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Calcium (Ca2+)/calmodulin (CaM)-dependent protein kinase (CCaMK) is an important positive regulator of abscisic acid (ABA) and abiotic stress signaling in plants and is believed to act upstream of mitogen-activated protein kinase (MAPK) in ABA signaling. However, it is unclear how CCaMK activates MAPK in ABA signaling. Here, we show that OsDMI3, a rice (Oryza sativa) CCaMK, directly interacts with and phosphorylates OsMKK1, a MAPK kinase (MKK) in rice, in vitro and in vivo. OsDMI3 was found to directly phosphorylate Thr-25 in the N-terminus of OsMKK1, and this Thr-25 phosphorylation is OsDMI3-specific in ABA signaling. The activation of OsMKK1 and its downstream kinase OsMPK1 is dependent on Thr-25 phosphorylation of OsMKK1 in ABA signaling. Moreover, ABA treatment induces phosphorylation in the activation loop of OsMKK1, and the two phosphorylations, in the N-terminus and in the activation loop, are independent. Further analyses revealed that OsDMI3-mediated phosphorylation of OsMKK1 positively regulates ABA responses in seed germination, root growth, and tolerance to both water stress and oxidative stress. Our results indicate that OsMKK1 is a direct target of OsDMI3, and OsDMI3-mediated phosphorylation of OsMKK1 plays an important role in activating the MAPK cascade and ABA signaling.The grass family (Poaceae) includes all commercial cereal crops and is a major contributor to biomass in various terrestrial ecosystems. selleck chemicals llc The ancestry of all grass genomes includes a shared whole-genome duplication (WGD), named rho (ρ) WGD, but the evolutionary significance of ρ-WGD remains elusive. We sequenced the genome of Pharus latifolius, a grass species (producing a true spikelet) in the subfamily Pharoideae, a sister lineage to the core Poaceae including the (Panicoideae, Arundinoideae, Chloridoideae, Micrairoideae, Aristidoideae, and Danthonioideae (PACMAD) and Bambusoideae, Oryzoideae, and Pooideae (BOP) clades. Our results indicate that the P. latifolius genome has evolved slowly relative to cereal grass genomes, as reflected by moderate rates of molecular evolution, limited chromosome rearrangements and a low rate of gene loss for duplicated genes. We show that the ρ-WGD event occurred approximately 98.2 million years ago (Ma) in a common ancestor of the Pharoideae and the PACMAD and BOP grasses. This was followed by contrasting patterns of diploidization in the Pharus and core Poaceae lineages. The presence of two FRIZZY PANICLE-like genes in P. latifolius, and duplicated MADS-box genes, support the hypothesis that the ρ-WGD may have played a role in the origin and functional diversification of the spikelet, an adaptation in grasses related directly to cereal yields. The P. latifolius genome sheds light on the origin and early evolution of grasses underpinning the biology and breeding of cereals.
Owing to concerns of coronavirus disease 2019 (COVID-19) outbreaks, many congregant settings are forced to close when cases are detected because there are few data on the risk of different markers of transmission within groups.
To determine whether symptoms and laboratory results on the first day of COVID-19 diagnosis are associated with development of a case cluster in a congregant setting.
This cohort study of trainees with COVID-19 from May 11 through August 24, 2020, was conducted at Joint Base San Antonio-Lackland, the primary site of entry for enlistment in the US Air Force. Symptoms and duration, known contacts, and cycle threshold for trainees diagnosed by reverse transcription-polymerase chain reaction were collected. A cycle threshold value represents the number of nucleic acid amplification cycles that occur before a specimen containing the target material generates a signal greater than the predetermined threshold that defines positivity. Cohorts with 5 or more individuals with COVID-19 infevalues were associated with subsequent development of clusters of individuals with COVID-19 infection. These values may be useful if validated in future studies.
In this cohort study of US Air Force trainees living in a congregant setting during the COVID-19 pandemic, higher numbers of symptoms and lower cycle threshold values were associated with subsequent development of clusters of individuals with COVID-19 infection. These values may be useful if validated in future studies.
