Beyond Body Mass Index: Accurate Metabolic Disease-Risk Phenotyping With 3D Smartphone Application.

Objective: Smartphone applications (apps) with optical imaging capabilities are transforming the field of physical anthropometry; digital measurements of body size and shape in clinical settings are increasingly feasible. Currently available apps are usually designed around the capture of two-dimensional images that are then transformed with app software to three-dimensional (3D) avatars that can be used for digital anthropometry. The aim of the current study was to compare waist circumference (WC), hip circumference (HC), four other circumferences (right/left upper arm, thigh) and WC/HC evaluated with a novel high-precision 3D smartphone app to ground-truth measurements made with a flexible tape by a trained anthropometrist.

Correspondence of Yolk Sac and Embryonic Genotypes in F0 Mouse CRISPants.

CRISPR-mediated genome editing can be accompanied by prolonged stability of the Cas9 protein in mouse embryos. Then, genome edited variant alleles will be induced as long as Cas9 protein is active, and unmodified wildtype target loci are available. The corollary is that CRISPR-modified alleles that arise after the first zygotic cell division potentially could be distributed asymmetrically to the cell lineages that are specified early during morula and blastocyst development.

Effects of Maternal Diabetes and Diet on Gene Expression in the Murine Placenta.

Adverse exposures during pregnancy have been shown to contribute to susceptibility for chronic diseases in offspring. Maternal diabetes during pregnancy is associated with higher risk of pregnancy complications, structural birth defects, and cardiometabolic health impairments later in life. We showed previously in a mouse model that the placenta is smaller in diabetic pregnancies, with reduced size of the junctional zone and labyrinth.

Broad spectrum of CRISPR-induced edits in an embryonic lethal gene.

Mendelian genetics poses practical limitations on the number of mutant genes that can be investigated simultaneously for their roles in embryonic development in the mouse. While CRISPR-based gene editing of multiple genes at once offers an attractive alternative strategy, subsequent breeding or establishment of permanent mouse lines will rapidly segregate the different mutant loci again. Direct phenotypic analysis of genomic edits in an embryonic lethal gene in F0 generation mice, or F0 mouse embryos, circumvents the need for breeding or establishment of mutant mouse lines.

Does gastric bypass surgery change body weight set point?

The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight.

Lifestyle modification intervention improves glycemic control in Mongolian adults who are overweight or obese with newly diagnosed type 2 diabetes.

Objective: To evaluate the effectiveness of a weight loss intervention in Mongolian adults with newly diagnosed type 2 diabetes mellitus and with BMIs ≥ 25.0 kg/m.

Methods: Eighty participants (33 men/47 women) aged 32-56 years old received education sessions to improve nutritional habits and increase physical activity.

Relationships between misreported energy intake and pregnancy in the pregnancy, infection and nutrition study: new insights from a dynamic energy balance model.

Objective: Providing effective dietary counselling so that pregnancy weight gain remains within the 2009 Institute of Medicine (IOM) guidelines requires accurate maternal energy intake measures. Current practice is based on self-reported intake that has been demonstrated unreliable. This study applies an objective calculation of energy intake from a validated mathematical model to identify characteristics of individuals more likely to misreport during pregnancy.

Developmental Patterning as a Quantitative Trait: Genetic Modulation of the Hoxb6 Mutant Skeletal Phenotype.

The process of patterning along the anterior-posterior axis in vertebrates is highly conserved. The function of Hox genes in the axis patterning process is particularly well documented for bone development in the vertebral column and the limbs. We here show that Hoxb6, in skeletal elements at the cervico-thoracic junction, controls multiple independent aspects of skeletal pattern, implicating discrete developmental pathways as substrates for this transcription factor.

The association between resistance exercise and cardiovascular disease risk in women.

Objectives: The objective of this study was to examine the association between resistance exercise and cardiovascular disease risk, independent of body composition, physical activity and aerobic capacity, in healthy women.

Design: A cross-sectional analysis including 7321 women with no history of heart disease, hypertension or diabetes was performed.

Methods: Participation in resistance exercise was self-reported and body weight and height was measured.

Feasibility, reliability, and validity of a smartphone based application for the assessment of cognitive function in the elderly.

While considerable knowledge has been gained through the use of established cognitive and motor assessment tools, there is a considerable interest and need for the development of a battery of reliable and validated assessment tools that provide real-time and remote analysis of cognitive and motor function in the elderly. Smartphones appear to be an obvious choice for the development of these "next-generation" assessment tools for geriatric research, although to date no studies have reported on the use of smartphone-based applications for the study of cognition in the elderly. The primary focus of the current study was to assess the feasibility, reliability, and validity of a smartphone-based application for the assessment of cognitive function in the elderly.

Obesity increases cerebrocortical reactive oxygen species and impairs brain function.

Nearly two-thirds of the population in the United States is overweight or obese, and this unprecedented level of obesity will undoubtedly have a profound impact on overall health, although little is currently known about the effects of obesity on the brain. The objective of this study was to investigate cerebral oxidative stress and cognitive decline in the context of diet-induced obesity (DIO). We demonstrate for the first time that DIO induces higher levels of reactive oxygen species (ROS) in the brain and promotes cognitive impairment.

Transgenic studies on homeobox genes in nervous system development: spina bifida in Isl1 transgenic mice.

To develop in vivo assays for homeobox gene function in neural development, we generated transgenic mice in which the expression of a homeobox gene is altered only within the nervous system, in neurons or neuronal precursor cells. Transgenic expression of Hoxc8 did not result in gross abnormalities, while a Hoxd4 transgene caused death shortly after birth. In neural progenitor cells, the motorneuron-specific homeodomain transcription factor Isl1 induced early developmental defects, including absence of anterior neural structures, profound defects in the neuroepithelium and defective neural tube closure.

