Inducible nitric oxide synthase mediates DNA double strand breaks in Human T-Cell Leukemia Virus Type 1-induced leukemia/lymphoma

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive and fatal malignancy of CD4(+) T-lymphocytes infected by the Human T-Cell Virus Type 1 (HTLV-1). The molecular mechanisms of transformation in ATLL have not been fully elucidated. However, genomic instability and cumulative DNA damage during the long period of latency is believed to be essential for HTLV-1 induced leukemogenesis. In addition, constitutive activation of the NF-κB pathway was found to be a critical determinant for transformation. Whether a connection exists between NF-κB activation and accumulation of DNA damage is not clear. We recently found that the HTLV-1 viral oncoprotein, Tax, the activator of the NF-κB pathway, induces DNA double strand breaks (DSBs). RESULTS: Here, we investigated whether any of the NF-κB target genes are critical in inducing DSBs. Of note, we found that inducible nitric oxide synthase (iNOS) that catalyzes the production of nitric oxide (NO) in macrophages, neutrophils and T-cells is over expressed in HTLV-1 infected and Tax-expressing cells. Interestingly, we show that in HTLV-1 infected cells, iNOS expression is Tax-dependent and specifically requires the activation of the classical NF-κB and JAK/STAT pathways. A dramatic reduction of DSBs was observed when NO production was inhibited, indicating that Tax induces DSBs through the activation of NO synthesis. CONCLUSIONS: Determination of the impact of NO on HTLV-1-induced leukemogenesis opens a new area for treatment or prevention of ATLL and perhaps other cancers in which NO is produced

Molecular taxonomic, epidemiological and population genetic approaches to understanding yam anthracnose disease

Water yam (Dioscorea alata L.) is the most widely cultivated yam species globally. The major limitation to the profitable and sustainable production of D. alata is its susceptibility to anthracnose disease. The availability of resistant varieties could potentially form the cornerstone of an integrated management strategy for yam anthracnose; however, anthracnose resistance breeding is hampered by the dearth of knowledge on pathogen identity and diversity. Four forms of Colletotrichum are now known to be associated with foliar anthracnose of yam: the slow-growing grey (SGG), the fast-growing salmon (FGS), the fast-growing olive (FGO), and the fast-growing grey (FGG) forms. The close phylogenetic relationship of the first three forms to reference isolates of Colletotrichum gloeosporioides, and the fact that only strains of these forms have been observed to induce typical anthracnose symptoms on D. alata, recently confirmed that C. gloeosporioides is the causal agent of yam anthracnose disease. The FGG form possibly represents a distinct, endophytic, species as indicated by morphological, biological and molecular criteria. Previous research emphasized epidemiology and control but limited progress was made in understanding yam anthracnose disease based on this classical approach. Molecular approaches have started to unravel the systematics and ecology of Colletotrichum strains associated with yam anthracnose, as well the population biology of C. gloeosporioides on yam. Sexual recombination is a likely mechanism contributing to the high genetic diversity of C. gloeosporioides in yam-based cropping systems. Studies have been initiated to understand the mechanisms that generate genetic variation in C. gloeosporioides, and to gain some insight into the biochemistry of the interactions between the pathogen and yam. Our thesis in this article is that integrating traditional and molecular approaches to understanding C. gloeosporioides systematics, epidemiology and population genetics will lead to a much better understanding of yam anthracnose disease, and thus to the development of effective and sustainable control measures. Research successes and challenges are discussed, as well as their implications for future studies on pathogen evolutionary potential, anthracnose resistance breeding, and the deployment of resistance genes. Key words: Anthracnose, Colletotrichum gloeosporioides, Dioscorea spp., molecular markers, molecular systematics, population biology, resistance breeding, yam. African Journal of Biotechnology Vol. 2 (12), pp. 486-496, December 200

Developing a Health Equity and Criminal Justice Concentration for a Master of Public Health (MPH) Program: Results From a Needs Assessment Among Community Partners and Potential Employers

The United States has experienced a 4-fold increase in jail and prison populations over the last 40 years, disproportionately burdening African American and Hispanic/Latinx communities. Mass incarceration threatens the health of individuals, families, and communities, and requires a public health response. The Master of Public Health (MPH) Program at Touro University California (TUC) trains students to become skillful, socially-conscious public health professionals. We are developing a concentration focused on the public health impacts of incarceration. Along with the core public health curriculum, students of this new Health Equity and Criminal Justice (HECJ) concentration will receive training in criminal justice, reentry, reintegration, recidivism, restorative justice, structural racism, and social and community impacts of incarceration. Our study gauges interest in an HECJ concentration in our local community, including potential employers. We surveyed a cross-section of community partners including public health departments, other governmental agencies, California correctional facilities, county jails, community groups, health clinics, and hospitals. A majority (89%) of respondents consider mass incarceration a public health problem and 86% believe specialized training would make graduates employable by criminal justice related organizations. The HECJ track will fill a gap in the field and train a future generation of public health professionals to address the epidemic of mass incarceration

