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Toll-like receptor 9 (TLR9) and Phosphatidylinositol-3-kinase gamma (PI3Kγ) are very important effectors of the immune response, however, the importance of such crosstalk for disease development is still a matter of discussion. Here we show that PI3Kγ is required for immune responses in which TLR9 is a relevant trigger. We demonstrate the requirement of PI3Kγ for TLR9-induced inflammation in a model of CpG-induced pleurisy. Such requirement was further observed in inflammatory models where DNA sensing via TLR9 contributes to disease, such as silicosis and drug-induced liver injury. Using adoptive transfer, we demonstrate that PI3Kγ is important not only in leukocytes but also in parenchymal cells for the progression of inflammation. We demonstrate this crosstalk between TLR9 and PI3Kγ in vitro using human PBMCs. The inhibition of PI3Kγ in CpG-stimulated PBMCs resulted in reduction of both cytokine production and phosphorylated Akt. Therefore, drugs that target PI3Kγ have the potential to treat diseases mediated by excessive TLR9 signalling.

The aim of this study was to investigate the acute effects of unilateral ankle plantar flexors static- stretching on surface electromyography (sEMG) and the center of pressure (COP) during a single-leg balance task in both lower limbs. Fourteen young healthy, non-athletic individuals performed unipodal quiet standing for 30s before and after (stretched limb: immediately post-stretch, 10 and 20 minutes and non-stretched limb: immediately post-stretch) a unilateral ankle plantar flexor static- stretching protocol [6 sets of 45s/15s, 70-90% point of discomfort (POD)]. Postural sway was described using the COP area, COP speed (antero-posterior and medio-lateral directions) and COP frequency (antero-posterior and medio-lateral directions). Surface EMG (EMG integral [IEMG] and Median frequency[FM]) was used to describe the muscular activity of gastrocnemius lateralis. Ankle dorsiflexion passive range of motion increased in the stretched limb before and after the static-stretching protocol (mean ± SD: 15.0° ± 6.0 and 21.5° ± 7.0 [p < 0.001]). COP area and IEMG increased in the stretch limb between pre-stretching and immediately post-stretching (p = 0.015 and p = 0.036, respectively). In conclusion, our static- stretching protocol effectively increased passive ankle ROM. The increased ROM appears to increase postural sway and muscle activity; however these finding were only a temporary or transient effect. Key PointsThe postural control can be affected by static- stretching protocol.The lateral gastrocnemius muscle action was increased after the static- stretching protocol.The static- stretching effects remain for less than 10 minutes.

Technological advances that involve computing and artificial intelligence (AI) have led to advances in analysis methods. Fuzzy logic (FL) serves as a qualitative interpretation tool for AI. The objective of this systematic review is to investigate the methods of human movement (HM) analysis using AI through FL to understand the characteristics of the movement of healthy people. To identify relevant studies published up to April 19, 2019, we conducted a study of the PubMed, Scopus, ScienceDirect, and IEEE Xplore databases. We included studies that evaluated HM through AI using FL in healthy people. A total of 951 articles were examined, of which six were selected because they met the criteria presented in the methods. The protocols had high heterogeneity, yet all articles selected presented statistically satisfactory results, in addition to low errors or a false positive index. Only one selected article presented protocol applicability within the free-living model. Generally, AI using FL is a good tool to help assess HM in healthy people, but the model still needs new data acquisition entries to make it applicability within the free-living model.

Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1 ) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1 exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1 and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1 mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1 mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1 mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation.

ObjectivesThis study evaluated the representation of black researchers as authors of articles published in four peer-reviewed journals with the highest impact factors (IFs) in the field of sports science and sports medicine.MethodsAn analysis was conducted on articles published between 2018 and 2022 in four leading sports science journals with high IFs (2022): The British Journal of Sports Medicine, Journal of Sport and Health Science, Sports Medicine and Exercise Immunology Review. Data extraction from the articles included the researcher’s names, sex/gender, total number of authors, number of black authors, their position in the author list, publication year, article title and type and digital object identifier. Sex/gender and race/skin colour were identified using publicly available photographs and methodologies aligned with previous studies and Brazilian racial heteroidentification practices.ResultsThe analysis included 1737 articles and 11 158 authors. Only 144 (1.30%) authors were identified as black, of which only 38 were women, corresponding to 0.34% and 26.4% of total authors and total black authors, respectively. When considering authorship positions, only 16 (0.92%) were the first author and 19 (1.09%) were the last (senior) author. Merely 13 (0.75%) articles had two or more black authors.ConclusionOur findings reveal a significant under-representation of black authors in sports science and sports medicine publications from high-impact journals, particularly in prominent authorship positions. Active initiatives and policies are urgently required to address and mitigate this inequity.

Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens.