Sex differences in dementia risk are unclear, but some studies have found greater risk for women.
To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.
This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017 Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.
Sex.
The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.
Among 34 349 participants, 26 088 who self-reported Black or Whitear declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61).
The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
Recent studies have revealed increases in population-level cannabis use after legalization of recreational cannabis. However, the association of cannabis legalization with maternal cannabis use during important life stages remains unknown.
To investigate the association of legalization of recreational cannabis with maternal cannabis use during the preconception, prenatal, and postpartum periods.
This repeated cross-sectional study used state-level data on women who delivered live-born infants in the US from the Pregnancy Risk Assessment Monitoring System from January 2004 to December 2018. Data from 2 states that had legalized recreational cannabis (Alaska and Maine) and 2 states that had not legalized recreational cannabis (New Hampshire and Vermont) were used. Women completed surveys 2 to 6 months after delivery, reporting preconception, prenatal, and postpartum cannabis use.
State recreational cannabis legalization.
The 3 primary outcomes were self-reported cannabis use during the 12 months beforctors.
Genetic disorders are historically defined through phenotype-first approaches. However, risk estimates derived from phenotype-linked ascertainment may overestimate severity and penetrance. Pathogenic variants in DICER1 are associated with increased risks of rare and common neoplasms and thyroid disease in adults and children. This study explored how effectively a genome-first approach could characterize the clinical traits associated with germline DICER1 putative loss-of-function (pLOF) variants in an unselected clinical cohort.
To examine the prevalence, penetrance, and phenotypic characteristics of carriers of germline DICER1 pLOF variants via genome-first ascertainment.
This cohort study classifies DICER1 variants in germline exome sequence data from 92 296 participants of the Geisinger MyCode Community Health Initiative. Data for each MyCode participant were used from the start of the Geisinger electronic health record to February 1, 2018.
Prevalence of germline DICER1 variation; penetrance of mal9). A female patient in her 80s who was a carrier of a germline DICER1 hotspot variant was apparently healthy on electronic health record review. The term DICER1 did not appear in any of the medical records of the 25 participants with a pLOF DICER1 variant, even in those affected with a known DICER1-associated tumor or thyroid phenotype.
This cohort study was able to ascertain individuals with germline DICER1 variants based on a genome-first approach rather than through a previously established DICER1-related phenotype. Use of the genome-first approach may complement more traditional approaches to syndrome delineation and may be an efficient approach for risk estimation.
This cohort study was able to ascertain individuals with germline DICER1 variants based on a genome-first approach rather than through a previously established DICER1-related phenotype. Use of the genome-first approach may complement more traditional approaches to syndrome delineation and may be an efficient approach for risk estimation.
Improved survival in patients with advanced cancer has increased the need for better understanding of how to manage common symptoms that they may experience, such as breathlessness.
To assess the benefits and harms associated with pharmacologic interventions for breathlessness in adults with advanced cancer.
PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies published from database inception through May 31, 2020, using predefined eligibility criteria within a PICOTS (population, intervention, comparator, outcome, timing, setting) format.
Randomized clinical trials (RCTs), non-RCTs, and observational studies with a comparison group that evaluated benefits and/or harms and cohort studies that reported harms were selected.
Two reviewers independently screened studies for eligibility, serially abstracted data, independently assessed risk of bias, and graded strength of evidence (SOE).
Benefits and harms of pharmacologic interventionontext of potential harms and evidence of an association of nonpharmacologic interventions with improved breathlessness.
In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method's application in real-world evidence research.
To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice.
This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020.
Undergoing treatment with immunotherapy or targeted therapy.
Tumor respecorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.
These findings suggest that comparing tumor lesion sizes and categorizing treatment response according to RECIST guidelines may be feasible using real-world data. This study found that physician-recorded assessments were associated with overestimation of treatment response, with the largest overestimation among complete responses. Real-world RECIST-based assessments were associated with better approximations of tumor response reported in clinical trials compared with those reported in EHRs.
Homepage: https://www.selleckchem.com/products/a-83-01.html
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