Competitive Mirror Image Phage Display Derived Peptide Modulates Amyloid Beta Aggregation and Toxicity

Alzheimer´s disease is the most prominent type of dementia and currently no causative treatment is available. According to recent studies, oligomeric species of the amyloid beta (Aβ) peptide appear to be the most toxic Aβ assemblies. Aβ monomers, however, may be not toxic per se and may even have a neuroprotective role. Here we describe a competitive mirror image phage display procedure that allowed us to identify preferentially Aβ_1–42 monomer binding and thereby stabilizing peptides, which destabilize and thereby eliminate toxic oligomer species. One of the peptides, called Mosd1 (monomer specific d-peptide 1), was characterized in more detail. Mosd1 abolished oligomers from a mixture of Aβ_1–42 species, reduced Aβ_1–42 toxicity in cell culture, and restored the physiological phenotype in neuronal cells stably transfected with the gene coding for human amyloid precursor protein.     

Overweight Is an Independent Risk Factor for Reduced Lung Volumes in Myotonic Dystrophy Type 1

Background

In this large observational study population of 105 myotonic dystrophy type 1 (DM1) patients, we investigate whether bodyweight is a contributor of total lung capacity (TLC) independent of the impaired inspiratory muscle strength.

Methods

Body composition was assessed using the combination of body mass index (BMI) and fat-free mass index. Pulmonary function tests and respiratory muscle strength measurements were performed on the same day. Patients were stratified into normal (BMI < 25 kg/m²) and overweight (BMI ≥ 25 kg/m²) groups. Multiple linear regression was used to find significant contributors for TLC.

Results

Overweight was present in 59% of patients, and body composition was abnormal in almost all patients. In overweight patients, TLC was significantly (p = 2.40×10⁻³) decreased, compared with normal-weight patients, while inspiratory muscle strength was similar in both groups. The decrease in TLC in overweight patients was mainly due to a decrease in expiratory reserve volume (ERV) further illustrated by a highly significant (p = 1.33×10⁻¹⁰) correlation between BMI and ERV. Multiple linear regression showed that TLC can be predicted using only BMI and the forced inspiratory volume in 1 second, as these were the only significant contributors.

Conclusions

This study shows that, in DM1 patients, overweight further reduces lung volumes, as does impaired inspiratory muscle strength. Additionally, body composition is abnormal in almost all DM1 patients.     

Extraction and Analysis of Microbial Phospholipid Fatty Acids in Soils

Phospholipid fatty acids (PLFAs) are key components of microbial cell membranes. The analysis of PLFAs extracted from soils can provide information about the overall structure of terrestrial microbial communities. PLFA profiling has been extensively used in a range of ecosystems as a biological index of overall soil quality, and as a quantitative indicator of soil response to land management and other environmental stressors.The standard method presented here outlines four key steps: 1. lipid extraction from soil samples with a single-phase chloroform mixture, 2. fractionation using solid phase extraction columns to isolate phospholipids from other extracted lipids, 3. methanolysis of phospholipids to produce fatty acid methyl esters (FAMEs), and 4. FAME analysis by capillary gas chromatography using a flame ionization detector (GC-FID). Two standards are used, including 1,2-dinonadecanoyl-sn-glycero-3-phosphocholine (PC(19:0/19:0)) to assess the overall recovery of the extraction method, and methyl decanoate (MeC10:0) as an internal standard (ISTD) for the GC analysis.     

Neanderthal genomics suggests a pleistocene time frame for the first epidemiologic transition

High quality Altai Neanderthal and Denisovan genomes are revealing which regions of archaic hominin DNA have persisted in the modern human genome. A number of these regions are associated with response to infection and immunity, with a suggestion that derived Neanderthal alleles found in modern Europeans and East Asians may be associated with autoimmunity. As such Neanderthal genomes are an independent line of evidence of which infectious diseases Neanderthals were genetically adapted to. Sympathetically, human genome adaptive introgression is an independent line of evidence of which infectious diseases were important for AMH coming in to Eurasia and interacting with Neanderthals. The Neanderthals and Denisovans present interesting cases of hominin hunter‐gatherers adapted to a Eurasian rather than African infectious disease package. Independent sources of DNA‐based evidence allow a re‐evaluation of the first epidemiologic transition and how infectious disease affected Pleistocene hominins. By combining skeletal, archaeological and genetic evidence from modern humans and extinct Eurasian hominins, we question whether the first epidemiologic transition in Eurasia featured a new package of infectious diseases or a change in the impact of existing pathogens. Coupled with pathogen genomics, this approach supports the view that many infectious diseases are pre‐Neolithic, and the list continues to expand. The transfer of pathogens between hominin populations, including the expansion of pathogens from Africa, may also have played a role in the extinction of the Neanderthals and offers an important mechanism to understand hominin–hominin interactions well back beyond the current limits for aDNA extraction from fossils alone. Am J Phys Anthropol 160:379–388, 2016. © 2016 Wiley Periodicals, Inc.     

Carbon emission along a eutrophication gradient in temperate riverine wetlands: effect of primary productivity and plant community composition

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Characterization of an anaerobic marine microbial community exposed to combined fluxes of perchlorate and salinity

Applied Microbiology and Biotechnology - The recent recognition of the environmental prevalence of perchlorate and its discovery on Mars, Earth’s moon, and in meteorites, in addition to its...     

Genomic and physiological analysis reveals versatile metabolic capacity of deep-sea <Emphasis Type="Italic">Photobacterium phosphoreum</Emphasis> ANT-2200

Bacteria of the genus Photobacterium thrive worldwide in oceans and show substantial eco-physiological diversity including free-living, symbiotic and piezophilic life styles. Genomic characteristics underlying this variability across species are poorly understood. Here we carried out genomic and physiological analysis of Photobacterium phosphoreum strain ANT-2200, the first deep-sea luminous bacterium of which the genome has been sequenced. Using optical mapping we updated the genomic data and reassembled it into two chromosomes and a large plasmid. Genomic analysis revealed a versatile energy metabolic potential and physiological analysis confirmed its growth capacity by deriving energy from fermentation of glucose or maltose, by respiration with formate as electron donor and trimethlyamine N-oxide (TMAO), nitrate or fumarate as electron acceptors, or by chemo-organo-heterotrophic growth in rich media. Despite that it was isolated at a site with saturated dissolved oxygen, the ANT-2200 strain possesses four gene clusters coding for typical anaerobic enzymes, the TMAO reductases. Elevated hydrostatic pressure enhances the TMAO reductase activity, mainly due to the increase of isoenzyme TorA1. The high copy number of the TMAO reductase isoenzymes and pressure-enhanced activity might imply a strategy developed by bacteria to adapt to deep-sea habitats where the instant TMAO availability may increase with depth.     

Widespread Distribution of <Emphasis Type="Italic">Dehalococcoides mccartyi</Emphasis> in the Houston Ship Channel and Galveston Bay,Texas, Sediments and the Potential for Reductive Dechlorination of PCDD/F in an Estuarine Environment

Sediments in the Houston Ship Channel and upper Galveston Bay, Texas, USA, are polluted with polychlorinated dibenzo-p-dioxins/furans (PCDD/F; ≤46,000 ng/kg dry weight (wt.)) with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener, contributing >50 % of the total toxic equivalents (TEQ) at most locations. We measured PCDD/F concentrations in sediments and evaluated the potential for enhanced in situ biodegradation by surveying for Dehalococcoides mccartyi, an obligate organohalide respiring bacterium. Dehalococcoides spp. (98 % similar to D. mccartyi) and 22 other members of the class Dehalococcoidia were predominant 16S ribosomal RNA (rRNA) phylotypes. Dehalococcoides spp. were also present in the active fraction of the bacterial community. Presence/absence PCR screening detected D. mccartyi in sediment cores and sediment grab samples having at least 1 ng/kg dry wt. TEQ at salinities ranging from 0.6 to 19.5 PSU, indicating that they are widespread in the estuarine environment. Organic carbon-only and organic carbon + sulfate-amended sediment microcosm experiments resulted in ～60 % reduction of ambient 2,3,7,8-TCDD in just 24 months leading to reductions in total TEQs by 38.4 and 45.0 %, respectively, indicating that 2,3,7,8-TCDD degradation is occurring at appreciable rates.