Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by adipocytes via activation of toll and Eiger/TNF signaling

High tumor burden is associated with increased levels of circulating inflammatory cytokines that influence the pathophysiology of the tumor and its environment. The cellular and molecular events mediating the organismal response to a growing tumor are poorly understood. Here, we report a bidirectional crosstalk between epithelial tumors and the fat body—a peripheral immune tissue—in Drosophila. Tumors trigger a systemic immune response through activation of Eiger/TNF signaling, which leads to Toll pathway upregulation in adipocytes. Reciprocally, Toll elicits a non-tissue-autonomous program in adipocytes, which drives tumor cell death. Hemocytes play a critical role in this system by producing the ligands Spätzle and Eiger, which are required for Toll activation in the fat body and tumor cell death. Altogether, our results provide a paradigm for a long-range tumor suppression function of adipocytes in Drosophila, which may represent an evolutionarily conserved mechanism in the organismal response to solid tumors

Dissociative Autoionization in (1+2)-photon Above Threshold Excitation of H2 Molecules

We have theoretically studied the effect of dissociative autoionization on the photoelectron energy spectrum in (1+2)-photon above threshold ionization(ATI) of H2 molecules. We have considered excitation from the ground state X-singlet-Sigma-g+(v=0,j) to the doubly excited autoionizing states of singlet-Sigma-u+ and singlet-Pi-u+ symmetry, via the intermediate resonant B-singlet-Sigma-u+(v=5,j) states. We have shown that the photoelectron energy spectrum is oscillatory in nature and shows three distinct peaks above the photoelectron energy 0.7 eV. This feature has been observed in a recent experiment by Rottke et al, J. Phys. B, Vol. 30, p-4049 (1997).Comment: 11 pages and 4 figure

Is the HCV-HIV co-infection prevalence amongst injecting drug users a marker for the level of sexual and injection related HIV transmission?

BACKGROUND: Amongst injecting drug users (IDUs), HIV is transmitted sexually and parenterally, but HCV is transmitted primarily parenterally. We assess and model the antibody prevalence of HCV amongst HIV-infected IDUs (denoted as HCV-HIV co-infection prevalence) and consider whether it proxies the degree of sexual HIV transmission amongst IDUs. METHODS: HIV, HCV and HCV-HIV co-infection prevalence data amongst IDU was reviewed. An HIV/HCV transmission model was adapted. Multivariate model uncertainty analyses determined whether the model's ability to replicate observed data trends required the inclusion of sexual HIV transmission. The correlation between the model's HCV-HIV co-infection prevalence and estimated proportion of HIV infections due to injecting was evaluated. RESULTS: The median HCV-HIV co-infection prevalence (prevalence of HCV amongst HIV-infected IDUs) was 90% across 195 estimates from 43 countries. High HCV-HIV co-infection prevalences (>80%) occur in most (75%) settings, but can be lower in settings with low HIV prevalence (0.75). The model without sexual HIV transmission reproduced some data trends but could not reproduce any epidemics with high HIV/HCV prevalence ratios (>0.85) or low HCV-HIV co-infection prevalence (10%. The model with sexual HIV transmission reproduced data trends more closely. The proportion of HIV infections due to injecting correlated with HCV-HIV co-infection prevalence; suggesting that up to 80/60/90%. CONCLUSION: Substantial sexual HIV transmission may occur in many IDU populations; HCV-HIV co-infection prevalence could signify its importance

Development of an inducible mouse model of iRFP713 to track recombinase activity and tumour development in vivo

While the use of bioluminescent proteins for molecular imaging is a powerful technology to further our understanding of complex processes, fluorescent labeling with visible light fluorescent proteins such as GFP and RFP suffers from poor tissue penetration and high background autofluorescence. To overcome these limitations, we generated an inducible knock-in mouse model of iRFP713. This model was used to assess Cre activity in a Rosa Cre-ER background and quantify Cre activity upon different tamoxifen treatments in several organs. We also show that iRFP can be readily detected in 3D organoid cultures, FACS analysis and in vivo tumour models. Taken together we demonstrate that iRFP713 is a progressive step in in vivo imaging and analysis that widens the optical imaging window to the near-infrared spectrum, thereby allowing deeper tissue penetration, quicker image acquisition without the need to inject substrates and a better signal to background ratio in genetically engineered mouse models (GEMMs)

Tuberculosis from Mycobacterium bovis in Binational Communities, United States

The incidence in San Diego is increasing and is concentrated mostly in persons of Mexican origin

BLACK HOLE MULTIPLETS AND SPONTANEOUS BREAKING OF LOCAL SUPERSYMMETRY

We classify states saturating a double or a single supersymmetric positivity bound of a four-dimensional N=4 supersymmetry. The massive four-dimensional double-bound states (Bogomolny states) are shown to form a light-like representation of ten-dimensional supersymmetry. The single-bound states form a massive representation (centrino multiplet) of a four-dimensional supersymmetry. The first component of the centrino multiplet is identified with extreme black holes with regular horizon which have one quarter of unbroken supersymmetry. The centrino multiplet includes a massive spin 3/2 state, the centrino, as a highest spin state. Existence of massive black hole supermultiplets may affect the massless sector of the theory. Assuming that gluino condensate is formed one can study its properties. The bilinear combination of covariantly constant Killing spinors supplies the possible form for a gluino condensate. The condensate has null properties, does not introduce a cosmological constant, and may lead to a spontaneous breaking of local supersymmetry. This suggests that centrino may provide a consistent super-Higgs mechanism.Comment: 15 pages, LaTe

