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The immune system is endowed with the capacity to distinguish between self and non-self, so-called immune tolerance or "consciousness of the immune system." This type of awareness is designed to achieve host protection by eliminating cells expressing a wide range of non-self antigens including microbial-derived peptides. Such a successful immune response is associated with the secretion of a whole spectrum of soluble mediators, e.g., cytokines and chemokines, which not only contribute to the clearance of infected host cells but also activate T cells that are not specific to the original cognate antigen. This kind of non-specific T-cell activation is called "bystander activation." Although it is well-established that this phenomenon is cytokine-dependent, there is evidence in the literature showing the involvement of peptide/MHC recognition depending on the type of T-cell subset (naive vs. memory). Here, we will summarize our current understanding of the mechanism(s) of bystander T-cell activation as well as its biological significance in a wide range of diseases including microbial infections, cancer, auto- and alloimmunity, and chronic inflammatory diseases such as atherosclerosis. [ABSTRACT FROM AUTHOR]

Purpose: The presence of T cells expressing TLR-2 and TLR-4 has been associated with relapsing-remitting multiple sclerosis (RRMS) pathogenesis. Here, we evaluated whether the effectiveness of DMT in controlling clinical activity of the disease would be associated with modulation of proportion of TLRs+ T cells. Patients and Methods: Whole peripheral blood mononuclear cells, purified CD4+ and CD8+ T cells from RRMS patients were cultured with different stimuli. The frequency of IL-17-secreting CD4+ and CD8+ T cells positive for TLR-2 and TLR-4 was determined by flow cytometry. The cytokine profile of these T cells following TLR-2 and TLR-4 stimulation was determined by Multiplex. Some of these T cell cultures were treated with hydrocortisone. The levels of LPS-binding protein (LBP) were dosed by ELISA. Clinical (occurrence of relapses) and radiological (number of active brain lesions) activity were evaluated during the 1-year follow-up. Results: Despite DMT, high intensity of TLR-2 and TLR-4 expression on (CD4+ and CD8+) T-cells, as well as the frequency of IL-17-secreting (CD4+ and CD8+) T-cells, are predictive of future RRMS relapses. Moreover, higher cytokine production related to Th17/Tc-17 phenotypes in response to TLR-2 and TLR-4 agonists was observed in DMT-treated patients and displayed an elevated number of brain lesions. The hyperresponsiveness of MS-derived T-cells to TLR-2 and TLR-4 ligands, with high levels of IL-1β, IL-6, IL-17, IFN-γ and GM-CSF in response to both TLR agonists, positively correlated with plasma LBP levels. Interestingly, corticoid was less efficient in reducing Th17 and Tc-17 cytokine production induced by TLR-2 and TLR-4 ligands in DMT-treated patients who relapsed during follow-up. Conclusion: Collectively, the data suggested that persistence of circulating Th17 and Tc17 cells expressing elevated levels of functional TLR-2 and TLR-4 could indicate high disease activity and lower therapeutic efficacy in RRMS patients. [ABSTRACT FROM AUTHOR]

Analyzing the impacts of climate change on phytosanitary problems in Brazil is crucial due to the country's special role in global food security as one of the largest producers of essential commodities. This review focuses on the effects of climate change on plant diseases and discusses its main challenges in light of Brazil's diverse agricultural landscape. To assess the risk of diseases caused by fungi, bacteria, viruses, oomycetes, nematodes, and spiroplasms, we surveyed 304 pathosystems across 32 crops of economic importance from 2005 to 2022. Results show that diseases caused by fungi account for 79% of the pathosystems evaluated. Predicting the occurrence of diseases in a changing climate is a complex challenge, and the continuity of this work is strategic for Brazil's agricultural defense. The future risk scenarios analyzed here aim to help guide disease mitigation for cropping systems. Despite substantial progress and ongoing efforts, further research will be needed to effectively prevent economic and environmental damage. [ABSTRACT FROM AUTHOR]

