Functional Characterization of a Chicken Major Histocompatibility Complex Class II B Gene Promoter

A 0.7 kilobase (kb) DNA fragment from the 5\u27 flanking region of a chicken major histocompatibility complex (MHC) class II B gene was cloned into chloramphenicol acetyltransferase (CAT) reporter vectors and was transfected into a chicken macrophage cell line that expresses a low level of MHC class II antigens. Positive orientation-dependent promoter activity of the chicken DNA was evident in a reporter construct containing an SV40 enhancer. Deletion analysis of this 0.7 kb DNA fragment revealed a short fragment in the 3\u27 end that was crucial for the promoter function and negative regulatory elements (NRE) located further upstream. The conserved MHC class II X and Y boxes did not have a significant effect on promoter activity. Sequence analysis of the 0.7 kb class II B gene upstream region suggests possible involvement of interferon (IFN), E twenty-six specific (ETS)-related proteins, and other factors in regulating this promoter. A chicken T-cell line culture supernatant increased surface expression of MHC class II antigens, as well as class II promoter activity, in this macrophage cell line. This first functional characterization of a chicken MHC class II B gene promoter will aid in understanding the regulatory mechanisms that control the expression of these genes

Cognitive effects of lamotrigine versus topiramate as adjunctive therapy in older adults with epilepsy

Older individuals may be more susceptible to cognitive side effects of antiepileptic drugs than are younger adults. This randomized, double-blind study compared the cognitive effects of lamotrigine (median maintenance dosage, 500.0 mg/d) and topiramate (median maintenance dosage, 300.0 mg/d) as adjunctive therapy for 16 weeks in patients ≥50 years of age. Fifty-one patients (lamotrigine, n=25; topiramate, n=26) were enrolled, and 28 patients (lamotrigine, n=15; topiramate, n=13) completed the study. In a combined analysis of all cognitive tests performed, no significant differences between treatment groups were noted. However, analyses of individual cognitive test results revealed that lamotrigine-treated patients had significantly better results on the Controlled Oral Word Association Test and the Symbol-Digit Modalities Test, whereas topiramate-treated patients had significantly more favorable results on the Digit Cancellation Test and the Rey Auditory-Verbal Learning Test. Larger studies are needed to further clarify the differences in the cognitive effects of lamotrigine and topiramate in older patients

Replication of a hepatitis C virus replicon clone in mouse cells

BACKGROUND: Hepatitis C Virus (HCV) is a significant public health burden and small animal models are needed to study the pathology and immunobiology of the virus. In effort to develop experimental HCV mouse models, we screened a panel of HCV replicons to identify clones capable of replicating in mouse hepatocytes. RESULTS: We report the establishment of stable HCV replication in mouse hepatocyte and fibroblast cell lines using replicons derived from the JFH-1 genotype 2a consensus sequence. Viral RNA replication efficiency in mouse cells was comparable to that observed in human Huh-7 replicon cells, with negative-strand HCV RNA and the viral NS5A protein being readily detected by Northern and Western Blot analysis, respectively. Although HCV replication was established in the absence of adaptive mutations that might otherwise compromise the in vitro infectivity of the JFH-1 clone, no infectious virus was detected when the culture medium from full length HCV RNA replicating mouse cells was titrated on Huh-7 cells, suggesting that the mouse cells were unable to support production of infectious progeny viral particles. Consistent with an additional block in viral entry, infectious JFH-1 particles produced in Huh-7 cells were not able to establish detectable HCV RNA replication in naïve mouse cells. CONCLUSION: Thus, this report expands the repertoire of HCV replication systems and possibly represents a step toward developing mouse models of HCV replication, but it also highlights that other species restrictions might continue to make the development of a purely murine HCV infectious model challenging

Secret Little Functions and Codebook for Protecting Users from Password Theft

Abstract—In this paper, we discuss how to prevent users’ passwords from being stolen by adversaries. We propose differentiated security mechanisms in which a user has the freedom to choose a virtual password scheme ranging from weak security to strong security. The tradeoff is that the stronger the scheme, the more complex the scheme may be. Among the schemes, we have a default method (i.e., traditional password scheme), system recommended function, user-specified function, user-specified program, etc. A function/program is used to implement the virtual password concept with a trade off of security for complexity requiring a small amount of human computing. We further propose codebook approach to serve as system recommended functions and provide a security analysis. For user-specified functions, we adopt secret little functions, in which security is enhanced by hiding secret functions/algorithms. I

A Bioinformatics Method Identifies Prominent Off-targeted Transcripts in RNAi Screens

