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Therapy resistance is the principal obstacle to achieving cures in cancer patients and its successful tackling requires a deep understanding of the resistance mediators. Increasing evidence indicates that tumor phosphatases are novel and druggable targets in translational oncology and their modulation may hinder tumor growth and motility and potentiate therapeutic sensitivity in various neoplasms via regulation of various signal transduction pathways. Dual-specificity phosphatases (DUSPs) are key players of cell growth, survival and death and have essential roles in tumor initiation, malignant progression and therapy resistance through regulation of the MAPK signaling pathway. In this review, different aspects of DUSPs are discussed.<br />A comprehensive literature review was performed using various websites including PubMed.<br />We provide mechanistic insights into the roles of well-known DUSPs in resistance to a wide range of cancer therapeutic approaches including chemotherapy, radiation and molecular targeted therapy in human malignancies. Moreover, we discuss the development of DUSP modulators, with a focus on DUSP1 and 6 inhibitors. Ultimately, the preclinical investigations of small molecule inhibitors of DUSP1 and 6 are outlined.<br />Emerging evidence indicates that the DUSP family is aberrantly expressed in human malignancies and plays critical roles in determining sensitivity to a wide range of cancer therapeutic strategies through regulation of the MAPK signaling pathways. Consequently, targeting DUSPs and their downstream molecules can pave the way for more effective cancer therapies.<br />Emerging evidence indicates that the DUSP family is aberrantly expressed in human malignancies and plays critical roles in determining sensitivity to a wide range of cancer therapeutic strategies through regulation of the MAPK signaling pathways. Consequently, targeting DUSPs and their downstream molecules can pave the way for more effective cancer therapies.To identify genes altered in a highly aggressive metastatic meningioma primary as well as its metastases. Exome sequencing of a primary anaplastic meningioma and metastatic lesions in which DNA could be extracted and compared to germline DNA. Genetic analysis of the metastatic sites found 31 common mutations among the primary tumor and two metastatic sites. Additionally, genetic mutations were identified which were either infrequently (MUC3A, ALDH1A3, HOXA1) or not at all previously described in meningiomas (CASS4, CMKLR1). Exome sequencing of a metastatic meningioma and its distant metastases outside the CNS identified mutations that were not previously well described.<br />Intramedullary (IM) nail use for metaphyseal fracture management is problematic in long bones like the femur because the larger medullary cavity allows increased fracture motion and potentially increased implant failure and malunion/nonunion risk; Achieving effective distal femur fracture fixation is even more difficult in osteoporotic bone. Blocking screws to control IM nail movement are known to be effective for tibia fracture management. Few studies have evaluated IM nail and blocking screw use efficacy for distal femur fracture fixation in osteoporotic bone.<br />This study used an osteoporosis simulation synthetic bone model to evaluate retrograde IM nail fixation of a standardized non-comminuted, extra-articular distal femur fracture with and without blocking screws. The hypothesis was that use of one or two blocking screws would increase IM nail fixation stability as evidenced by greater peak IM nail load and lesser movement. A servohydraulic device under displacement control collected loading force versides of the IM nail decreased coronal plane movement in the intramedullary canal. Combining retrograde IM nail implantation with blocking screws reduced medial-lateral IM nail movement and increased fracture stability. These characteristics may help prevent fixation failure, malunion, and even nonunion in patients with a distal femur fracture in osteoporotic bone.<br />Use of one or two blocking screws on the medial and lateral sides of the IM nail decreased coronal plane movement in the intramedullary canal. Combining retrograde IM nail implantation with blocking screws reduced medial-lateral IM nail movement and increased fracture stability. [https://www.selleckchem.com/products/ly2157299.html Galunisertib] These characteristics may help prevent fixation failure, malunion, and even nonunion in patients with a distal femur fracture in osteoporotic bone.Cassava, forming starch-rich, tuberous roots, is an important staple crop in smallholder farming systems in sub-Saharan Africa. Its relatively good tolerance to drought and nutrient-poor soils may be partly attributed to the crop's association with arbuscular mycorrhiza fungi (AMF). Yet insights into AMF-community composition and richness of cassava, and knowledge of its environmental drivers are still limited. Here, we sampled 60 cassava fields across three major cassava-growing agro-ecological zones in Nigeria and used a DNA meta-barcoding approach to quantify large-scale spatial variation and evaluate the effects of soil characteristics and common agricultural practices on AMF community composition, richness and Shannon diversity. We identified 515 AMF operational taxonomic units (OTUs), dominated by Glomus, with large variation across agro-ecological zones, and with soil pH explaining most of the variation in AMF community composition. High levels of soil available phosphorus reduced OTU richness without affecting Shannon diversity. Long fallow periods (&gt; 5 years) reduced AMF richness compared with short fallows, whereas both zero tillage and tractor