Studies of Phytophthora impact in forests generally focus on individual species without recognition that Phytophthora occur in multispecies communities. This study investigated community structure of Phytophthora species in the rhizosphere of Agathis australis (kauri) in Te Wao Nui o Tiriwa/Waitākere Ranges, New Zealand, in the context of kauri dieback disease expression. Soil sampling and tree monitoring were conducted on 767 randomly selected mature kauri trees. Phytophthora species were detected using both soil baiting and DNA metabarcoding of environmental DNA (eDNA). Four species were detected with soil baiting (P. agathidicida, P. cinnamomi, P. multivora, and P. pseudocryptogea/P. cryptogea) and an additional three species with metabarcoding (P. kernoviae, P. cactorum/P. aleatoria and an unknown clade 7 species). Phytophthora cinnamomi was the most abundant species and was distributed throughout the forest. Both P. multivora and P. agathidicida were limited to forest edges, suggesting more recent introductions. P. agathidicida presence was strongly correlated with declining canopy health, confirming its role as the main driver of kauri dieback. The limited distribution of P. agathidicida and infrequent detections (11.0% samples) suggests that that this species is spreading as an introduced invasive pathogen and provide hope that with strategic management (including track upgrades and closures, restricting access to uninfected areas, and continual monitoring) uninfected areas of the forest can be protected. The frequent detections of P. cinnamomi and P. multivora from symptomatic trees in the absence of P. agathidicida suggest more research is needed to understand their roles in kauri forest health. [ABSTRACT FROM AUTHOR]

Due to cryptic diversification, phenotypic plasticity and host associations, multilocus phylogenetic analyses have become the most important tool in accurately identifying and circumscribing species in the Diaporthe genus. However, the application of the genealogical concordance criterion has often been overlooked, ultimately leading to an exponential increase in novel Diaporthe spp. Due to the large number of species, many lineages remain poorly understood under the so-called species complexes. For this reason, a robust delimitation of the species boundaries in Diaporthe is still an ongoing challenge. Therefore, the present study aimed to resolve the species boundaries of the Diaporthe arecae species complex (DASC) by implementing an integrative taxonomic approach. The Genealogical Phylogenetic Species Recognition (GCPSR) principle revealed incongruences between the individual gene genealogies. Moreover, the Poisson Tree Processes' (PTPs) coalescent-based species delimitation models identified three well-delimited subclades represented by the species D. arecae, D. chiangmaiensis and D. smilacicola. These results evidence that all species previously described in the D. arecae subclade are conspecific, which is coherent with the morphological indistinctiveness observed and the absence of reproductive isolation and barriers to gene flow. Thus, 52 Diaporthe spp. are reduced to synonymy under D. arecae. Recent population expansion and the possibility of incomplete lineage sorting suggested that the D. arecae subclade may be considered as ongoing evolving lineages under active divergence and speciation. Hence, the genetic diversity and intraspecific variability of D. arecae in the context of current global climate change and the role of D. arecae as a pathogen on palm trees and other hosts are also discussed. This study illustrates that species in Diaporthe are highly overestimated, and highlights the relevance of applying an integrative taxonomic approach to accurately circumscribe the species boundaries in the genus Diaporthe. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a major cause of cancer-related deaths globally, yet its causes remain unclear. While human papillomavirus (HPV) is known to be associated with other cancers, such as cervical cancer and anal cancer, investigation of its connection to prostate cancer has yielded mixed results. This systematic review aimed to assess the relationship between HPV and prostate cancer using Bradford Hill's criteria. Out of 482 studies screened from PubMed, 60 were included and evaluated. Although the strength of association was not strong and certain criteria were not met, the review identified plausible biological mechanisms and reported the presence of HPV in prostate cancer tissues. However, the overall quality of evidence remains low, and further high-quality studies are needed to establish a definitive link. These findings have implications for understanding prostate cancer and guiding future research efforts. Globally, prostate cancer is the fifth most common cause of cancer-related death among men, and metastatic castration-resistant prostate cancer has a high cancer-related mortality rate. However, the aetiology of this disease is not yet fully understood. While human papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancers, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill's criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer. [ABSTRACT FROM AUTHOR]

Fungal species of the family Botryosphaeriaceae are distributed worldwide and are known important pathogens of a wide variety of forestry and agricultural plant hosts. The role of global changes impacts, especially climate change, on Botryosphaeriaceae-related diseases is still poorly understood. We mapped suitable areas for three Botryosphaeriaceae species, according to three different Shared Socio-economic Pathways (SSP) 126, 370 and 585 in different time slots: a historical climate series from 1970 to 2000 and two future projections 2021–2040 and 2081–2100. An overall increase of suitable areas for these pathogens is predicted in most of the studied scenarios. Also a possible range expansion is predicted in the northern hemisphere for Botryosphaeria dothidea and Neofusicoccum parvum. A consistent increase in the number of month with optimal growth conditions was found in most of the north hemisphere. This increase could impact on the phenology of these organisms and result in more frequent and intensive outbreaks. In this study, we explored the advantages and limitations of species distribution models, SDMs, to provide input data for Botryosphaeriaceae-related risk assessment and to improve our understanding of the ecological niche requirements of these species. A worldwide risk assessment was performed to categorise different risk levels based on current and future suitability of geographical areas to these organisms. The ability to predict plant pathogen occurrence in space and time with species distribution models at local or global scale can help decision-makers to develop management strategies to prevent or minimize the impact of future disease outbreaks. [ABSTRACT FROM AUTHOR]

Triacylglycerol (TG) metabolism is tightly regulated to maintain a pool of TG within circulating lipoproteins that can be hydrolyzed in a tissue‐specific manner by lipoprotein lipase (LPL) to enable the delivery of fatty acids to adipose or oxidative tissues as needed. Elevated serum TG concentrations, which result from a deficiency of LPL activity or, more commonly, an imbalance in the regulation of tissue‐specific LPL activities, have been associated with an increased risk of atherosclerotic cardiovascular disease through multiple studies. Among the most critical LPL regulators are the angiopoietin‐like (ANGPTL) proteins ANGPTL3, ANGPTL4, and ANGPTL8, and a number of different apolipoproteins including apolipoprotein A5 (ApoA5), apolipoprotein C2 (ApoC2), and apolipoprotein C3 (ApoC3). These ANGPTLs and apolipoproteins work together to orchestrate LPL activity and therefore play pivotal roles in TG partitioning, hydrolysis, and utilization. This review summarizes the mechanisms of action, epidemiological findings, and genetic data most relevant to these ANGPTLs and apolipoproteins. The interplay between these important regulators of TG metabolism in both fasted and fed states is highlighted with a holistic view toward understanding key concepts and interactions. Strategies for developing safe and effective therapeutics to reduce circulating TG by selectively targeting these ANGPTLs and apolipoproteins are also discussed. [ABSTRACT FROM AUTHOR]

Many oomycetes are important plant pathogens that cause devastating diseases in agricultural fields, orchards, urban areas, and natural ecosystems. Limitations and difficulties associated with isolating these pathogens have led to a strong uptake of DNA metabarcoding and mass parallel sequencing. At least 21 primer combinations have been designed to amplify oomycetes, or more specifically, Phytophthora species, from environmental samples. We used the Illumina sequencing platform to compare 13 primer combinations on mock communities and environmental samples. The primer combinations tested varied significantly in their ability to amplify Phytophthora species in a mock community and from environmental samples; this was due to either low sensitivity (unable to detect species present in low concentrations) or a lack of specificity (an inability to amplify some species even if they were present in high concentrations). Primers designed for oomycetes underestimated the Phytophthora community compared to Phytophthora-specific primers. We recommend using technical replicates, primer combinations, internal controls, and a phylogenetic approach for assigning a species identity to OTUs or ASVs. Particular care must be taken if sampling substrates where hybrid species could be expected. Overall, the choice of primers should depend upon the hypothesis being tested. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection remains to be a substantial global burden, especially for end-stage liver diseases. It is well accepted that HBVspecific T and B cells are essential for controlling HBV infection. Toll-like receptors (TLRs) represent one of the major first-line antiviral defenses through intracellular signaling pathways that induce antiviral inflammatory cytokines and interferons, thereby shaping adaptive immunity. However, HBV has evolved strategies to counter TLR responses by suppressing the expression of TLRs and blocking the downstream signaling pathways, thus limiting HBVspecific adaptive immunity and facilitating viral persistence. Recent studies have stated that stimulation of the TLR signaling pathway by different TLR agonists strengthens host innate immune responses and results in suppression of HBV replication. In this review, we will discuss how TLR-mediated responses shape HBV-specific adaptive immunity as demonstrated in different experimental models. This information may provide important insight for HBV functional cure based on TLR agonists as immunomodulators. [ABSTRACT FROM AUTHOR]

