Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth.

International audienceThe precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a(-/-)Myo3b(-/-) mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b(-/-) mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a(-/-)Myo3b(-/-) cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a(-/-)Myo3b(-/-) stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping

Safety, immunogenicity and duration of immunity elicited by an inactivated bovine ephemeral fever vaccine.

Bovine ephemeral fever (BEF) is an economically important viral vector-borne cattle disease. Several live-attenuated, inactivated and recombinant vaccines have been tested, demonstrating varying efficacy. However, to the best of our knowledge, duration of immunity conferred by an inactivated vaccine has never been reported. In the last decade, Israel has faced an increasing number of BEF outbreaks. The need for an effective vaccine compatible with strains circulating in the Middle East region led to the development of a MONTANIDE™ ISA 206 VG (water-in-oil-in-water), inactivated vaccine based on a local strain. We tested the safety, immunogenicity and duration of immunity conferred by this vaccine. The induced neutralizing antibody (NA) response was followed for 493 days in 40 cows vaccinated by different protocols. The vaccine did not cause adverse reactions or a decrease in milk production. All cows [except 2 (6.7%) which did not respond to vaccination] showed a significant rise in NA titer of up to 1:256 following the second, third or fourth booster vaccination. Neutralizing antibody levels declined gradually to 1:16 up to 120 days post vaccination. This decline continued in cows vaccinated only twice, whereas cows vaccinated 3 or 4 times showed stable titers of approximately 1:16 for up to 267 days post vaccination. At least three vaccinations with the inactivated BEF vaccine were needed to confer long-lasting immunity. These results may have significant implications for the choice of vaccination protocol with inactivated BEF vaccines. Complementary challenge data should however be added to the above results in order to determine what is the minimal NA response conferring protection from clinical disease

Breaking ground in cross-cultural research on the fear of being laughed at (gelotophobia): A multi-national study involving 73 countries

The current study examines whether the fear of being laughed at (gelotophobia) can be assessed reliably and validly by means of a self-report instrument in different countries of the world. All items of the GELOPH (Ruch and Titze, GELOPH46, University of Düsseldorf, 1998; Ruch and Proyer, Swiss Journal of Psychology 67:19–27, 2008b) were translated to the local language of the collaborator (42 languages in total). In total, 22,610 participants in 93 samples from 73 countries completed the GELOPH. Across all samples the reliability of the 15-item questionnaire was high (mean alpha of .85) and in all samples the scales appeared to be unidimensional. The endorsement rates for the items ranged from 1.31% through 80.00% to a single item. Variations in the mean scores of the items were more strongly related to the culture in a country and not to the language in which the data were collected. This was also supported by a multidimensional scaling analysis with standardized mean scores of the items from the GELOPH15. This analysis identified two dimensions that further helped explaining the data (i.e., insecure vs. intense avoidant-restrictive and low vs. high suspicious tendencies towards the laughter of others). Furthermore, multiple samples derived from one country tended to be (with a few exceptions) highly similar. The study shows that gelotophobia can be assessed reliably by means of a self-report instrument in cross-cultural research. This study enables further studies of the fear of being laughed at with regard to differences in the prevalence and putative causes of gelotophobia in comparisons to different cultures

Circulation of bovine ephemeral fever in the Middle East-Strong evidence for transmission by winds and animal transport

Bovine ephemeral fever virus (BEFV) is an economically important arbovirus of cattle. The main routes of its transmission between countries and continents are not completely elucidated. This study aimed to explore BEFV transmission in the Middle-East. A phylogenetic analysis was performed on the gene encoding the G protein of BEFV isolates from Israel from 2000 and 2008 with isolates from Turkey (2008), Egypt (2005), Australia (1968-1998) and East Asia (1966-2004). Calf sera collected during the years 2006-2007 were tested by serum neutralization in order to explore for recent exposure to BEFV before 2008. These were followed by a meteorological analysis, aimed to reveal movement of air parcels into Israel in the two weeks preceding the first case of BEF in Israel in 2008. The 2008 Israeli and Turkish isolates showed 99% identity and formed a new cluster with the 2000 Israeli isolate. The serological survey showed no new exposure to BEFV during 2006 and 2007. These results coincided with the meteorological analysis, which revealed that air parcels originating in Southern Turkey had reached the location of outbreak onset in Israel nine days before the discovery of the index case. The Egyptian isolate clustered phylogenetically with the Taiwanese isolates, coinciding with data on importation of cattle from China to the Middle East in the year preceding the isolation of the Egyptian isolates. These results suggest that both winds and animal transport may have an important role in trans-boundary transmission of BEFV. (C) 2012 Elsevier B.V. All rights reserved

Average neutralization antibody (NA) fractional dilutions induced by two or three to four vaccinations with inactivated BEF vaccine.

<p>Black squares: two vaccinations, Grey circles: three to four vaccinations. Whiskers represent standard deviation for each group.</p

Exocrine Pancreatic Insufficiency, Dyserythropoeitic Anemia, and Calvarial Hyperostosis Are Caused by a Mutation in the COX4I2 Gene

Steatorrhea and malabsorption of lipid-soluble vitamins due to exocrine pancreatic insufficiency are common in patients with cystic fibrosis and are predominant in Shwachman-Bodian-Diamond, Pearson, and Johanson-Blizzard syndromes. In four patients who suffered from congenital exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis, we excluded these disorders and identified, by using homozygosity mapping, a mutation in the COX4I2 gene. The COX4 protein is an essential structural subunit of cytochrome c oxidase complex and has two isoforms, encoded by two different genes. We show that the ratio of COX4I2 to COX4I1 mRNA is relatively high in human acinar cells. The mutation is associated with marked reduction of COX4I2 expression and with striking attenuation of the physiologic COX4I2 response to hypoxia. Mutation analysis of COX4I2 is warranted in patients with malabsorption due to exocrine pancreatic insufficiency and in patients with dyserythropoeitic anemia

Study flow diagram.

<p>Part I: study initiation. intramuscular vaccination: Group A; 1-ml vaccine, Group B; 2 -ml vaccine and Group C; non vaccinated. Part II: 1 month (30 days) post-study initiation (PSI), a second vaccination dose was administered to half of each vaccinated group as follows: A1; 1-ml, B1; 2- ml. Part III: 9 months (267 days) PSI, Group A was injected with 1 ml vaccine, Group B with 2 ml vaccine, Group C was not vaccinated and another group (Group D) was vaccinated with 1- ml. Part IV: 10 months (295 days) PSI, another vaccination dose was administered to half of each vaccinated group as follows: A3; 1- ml, B3; 2- ml, D1; 1- ml.</p