Quantitative Trait Loci for Phenology, Yield, and Phosphorus Use Efficiency in Cowpea.

Background/objectives: Cowpea is an important legume crop in sub-Saharan Africa (SSA) and beyond. However, access to phosphorus (P), a critical element for plant growth and development, is a significant constraint in SSA. Thus, it is essential to have high P-use efficiency varieties to achieve increased yields in environments where little-to- no phosphate fertilizers are applied.

Flexibility in PAM Recognition Expands DNA Targeting in xCas9.

xCas9 is an evolved variant of the CRISPR-Cas9 genome editing system, engineered to improve specificity and reduce undesired off-target effects. How xCas9 expands the DNA targeting capability of Cas9 by recognizing a series of alternative Protospacer Adjacent Motif (PAM) sequences while ignoring others is unknown. Here, we elucidate the molecular mechanism underlying xCas9's expanded PAM recognition and provide critical insights for expanding DNA targeting.

Engineering the Ratios of Nanoparticles Dispersed in Triphasic Nanocomposites for Biomedical Applications.

Polymer/ceramic nanocomposites integrated the advantages of both polymers and ceramics for a wide range of biomedical applications, such as bone tissue repair. Here, we reported triphasic poly(lactic--glycolic acid) (PLGA, LA/GA = 90:10) nanocomposites with improved dispersion of hydroxyapatite (HA) and magnesium oxide (MgO) nanoparticles using a process that integrated the benefits of ultrasonic energy and dual asymmetric centrifugal mixing. We characterized the microstructure and composition of the nanocomposites and evaluated the effects of the HA/MgO ratios on degradation behavior and cell-material interactions.

Acute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits.

Constrained β-Hairpins Targeting the EphA4 Ligand Binding Domain.

The activity of the receptor tyrosine kinase EphA4 has been implicated in several pathologies including oncology (gastric and pancreatic cancers) and neurodegenerative diseases (amyotrophic lateral sclerosis and Alzheimer's disease). However, advances in validating EphA4 as a possible drug target have been limited by the lack of suitable pharmacological inhibitors. Recently, we reported on the design of potent EphA4 agonistic agents targeting its ligand binding domain (LBD).

Graph theory approaches for molecular dynamics simulations.

Graph theory, a branch of mathematics that focuses on the study of graphs (networks of nodes and edges), provides a robust framework for analysing the structural and functional properties of biomolecules. By leveraging molecular dynamics (MD) simulations, atoms or groups of atoms can be represented as nodes, while their dynamic interactions are depicted as edges. This network-based approach facilitates the characterization of properties such as connectivity, centrality, and modularity, which are essential for understanding the behaviour of molecular systems.

CT and MRI bimodal radiomics for predicting EGFR status in NSCLC patients with brain metastases: A multicenter study.

Background: Leveraging the radiomics information from non-small cell lung cancer (NSCLC) primary lesion and brain metastasis (BM) to develop and validate a bimodal radiomics nomogram that can accurately predict epidermal growth factor receptor (EGFR) status.

Methods: A total of 309 NSCLC patients with BM from three independent centers were recruited. Among them, the patients of Center I were randomly allocated into the training and internal test cohorts in a 7:3 ratio.

Dimerization of the deaminase domain and locking interactions with Cas9 boost base editing efficiency in ABE8e.

CRISPR-based DNA adenine base editors (ABEs) hold remarkable promises to address human genetic diseases caused by point mutations. ABEs were developed by combining CRISPR-Cas9 with a transfer RNA (tRNA) adenosine deaminase enzyme and through directed evolution, conferring the ability to deaminate DNA. However, the molecular mechanisms driving the efficient DNA deamination in the evolved ABEs remain unresolved.

A fungal sRNA silences a host plant transcription factor to promote arbuscular mycorrhizal symbiosis.

Cross-kingdom RNA interference (ckRNAi) is a mechanism of interspecies communication where small RNAs (sRNAs) are transported from one organism to another; these sRNAs silence target genes in trans by loading into host AGO proteins. In this work, we investigated the occurrence of ckRNAi in Arbuscular Mycorrhizal Symbiosis (AMS). We used an in silico prediction analysis to identify a sRNA (Rir2216) from the AM fungus Rhizophagus irregularis and its putative plant gene target, the Medicago truncatula MtWRKY69 transcription factor.

Covalent Targeting of Histidine Residues with Aryl Fluorosulfates: Application to Mcl-1 BH3 Mimetics.

Covalent drugs provide pharmacodynamic and pharmacokinetic advantages over reversible agents. However, covalent strategies have been developed mostly to target cysteine (Cys) residues, which are rarely found in binding sites. Among other nucleophilic residues that could be in principle used for the design of covalent drugs, histidine (His) has not been given proper attention despite being in principle an attractive residue to pursue but underexplored.

Microplastics and Trash Cleaning and Harmonization (MaTCH): Semantic Data Ingestion and Harmonization Using Artificial Intelligence.

