Much recent marine microbial research has focused on sponges, but very little is known about how the sponge microbiome fits in the greater coral reef microbial metacommunity. Here, we present an ...extensive survey of the prokaryote communities of a wide range of biotopes from Indo-Pacific coral reef environments. We find a large variation in operational taxonomic unit (OTU) richness, with algae, chitons, stony corals and sea cucumbers housing the most diverse prokaryote communities. These biotopes share a higher percentage and number of OTUs with sediment and are particularly enriched in members of the phylum Planctomycetes. Despite having lower OTU richness, sponges share the greatest percentage (>90%) of OTUs with >100 sequences with the environment (sediment and/or seawater) although there is considerable variation among sponge species. Our results, furthermore, highlight that prokaryote microorganisms are shared among multiple coral reef biotopes, and that, although compositionally distinct, the sponge prokaryote community does not appear to be as sponge-specific as previously thought.
The aim of this study was to investigate the incidence and risk factors for handball injuries in Brazilian elite handball players. Overall, 339 athletes from 21 handball teams who participated in the ...two main Brazilian championships were followed up during a season. In total, 312 injuries were reported by 201 athletes. The injury incidence rate during training was 3.7/1000 h, and during matches was 20.3/1000 matches. Ankle (19.4%, n = 46) and knee (13.5%, n = 32) were the body regions most affected by traumatic injuries. Shoulders (44.0%, n = 33) and knee (26.7%, n = 20) were the body regions most affected by overuse injuries. Muscle injuries (27.1%, n = 68) was the traumatic injury type most reported. Tendinopathy (91.8%, n = 56) was the overuse injury type most observed. Previous injury (OR: 2.42, CI 95%: 1.51–3.89) and an additional match per week (OR: 1.31, CI 95%: 1.05–1.62) were associated with a higher risk of overuse injury. Female athletes (OR: 1.56, CI 95%: 1.08–2.25) and an additional hour of training per week (OR: 1.09, CI 95%: 1.02–1.15) were associated with a higher risk of traumatic injury. This study showed that athletes with previous injury have shown a high risk of developing an overuse injury.
Myrmecochory-seed dispersal by ants-is a mutualistic interaction in which ants attracted by seed appendices take them away from the parental plant location, where seeds usually have better ...development odds. Not all ant species benefit plants, and the mechanisms of those divergent outcomes are still unclear, especially from the perspective of microbial third parties. Here, we explore the effects of seed manipulation on fungi communities promoted by two ant species with contrasting effects on seed germination and antimicrobial cleaning strategies. We hypothesize that: i) fungi richness is higher in seeds manipulated by Acromyrmex subterraneus (species that negatively affect seed germination), followed by unmanipulated seeds and seeds manipulated by Atta sexdens (ant species that increase seed germination) and ii) seeds manipulated by A. sexdens, Ac. subterraneus and unmanipulated seeds present dissimilar fungi compositions. We identified fungal morphotypes in three groups of seeds: i) manipulated by A. sexdens; ii) manipulated by Ac. subterraneus; iii) unmanipulated. Seeds manipulated by Ac. subterraneus exhibited higher fungal richness than those manipulated by A. sexdens and unmanipulated seeds, indicating that the ant species known to impair germination increases the fungal load on seeds. Additionally, we found that A. sexdens ants were unable to reduce fungal richness compared to unmanipulated seeds. Furthermore, fungal composition differed among all three treatments. Our results underscore the significance of ant species identity in shaping the fungal communities associated with myrmecochorous seeds. Given the potential influence of microbial infection on seed fate, we suggest considering manipulation strategies when evaluating the overall quality of an ant as a seed disperser.
FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic ...fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated β-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer cells and deregulated in the paclitaxel-resistant MCF-7Tax(R) cells. KIF20A depletion also renders MCF-7 and MCF-7Tax(R) cells more sensitive to paclitaxel-induced cellular senescence. Crucially, resembling paclitaxel treatment, silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle morphology and chromosome alignment, which have been shown to induce mitotic catastrophe-dependent senescence. The physiological relevance of the regulation of KIF20A by FOXM1 is further highlighted by the strong and significant correlations between FOXM1 and KIF20A expression in breast cancer patient samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA expression significantly associates with poor survival, consistent with a role of FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A expression may confer paclitaxel resistance. These findings provide insights into the underlying mechanisms of paclitaxel resistance and have implications for the development of predictive biomarkers and novel chemotherapeutic strategies for paclitaxel resistance.