Influenza A virus (IAV) infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks) are central signaling enzymes, involved in cell growth, survival, and migration. Class IB PI3K or phosphatidyl inositol 3 kinase-gamma (PI3Kγ), mainly expressed by leukocytes, is involved in cell migration during inflammation. Here, we investigated the contribution of PI3Kγ for the inflammatory and antiviral responses to IAV. PI3Kγ knockout (KO) mice were highly susceptible to lethality following infection with influenza A/WSN/33 H1N1. In the early time points of infection, infiltration of neutrophils was higher than WT mice whereas type-I and type-III IFN expression and p38 activation were reduced in PI3Kγ KO mice resulting in higher viral loads when compared with WT mice. Blockade of p38 in WT macrophages infected with IAV reduced levels of interferon-stimulated gene 15 protein to those induced in PI3Kγ KO macrophages, suggesting that p38 is downstream of antiviral responses mediated by PI3Kγ. PI3Kγ KO-derived fibroblasts or macrophages showed reduced type-I IFN transcription and altered pro-inflammatory cytokines suggesting a cell autonomous imbalance between inflammatory and antiviral responses. Seven days after IAV infection, there were reduced infiltration of natural killer cells and CD8 T lymphocytes, increased concentration of inflammatory cytokines in bronchoalveolar fluid, reduced numbers of resolving macrophages, and IL-10 levels in PI3Kγ KO. This imbalanced environment in PI3Kγ KO-infected mice culminated in enhanced lung neutrophil infiltration, reactive oxygen species release, and lung damage that together with the increased viral loads, contributed to higher mortality in PI3Kγ KO mice compared with WT mice. In humans, we tested the genetic association of disease severity in influenza A/H1N1pdm09-infected patients with three potentially functional single-nucleotide polymorphisms (SNPs), rs1129293, rs17847825, and rs2230460. We observed that SNPs rs17847825 and rs2230460 (A and T alleles, respectively) were significantly associated with protection from severe disease using the recessive model in patients infected with influenza A(H1N1)pdm09. Altogether, our results suggest that PI3Kγ is crucial in balancing antiviral and inflammatory responses to IAV infection.

The aim of this study was to verify differences between boys contrasting in futsal practice level groups on gross motor coordination and growth indicators. A sample of 196 boys aged 11 to 14 years was measured for anthropometric variables and Körperkoordinationstest für Kinder (KTK). Results revealed that there were no significant associations of the futsal practice level on growth parameters. On the other hand, ANCOVA results (chronological age as a covariate) indicated that boys participating in futsal practice ≥ 2 days/week had significantly better performances in jumping sideways, hoping for height, and total score of KTK than their less practicing counterparts. These findings encourage the most frequent practice of sports for the development of gross motor coordination.

Rationale Elevated levels of CD11c+ myeloid cells are observed in various pulmonary disorders, including Idiopathic Pulmonary Fibrosis (IPF). Dendritic cells (DCs) and macrophages (MΦ) are critical antigen‐presenting cells (APCs) that direct adaptive immunity. However, the role of CD11c+ myeloid cells in lung extracellular matrix (ECM) accumulation and pulmonary fibrosis is poorly understood. Objective We aimed to investigate the impact of depleting CD11c+ myeloid cells, including DCs and macrophages, during bleomycin‐induced pulmonary fibrosis in mice. Methods We used a diphtheria toxin (DTx) receptor (DTR) transgenic mouse model (CD11c‐DTR‐Tg) to deplete CD11c+ myeloid cells through two methods: Systemic Depletion (SD) via intraperitoneal injection (i.p.) and local depletion (LD) via intranasal instillation (i.n.). We then assessed the effects of CD11c+ cell depletion during bleomycin‐induced lung inflammation and fibrosis. Results Fourteen days after bleomycin instillation, there was a progressive accumulation of myeloid cells, specifically F4/80‐MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ, preceding mortality and pulmonary fibrosis. Systemic depletion of CD11c+ DCs and MΦ via i.p. DTx administration in CD11c‐DTR‐Tg mice protected against bleomycin‐induced mortality and pulmonary fibrosis compared to wild‐type (WT) mice. Systemic depletion reduced myeloid cells, airway inflammation (total leukocytes, neutrophils, and CD4+ lymphocytes in bronchoalveolar lavage (BAL), inflammatory and fibrogenic mediators, and fibrosis‐related mRNAs (Collagen‐1α1 and α‐SMA). Increased anti‐inflammatory cytokine IL‐10 and CXCL9 levels were observed, resulting in lower lung hydroxyproline content and Ashcroft fibrosis score. Conversely, local depletion of CD11c+ cells increased mortality by acute leukocyte influx (predominantly neutrophils, DCs, and MΦ in BAL) correlated to IL‐1β, with lung hyper‐inflammation and early fibrosis development. Conclusion Systemic depletion of CD11c+ cells confers protection against inflammation and fibrosis induced by Bleomycin, underscoring the significance of myeloid cells expressing F4/80‐MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ orchestrating the inflammatory milieu within the lungs, potentially as a source of cytokines sustaining pulmonary chronic inflammation leading to progressive fibrosis and mortality. Dendritic cells (DCs) and macrophages (MΦ) are key antigen‐presenting cells (APCs) that direct adaptive immunity. The role of CD11c+ myeloid cells in lung extracellular matrix (ECM) accumulation and pulmonary fibrosis is not well understood. Systemic depletion of CD11c+ cells confers protection against inflammation and fibrosis induced by bleomycin, underscoring the significance of myeloid cells expressing F4/80‐MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ orchestrating the inflammatory milieu within the lungs, potentially as a source of cytokines sustaining pulmonary chronic inflammation leading to progressive fibrosis and mortality.