Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Sleep-dependent decorrelation of hippocampal spatial representations.

Neuronal ensembles are crucial for episodic memory and spatial mapping. Sleep, particularly non-REM (NREM), is vital for memory consolidation, as it triggers plasticity mechanisms through brain oscillations that reactivate neuronal ensembles. Here, we assessed their role in consolidating hippocampal spatial representations during sleep. We recorded hippocampus activity in rats performing a spatial object-place recognition (OPR) memory task, during encoding and retrieval periods, separated by intervening sleep. Successful OPR retrieval correlated with NREM duration, during which cortical oscillations decreased in power and density as well as neuronal spiking, suggesting global downregulation of network excitability. However, neurons encoding specific spatial locations (i.e., place cells) or objects during OPR showed stronger synchrony with brain oscillations compared to non-encoding neurons, and the stability of spatial representations decreased proportionally with NREM duration. Our findings suggest that NREM sleep may promote flexible remapping in hippocampal ensembles, potentially aiding memory consolidation and adaptation to novel spatial contexts.

Bacteria associated with the in hospite Symbiodiniaceae's phycosphere.

Symbiotic interactions between Symbiodiniaceae and bacteria are still poorly explored, especially those in hospite. Here, we adapted a technique that allows for the enrichment of intact and metabolically active in hospite Symbiodiniaceae cells (ihSC) and their associated bacteria from the tissue of the model coral Pocillopora damicornis, using a discontinuous gradient of solution of isotonic Percoll (SIP). The ihSC were concentrated in the 50% SIP fraction, as determined by microscopy. The presence of bacteria associated with ihSC was confirmed by fluorescence in situ hybridization, while microbiome analysis indicated that bacteria of the families Halieaceae, Flavobacteriaceae, and Alcanivoraceae are significantly associated with ihSC. Extracellular vesicles that could be exuding molecules were detected on the symbiosome membranes. Our technique and data contribute to elucidate ihSC-bacteria interactions.

Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro.

Psychedelics, recognized for their impact on perception, are resurging as promising treatments with rapid onset for mood and substance use disorders. Despite increasing evidence from clinical trials, questions persist about the cellular and molecular mechanisms and their precise correlation with treatment outcomes. Murine neurons and immortalized non-neural cell lines harboring overexpressed constructs have shed light on neuroplastic changes mediated by the serotonin 2A receptor (5-HT2AR) as the primary mechanism. However, limitations exist in capturing human- and disease-specific traits. Here, we discuss current accomplishments and prospects for incorporating human pluripotent stem cells (PSCs) to complement these models. PSCs can differentiate into various brain cell types, mirroring endogenous expression patterns and cell identities to recreate disease phenotypes. Brain organoids derived from PSCs resemble cell diversity and patterning, while region-specific organoids simulate circuit-level phenotypes. PSC-based models hold significant promise to illuminate the cellular and molecular substrates of psychedelic-induced phenotypic recovery in neuropsychiatric disorders.

An integrative multi-omics approach to characterize interactions between tuberculosis and diabetes mellitus.

Tuberculosis-diabetes mellitus (TB-DM) is linked to a distinct inflammatory profile, which can be assessed using multi-omics analyses. Here, a machine learning algorithm was applied to multi-platform data, including cytokines and gene expression in peripheral blood and eicosanoids in urine, in a Brazilian multi-center TB cohort. There were four clinical groups: TB-DM(n = 24), TB only(n = 28), DM(HbA1c ≥ 6.5%) only(n = 11), and a control group of close TB contacts who did not have TB or DM(n = 13). After cross-validation, baseline expression or abundance of MMP-28, LTE-4, 11-dTxB2, PGDM, FBXO6, SECTM1, and LINCO2009 differentiated the four patient groups. A distinct multi-omic-derived, dimensionally reduced, signature was associated with TB, regardless of glycemic status. SECTM1 and FBXO6 mRNA levels were positively correlated with sputum acid-fast bacilli grade in TB-DM. Values of the biomarkers decreased during the course of anti-TB therapy. Our study identified several markers associated with the pathophysiology of TB-DM that could be evaluated in future mechanistic investigations.

Brazilin is a natural product inhibitor of the NLRP3 inflammasome.

Excessive or aberrant NLRP3 inflammasome activation has been implicated in the progression and initiation of many inflammatory conditions; however, currently no NLRP3 inflammasome inhibitors have been approved for therapeutic use in the clinic. Here we have identified that the natural product brazilin effectively inhibits both priming and activation of the NLRP3 inflammasome in cultured murine macrophages, a human iPSC microglial cell line and in a mouse model of acute peritoneal inflammation. Through computational modeling, we predict that brazilin can adopt a favorable binding pose within a site of the NLRP3 protein which is essential for its conformational activation. Our results not only encourage further evaluation of brazilin as a therapeutic agent for NLRP3-related inflammatory diseases, but also introduce this small-molecule as a promising scaffold structure for the development of derivative NLRP3 inhibitor compounds.

