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Genomic-based epidemiology can provide insight into the origins and spread of herbicide resistance mechanisms in weeds. We used kochia (Bassia scoparia) populations resistant to the herbicide glyphosate from across western North America to test the alternative hypotheses that (i) a single EPSPS gene duplication event occurred initially in the Central Great Plains and then subsequently spread to all other geographical areas now exhibiting glyphosate-resistant kochia populations or that (ii) gene duplication occurred multiple times in independent events in a case of parallel evolution. We used qPCR markers previously developed for measuring the structure of the EPSPS tandem duplication to investigate whether all glyphosate-resistant individuals had the same EPSPS repeat structure. We also investigated population structure using simple sequence repeat markers to determine the relatedness of kochia populations from across the Central Great Plains, Northern Plains and the Pacific Northwest. We found that the original EPSPS duplication genotype was predominant in the Central Great Plains where glyphosate resistance was first reported. We identified two additional EPSPS duplication genotypes, one having geographical associations with the Northern Plains and the other with the Pacific Northwest. The EPSPS duplication genotype from the Pacific Northwest seems likely to represent a second, independent evolutionary origin of a resistance allele. We found evidence of gene flow across populations and a general lack of population structure. The results support at least two independent evolutionary origins of glyphosate resistance in kochia, followed by substantial and mostly geographically localized gene flow to spread the resistance alleles into diverse genetic backgrounds.Vegetative storage proteins (VSPs) are known to serve as nitrogen reserves in many dicot plants but remain undiscovered in grasses, most widely grown group of crops globally. We identified and characterized a VSP in maize and demonstrated that its overexpression improved drought tolerance. Nitrogen supplementation selectively induced a mesophyll lipoxygenase (ZmLOX6), which was targeted to chloroplasts by a novel N-terminal transit peptide of 62 amino acids. When ectopically expressed under the control of various tissue specific promoters, it accumulated to a five-fold higher level upon expression in the mesophyll cells than the wildtype plants. Constitutive expression or targeted expression specifically to the bundle sheath cells increased its accumulation by less than two-fold. The overexpressed ZmLOX6 was remobilized from the leaves like other major proteins during grain development. Epacadostat mw Evaluated in the field over locations and years, transgenic hybrids overexpressing ZmLOX6 in the mesophyll cells significantly outyielded non-transgenic sibs under managed drought stress imposed at flowering. Additional storage of nitrogen as a VSP in maize leaves ameliorated the effect of drought on grain yield.As both plant and animal species shift their ranges in response to a changing climate, maintaining connectivity between present habitat and suitable habitat in the future will become increasingly important to ensure lasting protection for biodiversity. Because the temporal period commensurate with planning for mid-century change is multi-generational for most species, connectivity designed to facilitate climate adaptation requires pathways with 'stepping-stones' between current and future habitat. These areas should have habitats suitable not only for dispersal, but for all aspects of species lifecycles. We integrated present-day land use, topographic diversity, and projections of shifting climate regimes into a single connectivity modeling approach to identify pathways for mid-century shifts in species ranges. Using Omniscape we identified climate linkages, or areas important for climate change-driven movement, as the areas with more current flow than would be expected in the absence of climate considerationach reveals "no-regrets" pathways to plan for a connected landscape in an uncertain future.Ubiquitin Conjugating Enzyme E2T (UBE2T) has been implicated in many types of cancer including hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) process plays a fundamental role during tumor metastasis and progression. However, the molecular mechanisms underlying EMT in HCC in accordance with UBE2T still remain unknown. In this study, we showed that UBE2T overexpression augmented the oncogenic properties and specifically EMT in HCC cell lines, while its silencing attenuated them. UBE2T affected the activation of EMT-associated signaling pathways MAPK/ERK, AKT/mTOR and Wnt/β-catenin. In addition, we revealed that the epithelial protein complex of E-cadherin/β-catenin, a vital regulator of signal transduction in tumor initiation and progression, was totally disrupted at the cell membrane. In particular, we observed that UBE2T overexpression led to E-cadherin loss accompanied by a simultaneous elevation of both cytoplasmic and nuclear β-catenin, while its silencing resulted in a strong E-cadherin turnover at the cell membrane. Interestingly, chemical inhibition of the MAPK/ERK, AKT/mTOR and Wnt/β-catenin signaling pathways demonstrated that the nuclear translocation of β-catenin and subsequent EMT were enhanced mainly by MAPK/ERK. Collectively, our findings demonstrate the UBE2T/MAPK-ERK/β-catenin axis as a critical regulator of cell