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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]

Background: Invasive fungal infections (IFIs) are important cause of mortality in acute myeloid leukemia (AML) patients on treatment with intensive induction chemotherapy. Toll-like receptors, mainly Toll-like receptors 2 and 4 (TLR2 and TLR4), play a considerable role in the host defense against microorganisms. The involvement of TLR signaling in modulation of innate immune response is extensively discussed, but the TLR expressions profiling on adaptive immune cells are not specified. Also, the expressions of TLRs and their association with the occurrence of IFIs in patients with AML are not studied. So, the novel aim of this study was to investigate the associations between the T-lymphocyte expression of TLR2 and TLR4 and the occurrence of IFIs in AML patients treated with intensive induction chemotherapy. Materials and Methods: One hundred twenty two newly diagnosed AML patients were evaluated. The laboratory diagnostic techniques for IFIs include culture, microscopic examination, histopathology, galactomannan assay and PCR. The expressions of TLR2 and TLR4 were analyzed by flow cytometry. The Control group included 20 age and sex-matched individuals. Results: There was a significant increase in the expression of TLR4 in AML patients with IFI compared to healthy controls (p = 0.001). TLR2 and TLR4 expressions increased significantly in AML patients with mixed fungal and bacterial infection compared to healthy controls (p= 0.002 and p=0.001, respectively). Conclusion: TLRs expressions could be important biological markers for the occurrence of IFI in non-M3 AML patients after intensive induction chemotherapy. [ABSTRACT FROM AUTHOR]

In the current context of environmental protection, a wide range of chemicals intended to control various pathogens in forest crops have been withdrawn due to the remnant of substances in the soil, thus polluting the natural environment. To achieve the proposed objective, experimental blocks were placed in the Sărata Nursery, Bistrița Forest District, and in the Rîtul de Jos Nursery, within the Livada Forest District, where sprays were made with fungicides with active substances - proquinazide 20% and azoxystrobin 200 g/l + difeconazole 125 g/l. Within the experimental blocks, three repetitions were established, in each repetition being materialized six treatment variants and an untreated control. In both experiments, after applying the treatments the degree of attack was distinctly significant between the treated variants (6.5-11.5%) and the untreated controls (18.2-31%). The effectiveness of the treatments has been moderate (47-69%), which requires new tests to evaluate the usefulness of these substances in the control of oak powdery mildew. [ABSTRACT FROM AUTHOR]

Background: Toll-like receptors (TLRs) play central roles in the initiation of innate immune response, and also control adaptive immunity activation. Thus, the aim of the study was to investigate the regulation of TLR activation to CD8+ T cells has not been fully elucidated in gastric cancer (GC). Materials and methods: Thirty-two GC patients and twenty-three healthy controls were enrolled. Expression profile of TLRs in peripheral and tumor-infiltrating CD8+ T cells was investigated. Purified CD8+ T cells were stimulated with Pam3Csk4, an agonist of TLR2, and cytotoxic and co-inhibitory molecules in CD8+ T cells was measured. Direct and indirect contact coculture system between CD8+ T cells and AGS cells was set up. Modulation of TLR2 activation to CD8+ T cells was assessed by measuring lactate dehydrogenase release and cytokine secretion. Results: TLR2 mRNA and TLR2+ cell percentage was down-regulated in GC derived peripheral and tumor-infiltrating CD8+ T cells. CD8+ T cells from GC patients showed exhausted phenotype, which presented as decreased perforin/granzyme B, increased programmed death-1, and reduced cytotoxicity to AGS cells. TLR2 activation by Pam3Csk4 enhanced perforin and granzyme B expression in CD8+ T cells, however, did not affect either proinflammatory cytokine production or co-inhibitory molecules expression. Pam3Csk4 stimulation enhanced cytolytic activation of peripheral and tumor-infiltrating CD8+ T cells from GC, but not those from healthy individuals. Conclusion: The present data revealed an important immunomodulatory activity of TLR2 to CD8+ T cells in GC patients. [ABSTRACT FROM AUTHOR]