Border Crossing to Inject Drugs in Mexico Among Injection Drug Users in San Diego, California

We examined correlates of ever injecting drugs in Mexico among residents of San Diego, California. From 2007 to 2010, injecting drug users (IDUs) in San Diego underwent an interviewer-administered survey. Logistic regression identified correlates of injection drug use in Mexico. Of 302 IDUs, 38% were Hispanic, 72% male and median age was 37; 27% ever injected in Mexico; 43% reported distributive syringe sharing there. Factors independently associated with ever injecting drugs in Mexico included being younger at first injection, injecting heroin, distributive syringe sharing at least half of the time, and transporting drugs over the last 6 months. One-quarter of IDUs reported ever injecting drugs in Mexico, among whom syringe sharing was common, suggesting possible mixing between IDUs in the Mexico-US border region. Prospective studies should monitor trends in cross-border drug use in light of recent Mexican drug policy reforms partially decriminalizing drug possession

Differential Effects of Migration and Deportation on HIV Infection among Male and Female Injection Drug Users in Tijuana, Mexico

HIV prevalence is rising, especially among high risk females in Tijuana, Baja California, a Mexico-US border city situated on major migration and drug trafficking routes. We compared factors associated with HIV infection among male and female injection drug users (IDUs) in Tijuana in an effort to inform HIV prevention and treatment programs. IDUs aged ≥18 years were recruited using respondent-driven sampling and underwent testing for HIV, syphilis and structured interviews. Logistic regression identified correlates of HIV infection, stratified by gender. Among 1056 IDUs, most were Mexican-born but 67% were born outside Tijuana. Reasons for moving to Tijuana included deportation from the US (56% for males, 29% for females), and looking for work/better life (34% for females, 15% for males). HIV prevalence was higher in females versus males (10.2% vs. 3.5%, p = 0.001). Among females (N = 158), factors independently associated with higher HIV prevalence included younger age, lifetime syphilis infection and living in Tijuana for longer durations. Among males (N = 898), factors independently associated with higher HIV prevalence were syphilis titers consistent with active infection, being arrested for having ‘track-marks’, having larger numbers of recent injection partners and living in Tijuana for shorter durations. An interaction between gender and number of years lived in Tijuana regressed on HIV infection was significant (p = 0.03). Upon further analysis, deportation from the U.S. explained the association between shorter duration lived in Tijuana and HIV infection among males; odds of HIV infection were four-fold higher among male injectors deported from the US, compared to other males, adjusting for all other significant correlates (p = 0.002). Geographic mobility has a profound influence on Tijuana's evolving HIV epidemic, and its impact is significantly modified by gender. Future studies are needed to elucidate the context of mobility and HIV acquisition in this region, and whether US immigration policies adversely affect HIV risk

Social and Structural Factors Associated with HIV Infection among Female Sex Workers Who Inject Drugs in the Mexico-US Border Region

BACKGROUND: FSWs who inject drugs (FSW-IDUs) can acquire HIV through high risk sexual and injection behaviors. We studied correlates of HIV infection among FSW-IDUs in northern Mexico, where sex work is quasi-legal and syringes can be legally obtained without a prescription. METHODS: FSW-IDUs>18 years old who reported injecting drugs and recent unprotected sex with clients in Tijuana and Ciudad Juarez underwent surveys and HIV/STI testing. Logistic regression identified correlates of HIV infection. RESULTS: Of 620 FSW-IDUs, prevalence of HIV, gonorrhea, Chlamydia, trichomonas, syphilis titers ≥1:8, or any of these infections was 5.3%, 4%, 13%, 35%, 10% and 72%, respectively. Compared to other FSW-IDUs, HIV-positive women were more likely to: have syphilis titers ≥1:8 (36% vs. 9%, p<0.001), often/always inject drugs with clients (55% vs. 32%, p = 0.01), and experience confiscation of syringes by police (49% vs. 28%, p = 0.02). Factors independently associated with HIV infection were syphilis titers ≥1:8, often/always injecting with clients and police confiscation of syringes. Women who obtained syringes from NEPs (needle exchange programs) within the last month had lower odds of HIV infection associated with active syphilis, but among non-NEP attenders, the odds of HIV infection associated with active syphilis was significantly elevated. CONCLUSIONS: Factors operating in both the micro-social environment (i.e., injecting drugs with clients) and policy environment (i.e., having syringes confiscated by police, attending NEPs) predominated as factors associated with risk of HIV infection, rather than individual-level risk behaviors. Interventions should target unjustified policing practices, clients' risk behaviors and HIV/STI prevention through NEPs

Supersymmetry reduction of N-extended supergravities in four dimensions

We consider the possible consistent truncation of N-extended supergravities to lower N' theories. The truncation, unlike the case of N-extended rigid theories, is non trivial and only in some cases it is sufficient just to delete the extra N-N' gravitino multiplets. We explore different cases (starting with N=8 down to N'\geq 2) where the reduction implies restrictions on the matter sector. We perform a detailed analysis of the interesting case N=2 \to N=1. This analysis finds applications in different contexts of superstring and M-theory dynamics.Comment: Version published on JHE