state transition and EMT in HCC.Phylogeography investigates historical drivers of the geographical distribution of intraspecific lineages. Particular attention has been given to ecological, climatic and geological processes in the diversification of the Neotropical biota. Several species sampled across the South American diagonal of open formations (DOF), comprising the Caatinga, Cerrado and Chaco biomes, experienced range shifts coincident with Quaternary climatic changes. However, comparative studies across different spatial, temporal and biological scales on DOF species are still meagre. Here, we combine phylogeographical model selection and machine learning predictive frameworks to investigate the influence of Pleistocene climatic changes on several plant and animal species from the DOF. We assembled mitochondrial/chloroplastic DNA sequences in public repositories and inferred the demographic responses of 44 species, comprising 70 intraspecific lineages of plants, lizards, frogs, spiders and insects. We then built a random forest model using biotic and abiotic information to identify the best predictors of demographic responses in the Pleistocene. Finally, we assessed the temporal synchrony of species demographic responses with hierarchical approximate Bayesian computation. Biotic variables related to population connectivity, gene flow and habitat preferences largely predicted how species responded to Pleistocene climatic changes, and demographic changes were synchronous primarily during the Middle Pleistocene. Although 22 (~31%) lineages underwent demographic expansion, presumably associated with the spread of aridity during the glacial Pleistocene periods, our findings suggest that nine lineages (~13%) exhibited the opposite response due to taxon-specific attributes.Exotic plant invasions alter ecosystem properties and threaten ecosystem functions globally. Interannual climate variability (ICV) influences both plant community composition (PCC) and soil properties, and interactions between ICV and PCC may influence nitrogen (N) and carbon (C) pools. We asked how ICV and non-native annual grass invasion covary to influence soil and plant N and C in a semiarid shrubland undergoing widespread ecosystem transformation due to invasions and altered fire regimes. We sampled four progressive stages of annual grass invasion at 20 sites across a large (25,000 km2 ) landscape for plant community composition, plant tissue N and C, and soil total N and C in 2013 and 2016, which followed 2 years of dry and wet conditions, respectively. Multivariate analyses and ANOVAs showed that in invasion stages where native shrub and perennial grass and forb communities were replaced by annual grass-dominated communities, the ecosystem lost more soil N and C in wet years. Path analysis showed that high water availability led to higher herbaceous cover in all invasion stages. In stages with native shrubs and perennial grasses, higher perennial grass cover was associated with increased soil C and N, while in annual-dominated stages, higher annual grass cover was associated with losses of soil C and N. Also, soil total C and CN ratios were more homogeneous in annual-dominated invasion stages as indicated by within-site standard deviations. Loss of native shrubs and perennial grasses and forbs coupled with annual grass invasion may lead to long-term declines in soil N and C and hamper restoration efforts. Restoration strategies that use innovative techniques and novel species to address increasing temperatures and ICV and emphasize maintaining plant community structure-shrubs, grasses, and forbs-will allow sagebrush ecosystems to maintain C sequestration, soil fertility, and soil heterogeneity.
Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses.
To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3.
Subjects were administered 200µg/kg (major procedures) or 75µg/kg eptacog beta (minor procedures) immediately prior to the initial surgical incision; subsequent 75µg/kg doses were administered to achieve postoperative haemostasis and wound healing. Efficacy was assessed on a 4-point haemostatic scale during the intra- and postoperative periods. Anti-drug antibodies, thrombotic events and changes in clinical/laboratory parameters were monitored throughout the perioperative period.
Twelve subjects underwent six major and six minor procedures. The primary efficacy endpoint success proportion was 100% (95% CI 47.8%-100%) for minor procedures and 66.7% (95% CI 22.3%-95.7%) for major procedures; 81.8% (95% CI 48.2%-97.7%) of the procedures were considered successful using eptacog beta. There was one death due to bleeding from a nonsurgical site; this was assessed as unlikely related to eptacog beta. No thrombotic events or anti-eptacog beta antibodies were reported.
Two eptacog beta dosing regimens in PwHABI undergoing major and minor surgical procedures were well-tolerated, and the majority of procedures were successful based on surgeon/investigator assessments. Eptacog beta offers clinicians a new potential therapeutic option for procedures in PwHABI.
Two eptacog beta dosing regimens in PwHABI undergoing major and minor surgical procedures were well-tolerated, and the majority of procedures were successful based on surgeon/investigator assessments. Eptacog beta offers clinicians a new potential therapeutic option for procedures in PwHABI.
Here's my website: https://www.selleckchem.com/products/epacadostat-incb024360.html
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