MicroRNAs mir‐184 and let‐7 alter Drosophila metabolism and longevity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140032/1/acel12673.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140032/2/acel12673-sup-0002-FigS1-S8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140032/3/acel12673_am.pd

Solvable senescence model with positive mutations

We build upon our previous analytical results for the Penna model of senescence to include positive mutations. We investigate whether a small but non-zero positive mutation rate gives qualitatively different results to the traditional Penna model in which no positive mutations are considered. We find that the high-lifespan tail of the distribution is radically changed in structure, but that there is not much effect on the bulk of the population. Th e mortality plateau that we found previously for a stochastic generalization of the Penna model is stable to a small positive mutation rate.Comment: 3 figure

Electrochemical micromachining: An Introduction

Copyright © 2016 The Author(s). Electrochemical machining (ECM) is a relatively new technique, only being introduced as a commercial technique within the last 70 years (1). A lot of research was conducted in the 1960s and 1970s but research on electrical discharge machining (EDM) around the same time slowed ECM research (2). The main influence for the development of ECM came from the aerospace industry where very hard alloys were required to be machined without leaving a defective layer in order to produce a component which would behave reliably (3). ECM was primarily used for the production of gas turbine blades (2) or to machine materials into complex shapes that would be difficult to machine using conventional machining methods (4). Tool wear is high and the metal removal rate is slow when machining hard materials with conventional machining methods such as milling. This increases the cost of the machining process overall and this method creates a defective layer on the machined surface (3). Whereas with ECM there is virtually no tool wear even when machining hard materials and it does not leave a defective layer on the machined surface. This paper reviews the application of electrochemical machining with regards to micro-manufacturing and present state of the art micro ECM considering different machined materials, electrolytes and conditions used.The research reported in this article was supported by the European Commission within the project ‘Minimizing Defects in Micro-Manufacturing Applications (MIDEMMA)’ (FP7-2011-NMP-ICT-FoF-285614)

Mitochondrial thioredoxin reductase 2 is elevated in long‐lived primate as well as rodent species and extends fly mean lifespan

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137684/1/acel12596-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137684/2/acel12596.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137684/3/acel12596_am.pd

Analytical solution of a generalized Penna model

In 1995 T.J.Penna introduced a simple model of biological aging. A modified Penna model has been demonstrated to exhibit behaviour of real-life systems including catastrophic senescence in salmon and a mortality plateau at advanced ages. We present a general steady-state, analytic solution to the Penna model, able to deal with arbitrary birth and survivability functions. This solution is employed to solve standard variant Penna models studied by simulation. Different Verhulst factors regulating both the birth rate and external death rate are considered.Comment: 6 figure

One Large Kindred Excludes a Locus for Multiple Endocrine Neoplasia Type 2A from about 25% of the Human Autosomal Genetic Map

This report presents pairwise linkage results from our search for the locus of the gene (MEN2A) for the multiple endocrine neoplasia type 2A (MEN-2A) syndrome in one large kindred (the N kindred), clearly segregating for an autosomal dominant form. About 25% of the autosomal genome is excluded when these new results are combined with those we have published previously. The genetic markers employed are distributed across at least 19 of the 22 autosomes. Seven genetic markers whose chromosomal locations are not yet established have also been studied

Nighttime Blood Pressure Dipping in Young Adults and Coronary Artery Calcium 10-15 Years Later: The Coronary Artery Risk Development in Young Adults Study

Nighttime blood pressure (BP) dipping can be quantified as the ratio of mean nighttime (sleep) BP to mean daytime (awake) BP. People whose dipping ratio is 0.90 have been referred to as nondippers, and nondipping is associated with cardiovascular disease events. We examined the relationship between systolic nighttime BP dipping in young adults and presence of coronary artery calcium (CAC) 10-15 years later using data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among 239 participants with adequate measures of both nighttime and daytime readings and coronary artery calcium, the systolic BP dipping ratio ranged from 0.72 to 1.24 (mean 0.88, SD 0.06), and CAC was present 10 to 15 years later in 54 participants (22.6%). Compared to those whose systolic BP dipping ratio ranged from 0.88 to 0.92 (Quartile 3), the 57 participants (23.9%) with less pronounced or absent dipping (ratio 0.92 to 1.24, Quartile 4) had an unadjusted odds ratio of 4.08 (95% CI 1.48-11.2) for presence of CAC. The 60 participants (25.1%) with a more pronounced dipping (ratio 0.72 to 0.85, Quartile 1) also had greater odds for presence of CAC (OR 4.76; 95% CI 1.76-12.9). When modeled as a continuous predictor, a U-shaped relationship between systolic BP dipping ratio and future CAC was apparent, and persisted after adjustment for multiple potential confounders (

Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>The inbred mouse strain BTBR T+ tf/J (BTBR) exhibits behavioral deficits that mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse, focusing on neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors.</p> <p>Methods</p> <p>Forebrains of 8 to 10-week-old male BTBR and age-matched C57Bl/6J control mice were evaluated by immunohistochemistry using free-floating and paraffin embedded sections. Twenty antibodies directed against antigens specific to neurons, synapses and glia were used. Nissl, Timm and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine (BrdU) were performed to determine hippocampal progenitor proliferation, survival and differentiation, and brain-derived neurotrophic factor (BDNF) mRNA was quantified by <it>in situ </it>hybridization. Quantitative image analysis was performed for NG2, doublecortin (DCX), NeuroD, GAD67 and Poly-Sialic Acid Neural Cell Adhesion Molecule (PSA-NCAM).</p> <p>Results</p> <p>In midline structures including the region of the absent corpus callosum of BTBR mice, the myelin markers 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP) were reduced, and the oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white-matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU) positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms.</p> <p>Conclusions</p> <p>We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.</p