Regenerative engineering of long bones using the small molecule forskolin.

Bone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.4 billion. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopedic surgeons to stimulate bone tissue formation alone and when paired with biomaterials.

Targeting the hallmarks of aging to improve influenza vaccine responses in older adults.

Age-related declines in immune response pose a challenge in combating diseases later in life. Influenza (flu) infection remains a significant burden on older populations and often results in catastrophic disability in those who survive infection. Despite having vaccines designed specifically for older adults, the burden of flu remains high and overall flu vaccine efficacy remains inadequate in this population.

High-resolution microbiome analysis reveals exclusionary Klebsiella species competition in preterm infants at risk for necrotizing enterocolitis.

Intestinal colonization with Klebsiella has been linked to necrotizing enterocolitis (NEC), but methods of analysis usually failed to discriminate Klebsiella species or strains. A novel ~ 2500-base amplicon (StrainID) that spans the 16S and 23S rRNA genes was used to generate amplicon sequence variant (ASV) fingerprints for Klebsiella oxytoca and Klebsiella pneumoniae species complexes (KoSC and KpSC, respectively) and co-occurring fecal bacterial strains from 10 preterm infants with NEC and 20 matched controls. Complementary approaches were used to identify cytotoxin-producing isolates of KoSC.

CRISPR gel: A one-pot biosensing platform for rapid and sensitive detection of HIV viral RNA.

CRISPR technology has recently emerged as a powerful biosensing tool for sensitive and specific nucleic acid detection when coupled with isothermal amplification (e.g., recombinase polymerase amplification (RPA)).

Outer-arm dynein light chain LC1 is required for normal motor assembly kinetics, ciliary stability, and motility.

Light chain 1 (LC1) is a highly conserved leucine-rich repeat protein associated with the microtubule-binding domain of the outer-dynein arm γ heavy chain. LC1 mutations in humans and trypanosomes lead to motility defects, while its loss in oomycetes results in aciliate zoospores. Here we describe a LC1 null mutant ().

Luteinizing hormone stimulates ingression of mural granulosa cells within the mouse preovulatory follicle.

Luteinizing hormone (LH) induces ovulation by acting on its receptors in the mural granulosa cells that surround a mammalian oocyte in an ovarian follicle. However, much remains unknown about how activation of the LH receptor modifies the structure of the follicle such that the oocyte is released and the follicle remnants are transformed into the corpus luteum. The present study shows that the preovulatory surge of LH stimulates LH receptor-expressing granulosa cells, initially located almost entirely in the outer layers of the mural granulosa, to rapidly extend inwards, intercalating between other cells.

Backbone and ILV side-chain methyl NMR resonance assignments of human Rev7/Rev3-RBM1 and Rev7/Rev3-RBM2 complexes.

Rev7 is a versatile HORMA (Hop1, Rev7, Mad2) family adaptor protein with multiple roles in mitotic regulation and DNA damage response, and an essential accessory subunit of the translesion synthesis (TLS) DNA polymerase Polζ employed in replication of damaged DNA. Within Polζ, the two copies of Rev7 interact with the two Rev7-bonding motifs (RBM1 and RBM2) of the catalytic subunit Rev3 by a mechanism characteristic of HORMA proteins whereby the "safety-belt" loop of Rev7 closes on the top of the ligand. Here we report the nearly complete backbone and Ile, Val, Leu side-chain methyl NMR resonance assignments of the 27 kDa human Rev7/Rev3-RBM1 and Rev7/Rev3-RBM2 complexes (BMRB deposition numbers 51651 and 51652) that will facilitate future NMR studies of Rev7 dynamics and interactions.

Transcriptomic profiling of retinal cells reveals a subpopulation of microglia/macrophages expressing Rbpms marker of retinal ganglion cells (RGCs) that confound identification of RGCs.

Analysis of retinal ganglion cells (RGCs) by scRNA-seq is emerging as a state-of-the-art method for studying RGC biology and subtypes, as well as for studying the mechanisms of neuroprotection and axon regeneration in the central nervous system (CNS). Rbpms has been established as a pan-RGC marker, and Spp1 has been established as an αRGC type and macrophage marker. Here, we analyzed by scRNA-seq retinal microglia and macrophages, and found Rbpms+ subpopulations of retinal microglia/macrophages, which pose a potential pitfall in scRNA-seq studies involving RGCs.

The Mediating Effect of Changes in Depression Symptoms on the Relationship between Health-Related Quality of Life and Alcohol Consumption: Findings from a Longitudinal Study among Men Living with HIV in India.

Heavy alcohol use is negatively affecting antiretroviral therapy adherence, mental health and health-related quality of life among people living with HIV (PLWH). This paper aims to test the mediation model examining whether changes in depression symptoms mediate in the relationship between health-related quality of life and alcohol use among male PLWH who consume alcohol in India. The study is guided by the stress-coping model, which posits that individuals facing stress may turn to maladaptive coping mechanisms such as alcohol use to alleviate their distress, which includes depression and a low health-related quality of life due to various physical, psychological, and social factors associated with the HIV infection.

Cardiac and noncardiac biomarkers in patients undergoing anthracycline chemotherapy - a prospective analysis.

Background: Biomarkers represent a potential tool to identify individuals at risk for anthracycline-induced cardiotoxicity (AICT) prior to symptom onset or left ventricular dysfunction.

Methods: This study examined the levels of cardiac and noncardiac biomarkers before, after the last dose of, and 3-6 months after completion of doxorubicin chemotherapy. Cardiac biomarkers included 5th generation high-sensitivity cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide, growth/differentiation factor-15 (GDF-15), and soluble suppression of tumorigenesis-2 (sST2).

Intraindividual variability in brain activation-A novel correlate of obesity risk among female college students.

There are published data describing impairments in the brain function of adolescents or young adults who have a genetic or familial predisposition for obesity. From these descriptions, it is often assumed that the impairments are appropriately captured by a central tendency estimate and therefore consistently detectable. The present study questions this assumption and shows that the variability in brain function over the time course of a cognitive task is a better predictor of familial risk than its central tendency.

Using participatory action research to develop a new self-management program: Results from the design stage of Managing My MS My Way.

Background: Self-management programs have been used with success in several clinical populations, and there is a growing body of evidence to support their use among persons with multiple sclerosis (MS). This group aimed to develop a novel self-management program, Managing My MS My Way (MW), which is based in social cognitive theory and contains evidence-based strategies that have been shown to be effective for persons with MS. Furthermore, persons with MS would serve as stakeholders throughout the development process to ensure that the program would be useful and encourage adoption.

Oral health-related quality of life after radiation therapy for head and neck cancer: the OraRad study.

Purpose: Head and neck cancer (HNC) treatment results in morbidity impacting quality of life (QOL) in survivorship. This analysis evaluated changes in oral health-related QOL (OH-QOL) up to 2 years after curative intent radiation therapy (RT) for HNC patients and factors associated with these changes.

Methods: 572 HNC patients participated in a multicenter, prospective observational study (OraRad).

Supplementing culture medium with the weak acid, 5,5-dimethyl-2,4-oxazolidinedione (DMO) limits the development of aneuploid mouse embryos through a Trp53-dependent mechanism.

Purpose: This study was designed to determine if DMO limits in vitro development of aneuploid-enriched mouse embryos by activating a Trp53-dependent mechanism.

Methods: Mouse cleavage-stage embryos were treated with reversine to induce aneuploidy or vehicle to generate controls, and then cultured in media supplemented with DMO to reduce the pH of the culture media. Embryo morphology was assessed by phase microscopy.

Effect of Nuts on Gastrointestinal Health.

Nuts are high nutrient-dense foods containing healthy lipids, dietary fiber, and bioactive phytochemicals, including vitamins and minerals. Although the beneficial effect of nut consumption on different chronic diseases has been well documented, especially in relation to their cardiometabolic benefits, less scientific evidence is available on their possible beneficial effects on gastrointestinal health. In this narrative review, we summarize the most important findings and new research perspectives in relation to the importance of nut consumption on gastrointestinal health.