Summary: The soil pathogen‐induced Janzen–Connell (JC) effect is considered as a primary mechanism regulating plant biodiversity worldwide. As predicted by the framework of the classic plant disease triangle, severity of plant diseases is often influenced by temperature, yet insufficient understanding of how increasing temperatures affect the JC effect contributes uncertainty in predictions about how global warming affects biodiversity.We conducted a 3‐yr field warming experiment, combining open‐top chambers with pesticide treatment, to test the effect of elevated temperatures on seedling mortality of a temperate tree species, Prunuspadus, from a genus with known susceptibility to soil‐borne pathogens.Elevated temperature significantly increased the mortality of P. padus seedlings in the immediate vicinity of parent trees, concurrent with increased relative abundance of pathogenic fungi identified to be virulent to Prunus species.Our study offers experimental evidence suggesting that global warming significantly intensifies the JC effect on a temperate tree species due to increased relative abundance of pathogenic fungi. This work advances our understanding about changes in the JC effect linked to ongoing global warming, which has important implications for predicting tree diversity in a warmer future. [ABSTRACT FROM AUTHOR]

Understanding variations in soil humus and fine root properties in Oriental beech (Fagus orientalis L.) stand in response to development stages in temperate Hyrcanian forests is essential for sustainable forest management. The development stages of beech stand (initial, optimal and decay) were determined, and three plots of 100 × 100 m (1 ha) were chosen at each development stage. Five subplots in size 20 × 20 m were randomly selected at plots of 1 ha. The concentrations of humus elements (C, P, K, Mg, Fe and Zn) differed significantly among the development stages in spring and autumn seasons within Beech forest. The comparison of mean chemical compounds of humus layer in spring and autumn seasons using t test showed significant difference for each the development stage. Differences in C, N and P concentrations and also C/N and N/P ratios in fine roots of beech trees were significant among development stages, while C/P ratio was insignificant. The mean values of N and P for initial stage were higher, but C and N/P ratio were higher for optimal stage. The highest C/N value was observed in decay stage. There were statistically significant effects of development stages on fine root biomass and morphology traits at different diameter classes in beech trees. No statistically significant impacts of development stages were observed on fine root morphology of beech trees, except for fine root density. Our results reveal the important role that different development stages may play in Beech forest regarding variations in chemical properties of fine roots and soil humus. [ABSTRACT FROM AUTHOR]

Background: OryzaGenome (http://viewer.shigen.info/oryzagenome21detail/index.xhtml), a feature within Oryzabase (https://shigen.nig.ac.jp/rice/oryzabase/), is a genomic database for wild Oryza species that provides comparative and evolutionary genomics approaches for the rice research community. Results: Here we release OryzaGenome2.1, the first major update of OryzaGenome. The main feature in this version is the inclusion of newly sequenced genotypes and their meta-information, giving a total of 217 accessions of 19 wild Oryza species (O. rufipogon, O. barthii, O. longistaminata, O. meridionalis, O. glumaepatula, O. punctata, O. minuta, O. officinalis, O. rhizomatis, O. eichingeri, O. latifolia, O. alta, O. grandiglumis, O. australiensis, O. brachyantha, O. granulata, O. meyeriana, O. ridleyi, and O. longiglumis). These 19 wild species belong to 9 genome types (AA, BB, CC, BBCC, CCDD, EE, FF, GG, and HHJJ), representing wide genomic diversity in the genus. Using the genotype information, we analyzed the genome diversity of Oryza species. Other features of OryzaGenome facilitate the use of information on single nucleotide polymorphisms (SNPs) between O. sativa and its wild progenitor O. rufipogon in rice research, including breeding as well as basic science. For example, we provide Variant Call Format (VCF) files for genome-wide SNPs of 33 O. rufipogon accessions against the O. sativa reference genome, IRGSP1.0. In addition, we provide a new SNP Effect Table function, allowing users to identify SNPs or small insertion/deletion polymorphisms in the 33 O. rufipogon accessions and to search for the effect of these polymorphisms on protein function if they reside in the coding region (e.g., are missense or nonsense mutations). Furthermore, the SNP Viewer for 446 O. rufipogon accessions was updated by implementing new tracks for possible selective sweep regions and highly mutated regions that were potentially exposed to selective pressures during the process of domestication. Conclusion: OryzaGenome2.1 focuses on comparative genomic analysis of diverse wild Oryza accessions collected around the world and on the development of resources to speed up the identification of critical trait-related genes, especially from O. rufipogon. It aims to promote the use of genotype information from wild accessions in rice breeding and potential future crop improvements. Diverse genotypes will be a key resource for evolutionary studies in Oryza, including polyploid biology. [ABSTRACT FROM AUTHOR]