Low frequency independent components: Internal neuromarkers linking cortical LFPs to behavior.

Local field potentials (LFPs) in the primate motor cortex have been shown to reflect information related to volitional movements. However, LFPs are composite signals that receive contributions from multiple neural sources, producing a complex mix of component signals. Using a blind source separation approach, we examined the components of neural activity recorded using multielectrode arrays in motor areas of macaque monkeys during a grasping and lifting task. We found a set of independent components in the low-frequency LFP with high temporal and spatial consistency associated with each task stage. We observed that ICs often arise from electrodes distributed across multiple cortical areas and provide complementary information to external behavioral markers, specifically in task stage detection and trial alignment. Taken together, our results show that it is possible to separate useful independent components of the LFP associated with specific task-related events, potentially representing internal markers of transition between cortical network states.

Threatening stimuli elicit a sequential cardiac pattern in arthropods.

In order to cope with the challenges of living in dynamic environments, animals rapidly adjust their behaviors in coordination with different physiological responses. Here, we studied whether threatening visual stimuli evoke different heart rate patterns in arthropods and whether these patterns are related with defensive behaviors. We identified two sequential phases of crab's cardiac response that occur with a similar timescale to that of the motor arrest and later escape response. The first phase was modulated by low salience stimuli and persisted throughout spaced stimulus presentation. The second phase was modulated by high-contrast stimuli and reduced by repetitive stimulus presentation. The overall correspondence between cardiac and motor responses suggests that the first cardiac response phase might be related to motor arrest while the second to the escape response. We show that in the face of threat arthropods coordinate their behavior and cardiac activity in a rapid and flexible manner.

Annual changes of Neohelice granulata cognitive abilities indicate opposition between short- and long-term memory retention.

Neohelice is a long-standing model for memory studies for its strong retention of a reduced escape response when trained to iterative presentations of a visual danger stimulus (VDS). Here we present year-round changes that are related to the memory acquisition, storage, and expression. First, we evaluated exploratory activity and response to the VDS, as necessary for memory acquisition and expression. Both parameters change year-round. Second, short-term memory (STM) and two types of long-term memory (LTM) were assessed throughout the year. STM and long-term context-dependent signal memory (CSM) change between periods of the year, whereas signal memory (SM) does not, indicating that the cognitive abilities of the crab display circannual rhythms. Third, during the reproductive period, STM retention is higher than both CSM and SM, indicating a trade-off between STM and LTM. This is the first report of memory retention abilities changing seasonally as a trade-off between short- and long-term memories.

Host macrocyclic acylcarnitines mediate symbiotic interactions between frogs and their skin microbiome.

The host-microbiome associations occurring on the skin of vertebrates significantly influence hosts' health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs' skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs' skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs' multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.

AIM2 promotes TH17 cells differentiation by regulating RORγt transcription activity.

AIM2 is an interferon-inducible HIN-200 protein family member and is well-documented for its roles in innate immune responses as a DNA sensor. Recent studies have highlighted AIM2's function on regulatory T cells (Treg) and follicular T cells (Tfh). However, its involvement in Th17 cell differentiation remains unclear. This study reveals that AIM2 promotes Th17 cell differentiation. AIM2 deficiency decreases IL-17A production and downregulates key Th17 associated proteins (RORγt, IL-1R1, IL-23R). AIM2 is located in the nucleus of Th17 cells, where it interacts with RORγt, enhancing its binding to the Il17a promoter. The absence of AIM2 hinders naive CD4 T cells from differentiating into functional Th17 cells and from inducing colitis in Rag1-/- mice. This study uncovers AIM2's role as a regulator of Th17 cell transcriptional programming, highlighting its potential as a therapeutic target for Th17 cell-mediated inflammatory diseases.

Sex and lifestyle dictate learning performance in a neotropical wasp.

In contrast to extensive investigations on bee cognition, the cognitive capacities of wasps remain largely unexplored despite their key role as pollinators and predators of insect pests. Here we studied learning and memory in the neotropical wasp Mischocyttarus cerberus using a Pavlovian conditioning in which harnessed wasps respond with conditioned movements of their mouthparts to a learned odorant. We focused on the different castes, sexes, and ages coexisting within a nest and found that adults of M. cerberus learned and memorized efficiently the odor-sugar associations. In contrast, newly emerged females, but not males, were unable to learn odorants. This difference concurs with their different lifestyle as young males perform regular excursions outside the nest while young females remain in it until older age. Our results thus highlight the importance of socio-ecological constraints on wasp cognition and set the basis for mechanistic studies on learning differences across ages and castes.

