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Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction—self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?—represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis.

Angiotensin converting enzyme 2 (ACE2) presents pleiotropic actions. It hydrolyzes angiotensin I (AngI) and angiotensin II (AngII) into angiotensin-(1-9) (Ang-(1-9)) and angiotensin-(1-7) (Ang-(1-7)), respectively, as well as participates in tryptophan uptake in the gut and in COVID-19 infection. Our aim was to investigate the metabolic effect of ACE2 deletion in young adults and elderly mice under conditions of high calorie intake. Male C57Bl/6 (WT) and ACE2-deficient (ACE2-/y) mice were analyzed at the age of 6 and 12 months under standard diet (StD) and high-fat diet (HFD). Under StD, ACE2-/y showed lower body weight and fat depots, improved glucose tolerance, enhanced insulin sensitivity, higher adiponectin, and lower leptin levels compared to WT. This difference was even more pronounced after HFD in 6-month-old mice, but, interestingly, it was blunted at the age of 12 months. ACE2-/y presented a decrease in adipocyte diameter and lipolysis, which reflected in the upregulation of lipid metabolism in white adipose tissue through the increased expression of genes involved in lipid regulation. Under HFD, both food intake and total energy expenditure were decreased in 6-month-old ACE2-/y mice, accompanied by an increase in liquid intake, compared to WT mice, fed either StD or HFD. Thus, ACE2-/y mice are less susceptible to HFD-induced obesity in an age-dependent manner, as well as represent an excellent animal model of human lipodystrophy and a tool to investigate new treatments.

Background The presence of Bacillus in very diverse environments reflects the versatile metabolic capabilities of a widely distributed genus. Traditional phylogenetic analysis based on limited gene sampling is not adequate for resolving the genus evolutionary relationships. By distinguishing between core and pan-genome, we determined the evolutionary and functional relationships of known Bacillus . Results Our analysis is based upon twenty complete and draft Bacillus genomes, including a newly sequenced Bacillus isolate from an aquatic environment that we report for the first time here. Using a core genome, we were able to determine the phylogeny of known Bacilli , including aquatic strains whose position in the phylogenetic tree could not be unambiguously determined in the past. Using the pan-genome from the sequenced Bacillus , we identified functional differences, such as carbohydrate utilization and genes involved in signal transduction, which distinguished the taxonomic groups. We also assessed the genetic architecture of the defining traits of Bacillus , such as sporulation and competence, and showed that less than one third of the B. subtilis genes are conserved across other Bacilli . Most variation was shown to occur in genes that are needed to respond to environmental cues, suggesting that Bacilli have genetically specialized to allow for the occupation of diverse habitats and niches. Conclusions The aquatic Bacilli are defined here for the first time as a group through the phylogenetic analysis of 814 genes that comprise the core genome. Our data distinguished between genomic components, especially core vs. pan-genome to provide insight into phylogeny and function that would otherwise be difficult to achieve. A phylogeny may mask the diversity of functions, which we tried to uncover in our approach. The diversity of sporulation and competence genes across the Bacilli was unexpected based on previous studies of the B. subtilis model alone. The challenge of uncovering the novelties and variations among genes of the non- subtilis groups still remains. This task will be best accomplished by directing efforts toward understanding phylogenetic groups with similar ecological niches.

The Cuatro Cienegas Basin (CCB) in Mexico, represents a unique ecological habitat, characterized by extreme and fluctuating conditions, providing a window into ancient evolutionary processes. This basin, characterized by hypersalinity and phosphorus scarcity, harbors diverse microbial communities that exhibit remarkable adaptations to oligotrophic conditions. Among these, Halobacterium salinarum , a halophilic archaeon known for its polyploid genome and metabolic versatility, has been extensively studied as a model for extremophile survival. However, only a limited number of H. salinarum strains have been successfully cultured and characterized to date. Here, we report the isolation and genomic analysis of a novel Halobacterium salinarum strain, AD88, from microbial mats at the Archaean Domes site in the CCB. This strain displays unique genomic features, including smaller plasmid sizes and distinctive metabolic pathways for phosphorus and sulfur utilization. Comparative analyses with other Halobacterium strains revealed genetic innovations, such as genes involved in sulfolipid biosynthesis, enabling membrane stability in phosphorus-depleted environments, and adaptations for horizontal gene transfer, which facilitate genomic flexibility in response to environmental pressures. This study reveals that H. salinarum AD88 is the first recorded diploid strain of Halobacterium , a feature previously undocumented in this genus. Phylogenomic reconstruction positioned AD88 tightly within the Halobacterium clade, reflecting its evolutionary history within the genus. Pangenome analysis further highlighted the open nature of the Halobacterium genus, with AD88 contributing novel accessory genes linked to ecological specialization. These findings emphasize the evolutionary significance of the CCB as a natural laboratory for studying microbial adaptation and expand our understanding of archaeal genomic diversity and functional innovation under extreme conditions.