The slope aspect is one of the most critical topographic factors in mountainous areas. Little is known, however, about the effect of the aspect on the ectomycorrhizal (ECM) fungal community. Additionally, we know very little about the composition of ECM fungal communities associated with Quercus variabilis, which is widely distributed in East Asia. In this study, we compared the richness, community composition, and exploration types of ECM fungi associated with Q. variabilis between predominantly south- and north-facing slopes in the Taihang Mountain, North China for the first time. DNA was extracted from the root tips of Q. variabilis, and Illumina MiSeq sequencing was used to identify ECM fungi. In total, 168 operational taxonomic units belonging to 28 genera were detected, and the ECM community was found to be dominated by Russula, Inocybe, Tomentella, Scleroderma, and Cortinarius. Compared with the north-facing slopes, the ECM communities on the south-facing slopes had higher diversity. The community composition and exploration types were directly affected by the slope aspect. Also, the aspect-induced edaphic variables, such as total phosphorus, total nitrogen, total potassium, pH, and soil water content, were important sources of variation in ECM fungal richness and distributions of exploration types. Different genera tended to be distributed in various slope aspects. Cenococcum, Genea, and Clavulina were significantly enriched in north-facing slopes, while Geopora, Helvelosebacina, Scleroderma, Gyroporus, Astraeus, Boletus, Tricholoma, Hebeloma, Cortinarius and unclassified Thelephoraceae were more abundant in south-facing slopes. Hydrophobic ECM fungi were obviously enriched in the south-facing slope, but there was no statistical difference between hydrophilic among the south- and north-facing slopes. Our study deepened our knowledge of the aspect-driven variation in ECM fungal communities associated with Q. variabilis. [ABSTRACT FROM AUTHOR]

A conceptual framework for evaluation of climate effects on tree diseases is presented. Climate can exacerbate tree diseases by favouring pathogen biology, including reproduction and infection processes. Climatic conditions can also cause abiotic disease—direct stress or mortality when trees' physiological limits are exceeded. When stress is sublethal, weakened trees may subsequently be killed by secondary organisms. To demonstrate climate's involvement in disease, associations between climatic conditions and disease expression provide the primary evidence of atmospheric involvement because experimentation is often impractical for mature trees. This framework tests spatial and temporal relationships of climate and disease at several scales to document climate effects, if any. The presence and absence of the disease can be contrasted with climate data and models at geographic scales: stand, regional and species range. Temporal variation in weather, climate and climate change is examined during onset, development and remission of the disease. Predisposing factors such as site and stand conditions can modify the climate effects of some diseases, especially at finer spatial scales. Spatially explicit climate models that display temperature and precipitation or derivative models such as snow and drought stress provide useful data, and however, information on disease extent at different spatial scales and monitoring through time are often incomplete. The framework can be used to overcome limitations in other disease causality approaches, such as Koch's postulates, and allow for the integration of vegetation, pathogen and environmental data into causality determinations. [ABSTRACT FROM AUTHOR]

Summary: The genus Phytophthora represents a group of plant pathogens with broad global distribution. The majority of them cause the collar and root‐rot of diverse plant species. Little is known about Phytophthora communities in forest ecosystems, especially in the Neotropical forests where natural enemies could maintain the huge plant diversity via negative density dependence. We characterized the diversity of soil‐borne Phytophthora communities in the North French Guiana rainforest and investigated how they are structured by host identity and environmental factors. In this little‐explored habitat, 250 soil cores were sampled from 10 plots hosting 10 different plant families across three forest environments (Terra Firme, Seasonally Flooded and White Sand). Phytophthora diversity was studied using a baiting approach and metabarcoding (High‐Throughput Sequencing) on environmental DNA extracted from both soil samples and baiting‐leaves. These three approaches revealed very similar communities, characterized by an unexpected low diversity of Phytophthora species, with the dominance of two cryptic species close to Phytophthora heveae. As expected, the Phytophthora community composition of the French Guiana rainforest was significantly impacted by the host plant family and environment. However, these plant pathogen communities are very small and are dominated by generalist species, questioning their potential roles as drivers of plant diversity in these Amazonian forests. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine if mouse bone marrow-derived mesenchymal stem cells (BMMSCs) ameliorate preterm birth and perinatal brain injury induced by intrauterine inflammation (IUI). A mouse model of IUI-induced perinatal brain injury at embryonic (E) day 17 was utilized. BMMSCs were derived from GFP-transgenic mice and phenotypically confirmed to be CD44+, Sca-1+, CD45−, CD34−, CD11b−, and CD11c− by flow cytometry and sorted by fluorescence-activated cell sorting (FACS). Dams were assigned to four groups: phosphate-buffered saline (PBS) + PBS, PBS + BMMSCs, lipopolysaccharide (LPS) + PBS, and LPS + BMMSCs. Following maternal IUI, there was a significant increase in CD8+ T cells in the placentas. Maternally administered BMMSCs trafficked to the fetal side of the placenta and resulted in significantly decreased placental CD8+ T cells. Furthermore, fetal trafficking of maternally administered BMMSCs correlated with an improved performance on offspring neurobehavioral testing in LPS + BMMSC group compared with LPS + PBS group. Our data support that maternal administration of BMMSCs can alleviate perinatal inflammation-induced brain injury and improve neurobehavioral outcomes in the offspring via CD8+ T cell immunomodulation at the feto-placental interface. [ABSTRACT FROM AUTHOR]