Self-assembly of dengue virus empty capsid-like particles in solution.

Nucleocapsid (NC) assembly is an essential step of the virus replication cycle. It ensures genome protection and transmission among hosts. Flaviviruses are human viruses for which envelope structure is well known, whereas no information on NC organization is available. Here we designed a dengue virus capsid protein (DENVC) mutant in which a highly positive spot conferred by arginine 85 in α4-helix was replaced by a cysteine residue, simultaneously removing the positive charge and restricting the intermolecular motion through the formation of a disulfide cross-link. We showed that the mutant self-assembles into capsid-like particles (CLP) in solution without nucleic acids. Using biophysical techniques, we investigated capsid assembly thermodynamics, showing that an efficient assembly is related to an increased DENVC stability due to α4/α4' motion restriction. To our knowledge, this is the first time that flaviviruses' empty capsid assembly is obtained in solution, revealing the R85C mutant as a powerful tool to understand the NC assembly mechanism.

Acute and chronic physical activity improves spatial memory in an immersive virtual reality task.

Physical activity benefits both fitness and cognition. However, its effect on long-term memory is unclear. In this study, we evaluated the effect of acute and chronic exercise on long-term spatial memory for a new virtual reality task. Participants were immersed in the virtual environment and navigated a wide arena that included target objects. We assessed spatial memory in two conditions (encoded targets separated by a short or long distance) and found that 25 min of cycling after encoding - but not before retrieval - was sufficient to improve the long-term memory retention for the short, but not for the long distance. Furthermore, we found that participants who engaged in regular physical activity showed memory for the short-distance condition whereas controls did not. Thus, physical activity could be a simple way to improve spatial memories.

Characterization of cell-to-cell variation in nuclear transport rates and identification of its sources.

Nuclear transport is an essential part of eukaryotic cell function. Here, we present scFRAP, a model-assisted fluorescent recovery after photobleaching (FRAP)- based method to determine nuclear import and export rates independently in individual live cells. To overcome the inherent noise of single-cell measurements, we performed sequential FRAPs on the same cell. We found large cell-to-cell variation in transport rates within isogenic yeast populations. For passive transport, the variability in NPC number might explain most of the variability. Using this approach, we studied mother-daughter cell asymmetry in the active nuclear shuttling of the transcription factor Ace2, which is specifically concentrated in daughter cell nuclei in early G1. Rather than reduced export in the daughter cell, as previously hypothesized, we found that this asymmetry is mainly due to an increased import in daughters. These results shed light on cell-to-cell variation in cellular dynamics and its sources.

Análisis bibliométrico de la producción científica y contribuciones en el campo biomédico de una facultad peruana de ciencias biológicas

La producción científica de las facultades de Ciencias Biológicas en el campo biomédico no ha sido evaluada en el Perú. El objetivo del estudio fue analizar las características de la producción científica y las contribuciones a las ciencias biomédicas de la Facultad de Ciencias Biológicas de la Universidad Nacional Pedro Ruiz Gallo, Perú (FCCBB-UNPRG). Se realizó un estudio descriptivo con enfoque bibliométrico; se consultaron tres bases de datos (Scopus, PubMed y LILACS) para buscar artículos que tuvieran, mínimo, un autor afiliado a la FCCBB-UNPRG. Se consignaron los siguientes datos: tipo de publicación, idioma, datos de autoría, financiamiento, año, área de publicación, datos de la revistas e instituciones colaborativas. Se realizó un análisis descriptivo y se elaboraron mapas de redes, utilizando el software VOSviewer. Se recopilaron 46 documentos; la mayoría son artículos (n = 36, 78,26 %), cartas (n = 9, 19,57 %) y reporte de casos (n = 1, 2,17 %); publicados en 30 revistas científicas, principalmente extranjeras. Existió mayor contribución en las áreas de microbiología, virología y parasitología. Se involucraron 42 instituciones colaborativas. Cerca del 90 % de las publicaciones no fueron financiadas. En los últimos años se observó un crecimiento en el número de publicaciones en diferentes áreas temáticas; esto demuestra el compromiso de la FCCBB-UNPRG con la investigación en el campo biomédico y la formación de investigadores. Se espera la implementación de políticas de investigación que involucren pautas y/o directrices para lograr un incremento sostenido de la producción científica.