tillage reduced AMF diversity compared with hoe tillage. This study reveals that the symbiotic relationship between cassava and AMF is strongly influenced by soil characteristics and agricultural management and that it is possible to adjust cassava cultivation practices to modify AMF diversity and community structure.Enriched surface ozone (O3) can impose harmful effects on plants. Conversely, arbuscular mycorrhizal (AM) symbiosis can enhance plant tolerance to various environmental stresses and facilitate plant growth. The interaction of AM fungi and O3 on plant performance, however, seldom has been investigated. In this study, alfalfa (Medicago sativa L.) was used as a test plant to study the effects of O3 and AM symbiosis on plant physiology and growth under two O3 levels (ambient air and elevated O3 with 60 nmol·mol-1 O3 enrichment) and three AM inoculation treatments (inoculation with exogenous or indigenous AM fungi and non-inoculation control). The results showed that elevated O3 decreased plant net photosynthetic rate and biomass, and increased malondialdehyde concentration, while AM inoculation (with both exogenous and indigenous AM fungi) could promote plant nutrient acquisition and growth irrespective of O3 levels. The positive effects of AM symbiosis on plant nutrient acquisition and antioxidant enzyme (superoxide dismutase and peroxidase) activities were most likely offset by increased stomatal conductance and O3 intake. As a result, AM inoculation and O3 generally showed no significant interactions on plant performance although elevated O3 did not diminish the beneficial effects of AM symbiosis on alfalfa plants, AM symbiosis also did not alleviate the harmful effects of O3 on plants.Animals and plants have NLRs (nucleotide-binding leucine-rich repeat receptors) that recognize the presence of pathogens and initiate innate immune responses. In plants, there are three types of NLRs distinguished by their N-terminal domain the CC (coiled-coil) domain NLRs, the TIR (Toll/interleukin-1 receptor) domain NLRs and the RPW8 (resistance to powdery mildew 8)-like coiled-coil domain NLRs. CC-NLRs (CNLs) and TIR-NLRs (TNLs) generally act as sensors of effectors secreted by pathogens, while RPW8-NLRs (RNLs) signal downstream of many sensor NLRs and are called helper NLRs. Recent studies have revealed three dimensional structures of a CNL (ZAR1) including its inactive, intermediate and active oligomeric state, as well as TNLs (RPP1 and ROQ1) in their active oligomeric states. Furthermore, accumulating evidence suggests that members of the family of lipase-like EDS1 (enhanced disease susceptibility 1) proteins, which are uniquely found in seed plants, play a key role in providing a link between sensor NLRs and helper NLRs during innate immune responses. Here, we summarize the implications of the plant NLR structures that provide insights into distinct mechanisms of action by the different sensor NLRs and discuss plant NLR-mediated innate immune signalling pathways involving the EDS1 family proteins and RNLs.For over half a century, deciphering the origins of the genomic loci that form the jawed vertebrate adaptive immune response has been a major topic in comparative immunogenetics. Vertebrate adaptive immunity relies on an extensive and highly diverse repertoire of tandem arrays of variable (V), diversity (D), and joining (J) gene segments that recombine to produce different immunoglobulin (Ig) and T cell receptor (TCR) genes. The current consensus is that a recombination-activating gene (RAG)-like transposon invaded an exon of an ancient innate immune VJ-bearing receptor, giving rise to the extant diversity of Ig and TCR loci across jawed vertebrates. However, a model for the evolutionary relationships between extant non-recombining innate immune receptors and the V(D)J receptors of the jawed vertebrate adaptive immune system has only recently begun to come into focus. In this review, we provide an overview of non-recombining VJ genes, including CD8β, CD79b, natural cytotoxicity receptor 3 (NCR3/NKp30), putative remnants of an antigen receptor precursor (PRARPs), and the multigene family of signal-regulatory proteins (SIRPs), that play a wide range of roles in immune function. We then focus in detail on the VJ-containing novel immune-type receptors (NITRs) from ray-finned fishes, as recent work has indicated that these genes are at least 50 million years older than originally thought. We conclude by providing a conceptual model of the evolutionary origins and phylogenetic distribution of known VJ-containing innate immune receptors, highlighting opportunities for future comparative research that are empowered by this emerging evolutionary perspective.Two novel bacterial strains, designated as BT186T and BT505, were isolated from a soil sample collected in South Korea and characterized. Both strains were Gram-stain-negative, rod-shaped, aerobic, circular, convex, and had red-colored colonies. The level of 16S rRNA gene sequence similarity between the strains BT186T and BT505 was 100%, indicating that they represent an identical species. 16S rRNA sequence analysis indicated that strains BT186T and BT505 belong to a distinct lineage within the genus Hymenobacter (family Hymenobacteraceae, order Cytophagales, class Cytophagia, phylum Bacteroidetes, Kingdom Bacteria). Both strains were closely related to Hymenobacter norwichensis DSM 15439T (98.3% 16S rRNA gene similarity), Hymenobacter aquaticus JCM 31653T (96.8%), and Hymenobacter perfusus LMG26000T (96.5%). Strain BT186T was found to have the MK-7 as the major respiratory quinone. The major polar lipid of strain BT186T was identified to be phosphatidylethanolamine (PE). The major cellular fatty acid profiles of strain BT186T were C161 ω5c (24.