Due to the environmental conditions presented in arid zones, it is expected to have a high influence of deterministic processes over the community assemblages. Symbiotic interactions with microorganisms could increase colonization and survival of plants in difficult conditions, independent of the plants physiological and morphological characteristics. In this context, the microbial communities associated to plants that inhabit these types of areas can be a good model to understand the community assembly processes. We investigated the influence of stochastic and deterministic processes in the assemblage of rhizosphere microbial communities of Agave lechuguilla and bulk soil on the Cuatro Cienegas Basin, a site known for its oligotrophic conditions. We hypothesize that rhizospheric microbial communities of A. lechuguilla differ from those of bulk soil as they differ in physicochemical properties of soil and biotic interactions, including not only the plant, but also their microbial co-occurrence networks, it is expected that microbial species usually critical for plant growth and health are more common in the rhizosphere, whereas in the bulk soil microbial species related to the resistance to abiotic stress are more abundant. In order to confirm this hypothesis, 16S rRNA gene was sequenced by Illumina from rhizospheric and bulk soil samples in two seasons, also the physicochemical properties of the soil were determined. Our results showed differences in bacterial diversity, community composition, potential functions, and interaction networks between the rhizosphere samples and the ones from bulk soil. Although community structure arises from a complex interplay between deterministic and stochastic forces, our results suggest that A. lechuguilla recruits specific rhizospheric microbes with functional traits that benefits the plant through growth promotion and nutrition. This selection follows principally a deterministic process that shapes the rhizospheric microbial communities, directed by the plant modifications around the roots but also subjected to the influence of other environmental variables, such as seasonality and soil properties. Interestingly, keystone taxa in the interactions networks, not necessarily belong to the most abundant taxonomic groups, but they have an important role by their functional traits and keeping the connections on the community network.

Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20-22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.

Due to the enormous diversity of non-culturable viruses, new viruses must be characterized using culture-independent techniques. The associated host is an important phenotypic feature that can be inferred from metagenomic viral contigs thanks to the development of several bioinformatic tools. Here, we compare the performance of recently developed virus-host prediction tools on a dataset of 1,046 virus-host pairs and then apply the best-performing tools to a metagenomic dataset derived from a highly diverse transiently hypersaline site known as the Archaean Domes (AD) within the Cuatro Ciénegas Basin, Coahuila, Mexico. Among host-dependent methods, alignment-based approaches had a precision of 66.07% and a sensitivity of 24.76%, while alignment-free methods had an average precision of 75.7% and a sensitivity of 57.5%. RaFAH, a virus-dependent alignment-based tool, had the best overall performance (F1_score = 95.7%). However, when predicting the host of AD viruses, methods based on public reference databases (such as RaFAH) showed lower inter-method agreement than host-dependent methods run against custom databases constructed from prokaryotes inhabiting AD. Methods based on custom databases also showed the greatest agreement between the source environment and the predicted host taxonomy, habitat, lifestyle, or metabolism. This highlights the value of including custom data when predicting hosts on a highly diverse metagenomic dataset, and suggests that using a combination of methods and qualitative validations related to the source environment and predicted host biology can increase the number of correct predictions. Finally, these predictions suggest that AD viruses infect halophilic archaea as well as a variety of bacteria that may be halophilic, halotolerant, alkaliphilic, thermophilic, oligotrophic, sulfate-reducing, or marine, which is consistent with the specific environment and the known geological and biological evolution of the Cuatro Ciénegas Basin and its microorganisms.

In 1988, the Brazilian Constitution defined health as a universal right and a state responsibility. Progress towards universal health coverage in Brazil has been achieved through a unified health system (Sistema Único de Saúde [SUS]), created in 1990. With successes and setbacks in the implementation of health programmes and the organisation of its health system, Brazil has achieved nearly universal access to health-care services for the population. The trajectory of the development and expansion of the SUS offers valuable lessons on how to scale universal health coverage in a highly unequal country with relatively low resources allocated to health-care services by the government compared with that in middle-income and high-income countries. Analysis of the past 30 years since the inception of the SUS shows that innovations extend beyond the development of new models of care and highlights the importance of establishing political, legal, organisational, and management-related structures, with clearly defined roles for both the federal and local governments in the governance, planning, financing, and provision of health-care services. The expansion of the SUS has allowed Brazil to rapidly address the changing health needs of the population, with dramatic upscaling of health service coverage in just three decades. However, despite its successes, analysis of future scenarios suggests the urgent need to address lingering geographical inequalities, insufficient funding, and suboptimal private sector–public sector collaboration. Fiscal policies implemented in 2016 ushered in austerity measures that, alongside the new environmental, educational, and health policies of the Brazilian government, could reverse the hard-earned achievements of the SUS and threaten its sustainability and ability to fulfil its constitutional mandate of providing health care for all.

