Cascade reservoirs affect mercury concentrations in fish from Teles Pires river, Brazilian Amazon.

Hydroelectric reservoirs favor mercury contamination in biota, but the contamination in cascade reservoirs is not yet clear. We investigated total mercury (THg) contamination in fish in four cascade reservoirs in the Brazilian Amazon between August 2022 and April 2023. Overall, downstream predatory fish showed higher mercury concentrations than those upstream.

Targeting RGMb interactions: Discovery and preclinical characterization of potent anti-RGMb antibodies blocking multiple ligand bindings.

Therapeutic efficacy with durable responses has been demonstrated with several antibody drugs that block key immune checkpoint receptors, including PD-1, PD-L1, and CTLA-4. Despite the success of these drugs, a substantial proportion of patients do not benefit. Targeting multiple inhibitory pathways simultaneously to augment anti-tumor immunity has proven to be a promising approach.

The microbiome diversifies -acyl lipid pools - including short-chain fatty acid-derived compounds.

-acyl lipids are important mediators of several biological processes including immune function and stress response. To enhance the detection of -acyl lipids with untargeted mass spectrometry-based metabolomics, we created a reference spectral library retrieving -acyl lipid patterns from 2,700 public datasets, identifying 851 -acyl lipids that were detected 356,542 times. 777 are not documented in lipid structural databases, with 18% of these derived from short-chain fatty acids and found in the digestive tract and other organs.

Temporal variation of mercury levels in fish, soil, and sediments in an Amazon reservoir: insights from 35 years of river impoundment in Pará State, Brazil.

The increase of mercury (Hg) concentrations in abiotic and biotic compartments of aquatic ecosystems following the river impoundment for building a hydroelectric reservoir is one of many environmental and social impacts that the construction of hydroelectric plants can trigger. Yet, long-term studies in Amazon reservoirs are still scarce. The present study aimed to understand the effects of dam impoundment in THg concentrations in an Amazon reservoir up to 35 years of its creation.

Mercury concentrations and differences in isotopic niches of fish from upstream and downstream of an Amazon reservoir dam.

Reservoir construction promotes many environmental impacts, including the enhancement of mercury concentrations in fish. The processes that can influence mercury concentrations in fish in Amazonian reservoirs are still little explored in depth, especially when we consider the possible particularities of the ecosystems in question. This study aims to investigate how mercury concentrations in fish could be influenced by the Tucuruí dam, considering possible changes in their feeding and trophic position according to the dam position (up or downstream).

Bacterial Sphingolipids Exacerbate Colitis by Inhibiting ILC3-derived IL-22 Production.

Background & Aims: Gut bacterial sphingolipids, primarily produced by Bacteroidetes, have dual roles as bacterial virulence factors and regulators of the host mucosal immune system, including regulatory T cells and invariant natural killer T cells. Patients with inflammatory bowel disease display altered sphingolipids profiles in fecal samples. However, how bacterial sphingolipids modulate mucosal homeostasis and regulate intestinal inflammation remains unclear.

Mercury biomagnification in the food chain of a piscivorous turtle species (Testudines: Chelidae: Chelus fimbriata) in the Central Amazon, Brazil.

Due to their natural history and ecological attributes, turtles are excellent organisms for studies of heavy metal contamination. Turtles have a large geographical distribution, occupy different aquatic habitats, and occupy various trophic levels. The present study investigated mercury bioaccumulation in the carnivorous chelonian Chelus fimbriata (Matamata turtle) and Hg biomagnification in relation to its aquatic food chain in the middle Rio Negro, AM-Brazil.

Higher precision, first tier newborn screening for metachromatic leukodystrophy using 16:1-OH-sulfatide.

Newborn screening (NBS) for metachromatic leukodystrophy (MLD) is based on first-tier measurement of sulfatides in dried blood spots (DBS) followed by second-tier measurement of arylsulfatase A in the same DBS. This approach is very precise with 0-1 false positives per ∼30,000 newborns tested. Recent data reported here shows that the sulfatide molecular species with an α-hydroxyl, 16‑carbon, mono-unsaturated fatty acyl group (16:1-OH-sulfatide) is superior to the original biomarker 16:0-sulfatide in reducing the number of first-tier false positives.

Subcutaneous pythiosis in human treated successfully with antimicrobial treatment, debridement and immunotherapy.

Pythiosis is caused due to a filamentous eukaryotic micro-organism called and the disease occurs commonly in horses and cattle. Subcutaneous pythiosis infection in humans is rare with no clear clinical guidelines for treatment. We present a case of a man in his 20s with non-resolving ulcers noted over lower extremity after exposure to swamp water draining animal remains.

Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8 T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8 T cell effector function. Mechanistically, DCA suppressed CD8 T cell responses by targeting plasma membrane Ca ATPase (PMCA) to inhibit Ca-nuclear factor of activated T cells (NFAT)2 signaling.

Gut complement induced by the microbiota combats pathogens and spares commensals.

Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells.

Long-Term Evaluation of Biomarkers in the Czech Cohort of Gaucher Patients.

A personalized treatment decision for Gaucher disease (GD) patients should be based on relevant markers that are specific to GD, play a direct role in GD pathophysiology, exhibit low genetic variation, reflect the therapy, and can be used for all patients. Thirty-four GD patients treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) were analyzed for platelet count, chitotriosidase, and tartrate-resistant acid phosphatase activity in plasma samples, and quantitative measurement of Lyso-Gb1 was performed in dried blood spots. In our ERT and SRT study cohorts, plasma lyso-GL1 correlated significantly with chito-triosidase (ERT: r = 0.

Comparison of sequential versus concurrent chemoradiation regimens in non-metastatic muscle-invasive bladder cancer.

Purpose: The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and mortality and is not suited for many patients.

Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy.

Our bodies are inhabited by trillions of microorganisms. The host immune system constantly interacts with the microbiota in barrier organs, including the intestines. Over decades, numerous studies have shown that our mucosal immune system is dynamically shaped by a variety of microbiota-derived signals.

Gut microbial fatty acid isomerization modulates intraepithelial T cells.

The human gut microbiome constantly converts natural products derived from the host and diet into numerous bioactive metabolites. Dietary fats are essential micronutrients that undergo lipolysis to release free fatty acids (FAs) for absorption in the small intestine. Gut commensal bacteria modify some unsaturated FAs-for example, linoleic acid (LA)-into various intestinal FA isomers that regulate host metabolism and have anticarcinogenic properties.

Vanadium oxide and a sharp onset of cold-trapping on a giant exoplanet.

The abundance of refractory elements in giant planets can provide key insights into their formation histories. Owing to the low temperatures of the Solar System giants, refractory elements condense below the cloud deck, limiting sensing capabilities to only highly volatile elements. Recently, ultra-hot giant exoplanets have allowed for some refractory elements to be measured, showing abundances broadly consistent with the solar nebula with titanium probably condensed out of the photosphere.

Functional and metagenomic level diversities of human gut symbiont-derived glycolipids.

Bioactive metabolites produced by symbiotic microbiota causally impact host health and disease, nonetheless, incomplete functional annotation of genes as well as complexities and dynamic nature of microbiota make understanding species-level contribution in production and actions difficult. Alpha-galactosylceramides produced by (BfaGC) are one of the first modulators of colonic immune development, but biosynthetic pathways and the significance of the single species in the symbiont community still remained elusive. To address these questions at the microbiota level, we have investigated the lipidomic profiles of prominent gut symbionts and the metagenome-level landscape of responsible gene signatures in the human gut.

Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance.

The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma.

Importance to include differential diagnostics for acid sphingomyelinase deficiency (ASMD) in patients suspected to have to Gaucher disease.

The clinical manifestation of sphingolipidosis leads often to misclassification between acid sphingomyelinase deficiency (ASMD) and Gaucher disease. In this multicenter, prospective study, we investigated a cohort of 31,838 individuals suspected to have Gaucher disease, due to clinical presentation, from 61 countries between 2017 and 2022. For all samples, both Acid-β-glucocerebrosidase and acid sphingomyelinase enzyme activities were measured in dried blood spot specimens by tandem mass spectrometry followed by genetic confirmatory testing in potential positive cases.

Kinetic and mechanistic diversity of intestinal immune homeostasis characterized by rapid removal of gut bacteria.

Symbiotic microbiota critically contribute to host immune homeostasis in effector cell-specific manner. For exclusion of microbial component, germ-free animals have been the gold standard method. However, total removal of the entire gut microbiota of an animal from birth significantly skews physiological development.

Acute ecotoxicological effects of Hg(CN) in Danio rerio (zebrafish).

Artisanal and small-scale gold mining (ASGM) is the largest source of anthropogenic Hg emissions on the planet. In addition, Hg-contaminated tailings are often reprocessed with sodium cyanide (NaCN) to extract the residual gold remaining in the material. This leads to the formation of mercury cyanide (Hg(CN)) complexes, which are often discharged in untreated form into local drainages, leading to large amounts of free cyanide being released.