Pten inhibition dedifferentiates long-distance axon-regenerating intrinsically photosensitive retinal ganglion cells and upregulates mitochondria-associated Dynlt1a and Lars2.

Central nervous system projection neurons fail to spontaneously regenerate injured axons. Targeting developmentally regulated genes in order to reactivate embryonic intrinsic axon growth capacity or targeting pro-growth tumor suppressor genes such as Pten promotes long-distance axon regeneration in only a small subset of injured retinal ganglion cells (RGCs), despite many RGCs regenerating short-distance axons. A recent study identified αRGCs as the primary type that regenerates short-distance axons in response to Pten inhibition, but the rare types which regenerate long-distance axons, and cellular features that enable such response, remained unknown.

Rare genetic variants in modify orofacial cleft phenotypes.

As one of the most common structural birth defects, orofacial clefts (OFCs) have been studied for decades, and recent studies have demonstrated that there are genetic differences between the different phenotypic presentations of OFCs. However, the contribution of rare genetic variation genome-wide to different subtypes of OFCs has been understudied, with most studies focusing on common genetic variation or rare variation within targeted regions of the genome. Therefore, we used whole-genome sequencing data from the Gabriella Miller Kids First Pediatric Research Program to conduct a gene-based burden analysis to test for genetic modifiers of cleft lip (CL) vs cleft lip and palate (CLP).

Cleanroom-Free Fabrication of Microneedles for Multimodal Drug Delivery.

Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high-resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials.

Geographic and Demographic Disparities in Colorectal Cancer: A National Cancer Database Analysis.

Background And Objectives: Area of residence may adversely affect survival and outcomes in many cancers. The objective of this study was to evaluate the impact of geographical and demographic disparities on survival of patients with colorectal cancer.

Materials And Methods: Data were obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal datasets.

Multiplexed electrochemical assays for clinical applications.

Rapid, accurate diagnoses are central to future efficient healthcare to identify diseases at early stages, avoid unnecessary treatment, and improve outcomes. Electrochemical techniques have been applied in many ways to support clinical applications by enabling the analysis of relevant disease biomarkers in user-friendly, sensitive, low-cost assays. Electrochemistry offers a launchpad for multiplexed biomarker assays that offer more accurate and precise diagnostics compared to single biomarker assays.

Modelling acute glucocorticoid transcriptome response in human embryonic stem cell derived neural cultures.

Our goal is to demonstrate and characterize acute glucocorticoid transcriptome response in human embryonic stem cell (hESC) derived neural cultures. Toward this, we confirmed the differentiation of hESC lines H9 and H1 into post-mitotic neurons and astrocytes, in addition to the expressions of glucocorticoid receptor (GR) protein, and the GR co-chaperone FK506 binding protein 51 (FKBP5). In a series of experiments in hESC-derived neural cultures treated with dexamethasone (Dex) for 6 h, glucocorticoid hormone (GH) response was detected through the transcriptional upregulation of GH-responsive genes, FKBP5 and PER1.

Chronic Morphine Modulates PDGFR-β and PDGF-B Expression and Distribution in Dorsal Root Ganglia and Spinal Cord in Male Rats.

The analgesic effect of opioids decreases over time due to the development of analgesic tolerance. We have shown that inhibition of the platelet-derived growth factor beta (PDGFR-β) signaling eliminates morphine analgesic tolerance in rats. Although the PDGFR-β and its ligand, the platelet-derived growth factor type B (PDGF-B), are expressed in the substantia gelatinosa of the spinal cord (SG) and in the dorsal root ganglia (DRG), their precise distribution within different cell types of these structures is unknown.

MolClustPy: A Python Package to Characterize Multivalent Biomolecular Clusters.

S Ummary: Low-affinity interactions among multivalent biomolecules may lead to the formation of molecular complexes that undergo phase transitions to become extra-large clusters. Characterizing the physical properties of these clusters is important in recent biophysical research. Due to weak interactions such clusters are highly stochastic, demonstrating a wide range of sizes and compositions.