Functional analysis of Ectodysplasin-A mutations causing selective tooth agenesis.

Mutations of the Ectodysplasin-A (EDA) gene are generally associated with the syndrome hypohidrotic ectodermal dysplasia (MIM 305100), but they can also manifest as selective, non-syndromic tooth agenesis (MIM300606). We have performed an in vitro functional analysis of six selective tooth agenesis-causing EDA mutations (one novel and five known) that are located in the C-terminal tumor necrosis factor homology domain of the protein. Our study reveals that expression, receptor binding or signaling capability of the mutant EDA1 proteins is only impaired in contrast to syndrome-causing mutations, which we have previously shown to abolish EDA1 expression, receptor binding or signaling. Our results support a model in which the development of the human dentition, especially of anterior teeth, requires the highest level of EDA-receptor signaling, whereas other ectodermal appendages, including posterior teeth, have less stringent requirements and form normally in response to EDA mutations with reduced activity.

Pooling of dentin microtensile bond strength data improves clinical correlation.

Purpose: To evaluate whether the correlation between in vitro bond strength data and estimated clinical retention rates of cervical restorations after two years depends on pooled data obtained from multicenter studies or single-test data. Materials and Methods: Pooled mean data for six dentin adhesive systems (Adper Prompt L-Pop, Clearfil SE, OptiBond FL, Prime & Bond NT, Single Bond, and Scotchbond Multipurpose) and four laboratory methods (macroshear, microshear, macrotensile and microtensile bond strength test) (Scherrer et al, 2010) were correlated to estimated pooled two-year retention rates of Class V restorations using the same adhesive systems. For bond strength data from a single test institute, the literature search in SCOPUS revealed one study that tested all six adhesive systems (microtensile) and two that tested five of the six systems (microtensile, macroshear). The correlation was determined with a database designed to perform a meta-analysis on the clinical performance of cervical restorations (Heintze et al, 2010). The clinical data were pooled and adjusted in a linear mixed model, taking the study effect, dentin preparation, type of isolation and bevelling of enamel into account. A regression analysis was carried out to evaluate the correlation between clinical and laboratory findings. Results: The results of the regression analysis for the pooled data revealed that only the macrotensile (adjusted R2 = 0.86) and microtensile tests (adjusted R2 = 0.64), but not the shear and the microshear tests, correlated well with the clinical findings. As regards the data from a single-test institute, the correlation was not statistically significant. Conclusion: Macrotensile and microtensile bond strength tests showed an adequate correlation with the retention rate of cervical restorations after two years. Bond strength tests should be carried out by different operators and/or research institutes to determine the reliability and technique sensitivity of the material under investigation.

Permanent stallion contact hastens onset of mares' cyclicity after winter anoestrus

The species Equus caballus is characterized as a seasonal polyoestrous herd mammal, providing continuous interactions between stallions and mares in feral herds throughout the year. Under domesticated conditions mares and stallions are stabled and kept separated mostly due to hygienic and safety concerns. Managing mares through the spring transitional phase until they show fertile cycles represents a high multifactorial challenge for horse breeders and veterinarians. The goal of this study was to examine the influence of a permanent stallion contact on the onset of cyclicity in anoestrous mares in the transition period.

Wear of two artificial tooth materials in vivo: a 12-month pilot study.

STATEMENT OF PROBLEM: Wear of methacrylate artificial teeth resulting in vertical loss is a problem for both dentists and patients. PURPOSE: The purpose of this study was to quantify wear of artificial teeth in vivo and to relate it to subject and tooth variables. MATERIAL AND METHODS: Twenty-eight subjects treated with complete dentures received 2 artificial tooth materials (polymethyl methacrylate (PMMA)/double-cross linked PMMA fillers; 35%/59% (SR Antaris DCL, SR Postaris DCL); experimental 48%/46%). At baseline and after 12 months, impressions of the dentures were poured with improved stone. After laser scanning, the casts were superimposed and matched. Maximal vertical loss (mm) and volumetric loss (mm(3)) were calculated for each tooth and log-transformed to reduce variability. Volumetric loss was related to the occlusally active surface area. Linear mixed models were used to study the influence of the factors jaw, tooth, and material on adjusted (residual) wear values (alpha=.05). RESULTS: Due to drop outs (n=5) and unmatchable casts (n=3), 69% of all teeth were analyzed. Volumetric loss had a strong linear relationship to surface area (P<.001); this was less pronounced for vertical loss (P=.004). The factor showing the highest influence was the subject. Wear was tooth dependent (increasing from incisors to molars). However, these differences diminished once the wear rates were adjusted for occlusal area, and only a few remained significant (anterior versus posterior maxillary teeth). Another influencing factor was the age of the subject. CONCLUSIONS: Clinical wear of artificial teeth is higher than previously measured or expected. The presented method of analyzing wear of artificial teeth using a laser-scanning device seemed suitable.