The scientific production of the faculties of Biological Sciences in the biomedical field has not been evaluated in Peru. The objective of this study was to analyze the characteristics of the scientific production and the contributions to the biomedical sciences of the Faculty of Biological Sciences of Pedro Ruiz Gallo National University, Peru (FCCBB-UNPRG). A descriptive study with a bibliometric approach was carried out. Three databases (Scopus, PubMed, and LILACS) were consulted to search for articles that had, at least, one author affiliated with the FCCBB-UNPRG. The following data were recorded: type of publication, language, authorship data, funding, year, publication area, journal data, and collaborating institutions. A descriptive analysis was carried out and network maps were elaborated, using the VOSviewer software. Forty-six documents were retrived; the majority were articles (n = 36, 78.26%), letters (n = 9, 19.57%) and case reports (n = 1, 2.17%); published in 30 scientific journals, mainly foreign. Greater contribution was observed in microbiology, virology and parasitology. Fotry-two collaborative institutions were involved. About 90% of the publications were not funded. A growth in the number of publications in different thematic areas has been noted in recent years, which demonstrates the commitment of FCCBB-UNPRG to research in the biomedical field and the training of researchers. The implementation of research policies including guidelines and/or directives is expected to achieve sustained increase in scientific production.

Ediacaran Corumbella has a cataphract calcareous skeleton with controlled biomineralization.

Corumbella is a terminal Ediacaran tubular, benthic fossil of debated morphology, composition, and biological affinity. Here, we show that Corumbella had a biomineralized skeleton, with a bilayered construction of imbricated calcareous plates and rings (sclerites) yielding a cataphract organization, that enhanced flexibility. Each sclerite likely possessed a laminar microfabric with consistent crystallographic orientation, within an organic matrix. Original aragonitic mineralogy is supported by relict aragonite and elevated Sr (mean = ca. 11,800 ppm in central parts of sclerites). In sum, the presence of a polarisation axis, sclerites with a laminar microfabric, and a cataphract skeletal organization reminiscent of early Cambrian taxa, are all consistent with, but not necessarily indicative of, a bilaterian affinity. A cataphract skeleton with an inferred complex microstructure confirms the presence of controlled biomineralization in metazoans by the terminal Ediacaran, and offers insights into the evolution of development and ecology at the root of the 'Cambrian radiation'.

The role of antigen expression in shaping the repertoire of HLA presented ligands.

Human leukocyte antigen (HLA) presentation of peptides is a prerequisite of T cell immune activation. The understanding of the rules defining this event has large implications for our knowledge of basic immunology and for the rational design of immuno-therapeutics and vaccines. Historically, most of the available prediction methods have been solely focused on the information related to antigen processing and presentation. Recent work has, however, demonstrated that method performance can be boosted by integrating information related to antigen abundance. Here we expand on these later findings and develop an extended version of NetMHCpan, called NetMHCpanExp, integrating information on antigen abundance from RNA-Seq experiments. In line with earlier works, the model demonstrates improved performance for both HLA ligand and cancer neoantigen epitope prediction. Optimal results are obtained by use of sample-specific abundance information but also reference datasets can be applied with a limited performance drop. The developed tool is available at https://services.healthtech.dtu.dk/service.php?NetMHCpanExp-1.0.

Evaluation of environmental, social, and behavioral modulations of the circadian phase of dancers trained in shifts.

The interplay of environmental, social, and behavioral factors influencing human circadian phase in ecological conditions remains elusive. The Uruguayan national dance school END-SODRE operating in two shifts (morning: 8:30-12:30 and night: 20:00-24:00) allowed us to evaluate how social demands, chronotype, environmental light, physical activity, and sleep patterns affected individual circadian phase measured by the onset of the nocturnal increase of melatonin (DLMO) in a single study. The DLMO was 1.5 h earlier in morning-shift dancers (n = 7) compared to night-shift dancers (n = 11). Sleep time and chronotype (only in night-shift dancers) were associated with the circadian phase. In training days, during each participant's phase-advance and phase-delay time windows, light exposure was similar between morning and night-shift dancers and did not correlate with DLMO. In contrast, the time spent in moderate-vigorous physical activity during each participant's phase-lag time window was higher in night-shift dancers than in morning-shift dancers and positively correlated with DLMO.

Phylogenetic-based inference reveals distinct transmission dynamics of SARS-CoV-2 lineages Gamma and P.2 in Brazil.

The COVID-19 epidemic in Brazil experienced two major lineage replacements until mid-2021. The first was driven by lineage P.2, in late 2020, and the second by lineage Gamma, in early 2021. To understand how these SARS-CoV-2 lineages spread in Brazil, we analyzed 11,724 genomes collected throughout the country between September 2020 and April 2021. Our findings indicate that lineage P.2 probably emerged in July 2020 in the Rio de Janeiro state and Gamma in November 2020 in the Amazonas state. Both states were the main hubs of viral disseminations to other Brazilian locations. We estimate that Gamma was 1.56-3.06 times more transmissible than P.2 in Rio de Janeiro and that the median effective reproductive number (Re) of Gamma varied according to the geographic context (Re = 1.59-3.55). In summary, our findings support that lineage Gamma was more transmissible and spread faster than P.2 in Brazil.