Experimental validation of genome-environment associations in Arabidopsis.

Identifying the genetic basis of local adaptation is a key goal in evolutionary biology. Allele frequency clines along environmental gradients, known as genotype-environment associations (GEA), are often used to detect potential loci causing local adaptation, but GEA are rarely followed by experimental validation. Here, we tested loci identified in three different moisture-related GEA studies on .

Maladaptation in cereal crop landraces following a soot-producing climate catastrophe.

Aerosol-producing global catastrophes such as nuclear war, super-volcano eruption, or asteroid strike, although rare, pose a serious threat to human survival. Light-absorbing aerosols would sharply reduce temperature and solar radiation reaching the earth's surface, decreasing crop productivity including for locally adapted traditional crop varieties, i.e.

Associations of circulating matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases with clinically relevant outcomes in idiopathic pulmonary fibrosis: Data from the IPF-PRO Registry.

Introduction: We assessed the prognostic utility of circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry.

Methods: MMP and TIMP concentrations were quantified by ELISA in plasma from 300 patients. A Cox proportional hazard regression model was used to assess associations between select MMPs and TIMPs and death and disease progression (absolute decline in forced vital capacity ≥10% predicted, death, or lung transplant).

Local adaptation to climate facilitates a global invasion.

Local adaptation may facilitate range expansion during invasions, but the mechanisms promoting destructive invasions remain unclear. Cheatgrass (), native to Eurasia and Africa, has invaded globally, with particularly severe impacts in western North America. We sequenced 307 genotypes and conducted controlled experiments.

Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation.

Lung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-Ras) mice with the murine γherpesvirus MHV68 via oropharyngeal aspiration. After 7 weeks, the infected mice displayed a more than 2-fold increase in lung tumors relative to their K-Ras uninfected littermates.

The genomics and physiology of abiotic stressors associated with global elevational gradients in Arabidopsis thaliana.

Phenotypic and genomic diversity in Arabidopsis thaliana may be associated with adaptation along its wide elevational range, but it is unclear whether elevational clines are consistent among different mountain ranges. We took a multi-regional view of selection associated with elevation. In a diverse panel of ecotypes, we measured plant traits under alpine stressors (low CO partial pressure, high light, and night freezing) and conducted genome-wide association studies.

Century-long timelines of herbarium genomes predict plant stomatal response to climate change.

Dissecting plant responses to the environment is key to understanding whether and how plants adapt to anthropogenic climate change. Stomata, plants' pores for gas exchange, are expected to decrease in density following increased CO concentrations, a trend already observed in multiple plant species. However, it is unclear whether such responses are based on genetic changes and evolutionary adaptation.

Estimating scale-specific and localized spatial patterns in allele frequency.

Characterizing spatial patterns in allele frequencies is fundamental to evolutionary biology because these patterns contain evidence of underlying processes. However, the spatial scales at which gene flow, changing selection, and drift act are often unknown. Many of these processes can operate inconsistently across space, causing nonstationary patterns.

Predicting gene expression responses to environment in using natural variation in DNA sequence.

The evolution of gene expression responses are a critical component of adaptation to variable environments. Predicting how DNA sequence influences expression is challenging because the genotype to phenotype map is not well resolved for regulatory elements, transcription factor binding, regulatory interactions, and epigenetic features, not to mention how these factors respond to environment. We tested if flexible machine learning models could learn some of the underlying regulatory genotype to phenotype map.

Climate biogeography of linking distribution models and individual variation.

Aim: Patterns of individual variation are key to testing hypotheses about the mechanisms underlying biogeographic patterns. If species distributions are determined by environmental constraints, then populations near range margins may have reduced performance and be adapted to harsher environments. Model organisms are potentially important systems for biogeographical studies, given the available range-wide natural history collections, and the importance of providing biogeographical context to their genetic and phenotypic diversity.

Chromosome-scale genome assembly of and population genomics reveal widespread gene flow in a cool-season grass seed production system.

(L.) is a cool-season grass species found in various environments worldwide. In addition to being a desired turfgrass species, it is a common weed of agricultural systems and natural areas.

Evidence that variation in root anatomy contributes to local adaptation in Mexican native maize.