Dietary glycerol supplementation in aquaculture feed is seen as an alternative and inexpensive way to fuel fish metabolism, attenuate metabolic utilization of dietary proteins and, subsequently, ...reduce nitrogen excretion. In this study, we evaluated the impact of dietary glycerol supplementation on nitrogen excretion of European seabass (
Dicentrarchus labrax
) and its effects on metabolite profile and bacterial community composition of gut digesta. These effects were evaluated in a 60-day trial with fish fed diets supplemented with 2.5% or 5% (w/w) refined glycerol and without glycerol supplementation. Nuclear magnetic resonance spectroscopy and high-throughput 16S rRNA gene sequencing were used to characterize the effects of glycerol supplementation on digesta metabolite and bacterial community composition of 6-h postprandial fish. Our results showed that ammonia excretion was not altered by dietary glycerol supplementation, and the highest glycerol dosage was associated with significant increases in amino acids and a decrease of ergogenic creatine in digesta metabolome. Concomitantly, significant decreases in putative amino acid degradation pathways were detected in the predicted metagenome analysis, suggesting a metabolic shift. Taxon-specific analysis revealed significant increases in abundance of some specific genera (e.g.,
Burkholderia
and
Vibrio
) and bacterial diversity. Overall, our results indicate glycerol supplementation may decrease amino acid catabolism without adversely affecting fish gut bacterial communities.
Key points
• Glycerol can be an inexpensive and energetic alternative in fish feed formulations
.
• Glycerol did not affect nitrogen excretion and gut bacteriome composition
.
• Glycerol reduced uptake of amino acids and increased uptake of ergogenic creatine
.
• Glycerol reduced putative amino acid degradation pathways in predicted metagenome
.
Dietary supplementation with triglyceride tributyrin (TBT), a butyrate precursor, has been associated with beneficial effects on fish health and improvements in the ability of carnivorous fish to ...tolerate higher levels of plant-based protein. In this study, we aimed to investigate the effects of a plant-based diet supplemented with TBT on the structural diversity and putative function of the digesta-associated bacterial communities of rainbow trout (Oncorhynchus mykiss). In addition to this, we also assessed the response of fish gut digestive enzyme activities and chyme metabolic profile in response to TBT supplementation. Our results indicated that TBT had no significant effects on the overall fish gut bacterial communities, digestive enzyme activities or metabolic profile when compared with non-supplemented controls. However, a more in-depth analysis into the most abundant taxa showed that diets at the highest TBT concentrations (0.2% and 0.4%) selectively inhibited members of the Enterobacterales order and reduced the relative abundance of a bacterial population related to Klebsiella pneumoniae, a potential fish pathogen. Furthermore, the predicted functional analysis of the bacterial communities indicated that increased levels of TBT were associated with depleted KEGG pathways related to pathogenesis. The specific effects of TBT on gut bacterial communities observed here are intriguing and encourage further studies to investigate the potential of this triglyceride to promote pathogen suppression in the fish gut environment, namely in the context of aquaculture.
Glioblastoma patients have a poor prognosis mainly due to temozolomide (TMZ) resistance. NRF2 is an important transcript factor involved in chemotherapy resistance due to its protective role in the ...transcription of genes involved in cellular detoxification and prevention of cell death processes, such as ferroptosis. However, the relation between NRF2 and iron-dependent cell death in glioma is still poorly understood. Therefore, in this study, we analyzed the role of NRF2 in ferroptosis modulation in glioblastoma cells. Two human glioblastoma cell lines (U251MG and T98G) were examined after treatment with TMZ, ferroptosis inducers (Erastin, RSL3), and ferroptosis inhibitor (Ferrostatin-1). Our results demonstrated that T98G was more resistant to chemotherapy compared to U251MG and showed elevated levels of NRF2 expression. Interestingly, T98G revealed higher sensitivity to ferroptosis, and significant GSH depletion upon system xc
blockage. NRF2 silencing in T98G cells (T98G-shNRF2) significantly reduced the viability upon TMZ treatment. On the other hand, T98G-shNRF2 was resistant to ferroptosis and reverted intracellular GSH levels, indicating that NRF2 plays a key role in ferroptosis induction through GSH modulation. Moreover, silencing of ABCC1, a well-known NRF2 target that diminishes GSH levels, has demonstrated a similar collateral sensitivity. T98G-siABCC1 cells were more sensitive to TMZ and resistant to Erastin. Furthermore, we found that NRF2 positively correlates with ABCC1 expression in tumor tissues of glioma patients, which can be associated with tumor aggressiveness, drug resistance, and poor overall survival. Altogether, our data indicate that high levels of NRF2 result in collateral sensitivity on glioblastoma via the expression of its pro-ferroptotic target ABCC1, which contributes to GSH depletion when the system xc
is blocked by Erastin. Thus, ferroptosis induction could be an important therapeutic strategy to reverse drug resistance in gliomas with high NRF2 and ABCC1 expression.
