New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Isolation and characterisation of an unusual bacterium, allied to the soil bacterium Bacillus benzoevorans, from feedlot manure pads in Australia

Strains of bacteria were obtained by anaerobic enrichment from feedlot manure pads and were phenotypically characterized. Colonies had a cotton wool or hairy appearance. When cultures grown in liquid media were exposed to a drying atmosphere, they produced a pellicle comprised of a cross-meshed array of cells. Colonies on agar media also produced spiral sheets of cells held well above the agar surface. The strains were Gram positive, according to ultrastructural features from transmission electron micrographs and KOH solubility, but Gram negative by Gram stain. The 16S rDNA from strain YEO5 was determined and is 99·3% similar to the type strain of Bacillus benzoevorans. The inability of our strains to grow aerobically and lack of endospores differentiated them from previously isolated strains of B. benzoevorans. In freshly broken feedlot pad material, a white, hairy coating of the exposed surface appeared within a few hours. We hypothesize that this is due to the insoluble extracellular matrix material produced by this Bacillus sp. to avoid desiccation and, additionally, the bacterial covering is responsible for retaining odours within the pad material

Desiccation Resistance of Bacteria Isolated From An Air-Handling System Biofilm Determined Using a Simple Quantitative Membrane-Filter Method

Twelve strains of bacteria recovered from a biofilm growing on cooling coil fins in an air-handling system, representing recognized members of the coil fin biofilm community, were assessed for their desiccation resistance. A quantitative membrane filter method was used to assess desiccation resistance over a 24 h period. The method proved to be a reliable and inexpensive means of quantitatively assessing desiccation resistance in bacterial isolates. Five pink-pigmented budding rod (PPBR) isolates, related to Methylobacterium, were resistant to desiccation over the test period (47-100% of original viable cfu were recoverable on R3A agar after 24 h desiccation). Methylobacterium-like PPBRs represented the dominant culturable members of the coil fin biofilm community. An unidentified Gram-negative filamentous rod was also somewhat desiccation-resistant (45% of original viable cfu were recoverable or, R3A agar after 24 h desiccation). The remaining six strains tested, three Gram-negative isolates and three Gram-positive isolates, were sensitive to desiccation with only 0-11% of the original viable cfu being recoverable on R3A agar after 24 h desiccation. Since the coil fin biofilm is subjected to extended periods of desiccation, the results suggest that desiccation resistance is at least partly responsible for the dominance of the coil fin biofilm community by the Methylobacterium-like PPBR

A Microbial Oasis in the Hypersaline Atacama Subsurface Discovered by a Life Detector Chip: Implications for the Search for Life on Mars

The Atacama Desert has long been considered a good Mars analogue for testing instrumentation for planetary exploration, but very few data (if any) have been reported about the geomicrobiology of its salt-rich subsurface. We performed a Mars analogue drilling campaign next to the Salar Grande (Atacama, Chile) in July 2009, and several cores and powder samples from up to 5 m deep were analyzed in situ with LDChip300 (a Life Detector Chip containing 300 antibodies). Here, we show the discovery of a hypersaline subsurface microbial habitat associated with halite-, nitrate-, and perchlorate-containing salts at 2 m deep. LDChip300 detected bacteria, archaea, and other biological material (DNA, exopolysaccharides, some peptides) from the analysis of less than 0.5 g of ground core sample. The results were supported by oligonucleotide microarray hybridization in the field and finally confirmed by molecular phylogenetic analysis and direct visualization of microbial cells bound to halite crystals in the laboratory. Geochemical analyses revealed a habitat with abundant hygroscopic salts like halite (up to 260 g kg(−1)) and perchlorate (41.13 μg g(−1) maximum), which allow deliquescence events at low relative humidity. Thin liquid water films would permit microbes to proliferate by using detected organic acids like acetate (19.14 μg g(−1)) or formate (76.06 μg g(−1)) as electron donors, and sulfate (15875 μg g(−1)), nitrate (13490 μg g(−1)), or perchlorate as acceptors. Our results correlate with the discovery of similar hygroscopic salts and possible deliquescence processes on Mars, and open new search strategies for subsurface martian biota. The performance demonstrated by our LDChip300 validates this technology for planetary exploration, particularly for the search for life on Mars. Key Words: Atacama Desert—Life detection—Biosensor—Biopolymers—In situ measurement. Astrobiology 11, 969–996

Impact of biocontrol strain Pseudomonas fluorescens CHA0 on rhizosphere bacteria isolated from barley (Hordeum vulgare L.) with special reference to Cytophaga-like bacteria.

AIMS: To assess the impact of the biocontrol strain Pseudomonas fluorescens CHA0 on a collection of barley rhizosphere bacteria using an agar plate inhibition assay and a plant microcosm, focusing on a CHA0-sensitive member of the Cytophaga-like bacteria (CLB). METHODS AND RESULTS: The effect of strain CHA0 on a collection of barley rhizosphere bacteria, in particular CLB and fluorescent pseudomonads sampled during a growth season, was assessed by a growth inhibition assay. On average, 85% of the bacteria were sensitive in the May sample, while the effect was reduced to around 68% in the July and August samples. In the May sample, around 95% of the CLB and around 45% of the fluorescent pseudomonads were sensitive to strain CHA0. The proportion of CHA0-sensitive CLB and fluorescent pseudomonad isolates decreased during the plant growth season, i.e. in the July and August samples. A particularly sensitive CLB isolate, CLB23, was selected, exposed to strain CHA0 (wild type) and its genetically modified derivatives in the rhizosphere of barley grown in gnotobiotic soil microcosms. Two dry-stress periods were imposed during the experiment. Derivatives of strain CHA0 included antibiotic or exopolysaccharide (EPS) overproducing strains and a dry-stress-sensitive mutant. Despite their inhibitory activity against CLB23 in vitro, neither wild-type strain CHA0, nor any of its derivatives, had a major effect on culturable and total cell numbers of CLB23 during the 23-day microcosm experiment. Populations of all inoculants declined during the two dry-stress periods, with soil water contents below 5% and plants reaching the wilting point, but they recovered after re-wetting the soil. Survival of the dry-stress-sensitive mutant of CHA0 was most affected by the dry periods; however, this did not result in an increased population density of CLB23. CONCLUSIONS: CLB comprise a large fraction of barley rhizosphere bacteria that are sensitive to the biocontrol pseudomonad CHA0 in vitro. However, in plant microcosm experiments with varying soil humidity conditions, CHA0 or its derivatives had no major impact on the survival of the highly sensitive CLB strain, CLB23, during two dry-stress periods and a re-wetting period; all co-existed well in the rhizosphere of barley plants. SIGNIFICANCE AND IMPACT OF THE STUDY: Results indicate a lack of interaction between the biocontrol pseudomonad CHA0 and a sensitive CLB when the complexity increases from agar plate assays to plant microcosm experiments. This suggests the occurrence of low levels of antibiotic production and/or that the two bacterial genera occupy different niches in the rhizosphere