Neuron specific toxicity of oligomeric amyloid-β: role for JUN-kinase and oxidative stress.

Recent studies have demonstrated a potential role for oligomeric forms of amyloid-β (Aβ) in the pathogenesis of Alzheimer's disease (AD), although it remains unclear which aspects of AD may be mediated by oligomeric Aβ. In the present study, we found that primary cultures of rat cortical neurons exhibit a dose-dependent increase in cell death following Aβ oligomer administration, while primary cultures of astrocytes exhibited no overt toxicity with even the highest concentrations of oligomer treatment. Neither cell type exhibited toxicity when treated by equal concentrations of monomeric Aβ.

Intersection between metabolic dysfunction, high fat diet consumption, and brain aging.

Deleterious neurochemical, structural, and behavioral alterations are a seemingly unavoidable aspect of brain aging. However, the basis for these alterations, as well as the basis for the tremendous variability in regards to the degree to which these aspects are altered in aging individuals, remains to be elucidated. An increasing number of individuals regularly consume a diet high in fat, with high-fat diet consumption known to be sufficient to promote metabolic dysfunction, although the links between high-fat diet consumption and aging are only now beginning to be elucidated.

Aging and dietary restriction alter proteasome biogenesis and composition in the brain and liver.

Interventions such as dietary restriction (DR) have been reported to ameliorate age-related proteasome inhibition in some tissues. Currently it is not known what effects aging and DR have on proteasome biogenesis in the liver and brain, nor have previous studies identified the links between changes in proteasome composition, biogenesis, and activity in the aging brain and liver. In the present study we demonstrate that the brain and liver exhibit age-dependent decreases in 26S and 20S proteasome activity.

Activation of PERK kinase in neural cells by proteasome inhibitor treatment.

Inhibition of the proteasome proteolytic pathway occurs as the result of normal aging, as well as in a variety of neurodegenerative conditions, and is believed to promote cellular toxicity in each of these conditions through diverse mechanisms. In the present study, we examined whether proteasome inhibition alters the protein kinase receptor-like endoplasmic reticulum kinase (PERK). Our studies demonstrate that proteasome inhibitors induce the transient activation of PERK in both primary rat neurons as well as the N2a neural cell line.

Proteasome inhibition modulates kinase activation in neural cells: relevance to ubiquitination, ribosomes, and survival.

In this study we examined whether established signal transduction cascades, p44/42 mitogen-activated protein kinase (ERK1/2) and Jun N-terminal kinases (JNK) pathways, are altered in N2a neural cells in response to proteasome inhibition. Additionally, we sought to elucidate the relative contribution of these signal transduction pathways to the multiple downstream effects of proteasome inhibition. Our data indicate that ERK1/2 and JNK are activated in response to proteasome inhibition.

Comparison of rat liver and brain proteasomes for oxidative stress-induced inactivation: Influence of ageing and dietary restriction.

The present study examined brain and liver derived proteasome complexes to elucidate if there is a differential susceptibility in proteasome complexes from these tissues to undergo inactivation following exposure to oxidative stressors. It then examined the influence of ageing and dietary restriction (DR) on the observed proteasome inactivation. Studies used a filtration based methodology that allows for enrichment of proteasome complexes with less tissue than is required for traditional chromatography procedures.

Diet-induced metabolic disturbances as modulators of brain homeostasis.

A number of metabolic disturbances occur in response to the consumption of a high fat western diet. Such metabolic disturbances can include the progressive development of hyperglycemia, hyperinsulemia, obesity, metabolic syndrome, and diabetes. Cumulatively, diet-induced disturbances in metabolism are known to promote increased morbidity and negatively impact life expectancy through a variety of mechanisms.

Cholecystokinin-8s excites identified rat pancreatic-projecting vagal motoneurons.

It is known that cholecystokinin (CCK) acts in a paracrine fashion to increase pancreatic exocrine secretion via vagal circuits. Recent evidence, however, suggests that CCK-8s actions are not restricted to afferent vagal fibers, but also affect brain stem structures directly. Within the brain stem, preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) send efferent fibers to subdiaphragmatic viscera, including the pancreas.

Vagally mediated, nonparacrine effects of cholecystokinin-8s on rat pancreatic exocrine secretion.

Cholecystokinin (CCK) has been proposed to act in a vagally dependent manner to increase pancreatic exocrine secretion via actions exclusively at peripheral vagal afferent fibers. Recent evidence, however, suggests the CCK-8s may also affect brain stem structures directly. We used an in vivo preparation with the aims of 1) investigating whether the actions of intraduodenal casein perfusion to increase pancreatic protein secretion also involved direct actions of CCK at the level of the brain stem and, if so, 2) determining whether, in the absence of vagal afferent inputs, CCK-8s applied to the dorsal vagal complex (DVC) can also modulate pancreatic exocrine secretion (PES).

Esophageal-gastric relaxation reflex in rat: dual control of peripheral nitrergic and cholinergic transmission.

It has long been known that the esophageal distension produced by swallowing elicits a powerful proximal gastric relaxation. Gastroinhibitory control by the esophagus involves neural pathways from esophageal distension-sensitive neurons in the nucleus tractus solitarius centralis (cNTS) with connections to virtually all levels of the dorsal motor nucleus of the vagus (DMV). We have shown recently that cNTS responses are excitatory and primarily involve tyrosine hydroxylase-immunoreactive cells, whereas the DMV response involves both an alpha1 excitatory and an alpha2 inhibitory response.