With the rapid expansion of microplastic research and reliance on semantic descriptors, there is an increasing need for plastic pollution data harmonization. Data standards have been developed but are seldom implemented across research sectors, geographic regions, environmental media, or size classes of plastic pollution. Harmonization of existing data is currently hindered by increasingly large datasets using thousands of different categorical variable descriptors, as well as various metrics used to describe particle abundance and differing size ranges studied across groups.

A Dominance Hypothesis Argument for Historical Genetic Gains and the Fixation of Heterosis in Octoploid Strawberry.

Heterosis was the catalyst for the domestication of cultivated strawberry (Fragaria × ananassa), an interspecific hybrid species that originated in the 1700s. The hybrid origin was discovered because the phenotypes of spontaneous hybrids transgressed those of their parent species. The transgressions included fruit yield increases and other genetic gains in the twentieth century that sparked the global expansion of strawberry production.

Machine Learning-Based Toxicological Modeling for Screening Environmental Obesogens.

The emerging presence of environmental obesogens, chemicals that disrupt energy balance and contribute to adipogenesis and obesity, has become a major public health challenge. Molecular initiating events (MIEs) describe biological outcomes resulting from chemical interactions with biomolecules. Machine learning models based on MIEs can predict complex toxic end points due to chemical exposure and improve the interpretability of models.

Patent Foramen Ovale and Hypoxemia.

Although the most common clinical manifestations of a patent foramen ovale (PFO) are cryptogenic stroke and migraine with aura, PFO is also associated with platypnea-orthodeoxia syndrome, obstructive sleep apnea, and chronic obstructive pulmonary disease with hypoxemia out of proportion to the extent of pulmonary disease. This article will discuss these conditions and summarize the related literature.

Reimagining the CARE in Systems to Combat the Pediatric Mental Health Crisis in America: A Healing-Centered Approach.

The US child mental health care system requires a revival and reimagination. We need to shift toward healing-centered models of care and prioritize access to high-quality mental health care through policy changes and resource allocation. Funding community-based programs that provide culturally responsive, antiracist, and equitable (CARE) systems is essential.

Goal-directed learning is multidimensional and accompanied by diverse and widespread changes in neocortical signaling.

New tasks are often learned in stages with each stage reflecting a different learning challenge. Accordingly, each learning stage is likely mediated by distinct neuronal processes. And yet, most rodent studies of the neuronal correlates of goal-directed learning focus on individual outcome measures and individual brain regions.

DNA methylation near MAD1L1, KDM2B, and SOCS3 mediates the effect of socioeconomic status on elevated body mass index in African American adults.

Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI.

Maximum Likelihood Estimation for Unrooted 3-Leaf Trees: An Analytic Solution for the CFN Model.

Maximum likelihood estimation is among the most widely-used methods for inferring phylogenetic trees from sequence data. This paper solves the problem of computing solutions to the maximum likelihood problem for 3-leaf trees under the 2-state symmetric mutation model (CFN model). Our main result is a closed-form solution to the maximum likelihood problem for unrooted 3-leaf trees, given generic data; this result characterizes all of the ways that a maximum likelihood estimate can fail to exist for generic data and provides theoretical validation for predictions made in Parks and Goldman (Syst Biol 63(5):798-811, 2014).

Locus coeruleus contrast and diffusivity metrics differentially relate to age and memory performance.

Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task.

Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium.

Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.

Fine-tuning pH sensor H98 by remote essential residues in the hydrogen-bond network of mTASK-3.

TASK-3 generates a background K conductance which when inhibited by acidification depolarizes membrane potential and increases cell excitability. These channels sense pH by protonation of histidine residue H98, but recent evidence revealed that several other amino acid residues also contribute to TASK-3 pH sensitivity, suggesting that the pH sensitivity is determined by an intermolecular network. Here we use electrophysiology and molecular modeling to characterize the nature and requisite role(s) of multiple amino acids in pH sensing by TASK-3.

Controlled Release of Diborane from Alkali Metal Borohydride using Ionic Liquid-Based Lewis Acids.

Alkali metal borohydrides present a rich source of energy dense materials of boron and hydrogen, however their potential in propellants has been hitherto untapped. Potassium borohydride is a promising fuel with high gravimetric energy density and relatively low sensitivity to air and moisture. Problems arise due to the dehydrogenation of the borohydride on heating with minimal energy release.

Identifying Precise Targets to Improve Child Mental Health Care Equity: Leveraging Advances in Clinical Research Informatics and Lived Experience.

To reduce child mental health disparities, it is imperative to improve the precision of targets and to expand our vision of social determinants of health as modifiable. Advancements in clinical research informatics and please state accurate measurement of child mental health service use and quality. Participatory action research promotes representation of underserved groups in informatics research and practice and may improve the effectiveness of interventions by informing research across all stages, including the identification of key variables, risk and protective factors, and data interpretation.