Multi-camera Simultaneous Total Internal Reflection and Interference Reflection Microscopy.

Interference Reflection Microscopy (IRM) is an optical technique that relies on the interference between the reflected light from an incident beam as it passes through materials of different refractive indices. This technique has been successfully used to image microtubules, biologically important biofilaments with a diameter of 25 nm. However, it is often desirable to image both the microtubule and microtubule interacting proteins simultaneously.

Cryo-electron tomography pipeline for plasma membranes.

Cryo-electron tomography (cryoET) provides sub-nanometer protein structure within the dense cellular environment. Existing sample preparation methods are insufficient at accessing the plasma membrane and its associated proteins. Here, we present a correlative cryo-electron tomography pipeline optimally suited to image large ultra-thin areas of isolated basal and apical plasma membranes.

Distinct mechanisms of inhibition of Kv2 potassium channels by tetraethylammonium and RY785.

Voltage-gated K channels play central roles in human physiology, both in health and disease. A repertoire of inhibitors that are both potent and specific would therefore be of great value, not only as pharmacological agents but also as research tools. The small molecule RY785 has been described as particularly promising in this regard, as it selectively inhibits channels in the Kv2 subfamily with high potency.

Regulatory Roles of Long Non-Coding RNAs in Arterial Stiffness and Hypertension: Insights from Two African American Studies.

Background: Arterial stiffness, commonly assessed via pulse wave velocity (PWV), is marked by reduced arterial elasticity and serves as a significant risk factor for cardiovascular disease and an early indicator of hypertension. This study investigated the regulatory roles of long non-coding RNAs (lncRNAs) in modulating mRNAs associated with arterial stiffness and hypertension, with a particular focus on African Americans, a population disproportionately impacted by hypertension.

Methods: We utilized whole-blood transcriptome sequencing data from two African American (AA) cohorts with high hypertension prevalence: the GENE-FORECAST study (436 subjects) and the MH-GRID study (179 subjects).

Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells.

Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although signaling circuits and gene regulatory networks that regulate pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations to control state transitions remains a fundamental open question. Here, we focus on two distinct models of pluripotency, primed pluripotent stem cells and pre-implantation inner cell mass cells of human embryos to discover that cell fate transitions associate with rapid changes in nuclear shape and volume which collectively alter the nuclear mechanophenotype.

Systemic identification of functionally conserved lncRNA metabolic regulators in human and mouse livers.

Background & Aims: Unlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) lack conservation based on their sequences, posing a challenge for investigating their role in a pathophysiological context for clinical translation. This study explores the hypothesis that non-conserved lncRNAs in human and mouse livers may share similar metabolic functions, giving rise to functionally conserved lncRNA metabolic regulators (fcLMRs).

Methods: We developed a sequence-independent strategy to select putative fcLMRs, and performed extensive analysis to determine the functional similarities of putative human and mouse LMR pairs (h/mLMRs).

Local keratinocyte-nociceptor interactions enhance obesity-mediated small fiber neuropathy via NGF-TrkA-PI3K signaling axis.

The pathology of diabetic small fiber neuropathy, characterized by neuropathic pain and axon degeneration, develops locally within the skin during the stages of obesity and pre-diabetes. However, the initiation and progression of morphological and functional abnormalities in skin sensory nerves remains elusive. To address this, we utilized ear skin from mice with diet-induced obesity (DIO), the mouse models for obesity and pre-type 2 diabetes.

A deficiency screen identifies genomic regions critical for sperm head-tail connection.

A stable connection between the sperm head and tail is critical for fertility in species with flagellated sperm. The head-tail coupling apparatus (HTCA) serves as the critical link between the nucleus (head) and the axoneme (tail) via the centriole. To identify regions of the genome that contain genetic elements that influence HTCA formation, we undertook a two part screen using the deficiency (Df) kit.

Identifying individuals at risk for surgical supravalvar aortic stenosis by polygenic risk score with graded phenotyping.

In a previous pathway-based, extreme phenotype study, we identified 1064 variants associated with supravalvar aortic stenosis (SVAS) severity in people with Williams syndrome (WS) and either no SVAS or surgical SVAS. Here, we use those variants to develop and test polygenic risk scores (PRS). We used the clumping and thresholding (CT) approach on the full 1064 variants and a 427-variant subset that was part of 13 biologically relevant pathways identified in the previous study.

Self-identified Race and Ethnicity and How this is Perceived: Associations with the Physical and Mental Health of Incarcerated Individuals.

Objectives: The singular focus on self-identified race and ethnicity in health disparities research may not fully convey the individual and structural components of experiencing race in society, or in a racialized context such as prison. Processes of racialization create boundaries between incarcerated individuals and regulate their daily interactions and access to resources, with possible effects on well-being. However, the relationship between perceived race and health has not been examined within the imprisoned population.

What Has the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry Learned About Consenting Families for DNA Banking and/or Genomic Research?

Since 2015, the Sudden Unexpected Infant Death (SUID) and Sudden Death in the Young (SDY) Case Registry has characterized sudden and unexpected deaths among young people (0-20 years). Families may provide informed consent to save biospecimens for banking and/or genomic research. We reviewed all consent-eligible cases to describe the frequency, time from death to consent, type (paper, phone, or electronic), and staffing method (Medical Examiner Office-based bereavement counselor vs outsourced genetic counselor).

[Development of hematopoietic stem cell-targeted gene therapy].

Hematopoietic stem cell (HSC)-targeted gene therapy is curative for various genetic blood diseases, and its efficacy has been demonstrated in recent clinical trials. HSCs have self-renewal and hematopoietic multipotency; therefore, repairing pathological mutations or defects in HSCs allows for a lifelong cure with a single treatment. Autologous HSC gene therapy has been developed by lentiviral gene addition or gene editing, and is an option for most patients because it does not require a compatible donor.

Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation.

Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels.

Tobacco Biomarkers by Latino Heritage and Race, US, 2007 to 2014 National Health and Nutrition Examination Survey.

Background: Tobacco biomarkers reflect smoking intensity and are used to assess cessation status. No study has evaluated variation by Latino heritage.

Methods: Data from the 2007 to 2014 National Health and Nutrition Examination Survey were used to evaluate geometric mean concentrations of serum cotinine and urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), stratified by smoking status and race and ethnicity, and ROC curves estimated values to distinguish smokers from nonsmokers by race and ethnicity and Latino heritage.

Non-invasive optical and laboratory hematologic biomarkers correlate in patients with sickle cell disease.

The goal of this study is to identify non-invasive optical hemodynamic biomarkers that can index laboratory hematology measurements in sickle cell disease (SCD). We acquired frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS) data from the forearms and foreheads of 17 participants in a randomized, double-blind, placebo-controlled trial evaluating effects of isoquercetin (IQ) on thromboinflammation in SCD. We observed multiple, significant correlations between optical and hematology biomarkers including cerebral tissue oxygen saturation (StO) and hematocrit (HCT); oxyhemoglobin ([OHb]) recovery rate and intercellular adhesion molecule 1 (ICAM-1); and blood flow index (BFI) reperfusion rate and coagulation index (CI).

Establishing NIH Community Implementation Programs to improve maternal health.

The United States has seen increasing trends of maternal mortality in recent years. Within this health crisis there are large disparities whereby underserved and minoritized populations are bearing a larger burden of maternal morbidity and mortality. While new interventions to improve maternal health are being developed, there are opportunities for greater integration of existing evidence-based interventions into routine practice, especially for underserved populations, including those residing in maternity care deserts.