Sensing of microbes or of danger signals has mainly been attributed to myeloid innate immune cells. However, T and B cells also express functional pattern recognition receptors (PRRs). In these cells, PRRs mediate signaling cascades that result in different functions depending on the cell's activation and/or differentiation status, on the environment, and on the ligand/agonist. Some of these functions are beneficial for the host; however, some are detrimental and are exploited by pathogens to establish persistent infections. In this review, we summarize the available literature on innate immune sensing by cells of the adaptive immune system and discuss possible implications for chronic infections. [ABSTRACT FROM AUTHOR]

Determines the effect of macronutrient composition of pre-exercise meals on exercise metabolism and performance in the field of sport nutrition as of December 2003. Primary purpose of the study; Criteria defining maximal oxygen consumption; Physical characteristics of the subjects; Determinant of a glucose isotopic enrichment.

The activation of TLR7 signaling in T cells accelerates antigen-specific responses. Such responses play an essential role in eliminating viral infections and can be anti-tumorigenic. However, the underlying mechanisms of how TLR7 can promote the optimal function of CD8+ T cells remain unclear. To investigate how TLR signaling directly contributes to CD8+ T cell functions, we examine the activation of cellular TLR7-related pathways and functional and metabolic alterations in TLR7-stimulated T cells during T cell receptor (TCR) signaling. In the present study, we investigated the activation of CD8+ T cells in response to direct stimulation by TLR7 ligands. TLR7 stimulation could promote the effector functions of purified CD8+ T cells in vitro. The TLR7-induced activation of CD8+ T cells occurs if CD8+ T cells were primed by αCD3 activation and increasingly expressed TLR7. MyD88 and AKT-mTOR signaling plays a critical role in TLR7-induced T cell activation. In addition to the upregulation of immune-related genes, metabolic alterations in CD8+ T cells, including the upregulation of glucose uptake and glycolysis, occurred by TLR7 stimulation. Glycolysis was found to be regulated by the AKT-mTOR pathway and a downstream transcription factor IRF4. Blocking glycolysis by either direct glucose deprivation or modulating the mTOR pathway and IRF4 expression was found to impair T cell activation and functions. Taken together, the activation of TLR7 signaling promotes the effector functions of CD8+ T cells by enhancing cellular glycolysis. [ABSTRACT FROM AUTHOR]

Oomycetes are eukaryotic plant pathogens that require health monitoring. High-throughput sequencing (HTS) methods replace progressively cultivation-based approaches in soil surveys of Oomycetes, but very little control has been done from synthetic communities. Indeed, several potential biases do exist and need to be assessed for Oomycetes communities. We created a mock community by mixing DNA from 24 Phytophthora species. We amplified two barcode regions with Oomycete-specific primers before HTS. With this aim, we used three primer sets in nested PCR amplification, targeting the ITS-1 region or the RAS gene region. The three nested PCR strategies proved to be a reliable qualitative approach, identifying approximately 95% of the species after Illumina Miseq sequencing and bioinformatic analysis. However, quantitative proportions of each species showed distortions compared to the original mixture of the mock. In addition, we compared the two ITS primer sets on soil environmental DNA sampled from temperate forests. The 'oom18S-ITS7/18ph2f-5.8S-1R' primer set, more specific to Phytophthora, was able to detect seven Phytophthora species, confirming what was expected for temperate forests. Using the 'DC6-ITS7/oom18S-ITS7' primer set that covers the broader Peronosporaceans, we detected only one Phytophthora species among the dominance of Pythium and Phytopythium species. We concluded that 'oom18S-ITS7/18ph2f-5.8S-1R' primer set is a reliable tool for the qualitative description of environmental Phytophthora communities. [ABSTRACT FROM AUTHOR]