FOXM1 is implicated in genotoxic drug resistance but its mechanism of action remains elusive. We show here that FOXM1-depletion can sensitize breast cancer cells and mouse embryonic fibroblasts ...(MEFs) into entering epirubicin-induced senescence, with the loss of long-term cell proliferation ability, the accumulation of γH2AX foci, and the induction of senescence-associated β-galactosidase activity and cell morphology. Conversely, reconstitution of FOXM1 in FOXM1-deficient MEFs alleviates the accumulation of senescence-associated γH2AX foci. We also demonstrate that FOXM1 regulates NBS1 at the transcriptional level through an forkhead response element on its promoter. Like FOXM1, NBS1 is overexpressed in the epirubicin-resistant MCF-7Epi(R) cells and its expression level is low but inducible by epirubicin in MCF-7 cells. Consistently, overexpression of FOXM1 augmented and FOXM1 depletion reduced NBS1 expression and epirubicin-induced ataxia-telangiectasia mutated (ATM)phosphorylation in breast cancer cells. Together these findings suggest that FOXM1 increases NBS1 expression and ATM phosphorylation, possibly through increasing the levels of the MRN(MRE11/RAD50/NBS1) complex. Consistent with this idea, the loss of P-ATM induction by epirubicin in the NBS1-deficient NBS1-LBI fibroblasts can be rescued by NBS1 reconstitution. Resembling FOXM1, NBS1 depletion also rendered MCF-7 and MCF-7Epi(R) cells more sensitive to epirubicin-induced cellular senescence. In agreement, the DNA repair-defective and senescence phenotypes in FOXM1-deficent cells can be effectively rescued by overexpression of NBS1. Moreover, overexpression of NBS1 and FOXM1 similarly enhanced and their depletion downregulated homologous recombination (HR) DNA repair activity. Crucially, overexpression of FOXM1 failed to augment HR activity in the background of NBS1 depletion, demonstrating that NBS1 is indispensable for the HR function of FOXM1. The physiological relevance of the regulation of NBS1 expression by FOXM1 is further underscored by the strong and significant correlation between nuclear FOXM1 and total NBS1 expression in breast cancer patient samples, further suggesting that NBS1 as a key FOXM1 target gene involved in DNA damage response, genotoxic drug resistance and DNA damage-induced senescence.
Amblyomma ticks are vectors of both Rickettsia rickettsii and R. parkeri in the Americas, where capybaras (Hydrochoerus hydrochaeris) are the main hosts in urban areas, thus contributing to the ...transmission of spotted fever. Herein, we studied: (i) the seasonal dynamics and abundance of ticks in areas where capybaras live, (ii) the effect of environmental variables on tick abundance, and (iii) the presence of Rickettsia-infected ticks. Between September 2021 and September 2022, we sampled ticks using cloth-dragging at 194 sites on the shore of Lake Paranoá in Brasília, Brazil. We measured environmental data (season, vegetation type, canopy density, temperature, humidity, and presence or vestige of capybara) at each site. Nymphs and adults were morphologically identified to the species level, and a selected tick sample including larvae was subjected to genotypic identification. We investigated Rickettsia-infected ticks by PCR (gltA, htrA, ompB, and ompA genes) and associations between tick abundance and environmental variables using Generalized Linear Models. A total of 30,334 ticks (96% larvae) were captured. Ticks were identified as Amblyomma, with A. sculptum comprising 97% of the adult/nymphs. Genotype identification of a larval sample confirmed that 95% belonged to A. dubitatum. Seasonal variables showed significant effects on tick abundance. Most larvae and nymphs were captured during the early dry season, while the adults were more abundant during the wet season. Vegetation variables and the presence of capybaras showed no association with tick abundance. Rickettsia parkeri group and R. bellii were identified in A. dubitatum, while A. sculptum presented R. bellii. We conclude that: (i) Amblyomma ticks are widely distributed in Lake Paranoá throughout the year, especially larvae at the dry season, (ii) the abundance of Amblyomma ticks is explained more by climatic factors than by vegetation or presence of capybaras, and (iii) A. dubitatum ticks are potential vectors of R. parkeri in Brasília.
Mutations in SARS-CoV-2 have shown effective evasion of population immunity and increased affinity to the cellular receptor angiotensin-converting enzyme 2 (ACE2). However, in the dynamic environment ...of the respiratory tract, forces act on the binding partners, which raises the question of whether not only affinity but also force stability of the SARS-CoV-2-ACE2 interaction might be a selection factor for mutations. Using magnetic tweezers, we investigate the impact of amino acid substitutions in variants of concern (Alpha, Beta, Gamma and Delta) and on force-stability and bond kinetic of the receptor-binding domain-ACE2 interface at a single-molecule resolution. We find a higher affinity for all of the variants of concern (>fivefold) compared with the wild type. In contrast, Alpha is the only variant of concern that shows higher force stability (by 17%) compared with the wild type. Using molecular dynamics simulations, we rationalize the mechanistic molecular origins of this increase in force stability. Our study emphasizes the diversity of contributions to the transmissibility of variants and establishes force stability as one of the several factors for fitness. Understanding fitness advantages opens the possibility for the prediction of probable mutations, allowing a rapid adjustment of therapeutics, vaccines and intervention measures.
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