Advancing Drug Development in Myelodysplastic Syndromes.

Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the United States Food and Drug Administration (FDA), (e.g.

Non-selective b adrenergic receptor inhibitors impair hematopoietic regeneration in mice and humans after hematopoietic cell transplants.

Peripheral nerves promote mouse bone marrow regeneration by activating b2 and b3 adrenergic receptor signaling, raising the possibility that non-selective b blockers could inhibit engraftment after hematopoietic cell transplants (HCTs). We observed no effect of b blockers on steady-state mouse hematopoiesis. However, mice treated with a non-selective b blocker (carvedilol), but not a b1-selective inhibitor (metoprolol), exhibited impaired hematopoietic regeneration after syngeneic or allogeneic HCTs.

High-resolution awake mouse fMRI at 14 tesla.

High-resolution awake mouse functional magnetic resonance imaging (fMRI) remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radio frequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion-induced artifacts.

Mastering the Copolymerization Behavior of Ethyl Cyanoacrylate as Gel Polymer Electrolyte for Lithium-metal Battery Application.

Polymers with strong electron-withdrawing groups (e.g., cyano-containing polymers) are attractive for a wide range of applications due to their high dielectric constant and outstanding electrochemical stability.

Aminoalkylation of Alkenes Enabled by Triple Radical Sorting.

The direct synthesis of C(sp)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there is a strong impetus to develop new methods by which to access sp-rich molecules from commercial feedstocks, such as alkenes.

The Effect of the Size of Gold Nanoparticle Contrast Agents on CT Imaging of the Gastrointestinal Tract and Inflammatory Bowel Disease.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. Contrast agents that provide enhanced imaging performance are highly valuable in this field.

Preservation of Cardiac Xenografts in a Model of Infant Human Cardiac Transplantation.

Introduction: There is no standard protocol for management of organ preservation for orthotopic, life-sustaining cardiac xenotransplantation, particularly for hearts from pediatric sized donors. Standard techniques and solutions successful in human allotransplantation are not viable. We theorized that a solution commonly used in reparative cardiac surgery in human children would suffice by exploiting the advantages inherent to xenotransplantation, namely the ability to reduce organ ischemic times by co-locating the donor and recipient.

The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial.

Background: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated.

Host tissue factors predict immune surveillance and therapeutic outcomes in gastric cancer.

The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma-an aggressive cancer often linked to chronic inflammation-remains poorly understood. We leveraged high-dimensional spectral cytometry to generate a comprehensive single-cell immune landscape of tumors, normal tissue, and lymph nodes from patients in the Western Hemisphere with gastric adenocarcinoma.

Abstraction of Hydride from Alkanes and Dihydrogen by the Perfluorotrityl Cation.

Lewis acids play a central role in a large variety of chemical transformations. The reactivity of the strongest Lewis acids is typically studied in the context of affinity towards hard bases, such as fluoride or oxygenous species. Carbocations can be viewed as soft Lewis acids, possessing significant affinity for softer bases, such as hydride.

Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function.

The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells.

Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis.

How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over 2 h. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes, and are sufficient to build the first interphase TAD structures.

α-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure.

Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin.

Riluzole is associated with reduced risk of heart failure.

Background: Reduction of intracellular Na accumulation through late Na current inhibition has been recognized as a target for cardiac Ca handling which underlies myocardial contractility and relaxation in heart failure (HF). Riluzole, an Na channel blocker with enhancement of Ca-activated K channel function, used for management of amyotrophic lateral sclerosis (ALS), is effective in suppressing Ca leak and therefore may improve cardiac function.

Objectives: The study aim was to investigate whether riluzole lowers HF incidence.

Biomarkers.

Background: Alzheimer's Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD.

Biomarkers.

Background: Use of neuroimaging [e.g. magnetic resonance imaging (MRI), positron emission tomography (PET), or computed tomography (CT) scan], cerebrospinal fluid (CSF), and blood biomarker tests can contribute to a more accurate and earlier diagnosis of Alzheimer's disease (AD).

Biomarkers.

Background: APOE genotype is the most important genetic risk factor for Alzheimer's disease (AD), but whether it affects the proteins associated with AD risk is unclear. Circulating proteins may reveal biology underlying pathologic processes.

Methods: We evaluated log2 standardized levels of 4979 proteins quantified using modified aptamer technology [SomaScan] in plasma from 2725 participants in the Cardiovascular Health Study who were free of dementia and stroke.

Socioeconomic Deprivation and Risk of Operative Mortality After Emergency Laparotomy: A Systematic Review and Meta-Analysis.

Aims: The aim was to determine the effect of socioeconomic deprivation on operative mortality after emergency laparotomy.

Methods: A PRISMA-compliant systematic review and meta-analysis (random-effects modeling) was performed searching for studies comparing operative mortality between the least and the most socioeconomically deprived patients undergoing emergency laparotomy. Both unadjusted and adjusted odds ratio (OR) were calculated as summary measure.

Altermagnetism: A Chemical Perspective.

Altermagnets have been recently introduced as a classification of collinear, spin compensated magnetic materials that host net-zero magnetization yet display some electronic behaviors typically associated with noncompensated magnetic materials like ferromagnets. The emergence of such properties are a consequence of spin-split bands that arise under specific symmetry conditions in the limit of zero spin-orbit coupling. In this Perspective, we summarize the fundamental criteria for realizing an altermagnetic phase and present a qualitative electronic band structure derivation and symmetry analysis through chemical principles.

Polyunsaturated fatty acids suppress PIEZO ion channel mechanotransduction in articular chondrocytes.

Osteoarthritis (OA) is characterized by articular cartilage degeneration, leading to pain and loss of joint function. Recent studies have demonstrated that omega-3 (ω3) polyunsaturated fatty acid (PUFA) supplementation can decrease injury-induced OA progression in mice fed a high-fat diet. Furthermore, PUFAs have been shown to influence the mechanical properties of chondrocyte membranes, suggesting that alterations in mechanosensitive ion channel signaling could contribute to the mechanism by which ω3 PUFAs decreased OA pathogenesis.

Environmental Exposures and Canine Bladder Cancer: A Case Control Study Using Silicone Passive Samplers.

Pet dogs offer valuable models for studying environmental impacts on human health due to shared environments and a shorter latency period for cancer development. We assessed environmental chemical exposures in a case-control study involving dogs at high risk of urothelial carcinoma, identified by a BRAF V595E mutation in urinary epithelial cells. Cases ( = 25) exhibited low-level BRAF mutations, while controls ( = 76) were matched dogs without the mutation.

Biomarkers.

Background: Canada and the United States are both aging and becoming increasingly diverse. Despite this demographic shift, non-White racial/ethnic groups remain underrepresented in research on cognitive impairment and dementia. A major barrier to inclusivity is the lack of cognitive assessments that are valid in individuals with diverse language and cultural backgrounds.

Biomarkers.

Background: Biorepositories play an integral role in the advancement of our understanding of neurodegenerative diseases and improving human health outcomes. Research efforts are accelerated when access to high-quality clinical specimens is made available from a large, diverse participant group. Indiana University is home to three important neurodegenerative disease-focused biorepositories including the NIA-funded National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), the NINDS-funded Biospecimen Exchange for Neurological Disorders (BioSEND), and the Michael J.