The innate immunity is frequently accepted as a first line of relatively primitive defense interfering with the pathogen invasion until the mechanisms of 'privileged' adaptive immunity with the production of antibodies and activation of cytotoxic lymphocytes 'steal the show'. Recent advancements on the molecular and cellular levels have shaken the traditional view of adaptive and innate immunity. The innate immune memory or 'trained immunity' based on metabolic changes and epigenetic reprogramming is a complementary process insuring adaptation of host defense to previous infections. Innate immune cells are able to recognize large number of pathogen- or danger- associated molecular patterns (PAMPs and DAMPs) to behave in a highly specific manner and regulate adaptive immune responses. Innate lymphoid cells (ILC1, ILC2, ILC3) and NK cells express transcription factors and cytokines related to subsets of T helper cells (Th1, Th2, Th17). On the other hand, T and B lymphocytes exhibit functional properties traditionally attributed to innate immunity such as phagocytosis or production of tissue remodeling growth factors. They are also able to benefit from the information provided by pattern recognition receptors (PRRs), e.g. γδT lymphocytes use T-cell receptor (TCR) in a manner close to PRR recognition. Innate B cells represent another example of limited combinational diversity usage participating in various innate responses. In the view of current knowledge, the traditional black and white classification of immune mechanisms as either innate or an adaptive needs to be adjusted and many shades of gray need to be included. [ABSTRACT FROM AUTHOR]

Eco-climatic niche models are powerful tools for assessing the potential range of plant pests and pathogens, widely applied in comprehensive pest risk assessments globally. We conducted a bibliometric analysis comparing the number of CLIMEX models developed for plant pathogens and plant arthropod pests. We found that plant pathogens were statistically significantly under-represented, with fungal plant pathogens less than half as likely as plant insect pests to be the subject of a published CLIMEX niche model. We explore key factors that may account for this disparity, including inconsistent experimental paradigms and lack of cross-disciplinary (i.e., plant pathology and modelling) expertise. [ABSTRACT FROM AUTHOR]

Summary: Casuarina equisetifolia (C. equisetifolia), a conifer‐like angiosperm with resistance to typhoon and stress tolerance, is mainly cultivated in the coastal areas of Australasia. C. equisetifolia, making it a valuable model to study secondary growth associated genes and stress‐tolerance traits. However, the genome sequence is unavailable and therefore wood‐associated growth rate and stress resistance at the molecular level is largely unexplored. We therefore constructed a high‐quality draft genome sequence of C. equisetifolia by a combination of Illumina second‐generation sequencing reads and Pacific Biosciences single‐molecule real‐time (SMRT) long reads to advance the investigation of this species. Here, we report the genome assembly, which contains approximately 300 megabases (Mb) and scaffold size of N50 is 1.06 Mb. Additionally, gene annotation, assisted by a combination of prediction and RNA‐seq data, generated 29 827 annotated protein‐coding genes and 1983 non‐coding genes, respectively. Furthermore, we found that the total number of repetitive sequences account for one‐third of the genome assembly. Here we also construct the genome‐wide map of DNA modification, such as two novel forms N6‐adenine (6mA) and N4‐methylcytosine (4mC) at the level of single‐nucleotide resolution using single‐molecule real‐time (SMRT) sequencing. Interestingly, we found that 17% of 6mA modification genes and 15% of 4mC modification genes also included alternative splicing events. Finally, we investigated cellulose, hemicellulose, and lignin‐related genes, which were associated with secondary growth and contained different DNA modifications. The high‐quality genome sequence and annotation of C. equisetifolia in this study provide a valuable resource to strengthen our understanding of the diverse traits of trees. Significance Statement: We constructed a high‐quality draft genome sequence of C. equisetifolia and systematically characterized 29,827 annotated protein‐coding genes and 1,983 non‐coding genes, respectively. Furthermore, we construct the genome‐wide map of DNA modification, such as two novel forms N6‐Adenine (6mA) and N4‐methylcytosine (4mC), including the genes in the regulation of lignin and cellulose. The high‐quality genome resource in this study provides valuable resources to strengthen our understanding of the diverse traits of trees. [ABSTRACT FROM AUTHOR]

In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 5l-o showed the most potent cytotoxicity on all cell lines with IC50 values in the range of 0.3-3.7 μM. To explore the mechanistic aspects fundamental to the observed activity, further biological studies with 5m and 5o in liver cancer cells were carried out. We have demonstrated that 5m and 5o induce oxidative stress in PTEN adequate Huh7 and PTEN deficient Mahlavu human liver cancer cells leading to apoptosis and cell cycle arrest at different phases. Further analysis of the proteins involved in apoptosis and cell cycle revealed that 5m and 5o caused an inhibition of cell survival pathway through Akt hyperphosphorylation and apoptosis and cell cycle arrest through p53 protein activation. [ABSTRACT FROM AUTHOR]

