Clonal Hematopoiesis is Associated With Protection From Alzheimer\u27s Disease

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer\u27s disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 1

Transcriptional Control of Steroid Biosynthesis Genes in the Drosophila Prothoracic Gland by Ventral Veins Lacking and Knirps.

Specialized endocrine cells produce and release steroid hormones that govern development, metabolism and reproduction. In order to synthesize steroids, all the genes in the biosynthetic pathway must be coordinately turned on in steroidogenic cells. In Drosophila, the steroid producing endocrine cells are located in the prothoracic gland (PG) that releases the steroid hormone ecdysone. The transcriptional regulatory network that specifies the unique PG specific expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we show that two transcription factors, the POU-domain Ventral veins lacking (Vvl) and the nuclear receptor Knirps (Kni), have essential roles in the PG during larval development. Vvl is highly expressed in the PG during embryogenesis and is enriched in the gland during larval development, suggesting that Vvl might function as a master transcriptional regulator in this tissue. Vvl and Kni bind to PG specific cis-regulatory elements that are required for expression of the ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in a larval developmental arrest due to failure in ecdysone production. Furthermore, Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic hormone (PTTH) signaling in the PG, two major pathways that control ecdysone biosynthesis and PG cell growth. We also show that the transcriptional regulator, Molting defective (Mld), controls early biosynthetic pathway steps. Our data show that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional control of biosynthetic gene expression and indirectly by affecting PTTH and TOR/S6K signaling. This provides new insight into the regulatory network of transcription factors involved in the coordinated regulation of steroidogenic cell specific transcription, and identifies a new function of Vvl and Knirps in endocrine cells during post-embryonic development

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

A possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren’t detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Thermal analysis of aluminum bronze BA1032

In this study, aluminum bronze BA1032 was analyzed thermally by differential scanning calorimetry (DSC). The article presents the results of measurements of phase transitions occurring in aluminum bronze at a temperature of up to 600°C. Thermal analyses were conducted at constant heating rates of 5°C/min, 10°C/min and 15°C/min

Functional and Fractal Properties of Fe-Al Coatings After Gas Detonation Spraying (GDS)

The paper presents the results and provides an analyse of the geometric structure of Fe-Al protective coatings, gas-treated under specified GDS conditions. The analysis of the surface topography was conducted on the basis of the results obtained from the SEM data. Topographic images were converted to three-dimensional maps, scaling the registered amplitude coordinates of specific gray levels to the relative range of 0÷1. This allowed us to assess the degree of surface development by determining the fractal dimension. At the same time, the generated three-dimensional spectra of the autocorrelation function enabled the researchers to determine the autocorrelation length (Sal) and the degree of anisotropy (Str) of the surfaces, in accordance with ISO 25178. Furthermore, the reconstructed three-dimensional images of the topography allowed us to evaluate the functional properties of the studied surfaces based on the Abbott-Firestone curve (A-F), also known as the bearing area curve. The ordinate describing the height of the profile was replaced by the percentage of surface amplitude in this method, so in effect the shares of the height of the three-dimensional topographic map profiles of various load-bearing properties were determined. In this way, both the relative height of peaks, core and recesses as well as their percentages were subsequently established

Application of Fractal Analysis Methods for Lift Height Optimization in Magnetic Force Microscopy Measurements

The paper presents results of a research on simulation of magnetic tip-surface interaction as a function of the lift height in the magnetic force microscopy. As expected, magnetic signal monotonically decays with increasing lift height, but the question aris es, whether or not optimal lift height eventually exists. To estimate such a lift height simple procedure is proposed in the paper based on the minimization of the fractal dimension of the averaged profile of the MFM signal. In this case, the fractal dimension ser ves as a measure of distortion of a pure tip-surface magnetic coupling by various side effects, e.g. thermal noise and contribution of topographic features. Obtained simulation results apparently agree with experimental data

The Influence of the Processing Temperature of Polylactide on Geometric Structure of the Surface Using FDM Technique

The influence of the processing temperature of polylactide (PLA) on the structure geometry changing (SGC) and its functional properties were analyzed. The PLA samples subjected to testing were manufactured using incremental fused deposition modeling technology (FDM) with processing temperatures ranging from 180°C to 230°C. The topography of the PLA surfaces formed during heat dissipation and generated by the work table was analyzed. The roughness measurements were carried out using the profile method in accordance with PN ISO 3274: 2011. Registered profiles of the surfaces were analyzed numerically in fractal terms using the method of the S(Δx) structure function. The functional properties of the PLA surface were evaluated on the basis of Abbott-Firestone curves, according to PN EN ISO 13565–2: 1999