Genetic background of semen parameters in Italian Simmental bulls

The aim of this study was to estimate genetic parameters and investigate the genomic background of scrotal circumference and semen parameters in the Italian Simmental bulls. Scrotal circumference, number of normal spermatozoa, ejaculate volume, spermatozoa motility, and total spermatozoa were measured on 622 bulls, of which 603 had genotypes for 42,141 SNP. Variance components of scrotal circumference were estimated with an animal model that included the fixed effects of birth year, animal age, and measurement method, and the random effects of day of measurement and animal. In the model for the other traits, the scrotal circumference was added as a covariate to account for its influence on the semen parameters. A genome-wide association study was carried out using the ssGBLUP-approach. Heritabilities ranged from 0.07 +/- 0.05 (spermatozoa motility) to 0.50 +/- 0.14 (scrotal circumference). A total of 13 SNP passed the Bonferroni correction threshold and the number of significantly associated markers ranged from 1 (ejaculate volume and spermatozoa motility) to 5 (total spermatozoa). Genes already associated with reproduction parameters were retrieved close to the significant SNP. Results of the present study gave preliminary insights about the genetic determinism of semen quality in Italian Simmental bulls

Processing of Body Odor Signals by the Human Brain

Brain development in mammals has been proposed to be promoted by successful adaptations to the social complexity as well as to the social and non-social chemical environment. Therefore, the communication via chemosensory signals might have been and might still be a phylogenetically ancient communication channel transmitting evolutionary significant information. In humans, the neuronal underpinnings of the processing of social chemosignals have been investigated in relation to kin recognition, mate choice, the reproductive state and emotional contagion. These studies reveal that human chemosignals are probably not processed within olfactory brain areas but through neuronal relays responsible for the processing of social information. It is concluded that the processing of human social chemosignals resembles the processing of social signals originating from other modalities, except that human social chemosignals are usually communicated without the allocation of attentional resources, that is below the threshold of consciousness. Deviances in the processing of human social chemosignals might be related to the development and maintenance of mental disorders

Unconstrained SU(2) Yang-Mills Quantum Mechanics with Theta Angle

The unconstrained classical system equivalent to spatially homogeneous SU(2) Yang-Mills theory with theta angle is obtained and canonically quantized. The Schr\"odinger eigenvalue problem is solved approximately for the low lying states using variational calculation. The properties of the groundstate are discussed, in particular its electric and magnetic properties, and the value of the "gluon condensate" is calculated. Furthermore it is shown that the energy spectrum of SU(2) Yang-Mills quantum mechanics is independent of the theta angle. Explicit evaluation of the Witten formula for the topological susceptibility gives strong support for the consistency of the variational results obtained.Comment: 20 pages REVTEX, no figures, one reference added, final version to appear in Phys. Rev.

Instantons and Gribov Copies in the Maximally Abelian Gauge

We calculate the Faddeev-Popov operator corresponding to the maximally Abelian gauge for gauge group SU(N). Specializing to SU(2) we look for explicit zero modes of this operator. Within an illuminating toy model (Yang-Mills mechanics) the problem can be completely solved and understood. In the field theory case we are able to find an analytic expression for a normalizable zero mode in the background of a single `t Hooft instanton. Accordingly, such an instanton corresponds to a horizon configuration in the maximally Abelian gauge. Possible physical implications are discussed.Comment: 31 pages, 8 figures, v3: references adde

The subcellular localization of the hepatitis C virus non-structural protein NS2 is regulated by an ion channel-independent function of the p7 protein