Background/Aims: The hepatitis B virus X protein (HBx) is a viral trans-activator that plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) via an unknown mechanism. The role of HBx in modulating cell proliferation and programmed cell death is replete with controversies. Thus, the goal of this study was to elucidate the effect of HBx and its deletion mutants on cell cycle progression in human hepatoma cells. Methods: Huh7 cells transfected with either full-length or truncated HBx were tested for their mitogenic potential based on their effect on the expression of key cell cycle-related proteins (p27, cyclin D1, p21, and p53) and pro-apoptotic proteins such as cleaved poly (ADP-ribose) polymerase (PARP) and Bax. Western blotting and immunofluorescence techniques were applied to detect changes in the expression levels and intracellular localization, respectively, of the investigated proteins. Also, Quantitative real-time PCR (qRT-PCR) was used to detect changes in RNA levels. Results: An increased anchorage-independent growth of cells transfected with HBx-WT and its deletion mutants was observed. The cell cycle regulatory molecules were differentially modulated by full-length HBx (1-154) and its different N- and C-terminal truncated forms (HBx (31-154), HBx (61-154), HBx (1-94), and HBx (61-124)). An enhanced modulation of p27, p21, and cyclin D1 was associated with HBx (1-154), whereas p53 expression was significantly inhibited by HBx (61-124). Similarly, the expression of cleaved PARP and Bax was efficiently suppressed by HBx (1-94) and HBx (61-154). Conclusion: The HBx-WT and its mutants play a critical role in the pathogenesis and progression of HCC by modulating cell cycle regulatory proteins. [ABSTRACT FROM AUTHOR]

Understanding how soil pedogenesis affects microbial communities and their in situ activities according to ecosystem functioning is a central issue in soil microbial ecology, as soils represent essential nutrient reservoirs and habitats for the biosphere. To address this question, soil chronosequences developed from a single, shared mineralogical parent material and having the same climate conditions are particularly useful, as they isolate the factor of time from other factors controlling the character of soils. In our study, we considered a natural succession of uplifted marine terraces in Mendocino, CA, ranging from highly fertile in the younger terrace (about 100,000 years old) to infertile in the older terraces (about 300,000 years old). Using ITS amplicon pyrosequencing, we analysed and compared the diversity and composition of the soil fungal communities across the first terraces (T1 to T3), with a specific focus in the forested terraces (T2 and T3) on soil samples collected below trees of the same species (Pinus muricata) and of the same age. While diversity and richness indices were highest in the grassland (youngest) terrace (T1), they were higher in the older forested terrace (T3) compared to the younger forested terrace (T2). Interestingly, the most abundant ectomycorrhizal (ECM) taxa that we found within these fungal communities showed high homology with ITS Sanger sequences obtained previously directly from ECM root tips from trees in the same study site, revealing a relative conservation of ECM diversity over time. Altogether, our results provide new information about the diversity and composition of the fungal communities as well as on the dominant ECM species in the soil chronosequence of Mendocino in relation to soil age and ecosystem development. [ABSTRACT FROM AUTHOR]

Immune defense against infection with the hepatitis B virus (HBV) is complex and involves both host innate and adaptive immune systems. It is well accepted that the development of sufficient HBV-specific T cell and B cell responses are required for controlling an HBV infection. However, the contribution of innate immunity to removing HBV has been explored in recent years. Toll-like receptors (TLRs) are recognized as the first line of antiviral immunity because they initiate intracellular signaling pathways to induce antiviral mediators such as interferons (IFNs) and other cytokines. Recent studies show that the activation of TLR-mediated signaling pathways results in a suppression of HBV replication in vitro and in vivo. However, HBV has also evolved strategies to counter TLR responses including the suppression of TLR expression and the blockage of downstream signaling pathways. Antiviral treatment in chronic HBV-infected patients leads to an upregulation of TLR expression and the restoration of its innate antiviral functions. Thus, TLR activation may serve as an additional immunotherapeutic option for treating chronic HBV infection in combination with antiviral treatment. [ABSTRACT FROM AUTHOR]