The fast and continued progress of high-throughput sequencing (HTS) and the drastic reduction of its costs have boosted new and unpredictable developments in the field of plant pathology. The cost of whole-genome sequencing, which, until few years ago, was prohibitive for many projects, is now so affordable that a new branch, phylogenomics, is being developed. Fungal taxonomy is being deeply influenced by genome comparison, too. It is now easier to discover new genes as potential targets for an accurate diagnosis of new or emerging pathogens, notably those of quarantine concern. Similarly, with the development of metabarcoding and metagenomics techniques, it is now possible to unravel complex diseases or answer crucial questions, such as "What's in my soil?", to a good approximation, including fungi, bacteria, nematodes, etc. The new technologies allow to redraw the approach for disease control strategies considering the pathogens within their environment and deciphering the complex interactions between microorganisms and the cultivated crops. This kind of analysis usually generates big data that need sophisticated bioinformatic tools (machine learning, artificial intelligence) for their management. Herein, examples of the use of new technologies for research in fungal diversity and diagnosis of some fungal pathogens are reported. [ABSTRACT FROM AUTHOR]

Cyclic GMP–phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and women (45 to 80 years) with long-duration (>3 years) and well-controlled type 2 diabetes mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according to echocardiographic signs of cardiac remodeling. Patients were randomly assigned (1:1) to placebo or oral tadalafil (20 mg, once daily). The primary outcome was to evaluate sex differences in cardiac torsion change. Secondary outcomes were changes in cardiovascular, metabolic, immune, and renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement in cardiac torsion (−3.40°, −5.96; −0.84, P = 0.011) and fiber shortening (−1.19%, −2.24; −0.14, P = 0.027) in men but not women. The primary outcome could not be explained by differences in cGMP concentrations or tadalafil pharmacodynamics. In both sexes, tadalafil improved hsa-miR-199-5p expression, biomarkers of cardiovascular remodeling, albuminuria, renal artery resistive index, and circulating Klotho concentrations. Immune cell profiling revealed an improvement in low-grade chronic inflammation: Classic CD14++CD16− monocytes reduced, and Tie2+ monocytes increased. Nine patients (14.5%) had minor adverse reactions after tadalafil administration. Continuous PDE5 inhibition could offer a strategy to target cardiorenal complications of T2DM, with sex- and tissue-specific responses. Further studies are needed to confirm Klotho and hsa-miR-199-5p as markers for T2DM complications. Conditional cardioprotection: Phosphodiesterase 5 (PDE5) inhibition has been shown to have inconsistent cardioprotective effects. Here, Pofi et al. conducted a small phase 4 trial to assess sex differences in cardiac remodeling in patients with diabetes and diabetic cardiomyopathy treated with the PDE5 inhibitor tadalafil. They observed an improvement in cardiac shortening and torsion in men but not women, whereas circulating has-miR-199-5p was reduced and Klotho increased with treatment in both sexes. Certain populations of monocytes were also altered with treatment. Results highlight the importance of considering sex-specific differences in treatment response. [ABSTRACT FROM AUTHOR]

Weather attributes play a crucial role in the infection process and spread of pathogen. Alternaria leaf spot incited by Alternaria alternata is most destructive disease of soybean appeared in southern and eastern parts of Rajasthan as well as India. The effect of various weather parameters along with different date of sowing on the development of Alternaria leaf spot in susceptible soybean cultivar RKS-24 was investigated during Kharif season 2018 and 2019. The various weather factors viz., temperature, relative humidity and rainfall under inoculated conditions and with staggered dates of sowing were taken to observe effect on disease progression and their effect on seed yield. The maximum increase in disease severity (57.82 and 58.22%) and AUDPC (389.45 and 394.42) recorded in crop sown on 18th June (inoculated on 8th July). Lowest disease severity (39.80 and 38.50%) and AUDPC (266.18 and 259.18) were observed during 39–43th standard meteorological week (September, 24–October, 28) in year 2018 and 2019, respectively. Maximum seed yield (1699 kg ha−1) was recorded in plants sown on 9th July, while, lowest seed yield was recorded in plants sown on 18th June with 1441.20 kg ha−1. The trend of disease severity and AUDPC value decreased from early sowing to late sowing (18th June–9th July). Major reasons were fluctuations in temperature, rainfall and relative humidity. It was also observed that the soybean plants for Alternaria leaf spot disease in early sowing were predisposed and so farmers should be advised to practice delayed sowing of soybean crop. [ABSTRACT FROM AUTHOR]

Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host's defense against infectious diseases, autoimmune diseases, and cancer. [ABSTRACT FROM AUTHOR]