Apicobasal polarity and cell proliferation during development

Cell polarization and cell division are two fundamental cellular processes. The mechanisms that establish and maintain cell polarity and the mechanisms by which cells progress through the cell cycle are now fairly well understood following decades of experimental work. There is also increasing evidence that the polarization state of a cell affects its proliferative properties. The challenge now is to understand how these two phenomena are mechanistically connected. The aim of the present chapter is to provide an overview of the evidence of cross-talk between apicobasal polarity and proliferation, and the current state of knowledge of the precise mechanism by which this cross-talk is achieved.     

Histopathology confirms white-nose syndrome in bats in Europe

White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans.     

Genome shrinkage and loss of nutrient-providing potential in the obligate symbiont of the primitive termite Mastotermes darwiniensis

Beneficial microbial associations with insects are common and are classified as either one or a few intracellular species that are vertically transmitted and reside intracellularly within specialized organs or as microbial assemblages in the gut. Cockroaches and termites maintain at least one if not both beneficial associations. Blattabacterium is a flavobacterial endosymbiont of nearly all cockroaches and the termite Mastotermes darwiniensis and can use nitrogenous wastes in essential amino acid and vitamin biosynthesis. Key changes during the evolutionary divergence of termites from cockroaches are loss of Blattabacterium, diet shift to wood, acquisition of a specialized hindgut microbiota, and establishment of advanced social behavior. Termite gut microbes collaborate to fix nitrogen, degrade lignocellulose, and produce nutrients, and the absence of Blattabacterium in nearly all termites suggests that its nutrient-provisioning role has been replaced by gut microbes. M. darwiniensis is a basal, extant termite that solely retains Blattabacterium, which would show evidence of relaxed selection if it is being supplanted by the gut microbiome. This termite-associated Blattabacterium genome is ～8% smaller than cockroach-associated Blattabacterium genomes and lacks genes underlying vitamin and essential amino acid biosynthesis. Furthermore, the M. darwiniensis gut microbiome membership is more consistent between individuals and includes specialized termite gut-associated bacteria, unlike the more variable membership of cockroach gut microbiomes. The M. darwiniensis Blattabacterium genome may reflect relaxed selection for some of its encoded functions, and the loss of this endosymbiont in all remaining termite genera may result from its replacement by a functionally complementary gut microbiota.     

Human-associated extended-spectrum β-lactamase in the Antarctic

Escherichia coli bacteria with extended-spectrum β-lactamase (ESBL) type CTX-M resistance were isolated from water samples collected close to research stations in Antarctica. The isolates had bla(CTX-M-1) and bla(CTX-M-15) genotypes and sequence types (ST) indicative of a human-associated origin. This is the first record of ESBL-producing enterobacteria from Antarctica.     

Phasing of many thousands of genotyped samples

Haplotypes are an important resource for a large number of applications in human genetics, but computationally inferred haplotypes are subject to switch errors that decrease their utility. The accuracy of computationally inferred haplotypes increases with sample size, and although ever larger genotypic data sets are being generated, the fact that existing methods require substantial computational resources limits their applicability to data sets containing tens or hundreds of thousands of samples. Here, we present HAPI-UR (haplotype inference for unrelated samples), an algorithm that is designed to handle unrelated and/or trio and duo family data, that has accuracy comparable to or greater than existing methods, and that is computationally efficient and can be applied to 100,000 samples or more. We use HAPI-UR to phase a data set with 58,207 samples and show that it achieves practical runtime and that switch errors decrease with sample size even with the use of samples from multiple ethnicities. Using a data set with 16,353 samples, we compare HAPI-UR to Beagle, MaCH, IMPUTE2, and SHAPEIT and show that HAPI-UR runs 18× faster than all methods and has a lower switch-error rate than do other methods except for Beagle; with the use of consensus phasing, running HAPI-UR three times gives a slightly lower switch-error rate than Beagle does and is more than six times faster. We demonstrate results similar to those from Beagle on another data set with a higher marker density. Lastly, we show that HAPI-UR has better runtime scaling properties than does Beagle so that for larger data sets, HAPI-UR will be practical and will have an even larger runtime advantage. HAPI-UR is available online (see Web Resources).     

Growth and translation inhibition through sequence-specific RNA binding by Mycobacterium tuberculosis VapC toxin

The Mycobacterium tuberculosis genome harbors an unusually large number of toxin-antitoxin (TA) modules. Curiously, over half of these are VapBC (virulence-associated protein) family members. Nonetheless, the cellular target, precise mode of action, and physiological role of the VapC toxins in this important pathogen remain unclear. To better understand the function of this toxin family, we studied the features and biochemical properties of a prototype M. tuberculosis VapBC TA system, vapBC-mt4 (Rv0596c-Rv0595c). VapC-mt4 expression resulted in growth arrest, a hallmark of all TA toxins, in Escherichia coli, Mycobacterium smegmatis, and M. tuberculosis. Its expression led to translation inhibition accompanied by a gradual decrease in the steady-state levels of several mRNAs. VapC-mt4 exhibited sequence-specific endoribonuclease activity on mRNA templates at ACGC and AC(A/U)GC sequences. However, the cleavage activity of VapC-mt4 was comparatively weak relative to the TA toxin MazF-mt1 (Rv2801c). Unlike other TA toxins, translation inhibition and growth arrest preceded mRNA cleavage, suggesting that the RNA binding property of VapC-mt4, not RNA cleavage, initiates toxicity. In support of this hypothesis, expression of VapC-mt4 led to an increase in the recovery of total RNA with time in contrast to TA toxins that inhibit translation via direct mRNA cleavage. Additionally, VapC-mt4 exhibited stable, sequence-specific RNA binding in an electrophoretic mobility shift assay. Finally, VapC-mt4 inhibited protein synthesis in a cell-free system without cleaving the corresponding mRNA. Therefore, the activity of VapC-mt4 is mechanistically distinct from other TA toxins because it appears to primarily inhibit translation through selective, stable binding to RNA.