Systematically Variable Planktonic Carbon Metabolism Along a Land-To-Lake Gradient in a Great Lakes Coastal Zone

During the summers of 2002–2013, we measured rates of carbon metabolism in surface waters of six sites across a land-to-lake gradient from the upstream end of drowned river-mouth Muskegon Lake (ML) (freshwater estuary) to 19 km offshore in Lake Michigan (LM) (a Great Lake). Despite considerable inter-year variability, the average rates of gross production (GP), respiration (R) and net production (NP) across ML (604 ± 58, 222 ± 22 and 381 ± 52 µg C L−1 day−1, respectively) decreased steeply in the furthest offshore LM site (22 ± 3, 55 ± 17 and −33 ± 15 µg C L−1day−1, respectively). Along this land-to-lake gradient, GP decreased by 96 ± 1%, whereas R only decreased by 75 ± 9%, variably influencing the carbon balance along this coastal zone. All ML sites were consistently net autotrophic (mean GP:R = 2.7), while the furthest offshore LM site was net heterotrophic (mean GP:R = 0.4). Our study suggests that pelagic waters of this Great Lakes coastal estuary are net carbon sinks that transition into net carbon sources offshore. Reactive and dynamic estuarine coastal zones everywhere may contribute similarly to regional and global carbon cycles

Association of Chronic Hepatitis C Infection With T-Cell Phenotypes in HIV-Negative and HIV-Positive Women

Background: Hepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4 + count). Methods: We used fresh blood from HIV-positive and at-risk HIVnegative women, with and without chronic HCV, to measure percentages of activated CD4 + and CD8 + T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic. Results: In multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4 + (P = 0.03), 33% more EM CD4 + (P = 0.0002), and 37% fewer central memory CD8 + (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4 + among HCV viremic women. Furthermore, the association with EM CD4 + among HIV positives was limited to individuals with diminished immune status (total CD4 + count #500 cells/mL), as were associations of HCV viremia with higher percentages of activated CD4 + and Tregs. Among HIV positives with high CD4 + count, no significant associations were observed. Conclusions: These data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4 + count

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Throug

Invasive Cervical Cancer Risk Among HIV-Infected Women: A North American Multicohort Collaboration Prospective Study

HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection – the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women

Changing Habitat Use Associated with Distributional Shifts of Wintering Raptors

There is widespread evidence that multiple drivers of global change, such as habitat degradation, invasive species, and climate change, are influencing wildlife. Understanding how these drivers interact with and affect species may be difficult because outcomes depend on the magnitude and duration of environmental change and the life history of the organism. In addition, various environmental drivers may be evaluated and managed at different spatial scales. We used a historical dataset from 1991 to 1994 and current information from 2010 to 2012 to examine whether occupancy patterns of wintering raptors were consistent with regional changes in distribution or habitat conditions within a local management unit, the Morley Nelson Snake River Birds of Prey National Conservation Area (NCA). We predicted that if local populations reflected regional shifts, then rates of raptor occupancy within the NCA would be higher compared to historical estimates and birds would use different habitats compared to historical use. Alternatively, if local populations were determined by habitat conditions, then we predicted that occupancy rate of raptors within the NCA would be lower compared to historical estimates and current habitat use would be consistent with historical use. Results support the hypothesis that northward distributional shifts influenced wintering raptor populations in southwest Idaho to a greater extent than local habitat conditions. Wintering raptors had higher occupancy rates in 2010–2012 compared to 1991–1994, whereas invasive grasses have increased and native shrubs have decreased suggesting that habitat suitability for raptors has declined over time. On the species level, changes in habitat use were associated with greater increases in occupancy rates in 2010–2012 compared to 1991–1994. Organisms flexible in their habitat use may be better able to respond to continental forces driving distribution shifts. Conversely, habitat or prey specialists may be poorly equipped to handle such rapid, large-scale global change. Further, Grinnellian niche models predicting species response to change by mapping current habitat use to forecasted vegetation maps should consider plasticity in habitat use and changes in the cost-benefits of life-history strategies

Molecular profiling of breast and lung cancer in women with HIV reveals high tumor mutational burden

ObjectiveThis study compared the mutation profile and tumor mutational burden (TMB) in women with HIV (WWH) diagnosed with lung adenocarcinoma (n = 8) or breast ductal neoplasm (n = 13) who were enrolled into the Women's Interagency HIV Study (WIHS).DesignPrevious studies tended to focus on single institutions based on sample availability. This study is based on a representative, multicenter cohort that represents the racial and ethnic composition of women with HIV in the United States.MethodsThe study sequenced the complete human exome of n = 26 cancer samples from HIV-positive women, using Ion torrent next-generation sequencing. The study cohort was compared with a HIV-negative cohort obtained from the Genomic Data Commons Data Portal of the NCI.ResultsThere were no differences in known cancer mutations between breast cancer and lung cancer that developed in WWH and those that developed in HIV-negative (HIV-) women; however, WWH presented a significantly higher TMB in comparison to HIV- patients. Seventy-five percent of lung cancers and 61% of breast cancers were defined as TMB-high (more than 10 mutation/mb of DNA).ConclusionThis study affirms the recommendation that WWH be included in clinical trials of novel treatments for these cancers. Although these data are preliminary, the high TMB in WLHV suggests, paradoxically, that this immune challenged population may benefit greatly from immune checkpoint inhibitor therapies

Molecular profiling of breast and lung cancer in women with HIV reveals high tumor mutational burden

This study compared the mutation profile and tumor mutational burden (TMB) in women with HIV (WWH) diagnosed with lung adenocarcinoma (n = 8) or breast ductal neoplasm (n = 13) who were enrolled into the Women's Interagency HIV Study (WIHS). Previous studies tended to focus on single institutions based on sample availability. This study is based on a representative, multicenter cohort that represents the racial and ethnic composition of women with HIV in the United States. The study sequenced the complete human exome of n = 26 cancer samples from HIV-positive women, using Ion torrent next-generation sequencing. The study cohort was compared with a HIV-negative cohort obtained from the Genomic Data Commons Data Portal of the NCI. There were no differences in known cancer mutations between breast cancer and lung cancer that developed in WWH and those that developed in HIV-negative (HIV-) women; however, WWH presented a significantly higher TMB in comparison to HIV- patients. Seventy-five percent of lung cancers and 61% of breast cancers were defined as TMB-high (more than 10 mutation/mb of DNA). This study affirms the recommendation that WWH be included in clinical trials of novel treatments for these cancers. Although these data are preliminary, the high TMB in WLHV suggests, paradoxically, that this immune challenged population may benefit greatly from immune checkpoint inhibitor therapies

Association of Chronic Hepatitis C Infection With T-Cell Phenotypes in HIV-Negative and HIV-Positive Women

BackgroundHepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4⁺ count).MethodsWe used fresh blood from HIV-positive and at-risk HIV-negative women, with and without chronic HCV, to measure percentages of activated CD4⁺ and CD8⁺ T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic.ResultsIn multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4⁺ (P = 0.03), 33% more EM CD4⁺ (P = 0.0002), and 37% fewer central memory CD8⁺ (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4⁺ among HCV viremic women. Furthermore, the association with EM CD4⁺ among HIV positives was limited to individuals with diminished immune status (total CD4⁺ count ≤500 cells/μL), as were associations of HCV viremia with higher percentages of activated CD4⁺ and Tregs. Among HIV positives with high CD4⁺ count, no significant associations were observed.ConclusionsThese data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4v count