Mexican native maize ( ssp. ) is adapted to a wide range of climatic and edaphic conditions. Here, we focus specifically on the potential role of root anatomical variation in this adaptation.

Efficacy and manageable safety of tagraxofusp in blastic plasmacytoid dendritic cell neoplasm: a case series of pediatric and adolescent/young adult patients.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) predominantly occurs in adults ≥60 years old; 10-20% of cases are pediatric or adolescent/young adult (AYA) patients. Tagraxofusp (TAG, Elzonris) is the only approved treatment for BPDCN; in the United States it is approved for patients aged ≥2 years. Data on treating pediatric and AYA BPDCN patients are limited.

Ontogenetic changes in ecophysiology are an understudied yet important component of plant adaptation.

Plants rely on adjustments in growth and development to respond to environmental stimuli. Developmental transitions, including germination, vegetative phase change, reproductive transition, and senescence, modify the growth patterns of plants and their requirements for survival. Consequently, the timing of developmental transitions and the developmental stage at which a plant encounters environmental stress hold significant implications for the performance of individuals, population dynamics, and community dynamics.

Hospitalization Rates in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Registry.

Little is known about hospitalization in other types of interstitial lung disease (ILD) besides idiopathic pulmonary fibrosis (IPF). To determine the frequency of hospitalizations in various types of ILD and elucidate the association of hospitalization with outcomes. An analysis of the Pulmonary Fibrosis Foundation Patient Registry data was performed.

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints.

Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report.

Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity and mortality. In recognition of the need to catalyze ongoing advances and collaboration in the field of pulmonary fibrosis, the NHLBI, the Three Lakes Foundation, and the Pulmonary Fibrosis Foundation hosted the Pulmonary Fibrosis Stakeholder Summit on November 8-9, 2022. This workshop was held virtually and was organized into three topic areas: ) novel models and research tools to better study pulmonary fibrosis and uncover new therapies, ) early disease risk factors and methods to improve diagnosis, and ) innovative approaches toward clinical trial design for pulmonary fibrosis.

Case Report: Blinatumomab as upfront consolidation and maintenance therapy in a pediatric patient with high-risk B-cell acute lymphoblastic leukemia.

Introduction: B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children. The current conventional chemotherapy regimens have high overall survival but with significant short- and long-term toxicities, sometimes requiring delay and termination of chemotherapy. Bispecific T-cell engager antibody blinatumomab has been successful in achieving bone marrow remission and acting as bridging therapy in minimal residual disease (MRD)-positive relapsed adult and pediatric B-ALL patients.

A haplotype-resolved chromosome-scale genome for Quercus rubra L. provides insights into the genetics of adaptive traits for red oak species.

Northern red oak (Quercus rubra L.) is an ecologically and economically important forest tree native to North America. We present a chromosome-scale genome of Q.

Vegetative phase change causes age-dependent changes in phenotypic plasticity.

Phenotypic plasticity allows organisms to optimize traits for their environment. As organisms age, they experience diverse environments that benefit from varying degrees of phenotypic plasticity. Developmental transitions can control these age-dependent changes in plasticity, and as such, the timing of these transitions can determine when plasticity changes in an organism.

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial.

Background: Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding.

Landscape transcriptomics as a tool for addressing global change effects across diverse species.

Landscape transcriptomics is an emerging field studying how genome-wide expression patterns reflect dynamic landscape-scale environmental drivers, including habitat, weather, climate, and contaminants, and the subsequent effects on organismal function. This field is benefitting from advancing and increasingly accessible molecular technologies, which in turn are allowing the necessary characterization of transcriptomes from wild individuals distributed across natural landscapes. This research is especially important given the rapid pace of anthropogenic environmental change and potential impacts that span levels of biological organization.

Enhanced Expression of a Novel Lamin A/C Splice Variant in Idiopathic Pulmonary Fibrosis Lung.

In idiopathic pulmonary fibrosis (IPF), the normal delicate lung architecture is replaced with rigid extracellular matrix (ECM) as a result of the accumulation of activated myofibroblasts and excessive deposition of ECM. Lamins have a role in fostering mechanosignaling from the ECM to the nucleus. Although there is a growing number of studies on lamins and associated diseases, there are no prior reports linking aberrations in lamins with pulmonary fibrosis.