Employment consequences of restrictive permanent contracts: Evidence from Spanish labor market reforms

Temporary employment contracts allowing unrestricted dismissals wereintroduced in Spain in 1984 and quickly came to account for most new jobs.As a result, temporary employment increased from around 10% in themid-eighties to more than 30% in the early nineties. In 1997, however,the Spanish government attempted to reduce the incidence of temporaryemployment by reducing payroll taxes and dismissal costs for permanentcontracts. In this paper, we use individual data from the Spanish LaborForce Survey to estimate the effects of reduced payroll taxes anddismissal costs on the distribution of employment and worker flows. Weexploit the fact that recent reforms apply only to certain demographicgroups to set up a natural experiment research design that can be usedto study the effects of contract regulations. Our results show that thereduction of payroll taxes and dismissal costs increased the employmentof young workers on permanent contracts, although the effects for youngwomen are not always significant. Results for older workers showinsignificant effects. The results suggest a moderately elastic responseof permanent employment to non-wage labor costs for young men. We alsofind positive effects on the transitions from unemployment and temporaryemployment into permanent employment for young and older workers, althoughthe effects for older workers are not always significant. On the otherhand, transitions from permanent employment to non-employment increasedonly for older men, suggesting that the reform had little effect ondismissals.

Award errors and permanent disability benefits in Spain

There is a controversial debate about the effects of permanent disability benefits on labormarket behavior. In this paper we estimate equations for deserving and receiving disabilitybenefits to evaluate the award error as the difference in the probability of receiving anddeserving using survey data from Spain. Our results indicate that individuals aged between55 and 59, self-employers or working in an agricultural sector have a probability of receiving a benefit without deserving it significantly higher than the rest of individuals. We also find evidence of gender discrimination since male have a significantly higher probability of receiving a benefit without deserving it. This seems to confirm that disability benefits are being used as an instrument for exiting the labor market for some individuals approaching the early retirement or those who do not have right to retire early. Taking into account that awarding process depends on Social Security Provincial Department, this means that some departments are applying loosely the disability requirements for granting disability benefits.

How binding are legal limits? Transitions from temporary to permanent work in Spain

This paper studies the duration pattern of xed-term contracts and the determinantsof their conversion into permanent ones in Spain, where the share of xed-termemployment is the highest in Europe. We estimate a duration model for temporaryemployment, with competing risks of terminating into permanent employment versusalternative states, and exible duration dependence. We nd that conversion rates aregenerally below 10%. Our estimated conversion rates roughly increase with tenure,with a pronounced spike at the legal limit, when there is no legal way to retain theworker on a temporary contract. We argue that estimated di¤erences in conversionrates across categories of workers can stem from di¤erences in worker outside optionsand thus the power to credibly threat to quit temporary jobs.

Outbreak of Mycobacterium haemophilum infections after permanent makeup of the eyebrows.

We report a Mycobacterium haemophilum outbreak after permanent make-up of the eyebrows performed by the same freelance artist. Twelve patients presented an eyebrow lesion and cervical lymphadenitis. All were treated with antibiotics. Surgery was required in 10 cases. M. haemophilum DNA was identified in the make-up ink.

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 August 2010-30 September 2010

This article documents the addition of 229 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acacia auriculiformis x Acacia mangium hybrid, Alabama argillacea, Anoplopoma fimbria, Aplochiton zebra, Brevicoryne brassicae, Bruguiera gymnorhiza, Bucorvus leadbeateri, Delphacodes detecta, Tumidagena minuta, Dictyostelium giganteum, Echinogammarus berilloni, Epimedium sagittatum, Fraxinus excelsior, Labeo chrysophekadion, Oncorhynchus clarki lewisi, Paratrechina longicornis, Phaeocystis antarctica, Pinus roxburghii and Potamilus capax. These loci were cross-tested on the following species: Acacia peregrinalis, Acacia crassicarpa, Bruguiera cylindrica, Delphacodes detecta, Tumidagena minuta, Dictyostelium macrocephalum, Dictyostelium discoideum, Dictyostelium purpureum, Dictyostelium mucoroides, Dictyostelium rosarium, Polysphondylium pallidum, Epimedium brevicornum, Epimedium koreanum, Epimedium pubescens, Epimedium wushanese and Fraxinus angustifolia.

Non-invasive diagnostic biomarkers for estimating the onset time of permanent cerebral ischemia.

The treatments for ischemic stroke can only be administered in a narrow time-window. However, the ischemia onset time is unknown in ~30% of stroke patients (wake-up strokes). The objective of this study was to determine whether MR spectra of ischemic brains might allow the precise estimation of cerebral ischemia onset time. We modeled ischemic stroke in male ICR-CD1 mice using a permanent middle cerebral artery filament occlusion model with laser Doppler control of the regional cerebral blood flow. Mice were then subjected to repeated MRS measurements of ipsilateral striatum at 14.1 T. A striking initial increase in γ-aminobutyric acid (GABA) and no increase in glutamine were observed. A steady decline was observed for taurine (Tau), N-acetyl-aspartate (NAA) and similarly for the sum of NAA+Tau+glutamate that mimicked an exponential function. The estimation of the time of onset of permanent ischemia within 6 hours in a blinded experiment with mice showed an accuracy of 33±10 minutes. A plot of GABA, Tau, and neuronal marker concentrations against the ratio of acetate/NAA allowed precise separation of mice whose ischemia onset lay within arbitrarily chosen time-windows. We conclude that (1)H-MRS has the potential to detect the clinically relevant time of onset of ischemic stroke.

SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral nerve myelination to endosomal recycling

Patients with Charcot-Marie-Tooth neuropathy and gene targeting in mice revealed an essential role for the SH3TC2 gene in peripheral nerve myelination. SH3TC2 expression is restricted to Schwann cells in the peripheral nervous system, and the gene product, SH3TC2, localizes to the perinuclear recycling compartment. Here, we show that SH3TC2 interacts with the small guanosine triphosphatase Rab11, which is known to regulate the recycling of internalized membranes and receptors back to the cell surface. Results of protein binding studies and transferrin receptor trafficking are in line with a role of SH3TC2 as a Rab11 effector molecule. Consistent with a function of Rab11 in Schwann cell myelination, SH3TC2 mutations that cause neuropathy disrupt the SH3TC2/Rab11 interaction, and forced expression of dominant negative Rab11 strongly impairs myelin formation in vitro. Our data indicate that the SH3TC2/Rab11 interaction is relevant for peripheral nerve pathophysiology and place endosomal recycling on the list of cellular mechanisms involved in Schwann cell myelination.

Auditory Neurons with Transitory Axons to Visual Areas Form Short Permanent Projections.

The kitten's auditory cortex (including the first and second auditory fields AI and AII) is known to send transient axons to either ipsi- or contralateral visual areas 17 and 18. By the end of the first postnatal month the transitory axons, but not their neurons of origin, are eliminated. Here we investigated where these neurons project after the elimination of the transitory axon. Eighteen kittens received early (postnatal day (pd) 2 - 5) injections of long lasting retrograde fluorescent traces in visual areas 17 and 18 and late (pd 35 - 64) injections of other retrograde fluorescent tracers in either hemisphere, mostly in areas known to receive projections from AI and AII in the adult cat. The middle ectosylvian gyrus was analysed for double-labelled neurons in the region corresponding approximately to AI and AII. Late injections in the contralateral (to the analysed AI, AII) hemisphere including all of the known auditory areas, as well as some visual and 'association' areas, did not relabel neurons which had had transient projections to either ipsi- or contralateral visual areas 17 - 18. Thus, AI and AII neurons after eliminating their transient juvenile projections to visual areas 17 and 18 do not project to the other hemisphere. In contrast, relabelling was obtained with late injections in several locations in the ipsilateral hemisphere; it was expressed as per cent of the population labelled by the early injections. Few neurons (0 - 2.5%) were relabelled by large injections in the caudal part of the posterior ectosylvian gyrus and the adjacent posterior suprasylvian sulcus (areas DP, P, VP). Multiple injections in the middle ectosylvian gyrus relabelled a considerably larger percentage of neurons (13%). Single small injections in the middle ectosylvian gyrus (areas AI, AII), the caudal part of the anterior ectosylvian gyrus and the rostral part of the posterior ectosylvian gyrus relabelled 3.1 - 7.0% of neurons. These neurons were generally near (&lt;2.0 mm) the outer border of the late injection sites. Neurons with transient projections to ipsi- or contralateral visual areas 17 and 18 were relabelled in similar proportions by late injections at any given location. Thus, AI or AII neurons which send a transitory axon to ipsi- or contralateral visual areas 17 and 18 are most likely to form short permanent cortical connections. In that respect, they are similar to medial area 17 neurons that form transitory callosal axons and short permanent axons to ipsilateral visual areas 17 and 18.

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells.