Chromatin State Maps of Blood Pressure-Relevant Renal Segments Reveal Potential Regulatory Role for SNPs.

Background: Hypertension or elevated blood pressure (BP) is a worldwide clinical challenge and the leading primary risk factor for kidney dysfunctions, heart failure, and cerebrovascular disease. The kidney is a central regulator of BP by maintaining sodium-water balance. Multiple genome-wide association studies revealed that BP is a heritable quantitative trait, modulated by several genetic, epigenetic, and environmental factors.

Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure.

Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. The constriction and dilation of arterioles regulate tissue perfusion and are primary determinants of systemic blood pressure (BP). Abnormalities in arterioles are central to the development of major diseases such as hypertension, stroke, and microvascular complications of diabetes.

Are clinical tests and biomechanical measures of gait stability able to differentiate fallers from non-fallers in hereditary spastic paraplegia?

Introduction: Balance and gait impairments are common in people with hereditary spastic paraplegia (HSP) and often result in falls. Measures that identify patients at risk of falling are clinically relevant, but relatively unexplored in HSP. Here, we evaluated the potential of different balance and gait constructs to (1) identify differences between healthy controls and people with HSP and (2) discriminate between fallers and non-fallers with HSP.

Physiological role and mechanisms of action for a long noncoding haplotype region.

Most common sequence variants associated with human traits are in noncoding regions of the genome, form haplotypes with other noncoding variants, and exhibit small effect sizes in the general population. Determining the physiological roles and mechanisms of action for these noncoding variants, particularly large haplotypes containing multiple variants, is both critical and challenging. To address this challenge, we developed an approach that integrates physiological studies in genetically engineered and phenotypically permissive animal models, precise editing of large haplotypes in human induced pluripotent stem cells (hiPSCs), and targeted chromatin conformation analysis.

Synthesis of the bicyclic butenolide core of pallamolide A: a biomimetic approach.

Pallamolide A is a 7,8--labdane terpenoid possessing a unique bicyclo[2.2.2]octane core and a spiro-butenolide moiety.

Efficacy of selective neurotomy for focal lower limb spasticity: a systematic review.

Objective: Selective neurotomy has been suggested as a permanent treatment for focal spasticity. A systematic literature review was performed to investigate the efficacy of selective neurotomy regarding focal lower limb spasticity.

Methods: A systematic search in PubMed, Medline, Cochrane, and Embase databases was carried out.

Effect of a soft exosuit on daily life gait performance in people with incomplete spinal cord injury: study protocol for a randomized controlled trial.

Background: People with incomplete spinal cord injury (iSCI) often have gait impairments that negatively affect daily life gait performance (i.e., ambulation in the home and community setting) and quality of life.

Real-world gait and turning in individuals scheduled for total knee arthroplasty.

Background: Improving mobility - specifically walking - is an important treatment goal of total knee arthroplasty. Objective indicators for mobility, however, are lacking in clinical evaluations. This study aimed to compare real-world gait and turning between individuals scheduled for total knee arthroplasty and healthy controls, using continuous monitoring with inertial measurement units.

Plantar pressure in relation to hindfoot varus in people with unilateral upper motor neuron syndrome.

Introduction: Hindfoot varus deformity is common in people with unilateral upper motor neuron syndrome (UMNS) and can be dynamic or persistent. The aims of this study were (1) to gain insight into plantar pressure characteristics of people with chronic UMNS in relation to hindfoot varus and (2) to propose a quantitative outcome measure, based on plantar pressure, for the scientific evaluation of surgical interventions.

Methods: In this retrospective study, a cohort comprising plantar pressure data of 49 people with UMNS (22 "no hindfoot varus", 18 "dynamic hindfoot varus", and 9 "persistent hindfoot varus"), and 586 healthy controls was analyzed.

Quantitative ultrasound of submental and masticatory muscles in children with cerebral palsy.

Purpose: Quantitative muscle ultrasound (QMUS) is potentially valuable as a diagnostic tool in central neurological disorders, as it provides information about changes in muscle architecture. This study aimed to investigate whether ultrasound images of the submental and masticatory muscles in children with spastic cerebral palsy (CP) differ from those obtained in a reference group, and whether observed ultrasound abnormalities differ between subgroups of children with different Eating and Drinking Ability Classification System (EDACS) levels to support its construct validity.

Methods: A prospective cohort study was conducted in 25 children with spastic CP aged 3-18 years.

Protein-coding mutation in increases adiposity and alters emotional behaviors sex-dependently in rats.

Objective: has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2 transmembrane (TM) helix of in rats, and similar obesity variants have been identified in humans. The current study investigates the role of a TM variant in adiposity and behavior.

Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype.

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils.

Efficacy of Walking Adaptability Training on Walking Capacity in Ambulatory People With Motor Incomplete Spinal Cord Injury: A Multicenter Pragmatic Randomized Controlled Trial.

Background And Objective: Balance and walking capacity are often impaired in people with motor incomplete spinal cord injury (iSCI), frequently resulting in reduced functional ambulation and participation. This study aimed to assess the efficacy of walking adaptability training compared to similarly dosed conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, and participation in ambulatory people with iSCI.

Methods: We conducted a 2-center, parallel-group, pragmatic randomized controlled trial.

Age-related changes in muscle coordination patterns of stepping responses to recover from loss of balance.

Introduction: Reactive stepping capacity to recover from a loss of balance declines with aging, which increases the risk of falling. To gain insight into the underlying mechanisms, we investigated whether muscle coordination patterns of reactive stepping differed between healthy young and older individuals.

Methods: We performed a cross-sectional study between 15 healthy young and 14 healthy older adults.

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets.

Individuals with knee osteoarthritis show few limitations in balance recovery responses after moderate gait perturbations.

Background: Knee osteoarthritis causes structural joint damage. The resultant symptoms can impair the ability to recover from unexpected gait perturbations. This study compared balance recovery responses to moderate gait perturbations between individuals with knee osteoarthritis and healthy individuals.

Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of .

We previously identified , , as a novel adiposity gene, but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between , adiposity, and stress, we exposed wild-type (WT) and knock-out (KO) rats to chronic stress then measured adiposity and behavioral outcomes. We found that KO rats displayed lower basal stress than WT rats under control conditions and exhibited metabolic and behavioral responses to chronic stress exposure.

Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice.

Agouti-related peptide (AgRP/) within the hypothalamic arcuate nucleus (ARC) contributes to the control of energy balance, and dysregulated may contribute to metabolic adaptation during prolonged obesity. In mice, three isoforms of are encoded via distinct first exons. (ENSMUST00000005849.

Histone Modifications and Their Contributions to Hypertension.

Essential hypertension, a multifaceted disorder, is a worldwide health problem. A complex network of genetic, epigenetic, physiological, and environmental components regulates blood pressure (BP), and any dysregulation of this network may result in hypertension. Growing evidence suggests a role for epigenetic factors in BP regulation.

Deletion of Vβ3CD4 T cells by endogenous mouse mammary tumor virus 3 prevents type 1 diabetes induction by autoreactive CD8 T cells.

In both humans and NOD mice, type 1 diabetes (T1D) develops from the autoimmune destruction of pancreatic beta cells by T cells. Interactions between both helper CD4 and cytotoxic CD8 T cells are essential for T1D development in NOD mice. Previous work has indicated that pathogenic T cells arise from deleterious interactions between relatively common genes which regulate aspects of T cell activation/effector function ( ), peptide presentation (, ), and T cell receptor (TCR) signaling ().

Mild Stroke, Serious Problems: Limitations in Balance and Gait Capacity and the Impact on Fall Rate, and Physical Activity.

Background: After mild stroke persistent balance limitations may occur, creating a risk factor for fear of falling, falls, and reduced activity levels. To investigate whether individuals in the chronic phase after mild stroke show balance and gait limitations, elevated fall risk, reduced balance confidence, and physical activity levels compared to healthy controls.

Methods: An observational case-control study was performed.

Protease-Activated Receptor 1-Mediated Damage of Podocytes in Diabetic Nephropathy.

Unlabelled: There is clinical evidence that increased urinary serine proteases are associated with the disease severity in the setting of diabetic nephropathy (DN). Elevation of serine proteases may mediate [Ca2+]i dynamics in podocytes through the protease-activated receptors (PARs) pathway, including associated activation of nonspecific cation channels. Cultured human podocytes and freshly isolated glomeruli were used for fluorescence and immunohistochemistry stainings, calcium imaging, Western blot analysis, scanning ion conductance microscopy, and patch clamp analysis.

Knockout of Matrix Metalloproteinase 2 Opposes Hypertension- and Diabetes-induced Nephropathy.

The progression of chronic kidney disease results from the accumulation of extracellular matrix leading to end-stage renal disease. We previously demonstrated that a broad-spectrum matrix metalloproteinase (MMP) inhibitor reduced renal injury in rat models of hypertension and diabetes. However, the isoforms and mechanisms involved are unclear.