A Study of Brain Networks Associated with Swallowing Using Graph-Theoretical Approaches

Functional connectivity between brain regions during swallowing tasks is still not well understood. Understanding these complex interactions is of great interest from both a scientific and a clinical perspective. In this study, functional magnetic resonance imaging (fMRI) was utilized to study brain functional networks during voluntary saliva swallowing in twenty-two adult healthy subjects (all females, 23.1±1.52 years of age). To construct these functional connections, we computed mean partial correlation matrices over ninety brain regions for each participant. Two regions were determined to be functionally connected if their correlation was above a certain threshold. These correlation matrices were then analyzed using graph-theoretical approaches. In particular, we considered several network measures for the whole brain and for swallowing-related brain regions. The results have shown that significant pairwise functional connections were, mostly, either local and intra-hemispheric or symmetrically inter-hemispheric. Furthermore, we showed that all human brain functional network, although varying in some degree, had typical small-world properties as compared to regular networks and random networks. These properties allow information transfer within the network at a relatively high efficiency. Swallowing-related brain regions also had higher values for some of the network measures in comparison to when these measures were calculated for the whole brain. The current results warrant further investigation of graph-theoretical approaches as a potential tool for understanding the neural basis of dysphagia. © 2013 Luan et al

Time-resolved photometric and spectroscopic analysis of a luminous Ap star HD103498

We present the results on the photometric and spectroscopic monitoring of a luminous Ap star HD103498. The time-series photometric observations were carried out on 17 nights using three-channel fast photometer attached to the 1.04-m optical telescope at ARIES, Nainital. The photometric data of five nights of year 2007 show clear signature of 15-min periodicity. However, the follow-up observations during 2007--2009 could not repeated any such periodicity. To confirm the photometric light variations, the time-series spectroscopic observations were carried out with the 2.56-m Nordic Optical Telescope (NOT) at La Palma on February 2, 2009. Any radial velocity variations were absent in this data set which is in full agreement with the photometric observations taken near the same night. Model atmosphere and abundance analysis of HD103498 show that the star is evolved from the Main Sequence and its atmospheric abundances are similar to two other evolved Ap stars HD133792 and HD204411: large overabundances of Si, Cr, and Fe and moderate overabundances of the rare-earth elements. These chemical properties and a higher effective temperature distinguish HD103498 from any known roAp star.Comment: 8 Figures, 2 Tables, 9 Pages, Accepted for publication in MNRA

Smy2p Participates in COPII Vesicle Formation Through the Interaction with Sec23p/Sec24p Subcomplex

The coat protein complex II (COPII) is essential for vesicle formation from the endoplasmic reticulum (ER) and is composed of two heterodimeric subcomplexes, Sec23p/Sec24p and Sec13p/Sec31p, and the small guanosine triphosphatase Sar1p. In an effort to identify novel factors that may participate in COPII vesicle formation, we isolated SMY2, a yeast gene encoding a protein of unknown function, as a multicopy suppressor of the temperature-sensitive sec24-20 mutant. We found that even a low-copy expression of SMY2 was sufficient for the suppression of the sec24-20 phenotypes, and the chromosomal deletion of SMY2 led to a severe growth defect in the sec24-20 background. In addition, SMY2 exhibited genetic interactions with several other genes involved in the ER-to-Golgi transport. Subcellular fractionation analysis showed that Smy2p was a peripheral membrane protein fractionating together with COPII components. However, Smy2p was not loaded onto COPII vesicles generated in vitro. Interestingly, coimmunoprecipitation between Smy2p and the Sec23p/Sec24p subcomplex was specifically observed in sec23-1 and sec24-20 backgrounds, suggesting that this interaction was a prerequisite for the suppression of the sec24-20 phenotypes by overexpression of SMY2. We propose that Smy2p is located on the surface of the ER and facilitates COPII vesicle formation through the interaction with Sec23p/Sec24p subcomplex

Clostridium septicum sepsis and colorectal cancer - a reminder

<p>Abstract</p> <p>Background</p> <p>Spontaneous clostridium septicum infections are rare and are associated with a high mortality. Association of clostridium infection with colorectal malignancies have been previously reported and most cases are described in tumours of the ascending colon. We report our experience of clostridium septicum infection in the presence of tumour perforation in a series of two patients as a reminder of its association with sepsis in the presence of colorectal malignancy.</p> <p>Case Presentation</p> <p>We isolated clostridium septicum infection in a series of two patients admitted as emergencies. One patient was found to have a perforated caecal tumour intraoperatively whilst the other had a perforated rectal tumour. The clinical outcome and management of each case are reported and underlying reasons for variations in outcome are discussed.</p> <p>Conclusion</p> <p>Although uncomman, the possibility of clostridium septicum sepsis should be borne in mind in patients who present with underlying malignancy and have sepsis. The cumulative effect of sepsis and malignant perforation is associated with a high morbidity and mortality. Awareness and early diagnosis of clostridium septicum may improve the prognosis of what is usually regarded as a fatal infection.</p