Relation of Patients Living Without a Partner or Spouse to Being Physically Active After Acute Coronary Syndromes (from the PULSE Accelerometry Substudy)

Living alone is associated with adverse outcomes after acute coronary syndromes (ACS). One potential mediator of the relation between partner status and outcomes after ACS is physical activity. To evaluate the association of partner status with physical activity after ACS, data from 107 participants enrolled in the Prescription Use, Lifestyle, and Stress Evaluation (PULSE) study, a prospective observational study of post-ACS patients, were analyzed. Accelerometers were used to measure physical activity after hospital discharge. The primary outcome measure was a maximum 10 hours of daytime activity 1 month after discharge. One month after discharge from ACS hospitalizations, participants without a partner or spouse exhibited 24.4% lower daytime activity than those with a partner or spouse (p = 0.003). After controlling for age, gender, body mass index, Charlson co-morbidity index, and traditional psychosocial and clinical cardiovascular correlates of post-ACS physical activity, partner status remained an independent predictor of post-ACS physical activity (20.5% lower daytime activity among those without a partner or spouse, p = 0.008). In conclusion, in this study of accelerometer-measured physical activity after an ACS hospitalization, those without a partner or spouse exhibit significantly less physical activity than those with a partner or spouse 1 month after discharge from the hospital. Low physical activity may be an important mediator of the prognosis associated with partner status after ACS

Interaction and architectural space

For many in the field of HCI, location and space are synonymous; yet, as we move from the mobile era to the ubiquitous era, computing becomes entangled with notions of space. This workshop critically examines the role of space in human-computer interfaces. The objective is to bring together diverse perspectives of space, drawing from architecture, philosophy, art, geography, design, dance, spatial-cognition, mathematics, computing, and still other domains, towards foregrounding space in theoretical discussions and explorations within the CHI community. Expected outcomes are the reporting of fresh insights into the impact and role of space in the interaction process

Estimating the total incidence of kidney failure in australia including individuals who are not treated by dialysis or transplantation

Background: To date, incidence data for kidney failure in Australia have been available for only those who start renal replacement therapy (RRT). Information about the total incidence of kidney failure, including non-RRT-treated cases, is important to help understand the burden of kidney failure in the community and the characteristics of patients who die without receiving treatment

Robust Intrapulmonary CD8 T Cell Responses and Protection with an Attenuated N1L Deleted Vaccinia Virus

BACKGROUND: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2 logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV-specific antibodies were also detected in the sera of mice infected 3-5 months prior with the attenuated vGK5 virus. Finally, mice immunized with vGK5 were significantly protected when challenged with a lethal dose of VACV-WR. CONCLUSIONS: These results indicate that the attenuated vGK5 virus protects against subsequent infection and suggest that the N1L protein limits the strength of the early antiviral CD8 T cell response following respiratory infection

Predicting the Effects of Reservoir Water Level Management on the Reproductive Output of a Riparian Songbird

Dams and reservoirs alter natural water flow regimes with adverse effects on natural ecosystems. Quantifying and reducing these effects are important as global demands for energy and water, and the number of dams and reservoir, increase. However, costs and logistic constraints typically preclude experimental assessment of reservoir effects on the environment. We developed a stochastic individual-based model (IBM), parameterized using empirical data, to estimate the annual productivity of yellow warblers that breed in riparian habitat within the footprint of the Arrow Lakes Reservoir in British Columbia, Canada. The IBM incorporated information on breeding phenology, nest site selection, brood parasitism, daily nest survival, re-nesting probabilities and post-fledging survival. We used the IBM to estimate the effect of four different water management scenarios on annual productivity. We found that the IBM accurately estimated average nest success (0.39 ± 0.10 SD), the proportion of females that produced at least one fledgling during a breeding season (0.56 ± 0.11), and annual fledging success (2.06 ± 0.43) under current conditions. The IBM estimated that reservoir operations currently reduce the annual productivity of this population by 37%, from an average of 1.62 to 1.06 independent young/female. Delaying when reservoir water levels reach 435m asl (the minimum elevation occupied by yellow warblers) by approximately 2 weeks was predicted to increase annual productivity to 1.44 independent young/female. The standardized effect on annual productivity of reducing the maximum elevation of the reservoir so that yellow warbler habitat is not inundated (Cohen’s d = 1.52) or delaying when water is stored (Cohen’s d = 0.83) was primarily driven by inundation effects on post-fledging survival. Reservoir operation effects on breeding birds will be species specific, but this IBM can easily be modified to allow the environmental impacts on the entire breeding bird community to be incorporated into water management decisions

Self-interest And Public Interest: The Motivations Of Political Actors

Self-Interest and Public Interest in Western Politics showed that the public, politicians, and bureaucrats are often public spirited. But this does not invalidate public-choice theory. Public-choice theory is an ideal type, not a claim that self-interest explains all political behavior. Instead, public-choice theory is useful in creating rules and institutions that guard against the worst case, which would be universal self-interestedness in politics. In contrast, the public-interest hypothesis is neither a comprehensive explanation of political behavior nor a sound basis for institutional design