The Search for Antidotes Against Ricin.

The castor plant (Ricinus communis) is primarily known for its seeds, which contain a unique fatty acid called ricinoleic acid with several industrial and commercial applications. Castor seeds also contain ricin, a toxin considered a chemical and biological warfare agent. Despite years of investigation, there is still no effective antidote or vaccine available.

Oncostatin M and STAT3 Signaling Pathways Support Human Trophoblast Differentiation by Inhibiting Inflammatory Stress in Response to IFNγ and GM-CSF.

Interleukin-6 (IL-6) superfamily cytokines play critical roles during human pregnancy by promoting trophoblast differentiation, invasion, and endocrine function, and maintaining embryo immunotolerance and protection. In contrast, the unbalanced activity of pro-inflammatory factors such as interferon gamma (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at the maternal-fetal interface have detrimental effects on trophoblast function and differentiation. This study demonstrates how the IL-6 cytokine family member oncostatin M (OSM) and STAT3 activation regulate trophoblast fusion and endocrine function in response to pro-inflammatory stress induced by IFNγ and GM-CSF.

The end of the reign of a "master regulator''? A defect in function of the LasR quorum sensing regulator is a common feature of isolates.

, a bacterium causing infections in immunocompromised individuals, regulates several of its virulence functions using three interlinked quorum sensing (QS) systems (, , and ). Despite its presumed importance in regulating virulence, dysfunction of the system regulator LasR occurs frequently in strains isolated from various environments, including clinical infections. This newfound abundance of LasR-defective strains calls into question existing hypotheses regarding their selection.

Three-Dimensional Cell Culture of Epididymal Basal Cells and Organoids: A Novel Tool for Toxicology.

Spermatozoa are formed in the testis but must transit through the epididymis to acquire motility and the ability to fertilize. The epididymis is a single convoluted tubule comprising several anatomically and physiologically distinct regions. The pseudostratified epithelium consists of multiple cell types, including principal cells, clear cells, narrow cells, and apical cells, that line the lumen of the epididymis.

Evidence for heterodimerization and functional interaction of the urotensin II and the angiotensin II type 1 receptors.

Despite the observation of synergistic interactions between the urotensinergic and angiotensinergic systems, the interplay between the urotensin II receptor (hUT) and the angiotensin II type 1 receptor (hAT1R) in regulating cellular signaling remains incompletely understood. Notably, the putative interaction between hUT and hAT1R could engender reciprocal allosteric modulation of their signaling signatures, defining a unique role for these complexes in cardiovascular physiology and pathophysiology. Using a combination of co-immunoprecipitation, bioluminescence resonance energy transfer (BRET) and FlAsH BRET-based conformational biosensors, we first demonstrated the physical interaction between hUT and hAT1R.

NMR spectroscopy can help accelerate antiviral drug discovery programs.

Small molecule drugs have an important role to play in combating viral infections, and biophysics support has been central for contributing to the discovery and design of direct acting antivirals. Perhaps one of the most successful biophysical tools for this purpose is NMR spectroscopy when utilized strategically and pragmatically within team workflows and timelines. This report describes some clear examples of how NMR applications contributed to the design of antivirals when combined with medicinal chemistry, biochemistry, X-ray crystallography and computational chemistry.

The host Rab9a/Rab32 axis is actively recruited to the Trypanosoma cruzi parasitophorous vacuole and benefits the infection cycle.

Trypanosoma cruzi, the etiological agent of Chagas disease is a protozoan parasite that infects phagocytic and non-phagocytic mammalian cells. At early stages of infection, trypomastigotes, the infective forms of this parasite, localize in a vesicular compartment called the T. cruzi parasitophorous vacuole until the exit of parasites to the host cell cytoplasm where continue their infective cycle.

Prevalent occupational exposures and risk of lung cancer among women: Results from the application of the Canadian Job-Exposure Matrix (CANJEM) to a combined set of ten case-control studies.

Background: Worldwide, lung cancer is the second leading cause of cancer death in women. The present study explored associations between occupational exposures that are prevalent among women, and lung cancer.

Methods: Data from 10 case-control studies of lung cancer from Europe, Canada, and New Zealand conducted between 1988 and 2008 were combined.

Multimodal vaccination targeting the receptor binding domains of toxins A and B with an attenuated Typhimurium vector (YS1646) protects mice from lethal challenge.

Developing a vaccine against is a key strategy to protect the elderly. Two candidate vaccines using a traditional approach of intramuscular (IM) delivery of recombinant antigens targeting toxins A (TcdA) and B (TcdB) failed to meet their primary endpoints in large phase 3 trials. To elicit a mucosal response against , we repurposed an attenuated strain of Typhimurium (YS1646) to deliver the receptor binding domains (rbd) of TcdA and TcdB to the gut-associated lymphoid tissues, to elicit a mucosal response against .

An imputed ancestral reference genome for the complex better captures structural genomic diversity for reference-based alignment workflows.

Reference-based alignment of short-reads is a widely used technique in genomic analysis of the complex (MTBC) and the choice of reference sequence impacts the interpretation of analyses. The most widely used reference genomes include the ATCC type strain (H37Rv) and the putative MTBC ancestral sequence of Comas both of which are based on a lineage 4 sequence. As such, these reference sequences do not capture all of the structural variation known to be present in the ancestor of the MTBC.

Biallelic BORCS8 variants cause an infantile-onset neurodegenerative disorder with altered lysosome dynamics.