The hepatitis C virus (HCV) p7 ion channel and non-structural protein 2 (NS2) are both required for efficient assembly and release of nascent virions, yet precisely how these proteins are able to influence this process is unclear. Here, we provide both biochemical and cell biological evidence for a functional interaction between p7 and NS2. We demonstrate that in the context of a genotype 1b subgenomic replicon the localization of NS2 is affected by the presence of an upstream p7 with its cognate signal peptide derived from the C terminus of E2 (SPp7). Immunofluorescence analysis revealed that the presence of SPp7 resulted in the targeting of NS2 to sites closely associated with viral replication complexes. In addition, biochemical analysis demonstrated that, in the presence of SPp7, a significant proportion of NS2 was found in a detergent (Triton X-100)-insoluble fraction, which also contained a marker of detergent resistant rafts. In contrast, in replicons lacking p7, NS2 was entirely detergent soluble and the altered localization was lost. Furthermore, we found that serine 168 within NS2 was required for its localization adjacent to replication complexes, but not for its accumulation in the detergent-insoluble fraction. NS2 physically interacted with NS5A and this interaction was dependent on both p7 and serine 168 within NS2. Mutational and pharmacological analyses demonstrated that these effects were not a consequence of p7 ion channel function, suggesting that p7 possesses an alternative function that may influence the coordination of virus genome replication and particle assembly

COMMD1 promotes the ubiquitination of NF‐κB subunits through a cullin‐containing ubiquitin ligase

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102213/1/emboj7601489.pd

Activation of mTOR coincides with autophagy during ligation-induced atrophy in the rat submandibular gland

Salivary gland atrophy is a common consequence of pathology, including Sjögren's syndrome, irradiation therapy and obstructive sialadenitis. During severe atrophy of the rat submandibular gland caused by excretory duct ligation, the majority of acinar cells disappear through apoptosis, whereas ductal cells proliferate and dedifferentiate; yet, the gland can survive in the atrophic state almost indefinitely, with an ability to fully recover if deligated. The control mechanisms governing these observations are not well understood. We report that ∼10% of acinar cells survive in ligation-induced atrophy. Microarray and quantitative real-time PCR analysis of ligated glands indicated sustained transcription of acinar cell-specific genes, whereas ductal-specific genes were reduced to background levels. After 3 days of ligation, activation of the mammalian target of rapamycin (mTOR) pathway and autophagy occurred as shown by phosphorylation of 4E-BP1 and expression of autophagy-related proteins. These results suggest that activation of mTOR and the autophagosomal pathway are important mechanisms that may help to preserve acinar cells during atrophy of salivary glands after injury

Time-Frequency Analysis of Chemosensory Event-Related Potentials to Characterize the Cortical Representation of Odors in Humans

BACKGROUND: The recording of olfactory and trigeminal chemosensory event-related potentials (ERPs) has been proposed as an objective and non-invasive technique to study the cortical processing of odors in humans. Until now, the responses have been characterized mainly using across-trial averaging in the time domain. Unfortunately, chemosensory ERPs, in particular, olfactory ERPs, exhibit a relatively low signal-to-noise ratio. Hence, although the technique is increasingly used in basic research as well as in clinical practice to evaluate people suffering from olfactory disorders, its current clinical relevance remains very limited. Here, we used a time-frequency analysis based on the wavelet transform to reveal EEG responses that are not strictly phase-locked to onset of the chemosensory stimulus. We hypothesized that this approach would significantly enhance the signal-to-noise ratio of the EEG responses to chemosensory stimulation because, as compared to conventional time-domain averaging, (1) it is less sensitive to temporal jitter and (2) it can reveal non phase-locked EEG responses such as event-related synchronization and desynchronization. METHODOLOGY/PRINCIPAL FINDINGS: EEG responses to selective trigeminal and olfactory stimulation were recorded in 11 normosmic subjects. A Morlet wavelet was used to characterize the elicited responses in the time-frequency domain. We found that this approach markedly improved the signal-to-noise ratio of the obtained EEG responses, in particular, following olfactory stimulation. Furthermore, the approach allowed characterizing non phase-locked components that could not be identified using conventional time-domain averaging. CONCLUSION/SIGNIFICANCE: By providing a more robust and complete view of how odors are represented in the human brain, our approach could constitute the basis for a robust tool to study olfaction, both for basic research and clinicians

VHL Type 2B Mutations Retain VBC Complex Form and Function

Background: von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1a and HIF-2a), resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease. Methodology/Principal Findings: This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1a. Conclusions: Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition fo