Copy Number Variants in Patients with Severe Oligozoospermia and Sertoli-Cell-Only Syndrome

A genetic origin is estimated in 30% of infertile men with the common phenotypes of oligo- or azoospermia, but the pathogenesis of spermatogenic failure remains frequently obscure. To determine the involvement of Copy Number Variants (CNVs) in the origin of male infertility, patients with idiopathic severe oligozoospermia (N = 89), Sertoli-cell-only syndrome (SCOS, N = 37)) and controls with normozoospermia (N = 100) were analysed by array-CGH using the 244A/400K array sets (Agilent Technologies). The mean number of CNVs and the amount of DNA gain/loss were comparable between all groups. Ten recurring CNVs were only found in patients with severe oligozoospermia, three only in SCOS and one CNV in both groups with spermatogenic failure but not in normozoospermic men. Sex-chromosomal, mostly private CNVs were significantly overrepresented in patients with SCOS. CNVs found several times in all groups were analysed in a case-control design and four additional candidate genes and two regions without known genes were associated with SCOS (P<1×10−3). In conclusion, by applying array-CGH to study male infertility for the first time, we provide a number of candidate genes possibly causing or being risk factors for the men's spermatogenic failure. The recurring, patient-specific and private, sex-chromosomal CNVs as well as those associated with SCOS are candidates for further, larger case-control and re-sequencing studies

Variation of selfing rate and inbreeding depression among individuals and across generations within an admixed Cedrus population

[EN] We investigated the variation and short-term evolution of the selfing rate and inbreeding depression (ID) across three generations within a cedar forest that was established from admixture ca 1860. The mean selfing rate was 9.5%, ranging from 0 to 48% among 20 seed trees (estimated from paternally inherited chloroplast DNA). We computed the probability of selfing for each seed and we investigated ID by comparing selfed and outcrossed seeds within progenies, thus avoiding maternal effects. In all progenies, the germination rate was high (88-100%) and seedling mortality was low (0-12%). The germination dynamics differed significantly between selfed and outcrossed seeds within progenies in the founder gene pool but not in the following generations. This transient effect of selfing could be attributed to epistatic interactions in the original admixture. Regarding the seedling growth traits, the ID was low but significant: 8 and 6% for height and diameter growth, respectively. These rates did not vary among generations, suggesting minor gene effects. At this early stage, outcrossed seedlings outcompeted their selfed relatives, but not necessarily other selfed seedlings from other progenies. Thus, purging these slightly deleterious genes may only occur through within-family selection. Processes that maintain a high level of genetic diversity for fitness-related traits among progenies also reduce the efficiency of purging this part of the genetic load. © 2011 Macmillan Publishers Limited All rights reserved. Guardar / Salir Siguiente >This work has been partially supported by Grant PPI-00-04 from the Polytechnic University of Valencia (Spain). We thank B Fady and E Klein as well as two anonymous reviewers for their helpful comments on a previous version of the paper. 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Protein tyrosine phosphatases expression during development of mouse superior colliculus

Protein tyrosine phosphatases (PTPs) are key regulators of different processes during development of the central nervous system. However, expression patterns and potential roles of PTPs in the developing superior colliculus remain poorly investigated. In this study, a degenerate primer-based reverse transcription-polymerase chain reaction (RT-PCR) approach was used to isolate seven different intracellular PTPs and nine different receptor-type PTPs (RPTPs) from embryonic E15 mouse superior colliculus. Subsequently, the expression patterns of 11 PTPs (TC-PTP, PTP1C, PTP1D, PTP-MEG2, PTP-PEST, RPTPJ, RPTPε, RPTPRR, RPTPσ, RPTPκ and RPTPγ) were further analyzed in detail in superior colliculus from embryonic E13 to postnatal P20 stages by quantitative real-time RT-PCR, Western blotting and immunohistochemistry. Each of the 11 PTPs exhibits distinct spatiotemporal regulation of mRNAs and proteins in the developing superior colliculus suggesting their versatile roles in genesis of neuronal and glial cells and retinocollicular topographic mapping. At E13, additional double-immunohistochemical analysis revealed the expression of PTPs in collicular nestin-positive neural progenitor cells and RC-2-immunoreactive radial glia cells, indicating the potential functional importance of PTPs in neurogenesis and gliogenesis

Analysis of gas exchange in seedlings of Acer saccharum : integration of field and laboratory studies

In the field, photosynthesis of Acer saccharum seedlings was rarely light saturated, even though light saturation occurs at about 100 μmol quanta m -2 s -1 photosynthetic photon flux density (PPFD). PPFD during more than 75% of the daylight period was 50 μmol m -2 s -1 or less. At these low PPFD's there is a marked interaction of PPFD with the initial slope (CE) of the CO 2 response. At PPFD-saturation CE was 0.018 μmol m -2 s -1 /(μl/l). The apparent quantum efficiency (incident PPFD) at saturating CO 2 was 0.05–0.08 mol/mol. and PPFD-saturated CO 2 exchange was 6–8 μmol m -2 s -1 . The ratio of internal CO 2 concentration to external ( C i / C a ) was 0.7 to 0.8 except during sunflecks when it decreased to 0.5. The decrease in C i / C a during sunflecks was the result of the slow response of stomates to increased PPFD compared to the response of net photosynthesis. An empirical model, which included the above parameters was used to simulate the measured CO 2 exchange rate for portions of two days. Parameter values for the model were determined in experiments separate from the daily time courses being sumulated. Analysis of the field data, partly through the use of simulations, indicate that the elimination of sunflecks would reduce net carbon gain by 5–10%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47755/1/442_2004_Article_BF00378907.pd

Competence-based curriculum development for general practice in Germany: a stepwise peer-based approach instead of reinventing the wheel

BACKGROUND: Improving postgraduate medical training is one important step to attract more medical students into general practice. Keeping pace with international developments moving to competence-based curricula for general practice training, the aim of this project was to develop and implement such a curriculum in Germany. METHODS: A five-step, peer-based method was used for the curriculum development process including panel testing and a “test version” of the curriculum for the pilot implementation phase. The CanMEDS framework served as a basis for a new German competence-based curriculum in general practice training. Four curricula from European countries and Canada were reviewed and, following required cultural adaptions, key strengths from these were integrated. For the CanMEDS “medical expertise” element of the curriculum, the WONCA ICPC-2 classification of patient’s “reason for encounters” was also integrated. RESULTS: Altogether, 37 participants were involved in the development process representing 12 different federal states in Germany, and including an expert advisor from Denmark. An official “test version” of the curriculum consisting of three parts: medical expertise, additional competencies and medical procedures was established. A system of self-assessment for trainees was integrated into the curriculum using a traffic light scale. Since March 2012, the curriculum has been made freely available online as a “test version”. In 2014, an evaluation is planned using feedback from users of the test model as a further stage of the implementation process. CONCLUSIONS: The first German competence-based curriculum for general practice training has been developed using a pragmatic peer controlled approach and implementation is being trialed with a “test version” of the curriculum. This model project and its peer-based methodology may support competence-based curriculum development for other medical specialties both inside and outside Germany