Jelly belly trans‐synaptic signaling to anaplastic lymphoma kinase regulates neurotransmission strength and synapse architecture

In Drosophila, the secreted signaling molecule Jelly Belly (Jeb) activates anaplastic lymphoma kinase (Alk), a receptor tyrosine kinase, in multiple developmental and adult contexts. We have shown previously that Jeb and Alk are highly enriched at Drosophila synapses within the CNS neuropil and neuromuscular junction (NMJ) and postulated a conserved intercellular signaling function. At the embryonic and larval NMJ, Jeb is localized in the motor neuron presynaptic terminal whereas Alk is concentrated in the muscle postsynaptic domain surrounding boutons, consistent with anterograde trans‐synaptic signaling. Here, we show that neurotransmission is regulated by Jeb secretion by functional inhibition of Jeb–Alk signaling. Jeb is a novel negative regulator of neuromuscular transmission. Reduction or inhibition of Alk function results in enhanced synaptic transmission. Activation of Alk conversely inhibits synaptic transmission. Restoration of wild‐type postsynaptic Alk expression in Alk partial loss‐of‐function mutants rescues NMJ transmission phenotypes and confirms that postsynaptic Alk regulates NMJ transmission. The effects of impaired Alk signaling on neurotransmission are observed in the absence of associated changes in NMJ structure. Complete removal of Jeb in motor neurons, however, disrupts both presynaptic bouton architecture and postsynaptic differentiation. Nonphysiologic activation of Alk signaling also negatively regulates NMJ growth. Activation of Jeb–Alk signaling triggers the Ras‐MAP kinase cascade in both pre‐ and postsynaptic compartments. These novel roles for Jeb–Alk signaling in the modulation of synaptic function and structure have potential implications for recently reported Alk functions in human addiction, retention of spatial memory, cognitive dysfunction in neurofibromatosis, and pathogenesis of amyotrophic lateral sclerosis. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013     

First isolation and molecular characterization of pseudorabies virus detected in Turkey

Background

Pigs are the main host species for the pseudorabies virus. It causes fatal encephalitis in many species, including humans. This article aims to report the first clinical case of pseudorabies as well as isolation and molecular characterization of the virus from a hunting dog in Bursa province, Turkey.

Methods and results

The dog shows clinical signs including pruritus and neurological signs such as stumbling and inability to stand up compatible with pseudorabies. The virus isolates were obtained from the supernatant of fresh tissue samples from the cerebellum, cornu ammonis, spleen, salivary gland, conjunctival swab, serum, and PBMC samples. The glycoprotein C region is targeted for viral DNA amplification. Pseudorabies virus genome detected both in fresh tissues and supernatants of third passage on Vero cells. The number of PCR positive samples was dramatically increased after cell culture inoculations. Genome sequencing of strain Bursa-10303, which was isolated from a non-endemic area, identified it to belong to clade A.

Conclusions

This study confirms the possible presence of pseudorabies infection in the wildlife reservoirs in Turkey. Future studies may clarify the importance of the infection in Turkey region, where there is no prevalent pig production.

     

Corelike structures in a stable L-form ofStreptococcus pyogenes

Corelike structures, which were interpreted as straight, large cylinders containing ribosome-like particles surrounded by an amorphous substance of low electron density, were found in a stable L-form ofStreptococcus pyogenes grown in the absence of antibiotics.     

Species diversity and phylogeography of Cornus kousa (Asian dogwood) captured by genomic and genic microsatellites

Cornus kousa (Asian dogwood), an East Asia native tree, is the most economically important species of the dogwood genus, owing to its desirable horticultural traits and ability to hybridize with North America‐native dogwoods. To assess the species genetic diversity and to better inform the ongoing and future breeding efforts, we assembled an herbarium and arboretum collection of 131 noncultivated C. kousa specimens. Genotyping and capillary electrophoresis analyses of our C. kousa collection with the newly developed genic and published nuclear genomic microsatellites permitted assessment of genetic diversity and evolutionary history of the species. Regardless of the microsatellite type used, the study yielded generally similar insights into the C. kousa diversity with subtle differences deriving from and underlining the marker used. The accrued evidence pointed to the species distinct genetic pools related to the plant country of origin. This can be helpful in the development of the commercial cultivars for this important ornamental crop with increased pyramided utility traits. Analyses of the C. kousa evolutionary history using the accrued genotyping datasets pointed to an unsampled ancestor population, possibly now extinct, as per the phylogeography of the region. To our knowledge, there are few studies utilizing the same gDNA collection to compare performance of genomic and genic microsatellites. This is the first detailed report on C. kousa species diversity and evolutionary history inference.     

Is problematic mobile phone use explained by chronotype and personality?

In this study, the relationships among problematic mobile phone use, age, gender, personality and chronotype of Turkish university students were examined. The study included 902 university students (73% female, 27% male) and their participation in the study was anonymous and voluntary. Data were collected from each participant by assessing a demographic questionnaire, Composite Scale of Morningness (CSM) as a measure of chronotype, the Big Five Inventory (BIG-5) for personality assessment and Mobile Phone Problem Usage Scale (MPPUS). The most important result was that CSM scores were the best predictor for problematic mobile phone usage, and as a consequence, evening-oriented university students scored higher on the MPPUS. This result remained, even when compared with the most influential personality predictor, conscientiousness. In addition, while extraversion positively predicted, emotional stable and chronotype negatively predicted problematic mobile phone use. Lastly, age and gender were not predictors of problematic mobile phone use.     

Anaerobic coryneforms isolated from human bone marrow and skin. Chemical, biochemical and serological studies and some of their biological activities.

Eighteen isolates if anaerobic coryneforms from human bone marrow and skin and four type strains of Propionibacterium were studied chemically, biochemically and antigenically. All of the isolates were identified as Propionibacterium acnes; of the 18 isolates,16 belonged to sterotype I and two to serotype II. By means of gas liquid chromatography and mass spectral analysis, a large amount of iso-type fatty acids, such as iso-pentadecanoic and iso-heptadecanoic acids were detected in whole cells of isolates and type strains. Antitumor and adjuvant effects of the isolates and type strains were found to differ considerably among the strains. One of the isolates, P. acnes C-7, which showed potent biological activities was fractionated by hot phenol-water extraction. The resulting insoluble middle layer was found the most effective in tumor protection, adjuvant action in immune response and phagocytic activity in mice.     

Insult

INSULT, a novel method for the creation of insertions, deletions, and point mutations without subcloning, requires only one new primer per mutant, and produces circular plasmids, obviating the need for special “ultracompetent” cells. The method includes cycles of linear amplification with a thermophilic polymerase, and nick repair after each cycle with a thermophilic ligase. After production of multiple single-stranded copies of circular mutation-bearing plasmid DNA, addition of a “generic” primer followed by one or more polymerase reaction cycles generates double-stranded circular DNA bearing the desired mutation.     

Gene Silencing Mediated by Endogenous MicroRNAs under Heat Stress Conditions in Mammalian Cells

Heat shock, sudden change in temperature, triggers various responses in cells for protecting the cells from such a severe circumstance. Here we investigated gene silencing mediated by endogenous microRNAs (miRNAs) in mammalian cells exposed to a mild hyperthermia, by means of miRNA activity assay using a luciferase reporter gene as well as miRNA expression analysis using a DNA microarray. Our findings indicated that the gene silencing activities involving miRNAs were enhanced without increasing in their expression levels under heat-stress conditions. Additionally, the gene silencing activity appeared to be independent of the cytoprotective action involving heat shock proteins that are immediately activated in heat-shocked cells and that function as molecular chaperons for restoring heat-denatured proteins to normal proteins. Our current findings suggested the possibility that gene silencing involving endogenous miRNAs might play a subsidiary role in heat-shocked cells for an aggressive inhibition of the expression of heat-denatured proteins.     

The CUPID (Cultural and Psychosocial Influences on Disability) study: methods of data collection and characteristics of study sample

Background

The CUPID (Cultural and Psychosocial Influences on Disability) study was established to explore the hypothesis that common musculoskeletal disorders (MSDs) and associated disability are importantly influenced by culturally determined health beliefs and expectations. This paper describes the methods of data collection and various characteristics of the study sample.

Methods/Principal Findings

A standardised questionnaire covering musculoskeletal symptoms, disability and potential risk factors, was used to collect information from 47 samples of nurses, office workers, and other (mostly manual) workers in 18 countries from six continents. In addition, local investigators provided data on economic aspects of employment for each occupational group. Participation exceeded 80% in 33 of the 47 occupational groups, and after pre-specified exclusions, analysis was based on 12,426 subjects (92 to 1018 per occupational group). As expected, there was high usage of computer keyboards by office workers, while nurses had the highest prevalence of heavy manual lifting in all but one country. There was substantial heterogeneity between occupational groups in economic and psychosocial aspects of work; three- to five-fold variation in awareness of someone outside work with musculoskeletal pain; and more than ten-fold variation in the prevalence of adverse health beliefs about back and arm pain, and in awareness of terms such as “repetitive strain injury” (RSI).

Conclusions/Significance

The large differences in psychosocial risk factors (including knowledge and beliefs about MSDs) between occupational groups should allow the study hypothesis to be addressed effectively.