its contribution to metabolic syntrophy - 7 hour(s) ago
The single step methioninase-mediated degradation of methionine (as a sulfur containing amino acid) is a reaction at the interface of carbon, nitrogen, sulfur, and methane metabolism in microbes. This enzyme is also a therapeutic target for its role in starving auxotrophic cancer cells. Applying our refined in-silico screening pipeline on 33,469 publicly available genome assemblies and 1878 MAGs/SAGs from brackish waters of the Caspian Sea and the Fennoscandian shield deep groundwater resulted in recovering 1845 methioninases. The majority of recovered methioninases belong to representatives of phyla Proteobacteria (50%), Firmicutes (29%), and Firmicutes_A (13%). Prevalence of methioninase among anaerobic microbes and in the anoxic deep groundwater together with the relevance of its products for energy conservation in anaerobic metabolism highlights such environments as desirable targets for screening novel methioninases and resolving its contribution to microbial metabolism and intera
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Mashup Score: 0Rationally Designed Pooled CRISPRi-seq Uncovers a Novel Inhibitor of Bacterial Peptidyl-tRNA Hydrolase - 7 hour(s) ago
Pooled knockdown libraries of essential genes are useful tools for elucidating the mechanisms of action of antibacterial compounds, a pivotal step in antibiotic discovery. However, achieving genomic coverage of antibacterial targets poses a challenge due to the uneven proliferation of knockdown mutants during pooled growth, leading to the unintended loss of important targets. To overcome this issue, we introduce CIMPLE (CRISPRi-mediated pooled library of essential genes), a rationally designed pooled knockdown library built in a model antibiotic-resistant bacteria, Burkholderia cenocepacia. By analysing growth parameters of clonal knockdown populations of an arrayed CRISPRi library, we predicted strain depletion levels during pooled growth and adjusted mutant relative abundance, achieving genomic coverage of antibacterial targets during antibiotic exposure. We demonstrate the utility of CIMPLE for chemogenetic profiling of known antibacterials and a previously discovered bacterial grow
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Mashup Score: 0Imaging flow cytometry enables label-free cell sorting of morphological variants from unculturable bacterial populations. - 7 hour(s) ago
Bacterial populations often display remarkable morphological heterogeneity. Fluorescence activated cell sorting (FACS) is an important tool for understanding the biological significance of this morphological diversity, as it permits the separation and study of distinct morphological variants (morphotypes) from each other and their environmental milieu. In FACS, cells are first labeled with fluorescent markers such as antibodies or transgenic constructs, and then sorted based on their possession of such labels. However, since the development of fluorescent labels requires a priori knowledge of bacterial biology, it is often impossible to apply FACS to understudied and/or unculturable bacteria. This challenge has limited our capacity to investigate the role of bacterial size and shape in all but a small, largely culturable subset of bacterial taxa. Here, we present an innovative strategy that allows for label-free cell sorting of bacterial morphotypes, using an unculturable, pleiomorphic
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Mashup Score: 0Proteome profiling identifies a link between the mitochondrial pathways and host-microbial sensor ELMO1 following Salmonella infection. - 7 hour(s) ago
The host EnguLfment and cell MOtility protein 1 (ELMO1) is a cytosolic microbial sensor that facilitates bacterial sensing, internalization, clearance, and inflammatory responses. We have shown previously that ELMO1 binds bacterial effector proteins, including pathogenic effectors from Salmonella and controls host innate immune signaling. To understand the ELMO1-regulated host pathways, we have performed liquid chromatography Multinotch MS3-Tandem Mass Tag (TMT) multiplexed proteomics to determine the global quantification of proteins regulated by ELMO1 in macrophages during Salmonella infection. Comparative proteome analysis of control and ELMO1-depleted murine J774 macrophages after Salmonella infection quantified more than 7000 proteins with a notable enrichment in mitochondrial-related proteins. Gene ontology enrichment analysis revealed 19 upregulated and 11 downregulated proteins exclusive to ELMO1-depleted cells during infection, belonging to mitochondrial functions, metabolism,
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Mashup Score: 1Higher multiplication rates of Plasmodium falciparum in isolates from hospital cases compared with community infections - 7 hour(s) ago
Background. Parasite multiplication rates vary among Plasmodium falciparum isolates from patients with malaria, suggesting differences in virulence potential, although direct comparisons between hospital-based clinical cases and community infections are needed. Methods. Cryopreserved blood samples from malaria cases presenting to a district hospital in The Gambia and infections detected in local communities were introduced to continuous culture under the same conditions. Thirty-four isolates (23 hospital-based and 11 community-based) were successfully established and then tested under exponential growth conditions over six days to derive estimated P. falciparum multiplication rates per cycle based on a 48-hour typical cycle length. Results. A range of parasite multiplication rates in culture was seen across isolates, from 1.5-fold to 5.0-fold per cycle. Multiplication rates were significantly higher in the hospital-based isolates than the community-based isolates. There was a significa
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Mashup Score: 2Uterus and cervix anatomical changes and cervix stiffness evolution throughout pregnancy - 9 hour(s) ago
The coordinated biomechanical performance, such as uterine stretch and cervical barrier function, within maternal reproductive tissues facilitates healthy human pregnancy and birth. Quantifying normal biomechanical function and detecting potentially detrimental biomechanical dysfunction (e.g., cervical insufficiency, uterine overdistention, premature rupture of membranes) is difficult, largely due to minimal data on the shape and size of maternal anatomy and material properties of tissue across gestation. This study quantitates key structural features of human pregnancy to fill this knowledge gap and facilitate three-dimensional modeling for biomechanical pregnancy simulations to deeply explore pregnancy and childbirth. These measurements include the longitudinal assessment of uterine and cervical dimensions, fetal weight, and cervical stiffness in 47 low-risk pregnancies at four time points during gestation (late first, middle second, late second, and middle third trimesters). The ute
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Mashup Score: 0
Since 1998, California sea lion (Zalophus californianus) stranding events associated with domoic acid toxicosis have consistently increased. Outside of direct measurement of DA in bodily fluids at the time of stranding, currently there are no practical non-lethal clinical tests for the diagnosis of domoic acid toxicosis (DAT) that can be utilized in a large-scale rehabilitation facility. Proteomic analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid from stranded California sea lions with acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005 protein families were identified experiment-wide (FDR < 0.01). Of these proteins, 83 were significantly different in abundance across the three groups (adj. p < 0.05). Cytoplasmic malate dehydrogenase (MDH1), 5'-3' exonuclease PLD3, disintegrin and metalloproteinase domain-containing protein 22 (ADAM22), 14-3-3 protein gamma (YWHAG), neurosecretory protein VGF, and calsyntenin-1 (
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Mashup Score: 0Dark exposure reduces high-frequency hearing loss in C57BL/6J mice - 10 hour(s) ago
Plastic changes in the brain are primarily limited to early postnatal periods. Recovery of adult brain plasticity is critical for the effective development of therapies. A brief (1-2 week) duration of visual deprivation (dark exposure, DE) in adult mice can trigger functional plasticity of thalamocortical and intracortical circuits in the primary auditory cortex suggesting improved sound processing. We tested if DE enhances the ability of adult mice to detect sounds. We trained and continuously evaluated the behavioral performance of mice in control and DE conditions using automated home-cage training. Consistent with age-related peripheral hearing loss present in C57BL/6J mice, we observed decreased performance for high-frequency sounds with age, which was reduced by DE. In CBA mice with preserved peripheral hearing, we also found that DE enhanced auditory performance in low and mid frequencies over time compared to the control. ### Competing Interest Statement The authors have declar
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Mashup Score: 0Two routes to value-based decisions in Parkinsons disease: differentiating incremental reinforcement learning from episodic memory - 12 hour(s) ago
Patients with Parkinsons disease are impaired at incremental reward-based learning. It is typically assumed that this impairment reflects a loss of striatal dopamine. However, many open questions remain about the nature of reward-based learning deficits in Parkinsons. Recent studies have found that a combination of different cognitive and computational strategies contribute even to simple reward-based learning tasks, suggesting a possible role for episodic memory. These findings raise critical questions about how incremental learning and episodic memory interact to support learning from past experience and what their relative contributions are to impaired decision-making in Parkinsons disease. Here we addressed these questions by asking patients with Parkinsons disease (n=26) both on and off their dopamine replacement medication and age- and education-matched healthy controls (n=26) to complete a task designed to isolate the contributions of incremental learning and episodic memory to
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Mashup Score: 1
Self-incompatibility in flowering plants is a common mechanism that prevents self-fertilization and promotes outcrossing. In Brassicaceae, there is high genetic diversity at the locus controlling self-incompatibility, and dozens of distinct alleles are organized in a complex dominance hierarchy: the gene controlling self-incompatibility specificity in pollen shows monoallelic expression in heterozygote individuals, and this is achieved through the action of sRNA precursors that resemble miRNAs, although the underlying molecular mechanisms remain elusive. Here, we engineered Arabidopsis thaliana lines expressing components of the Arabidopsis halleri self-incompatibility system, and we then used a reverse genetics approach to pinpoint the pathways underlying the function of these sRNA precursors. We showed that they trigger a robust decrease in transcript abundance of the recessive pollen self-incompatibility genes, but not through the canonical transcriptional or post-transcriptional ge
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Niche-aware metagenomic screening for enzyme methioninase illuminates its contribution to metabolic syntrophy https://t.co/B5oX9XNouR #bioRxiv