Because off-target effects hamper interpretation and validation of RNAi screens, we developed a bioinformatics method, Genome-wide Enrichment of Seed Sequence matches (GESS), to identify candidate off-targeted transcripts from direct analysis of primary screening data. GESS identified a prominent off-targeted transcript in several screens, including MAD2 in a screen for components of the spindle assembly checkpoint. We demonstrate how incorporation of the results of GESS analysis can enhance the validation rate in RNAi screens

A history of concussions is associated with symptoms of common mental disorders in former male professional athletes across a range of sports

Objective: Recent reports suggest that exposure to repetitive concussions in sports is associated with an increased risk of symptoms of distress, anxiety and depression, sleep disturbance or substance abuse/dependence (typically referred as symptoms of common mental disorders[CMD]) and of later development of neurodegenerative disease, in particular chronic traumatic encephalopathy (CTE). The primary aim of this study was to explore the relationship between sports career-related concussions and the subsequent occurrence of symptoms of CMD among former male professional athletes retired from football (soccer), ice hockey and rugby (union). Methods: Cross-sectional analyses were performed on baseline electronic questionnaires from three prospective cohort studies among former male professional athletes retired from football (soccer), ice hockey and rugby (union). The number of confirmed concussions was examined through a single question, while symptoms of distress, anxiety and depression, sleep disturbance and adverse alcohol use were assessed using validated questionnaires. Results: From 1,957 former professional athletes contacted, a total of 576 (29%) completed the questionnaire. Of these, 23% had not incurred a concussion during their career, 34% had two or three, 18% four or five, and 11% six or more concussions. The number of sports career-related concussions was a predictor for all outcome measures (β = 0.072–0.109; P ≤ 0.040). Specifically, former professional athletes who reported a history of four or five concussions were approximately 1.5 times more likely to report symptoms of CMD, rising to a two- to five-fold increase in those reporting a history of six or more sports career-related concussions. Conclusions: These data demonstrate an association between exposure to sports concussion and subsequent risk of symptoms of CMD in former professional athletes across a range of contact sports. Further work to explore the association between sports concussion and symptoms of CMD is required; in the meanwhile, strategies for effective risk reduction and improved management appear indicated

Integrated responses to domestic violence: legally mandated intervention programmes for male perpetrators

International surveys have suggested that around one-third of all adult women will, at some point in their lifetime, experience abuse perpetrated by an intimate male partner. Domestic violence is considered to be one of the major risk factors affecting women’s health in Australia and there is a need for the community to respond in ways that reduce the likelihood of further violence occurring. One way of doing this is to deliver programs that aim to reduce the risk of known perpetrators committing further offences. This paper describes the outcomes of a Gold Coast program delivered to men who perpetrate domestic violence and who are legally obliged to participate. The data show that this type of program can produce positive changes in participants. However, the extent to which such changes lead to direct behavioural change is less clear and further research and evaluation is required to develop the evidence base that is needed to ensure that programs for perpetrators produce significant and enduring improvements to community safety.<br/

Crystallographic Interdigitation in Oyster Shell Folia Enhances Material Strength

Shells of oyster species belonging to the genus Crassostrea have similar shell microstructural features comprising well-ordered calcite folia. However, the mechanical strengths of folia differ dramatically between closely related species. For example, the calcareous shells of the Hong Kong oyster Crassostrea hongkongensis are stronger than those of its closest relative, the Portuguese oyster, Crassostrea angulata. Specifically, after removal of organic content, the folia of C. hongkongensis are 200% tougher and able to withstand a 100% higher crushing force than that of C. angulata. Detailed analyses of shell structural and mechanical features support the hypothesis that crystallographic interdigitations confer elevated mechanical strength in C. hongkongensis oyster shells compared to C. angulata shells. Consequently, the folia of C. hongkongensis are structurally equipped to withstand a higher external load compared to C. angulata. The observed relationships between oyster shell structure, crystallography, and mechanical properties provided an insightful context in which to consider the likely fate of these two species in future climate change scenarios. Furthermore, the interdisciplinary approach developed in this study through integrating electron backscatter diffraction (EBSD) data into finite element analysis (FEA) could be applied to other biomineral systems to investigate the relationship between crystallography and mechanical behavior

Using hearing aid directional microphones and noise reduction algorithms to enhance cochlear implant performance

Abstract: Hearing aids and cochlear implants are two major hearing enhancement technologies but yet share little in research and development. The purpose of this study was to determine whether hearing aid directional microphones and noise reduction technologies could enhance cochlear implant users&apos; speech understanding and ease of listening. Digital hearing aids serving as preprocessors were programmed to omni-directional microphone, directional microphone, and directional microphone plus noise reduction conditions. Three groups of subjects were tested with the hearing aid processed speech stimuli. Results indicated that hearing aids with directional microphones and noise reduction algorithms significantly enhanced speech understanding and listening comfort