Hazelnut (Corylus avellana L.) which is intensively grown in the Black Sea region is the most important agricultural product of Turkey. Hazelnut production and quality are negatively affected by several diseases and pests. Powdery mildew is nowadays one of the most common diseases in almost whole hazelnut producing areas. The disease is caused by two different species, Phyllactinia guttata (Wallr. et Lev.) Fr. and Erysiphe corylacearum U. Braun & S. Takam. For the last 4 years, E. corylacearum, a newly invasive fungus in Turkey, has been caused significant economic losses. In the present study, the efficacy of ammonium, potassium and sodium bicarbonates, and two fungicides were evaluated in field trials against powdery mildew on hazelnuts in Samsun in 2016. The application rates of compounds used in the experiment were as follows: ammonium, potassium and sodium bicarbonates (Sigma-Aldrich, Seelze, Germany) at 1.5, 3, 4.5 and 6% (w/v); Collis® SC (100 g/l Kresoxim methyl +200 g/l Boscalid, BASF, Spain) at 30 ml/100 l and Sulflow® 80 WG (Sulphur 800 g/l, Agrofarm, Turkey) at 400 g/100 l. Of the compounds tested, except for fungicides, sodium was found to be the most effective in controlling the powdery mildew on hazelnuts, followed by potassium and ammonium, respectively. Among those three, ammonium bicarbonate was ineffective against fruit infections of the disease. There was also no significant difference between inhibitory effects of 6% sodium bicarbonate, Collis and Sulflow against the disease (P < 0.05). In addition, bicarbonate salts was phytotoxic to hazelnut leaves at concentrations greater than 1.5%. The results indicate that sodium or potassium bicarbonate solutions seems to be a useful biocompatible fungicide for controlling the powdery mildew on hazelnuts. [ABSTRACT FROM AUTHOR]

Quercus roburL. was micropropagated by axillary bud proliferation testing two different shoot culture systems: (i) on gelled medium in Microbox (plastic vessel with a strip for ventilation) and (ii) in liquid culture in PlantformTMbioreactor (a temporary immersion system). Two different conditions of temporary immersion were assessed: 12 min/8 h (Plantform 1) and 8 min/16 h (Plantform 2). The effect of the two culture systems was evaluated also during subsequent rooting phase, carried out on gelled medium. Finally, the influence of the different culture conditions on leaf structure was considered, taking also into consideration the micromorphological characters of young leaves from in-field-grown oaks. Nodal segments, excised from establishedin vitroshoots and cultured on modified Woody Plant Medium, showed a higher Relative Growth Rate in Plantform than in Microbox, but culture conditions provided in Plantform 1 favored shoot and leaf hyperhydricity. Shoots cultured in Microbox or Plantform 2 presented the same percentage of rooting after their transfer on gelled rooting medium. Leaves developed in the two different microenvironments had large stomata with elliptical shape, which indicates good functionality, and formed hairs, and epicuticolar waxes. These leaf features are considered to provide a good adaptability toex vitroconditions. [ABSTRACT FROM PUBLISHER]

Brenneria goodwinii is one of the most frequently isolated Gram-negative bacteria from native oak species, Quercus robur and Q. petraea, affected by acute oak decline (AOD) in the UK. We investigated the population biology of this bacterial species using a multilocus sequence analysis to determine the population structure and evolutionary potential. Seven partial housekeeping genes were used in the analyses. Amongst 44 bacterial strains from seven different locations, we identified 22 unique sequence types [STs]; only one ST was found at two separate locations. Phylogenetic and cluster-based analyses suggested that B. goodwinii STs form two main distinct groups; however, no geographical pattern of their distribution could be observed. Clonality and recombination tests demonstrated that the studied population is primarily clonal, however both mutation and recombination processes play a role in shaping the genetic structure and evolution of the population. Our study suggests that the B. goodwinii population on oak in the UK has an endemic form, with background recombination appearing to generate new alleles more frequently than mutation, despite the introduction of nucleotide substitutions being approximately twice less likely than mutation. The newly emerged STs subsequently undergo clonal expansion to become dominant genotypes within their specific geographical locations and even within the individual host oak trees. [ABSTRACT FROM AUTHOR]