BLOC-one-related complex (BORC) is a multiprotein complex composed of eight subunits named BORCS1-8. BORC associates with the cytosolic face of lysosomes, where it sequentially recruits the small GTPase ARL8 and kinesin-1 and -3 microtubule motors to promote anterograde transport of lysosomes toward the peripheral cytoplasm in non-neuronal cells and the distal axon in neurons. The physiological and pathological importance of BORC in humans, however, remains to be determined.

Identification of glycosylated nucleosides in small synthetic glyco-RNAs.

Recently, the post-transcriptional modification of RNA with N-glycans was reported, changing the paradigm that RNAs are not commonly N-glycosylated. Moreover, glycan modifications of RNA are investigated for therapeutic targeting purposes. But the glyco-RNA field is in its infancy with many challenges to overcome.

Thioarylation of 6-Amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic Acid (IminoKdo): Access to 3,6-Disubstituted Picolinates and Mechanistic Insights.

In this work, we present a metal-free coupling protocol for the regio- and stereoselective C3-thioarylation of 6-amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic acid (iminoKdo). The developed procedure enables the coupling of electron-rich, electron-deficient, and hindered arylthiols, providing a series of C3-modified iminoKdo derivatives in moderate to good yields. Elucidation of active species through controlled experimental studies and time-lapse P NMR analysis provides insights into the reaction mechanism.

Phylogenetic diversity of functional genes in deep-sea cold seeps: a novel perspective on metagenomics.

Background: Leakages of cold, methane-rich fluids from subsurface reservoirs to the sea floor are termed cold seeps. Recent exploration of the deep sea has shed new light on the microbial communities in cold seeps. However, conventional metagenomic methods largely rely on reference databases and neglect the phylogeny of functional genes.

Copper management strategies in obligate bacterial symbionts: balancing cost and benefit.

Bacteria employ diverse mechanisms to manage toxic copper in their environments, and these evolutionary strategies can be divided into two main categories: accumulation and rationalization of metabolic pathways. The strategies employed depend on the bacteria's lifestyle and environmental context, optimizing the metabolic cost-benefit ratio. Environmental and opportunistically pathogenic bacteria often possess an extensive range of copper regulation systems in order to respond to variations in copper concentrations and environmental conditions, investing in diversity and/or redundancy as a safeguard against uncertainty.

Structural characterization of a nonionic rhamnolipid from Burkholderia lata.

We present the isolation and structural characterization of a novel nonionic dirhamnolipid methyl ester produced by the bacterium Burkholderia lata. The structure and the absolute configuration of the isolated dirhamnolipid bearing a symmetrical C-C methyl ester chain were thoroughly investigated through chemical degradation and spectroscopic methods including 1D and 2D NMR analysis, HR-ESI-TOF-MS, chiral GC-MS, and polarimetry. Our work represents the first mention in the literature of a rhamnolipid methyl ester from Burkholderia species.

Recommendations to Improve Quality of Probiotic Systematic Reviews With Meta-Analyses.

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing.

Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity.

NMJ Analyser: a novel method to quantify neuromuscular junction morphology in zebrafish.

Motivation: Neuromuscular junction (NMJ) structural integrity is crucial for transducing motor neuron signals that initiate skeletal muscle contraction. Zebrafish has emerged as a simple and efficient model to study NMJ structural morphology and function in the context of developmental neurobiology and neuromuscular diseases. However, methods to quantify NMJ morphology from voluminous data of NMJ confocal images accurately, rapidly, and reproducibly are lacking.

Epistemology of synthetic biology: a new theoretical framework based on its potential objects and objectives.

Synthetic biology is a new research field which attempts to understand, modify, and create new biological entities by adopting a modular and systemic conception of the living organisms. The development of synthetic biology has generated a pluralism of different approaches, bringing together a set of heterogeneous practices and conceptualizations from various disciplines, which can lead to confusion within the synthetic biology community as well as with other biological disciplines. I present in this manuscript an epistemological analysis of synthetic biology in order to better define this new discipline in terms of objects of study and specific objectives.

Carbon amendments in soil microcosms induce uneven response on H2 oxidation activity and microbial community composition.

High-affinity H2-oxidizing bacteria (HA-HOB) thriving in soil are responsible for the most important sink of atmospheric H2. Their activity increases with soil organic carbon content, but the incidence of different carbohydrate fractions on the process has received little attention. Here we tested the hypothesis that carbon amendments impact HA-HOB activity and diversity differentially depending on their recalcitrance and their concentration.

Inhibition of PQS signaling by the Pf bacteriophage protein PfsE enhances viral replication in Pseudomonas aeruginosa.

Quorum sensing, a bacterial signaling system that coordinates group behaviors as a function of cell density, plays an important role in regulating viral (phage) defense mechanisms in bacteria. The opportunistic pathogen Pseudomonas aeruginosa is a model system for the study of quorum sensing. P.

Microbial degradation of naphthenic acids using constructed wetland treatment systems: metabolic and genomic insights for improved bioremediation of process-affected water.

Naphthenic acids (NAs) are a complex mixture of organic compounds released during bitumen extraction from mined oil sands that are important contaminants of oil sands process-affected water (OSPW). NAs can be toxic to aquatic organisms and, therefore, are a main target compound for OSPW. The ability of microorganisms to degrade NAs can be exploited for bioremediation of OSPW using constructed wetland treatment systems (CWTS), which represent a possible low energy and low-cost option for scalable in situ NA removal.