Mutation analysis of a Sandhoff disease patient in the Maronite community in Cyprus

Sandhoff disease occurs in the Christian Maronite community in Cyprus, a community that established over a thousand years ago. Nowadays, this community comprises less than 1% of the whole population, and has been culturally and socially isolated. Cultured fibroblasts from a patient from this inbred group showed a -hexosaminidase subunit mRNA of apparently the normal size but of reduced quantity. A mutational analysis of cDNA obtained by polymerase chain reaction amplification of mRNA showed a deletion of A at nt 76 (counted from A of the initiation codon, ATG). The deletion results in a frame shift and a premature termination within 20 amino acids from the N-terminus of the normal mature enzyme protein. The patient was homozygous for the deletion. The 5-end of the gene showed many discrepancies from the previously published sequence. We consider that these differences are probably polymorphisms of little functional significance, because the patient's fibroblasts generate decreased but stable mRNA and because some of these base changes were also found in the genes from control fibroblasts. An extensive evaluation of the prevalence of this mutant allele in this community is being initiated.     

Apilimod inhibits the production of IL-12 and IL-23 and reduces dendritic cell infiltration in psoriasis

Psoriasis is characterized by hyperplasia of the epidermis and infiltration of leukocytes into both the dermis and epidermis. IL-23, a key cytokine that induces T(H)17 cells, has been found to play a critical role in the pathogenesis of psoriasis. Apilimod is a small-molecule compound that selectively suppresses synthesis of IL-12 and IL-23. An open-label clinical study of oral administration of apilimod was conducted in patients with psoriasis. Substantial improvements in histology and clinical measurements were observed in patients receiving 70 mg QD. The expression of IL-23p19 and IL-12/IL-23p40 in skin lesions was significantly reduced in this dose group, with a simultaneous increase in IL-10 observed. A decrease in the levels of T(H)1 and T(H)17 cytokines/chemokines in skin lesions followed these p19 and p40 changes. In parallel, a reduction in skin-infiltrating CD11c(+) dendritic cells and CD3(+) T cells was seen, with a greater decrease in the CD11c(+) population. This was accompanied by increases in T and B cells, and decreases in neutrophils and eosinophils in the periphery. This study demonstrates the immunomodulatory activity of apilimod and provides clinical evidence supporting the inhibition of IL-12/IL-23 synthesis for the treatment of T(H)1- and T(H)17-mediated inflammatory diseases.     

Partial edentulism and removable partial denture design in a dental school population: a survey in Greece

Gerodontology 2011; doi: 10.1111/j.1741‐2358.2010.00382.x Partial edentulism and removable partial denture design in a dental school population: a survey in Greece Objectives: To investigate the pattern of partial edentulism and the most frequent designs of cobalt‐chromium removable partial dentures (RPDs), constructed at the Dental School of Athens, Greece. Methods and materials: Five hundred and fifty‐three patients, between 42 and 81 years old, mostly males, treated by undergraduate dental students, were included. The survey was based on visual evaluation of master casts and work authorisation to dental technicians. Aspects examined were: Kennedy Classification, modification areas, major connectors, clasping, placement of rest seats and indirect retention. Results: Kennedy Class I was the most common encountered in the maxilla (50.5%) and in the mandible (70%). The most frequent major connectors were the lingual bar (92.6%) and the U‐shaped palatal strap (54%). The most common clasp was the Roach (69.2%) in Class I and Class II. In Class III and IV, the most common was the occlusally approaching clasp (55% and 70%). The most frequent location of the rest was mesial of abutment teeth. On the average, 39.5% of Class I RPDs and 58.6% of Class II RPDs had indirect retainers. Conclusion: A combination of the two major philosophies of RPD design (biomechanical and hygienic) was evident in the RPDs examined in our study.     

An update on plant membrane rafts

The dynamic segregation of membrane components within microdomains, such as the sterol-enriched and sphingolipid-enriched membrane rafts, emerges as a central regulatory mechanism governing physiological responses in various organisms. Over the past five years, plasma membrane located raft-like domains have been described in several plant species. The protein and lipid compositions of detergent-insoluble membranes, supposed to contain these domains, have been extensively characterised. Imaging methods have shown that lateral segregation of lipids and proteins exists at the nanoscale level at the plant plasma membrane, correlating detergent insolubility and membrane-domain localisation of presumptive raft proteins. Finally, the dynamic association of specific proteins with detergent-insoluble membranes upon environmental stress has been reported, confirming a possible role for plant rafts as signal transduction platforms, particularly during biotic interactions.     

