Idiopathic orthostatic hypotension: Recent data (eleven cases) and review of the literature

Eight cases of Shy-Drager syndrome and three of Bradbury-Eggleston idiopathic orthostatic hypotension were examined. In all cases, examination of circulatory reflexes showed major dysfunction of the sympathetic vasoconstrictor system. Anomalies in the vagal cardiomoderator system were less constant. Normal urinary elimination of catecholamines was recorded daily. Characteristically, no elevation of blood or urine norepinephrine levels were found in orthostatism. Insulin hypoglycemia normally raised urinary adrenalin elimination in three of ten patients. Plasma dopa-beta-hydroxylase activity was normal. Renin-angiotensin-aldosterone system showed variable activity at basal state but usually rose during orthostatism. On the average, very low homovanillic acid levels were found in cerebrospinal fluid before and after probenecid; hydroxyindolacetic acid was normal. Cerebral autoregulation had deteriorated in two of four cases. Physiopathologically the two clinical types are indistinguishable with or without central neurological signs

Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer\u27s disease.

INTRODUCTION: Our limited understanding of the mechanisms that trigger the emergence of Alzheimer\u27s disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that the development of a non-human primate model of AD will be an essential step toward overcoming limitations of other model systems and is crucial for investigating primate-specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD. METHODS: A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets As Research Models of AD (MARMO-AD). This consortium will study gene-edited marmoset models carrying genetic risk for AD and wild-type genetically diverse aging marmosets from birth throughout their lifespan, using non-invasive longitudinal assessments. These include characterizing the genetic, molecular, functional, behavioral, cognitive, and pathological features of aging and AD. RESULTS: The consortium successfully generated viable founders carrying DISCUSSION: By establishing marmoset models of AD, we will be able to investigate primate-specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients

Variation in histone configurations correlates with gene expression across nine inbred strains of mice.

The diversity outbred (DO) mice and their inbred founders are widely used models of human disease. However, although the genetic diversity of these mice has been well documented, their epigenetic diversity has not. Epigenetic modifications, such as histone modifications and DNA methylation, are important regulators of gene expression, and as such are a critical mechanistic link between genotype and phenotype. Therefore, creating a map of epigenetic modifications in the DO mice and their founders is an important step toward understanding mechanisms of gene regulation and the link to disease in this widely used resource. To this end, we performed a strain survey of epigenetic modifications in hepatocytes of the DO founders. We surveyed four histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac), and DNA methylation. We used ChromHMM to identify 14 chromatin states, each of which represented a distinct combination of the four histone modifications. We found that the epigenetic landscape was highly variable across the DO founders and was associated with variation in gene expression across strains. We found that epigenetic state imputed into a population of DO mice recapitulated the association with gene expression seen in the founders suggesting that both histone modifications and DNA methylation are highly heritable mechanisms of gene expression regulation. We illustrate how DO gene expression can be aligned with inbred epigenetic states to identify putative cis-regulatory regions. Finally, we provide a data resource that documents strain-specific variation in chromatin state and DNA methylation in hepatocytes across nine widely used strains of laboratory mice

Data from: Constraints on geographic variation in fiddler crabs (Ocypodidae: Uca) from the western Atlantic

A key question in evolutionary biology is how intraspecific variation biases the evolution of a population and its divergence from other populations. Such constraints potentially limit the extent to which populations respond to selection, but may endure long enough to have macroevolutionary consequences. Previous studies have focused on the association between covariation patterns and divergence among isolated populations. Few have focused on geographic variation among semi-connected populations, however, even though this may be indicative of early selective pressures that could lead to long-term divergence and speciation. Here, we test whether covariation in the shape of the carapace of fiddler crabs (genus Uca Leach, 1814) is important for structuring geographic variation. We find that morphological divergence among populations is associated with evolvability in the direction of divergence in only a few species. The shape of the ancestral covariation matrix in these species differs from other species in having notably more variation concentrated along fewer directions (i.e., higher eccentricity). For most species, there is some evidence that covariation has constrained the range of directions into which populations have diverged but not the degree of divergence. These results suggest that even though fiddler crab populations have diverged morphologically in directions predicted by covariation, constraints on the extent to which divergence has occurred may only be manifested in species where variation patterns are eccentric enough to limit populations’ ability to respond effectively in many directions

Solid state ion transport and phase behaviour in composites of N,N-methyl propylpyrrolidinium tetrafluoroborate and amorphous polyethylene oxide

The binary and ternary addition of 2 wt.% LiBF4 and 2 wt.% amorphous polyethylene oxide (aPEO) respectively to the plastic crystal forming salt P13BF4 (where P13+=methylpropyl pyrrolidinium cation) was investigated with specific focus on the phase behaviour and evaluation of transport characteristics. Differential scanning calorimetry (DSC), optical thermomicroscopy, solid state nuclear magnetic resonance (NMR), and AC impedance spectroscopy were used to develop an understanding of the conduction process in the pure and mixed systems. The morphology of the ternary compound appeared as hexagonal spherulites upon solidification. Multinuclear NMR Pulsed Field Gradient measurements (1H,19F,7Li) to probe both cation and anion diffusion coefficients are reported. The anion is shown to be the most diffusive (at 320 K:19F=2.5&times;10&minus;11 m2 s&minus;1; 1H: 1.8&times;10&minus;11 m2 s&minus;1; 7Li: 1.1&times;10&minus;11 m2 s&minus;1) in the ternary compound, with enhanced conductivity (2.7&times;10&minus;5 S cm&minus;1 at 310 K) just below the melt.<br /