Background: There is global variation in the onset of hepatocellular carcinoma (HCC). The objective of the current study was to investigate the impact of country of birth on age at the time of HCC diagnosis in the United States.Methods: Incident HCC cases diagnosed between 2000 and 2012 in the Surveillance, Epidemiology, and End Results program 18 registry were included. Factors associated with very early onset (age at diagnosis < 40 years) and early onset (age at diagnosis < 50 years) were identified by logistic regression.Results: A total of 59,907 patients were included. The median age at the time of diagnosis of HCC was 62 years and 76% of the patients were male. Of the 75% of patients for whom information regarding birth country was available, 29% were foreign born. In multivariate logistic regression, birth in West Africa (adjusted odds ratio [AOR], 16.3; 95% confidence interval [95% CI], 9.2-27.9 [P<.01]), Central/South/other Africa (AOR, 11.0; 95% CI, 4.5-23.7 [P<.01]), Oceania (AOR, 4.9; 95% CI, 2.9-8.0 [P<.01]), and East Africa (AOR, 3.5; 95% CI, 1.5-6.8 [P<.01]) was found to have the strongest association with very early-onset HCC after adjusting for sex and race/ethnicity. Birth in West Africa, Central/South/other Africa, Oceania, or East Africa also was found to be strongly associated with early-onset HCC.Conclusions: Birth country was found to be independently associated with age at the time of HCC diagnosis in the United States. Birth in Africa (except for North Africa) and Oceania was strongly associated with very early-onset HCC. These findings have implications for the design of comprehensive HCC surveillance programs in the United States. Cancer 2016. © 2016 American Cancer Society. Cancer 2017;81-89. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Mycelial fan formation was studied in five Armillaria cepistipes, ten A. borealis and ten diploid and six haploid A. ostoyae strains on excised stem segments of Picea abies. Stem segments were either non-autoclaved or autoclaved, representing dying and dead wood, respectively. To confirm the identity of mycelial fans on non-autoclaved stem segments, re-isolations were made and isolates characterized with microsatellite markers. Mycelial fan formation on autoclaved stem segments was fast and reliable for most of the tested Armillaria strains. On non-autoclaved stem segments, mycelial fan formation was slower, more erratic and less predictable. Mycelial fan formation was fastest in A. cepistipes closely followed by A. borealis and was slowest in A. ostoyae. For two A. cepistipes and four A. ostoyae strains (all diploid), growth rates of mycelial fans were estimated in a time course experiment. They ranged between 5.1 and 8.7 mm/day for autoclaved and between 1.4 and 4.7 mm/day for non-autoclaved stem segments. The haploid A. ostoyae strains also formed mycelial fans on autoclaved stem segments, but typically slower and less reliably than the diploid strains. Whether haploid strains are able to produce mycelial fans on non-autoclaved stem segments remains unknown because of accidental diploidization of the original haploid strains which was likely caused by basidiospores introduced into the study system on the non-autoclaved stems. Overall, the method developed in this study may be useful for further investigations into the genetic, physiological and biochemical nature of mycelial fan formation in the genus Armillaria. [ABSTRACT FROM AUTHOR]

Context: Fusarium circinatum is an invasive forest pathogen causing pitch canker in Europe. It attacks several pine species and Douglas firs. It has already invaded a few places in the Iberian Peninsula and Italy. Aims: The aim of this study is to develop a model for simulating the spread of F. circinatum once it enters Europe via various entry points such as harbours, border stations and from nurseries containing tree seedlings. Methods: The spread rate was modelled as a function of the spatial distribution of pine and Douglas firs, climatic suitability of different locations to F. circinatum, seedling transportation, insect-mediated transfer from tree to tree, and spread of airborne spores. Results: The fungus is likely to spread to the pine forests of northern Spain (Galicia, Cantabria and Basque Country) and southwest France (Aquitania). There will be some spread towards northern Portugal and southern Italy. Unless there are new arrivals to Central and North Europe, the fungus will not spread to the more northern parts of Europe. Due to the short dispersal distance of spores, F. circinatum cannot easily cross spatial discontinuities in the distribution of host species. Conclusion: F. circinatum is a serious potential invasive forest pathogen in Europe. New admittances of the spores from international trading should be controlled. [ABSTRACT FROM AUTHOR]

The role of adaptive immune responses in the control of hepatitis B virus (HBV) infection is well accepted. The contribution of innate immune responses to the viral control is recognized but yet not fully understood. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms including the intracellular antiviral pathways and the production of antiviral effectors like interferons (IFNs) and pro-inflammatory cytokines. Activation of the TLR3 pathway and the production of IFN-β represent one of the major mechanisms leading to the suppression of HBV replication in the liver, as shown in different in vitro and in vivo models. TLR4 signaling and TLR2 signaling result in the activation of intracellular pathways including MAPK and PI-3 K/Akt in hepatocytes and reduce HBV replication in an IFN-independent manner. HBV is able to counteract the actions of TLR3 and TLR2/4 through downregulation of TLR expression and attenuation of the cellular signaling pathways. Thus, TLR ligands are promising candidates as immunomodulators and therapeutics for the treatment of chronic HBV infection. Specific antiviral treatment against HBV could recover the TLR functions in chronic HBV infection and increase the effectiveness of therapeutic approaches based on TLR activation. [ABSTRACT FROM AUTHOR]