Barriers to microbial migrations can lead adaptive radiations and increased endemism. We propose that extreme unbalanced nutrient stoichiometry of essential nutrients can be a barrier to microbial immigration over geological timescales. At the oasis in the Cuatro Ciénegas Basin in Mexico, nutrient stoichiometric proportions are skewed given the low phosphorus availability in the ecosystem. We show that this endangered oasis can be a model for a lost world. The ancient niche of extreme unbalanced nutrient stoichiometry favoured survival of ancestral microorganisms. This extreme nutrient imbalance persisted due to environmental stability and low extinction rates, generating a diverse and unique bacterial community. Several endemic clades of Bacillus invaded the Cuatro Cienegas region in two geological times, the late Precambrian and the Jurassic. Other lineages of Bacillus, Clostridium and Bacteroidetes migrated into the basin in isolated events. Cuatro Ciénegas Basin conservation is vital to the understanding of early evolutionary and ecological processes. Water is a rare sight in a barren land, but there are many more reasons that make the Cuatro Cienegas Basin, an oasis in the North Mexican desert, a puzzling environment. With little phosphorous and nutrients but plenty of sulphur and magnesium, the conditions in the turquoise blue lagoons of the Basin mimic the ones found in the ancient seas of the end of the Precambrian. In fact, Cuatro Cienegas is one of the rare sites where we can still find live stromatolites, a bacterial form of life that once dominated the oceans. Many bacteria of marine origin exist alongside these living fossils, prompting scientists to wonder if the Basin could be a true lost world, a safe haven where ancient microorganisms found refuge and have kept evolving until this day. But to confirm whether this is the case would require scientists to hunt for clues within the genetic information of local bacteria. Souza, Moreno-Letelier et al. came across these hints after sampling for bacteria in a small (about 1km2) lagoon named Churince, and analysing the DNA collected. The results yielded an astonishing amount of biodiversity: 5,167 species representing at least two-third of all known major groups of bacteria were identified, nearly as much as what was found in over 2,000 kilometres in the Pearl River in China. This is unusual, as most other extreme environments with little nutrients have low levels of diversity. Closer investigation into the genomes of 2,500 species of Bacillus bacteria revealed that the sample increased by nearly 21% the number of previously known species in the group. Most of these bacteria were only found in the Basin. These native or ‘endemic’ species have evolved from ancestors that came to the area in two waves. The oldest colonization event happened 680 million years ago, as the first animal forms just started to emerge. The most recent one took place while dinosaurs roamed the Earth about 160 million years ago, when geological events opened again the Basin to the ancient Pacific Ocean. Previous experiments have shown that different species of bacteria in the Churince have evolved to form a close-knit community which ferociously competes with microbes from the outside world. Paired with the extreme conditions found in the lagoon, this may have prevented other microorganisms from proliferating in the environment and replacing the ancient lineages. The days of this lost world may now be numbered. Drained by local farming, the wetlands of the Basin have shrunk by 90% over the past five decades. The Churince lagoon, the most diverse and fragile site where the samples were collected, is now completely dry. Human activities also disrupt the delicate and unique balance of nutrients in the oasis. But all may not be lost – yet. Local high school students have become involved in the research effort to describe and protect these unique microbial communities, and to change agricultural traditions in the area. Closing the canals that export spring water out of the Basin could give the site a chance to recover, and the microbes that are now seeking refuge in underground waters could re-emerge. Maybe there will still be time to celebrate, rather than mourn, the unique life forms of the Cuatro Cienegas Basin.

We estimated the effect of oligosaccharide supplementation and feed restriction on calves. The study was divided into two experimental periods of 28 days each with 20 crossbred calves that had initial body weight of 37 Kg and housed in individual pens. The animals were split in four experimental groups: animals fed 6 L milk/day (CON) in the two periods, animals fed milk restricted (3 L milk/day) in the first period and followed by CON feeding in the second period (RES), animals receiving supplementation of 5 g/day of mannanoligosaccharide (MOS) and animals receiving supplementation of 5 g/day mannan and frutoligosaccharide (MFOS). At the end of the study, all the animals were slaughtered. The average weight gain was lower in the restricted group when compared with CON and MFOS groups in the first period (P < 0.05) and there were no difference among the groups in the second period. Animals supplemented with MOS showed a significant increases in jejunal villus height and rumen papillae, which were not observed for MFOS group (P < 0.05) compared with RES and CON groups. There were no difference in ghrelin and leptin levels among treatments during periods 1 and 2 (P > 0.05). Also, the expression of ghrelin receptors in the paraventricular region of the hypothalamus did not differ among groups. We conclude that milk restriction during the first weeks of life in calves resulted in compensatory gain and did not modify the hormonal profile and expression of the ghrelin receptor in the hypothalamus. Moreover, a prebiotic supplementation changed the development of intestinal and ruminal epithelium.