Dynamic proton-dependent motors power type IX secretion and gliding motility in Flavobacterium

Motile bacteria usually rely on external apparatus like flagella for swimming or pili for twitching. By contrast, gliding bacteria do not rely on obvious surface appendages to move on solid surfaces. Flavobacterium johnsoniae and other bacteria in the Bacteroidetes phylum use adhesins whose movement on the cell surface supports motility. In F. johnsoniae, secretion and helicoidal motion of the main adhesin SprB are intimately linked and depend on the type IX secretion system (T9SS). Both processes necessitate the proton motive force (PMF), which is thought to fuel a molecular motor that comprises the GldL and GldM cytoplasmic membrane proteins. Here, we show that F. johnsoniae gliding motility is powered by the pH gradient component of the PMF. We further delineate the interaction network between the GldLM transmembrane helices (TMHs) and show that conserved glutamate residues in GldL TMH2 are essential for gliding motility, although having distinct roles in SprB secretion and motion. We then demonstrate that the PMF and GldL trigger conformational changes in the GldM periplasmic domain. We finally show that multiple GldLM complexes are distributed in the membrane, suggesting that a network of motors may be present to move SprB along a helical path on the cell surface. Altogether, our results provide evidence that GldL and GldM assemble dynamic membrane channels that use the proton gradient to power both T9SS-dependent secretion of SprB and its motion at the cell surface.

Motile bacteria usually rely on external apparatus like flagella or pili, but gliding bacteria do not rely on obvious surface appendages for their movement. This study shows that bacteria in the phylum Bacteroidetes use proton-dependent motors to power protein secretion and gliding motility.     

Connecting the dots: from nanodomains to physiological functions of REMORINs

REMORINs (REMs) are a plant-specific protein family, proposed regulators of membrane-associated molecular assemblies and well-established markers of plasma membrane nanodomains. REMs play a diverse set of functions in plant interactions with pathogens and symbionts, responses to abiotic stresses, hormone signaling and cell-to-cell communication. In this review, we highlight the established and more putative roles of REMs throughout the literature. We discuss the physiological functions of REMs, the mechanisms underlying their nanodomain-organization and their putative role as regulators of nanodomain-associated molecular assemblies. Furthermore, we discuss how REM phosphorylation may regulate their functional versatility. Overall, through data-mining and comparative analysis of the literature, we suggest how to further study the molecular mechanisms underpinning the functions of REMs.     

The effect of immersion cleansers on gloss,colour and sorption of acetal denture base material

doi: 10.1111/j.1741‐2358.2012.00657.x The effect of immersion cleansers on gloss, colour and sorption of acetal denture base material Objective: To study the effect of peroxide and hypochlorite cleansers on gloss, colour and sorption of acetal denture resins. Materials and methods: Pink acetal and thermoplastic acrylic resins were evaluated. Thirty‐five specimens 39 × 39 × 1.8 mm of each resin were prepared. Each group of specimens (n = 7) was then immersed into cleansers for 100 days. Group I immersed in tap water, Group II in Corega Extradent for 5 min, Group III in Corega Extradent for 8 h, Group IV in NitrAdine? Seniors for 15 min and Group V in NaOCl 5.25%. Gloss, colour and weight measurements were taken initially and after 100 days. Data subjected to two‐way anova and Tukey’s test at α = 0.05. Results: Acrylic resin showed reductions of glossiness from ?5 to ?15 and acetal from ?0.2 to ?6. Colour changes (ΔΕ*) ranged from 2.64 to 7.64 for acrylic and 2.77 to 26.54 for acetal resin. Sorption for acrylic ranged from 11.64 to 17.06 μg/mm³ and 9.18 to 24.79 μg/mm³ for acetal resin. The results of (ΔΕ*) and sorption showed an interaction between denture resins and cleansers. Conclusions: The gloss of acetal resin was less affected by water, peroxides and NaOCl 5.25% compared with acrylic resin. Acetal resin showed clinically acceptable (ΔΕ*) whereas acrylic resin unacceptable ones for water and peroxide solutions. The immersion of acetal resin in NaOCl 5.25% showed clinically unacceptable (ΔΕ*) and higher sorption and should be avoided or should be managed with care.     

A Putative Mechanism for Magnetoreception by Electromagnetic Induction in the Pigeon Inner Ear

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Translation initiation start prediction in human cDNAs with high accuracy

MOTIVATION: Correct identification of the Translation Initiation Start (TIS) in cDNA sequences is an important issue for genome annotation. The aim of this work is to improve upon current methods and provide a performance guaranteed prediction. METHODS: This is achieved by using two modules, one sensitive to the conserved motif and the other sensitive to the coding/non-coding potential around the start codon. Both modules are based on Artificial Neural Networks (ANNs). By applying the simplified method of the ribosome scanning model, the algorithm starts a linear search at the beginning of the coding ORF and stops once the combination of the two modules predicts a positive score. RESULTS: According to the results of the test group, 94% of the TIS were correctly predicted. A confident decision is obtained through the use of the Las Vegas algorithm idea. The incorporation of this algorithm leads to a highly accurate recognition of the TIS in human cDNAs for 60% of the cases. Availability: The program is available upon request from the author.