Development and Function of CD94-Deficient Natural Killer Cells

The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

Engaging media in communicating research on sexual and reproductive health and rights in sub-Saharan Africa: experiences and lessons learned

Background: The mass media have excellent potential to promote good sexual and reproductive health outcomes, but around the world, media often fail to prioritize sexual and reproductive health and rights issues or report them in an accurate manner. In sub-Saharan Africa media coverage of reproductive health issues is poor due to the weak capacity and motivation for reporting these issues by media practitioners. This paper describes the experiences of the African Population and Health Research Center and its partners in cultivating the interest and building the capacity of the media in evidence-based reporting of reproductive health issues in sub-Saharan Africa. Methods: The paper utilizes a case study approach based primarily on the personal experiences and reflections of the authors (who played a central role in developing and implementing the Center’s communication and policy engagement strategies), a survey that the Center carried out with science journalists in Kenya, and literature review. Results: The African Population and Health Research Center’s media strategy evolved over the years, moving beyond conventional ways of communicating research through the media via news releases and newspaper stories, to varying approaches that sought to inspire and build the capacity of journalists to do evidence-based reporting of reproductive health issues. Specifically, the approach included 1) enhancing journalists’ interest in and motivation for reporting on reproductive health issues through training and competitive grants for outstanding reporting ; 2) building the capacity of journalists to report reproductive health research and the capacity of reproductive health researchers to communicate their research to media through training for both parties and providing technical assistance to journalists in obtaining and interpreting evidence; and 3) establishing and maintaining trust and mutual relationships between journalists and researchers through regular informal meetings between journalists and researchers, organizing field visits for journalists, and building formal partnerships with professional media associations and individual journalists. Conclusion: Our experiences and reflections, and the experiences of others reviewed in this paper, indicate that a sustained mix of strategies that motivate, strengthen capacity of, and build relationships between journalists and researchers can be effective in enhancing quality and quantity of media coverage of research

Presymptomatic genetic testing for hereditary cancer in young adults: a survey of young adults and parents

Presymptomatic testing for hereditary cancer syndromes should involve a considered choice. This may be particularly challenging when testing is undertaken in early adulthood. With the aim of exploring the psychosocial implications of presymptomatic testing for hereditary cancer in young adults and their parents, a cross-sectional survey was designed. Two questionnaires were developed (one for young adults who had considered presymptomatic testing, one for parents). Questionnaires were completed by 152 (65.2%) young adults and 42 (73.7%) parents. Data were analysed using descriptive statistics, inferential testing, and exploratory factor analysis and linear regression analysis. Young adults were told about their potential genetic risk at a mean age of 20 years; in most cases, information was given by a parent, often in an unplanned conversation. Although testing requests were usually made by young adults, the majority of parents felt they had control over the young adult’s decision and all felt their children should be tested. Results suggest that some young adults did not understand the implications of the genetic test but complied with parental pressure. Counselling approaches for presymptomatic testing may require modification both for young adults and their parents. Those offering testing need to be aware of the complex pressures that young adults can experience, which can influence their autonomous choices. It is therefore important to emphasise to both parents and young adults that, although testing can bring benefits in terms of surveillance and prevention, young adults have a choice

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Spectroscopy of geo-neutrinos from 2056 days of Borexino data

We report an improved geo-neutrino measurement with Borexino from 2056 days of data taking. The present exposure is $(5.5\pm0.3)\times10^{31}$ proton$\times$yr. Assuming a chondritic Th/U mass ratio of 3.9, we obtain $23.7 ^{+6.5}_{-5.7} (stat) ^{+0.9}_{-0.6} (sys)$ geo-neutrino events. The null observation of geo-neutrinos with Borexino alone has a probability of $3.6 \times 10^{-9}$ (5.9$\sigma$). A geo-neutrino signal from the mantle is obtained at 98\% C.L. The radiogenic heat production for U and Th from the present best-fit result is restricted to the range 23-36 TW, taking into account the uncertainty on the distribution of heat producing elements inside the Earth.Comment: 4 pages, 4 figure