miR126-5p Downregulation Facilitates Axon Degeneration and NMJ Disruption via a Non-Cell-Autonomous Mechanism in ALS.

Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in amyotrophic lateral sclerosis (ALS) pathology. Although the disease\u27s etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR126-5p in presymptomatic ALS male mice models, and an increase in its targets: axon destabilizing Type 3 Semaphorins and their coreceptor Neuropilins. Using compartmentalize

Genotypic Diversity of Francisella tularensis Infecting Dermacentor variabilis Ticks on Martha's Vineyard, Massachusetts

Martha's Vineyard, Mass., has been the site of two outbreaks of tularemia (1978 and 2000). Although most patients from both outbreaks presented with pneumonic disease and although aerosol transmission has been suggested, the bite of a dog tick and exposure to rabbits remain the only proven modes of transmission. The factors that precipitated the tularemia outbreaks or the proximal determinants of human risk remain undescribed. We sought to test the hypothesis that the ongoing outbreak is due to a recent introduction event as opposed to amplification of a cryptic enzootic cycle. From 2001-2003, we collected 4,246 dog ticks and tested them in pools for evidence of tularemia by PCR. We then measured the genetic diversity of Francisella tularensis by using multiple-locus variable-number tandem repeat analysis. The prevalence of F. tularensis in dog ticks averaged 0.7%. From 29 positive pools, we identified 10 unique genotypes, which was an unexpectedly large degree of diversity (Simpson's index = 0.86). This degree of genetic diversity is inconsistent with a recent introduction event. We conclude that there has been long-standing enzootic transmission of tularemia on the island

Comparative study of population genomic approaches for mapping colony-level traits.

Social insect colonies exhibit colony-level phenotypes such as social immunity and task coordination, which are produced by the individual phenotypes. Mapping the genetic basis of such phenotypes requires associating the colony-level phenotype with the genotypes in the colony. In this paper, we examine alternative approaches to DNA extraction, library construction, and sequencing for genome wide association studies (GWAS) of colony-level traits using a population sample of Cataglyphis niger ants. We evaluate the accuracy of allele frequency estimation from sequencing a pool of individuals (pool-seq) from each colony using either whole-genome sequencing or reduced representation genomic sequencing. Based on empirical measurement of the experimental noise in sequenced DNA pools, we show that reduced representation pool-seq is drastically less accurate than whole-genome pool-seq. Surprisingly, normalized pooling of samples did not result in greater accuracy than un-normalized pooling. Subsequently, we evaluate the power of the alternative approaches for detecting quantitative trait loci (QTL) of colony-level traits by using simulations that account for an environmental effect on the phenotype. Our results can inform experimental designs and enable optimizing the power of GWAS depending on budget, availability of samples and research goals. We conclude that for a given budget, sequencing un-normalized pools of individuals from each colony provides optimal QTL detection power

The interplay between incipient species and social polymorphism in the desert ant Cataglyphis

In social insects, due to considerable polyphenism as well as high level of hybridization, the delimitation of species can be challenging. The genus Cataglyphis presents a high level of diversification, making it an excellent model with which to study evolutionary paths. Israel appears to be a “hot spot” for recent speciation in this genus. Although previous studies have described multiple species of Cataglyphis in Israel, a recent genetic study has questioned the existence of some of these historically described species. The present study focuses on an apparent species complex, the C. niger species complex which includes C. niger, C. savigyi, and C. drusus that are distinguishable by their mitochondrial DNA (and therefore named mitotypes) but not by their nuclear DNA. Using a multi-method approach (genetics, chemistry and behavior), we show that these mitotypes also differ in their social structures and are readily distinguishable by their cuticular hydrocarbons profiles. While most populations of the different mitotypes are allopatric, at our study site they are sympatric, but nonetheless maintain the observed differences between them. This raises the evolutionary question: Are these incipient species that have diverged with gene flow, or is this a case of social and chemical polymorphism that is maintained within a single species? Unveiling the interplay between social polyphenism and species segregation is at the core of evolutionary biology.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluation of colony losses in Israel in relation to the incidence of pathogens and pests

To evaluate symptoms, extent, and possible causes of colony decline and losses in Israel, we carried out (1) a survey of honeybee colony losses and potential causes via mail and phone; (2) systematic sampling of healthy and problematic beehives after requeening in the winter; (3) detection of Varroa and pathogens including, viruses and Nosema ceranae, by microbiological means and sensitive RT-PCR. From 58 beekeepers (46000 colonies) interviewed, 40% complained of extensive colony loses during 2008. Examination and sampling for pests and pathogens of 113 hives in the winter of 2009 showed 35% of hives with Nosema and 21% with V. destructor. The most frequent viruses detected were Black Queen Cell Virus, Israeli Acute Paralysis Virus, and Deformed Wing Virus. A significant negative correlation was found between worker population in the hive and the presence of viral and Nosema infections

ATP-citrate lyase promotes axonal transport across species.

Microtubule (MT)-based transport is an evolutionary conserved process finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, primarily catalyzed by a vesicular pool of α-tubulin N-acetyltransferase 1 (Atat1), promotes the recruitment and processivity of molecular motors along MT tracks. However, the mechanism that controls Atat1 activity remains poorly understood. Here, we show that ATP-citrate lyase (Acly) is enriched in vesicles and provide Acetyl-Coenzyme-A (Acetyl-CoA) to Atat1. In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in a pathway regulating α-tubulin acetylation and MT-dependent transport in projection neurons, across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine light on the pathophysiological mechanisms underlying FD

Sequence variation in PPP1R13L results in a novel form of cardio‐cutaneous syndrome

Dilated cardiomyopathy (DCM) is a life‐threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4–30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein was identified in three infants and in the mother of the other two. Patients’ fibroblasts and PPP1R13L‐knocked down human fibroblasts presented higher expression levels of pro‐inflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13l‐knocked down murine cardiomyocytes and hearts of Ppp1r13l‐deficient mice. The hypersensitivity to lipopolysaccharide was NF‐κB‐dependent, and its inducible binding activity to promoters of pro‐inflammatory cytokine genes was elevated in patients’ fibroblasts. RNA sequencing of Ppp1r13l‐knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in Ppp1r13l‐deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomal‐recessive cardio‐cutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors