Spatial Ecology and Habitat Use of the Endangered Iguana, \u3ci\u3eCyclura lewisi\u3c/i\u3e, in an Unnatural Setting

The Grand Cayman blue iguana, Cyclura lewisi, is critically endangered with an estimated 7-25 individuals remaining in the wild. This taxon is in need of intensive management, but little has been published on any aspect of its biology, and the remaining wild population is too small to be the basis of a research program. In order to aid in the conservation of this and other iguanid species, I investigated the spatial ecology and habitat use of a population of captive-bred, released C. lewisi in a botanic park on Grand Cayman. Movements and locations of these iguanas were verified through routine monitoring, radio tracking, and focal animal observation in the mating and post-mating seasons of 2001 and 2002. Male iguanas had larger home ranges and moved greater distances than did females during the breeding season. Although home range size varied by two orders of magnitude among individuals, larger maximum home range size estimates were found in this population than have been previously reported for any species of Cyclura. Radio tracking revealed that several iguanas, especially males during the breeding season, used areas outside of the park where they are vulnerable to increased predation, death by vehicle, and hunting or collection by humans. The reintroduced iguanas in this study preferred modified habitat to unmodified habitat throughout the year, both within the landscape and within their home ranges. Potential threats in modified and human-occupied habitats that were identified in this study included uncontrolled supplemental feeding, predation by nonnative predators, and vehicular collision. Iguanas frequently used artificial retreats and nests, and commonly occupied retreats in modified areas. The use of modified habitats and artificial retreats by reintroduced C. lewisi is encouraging, because this species may depend on disturbed landscapes and supplemental resources for future survival

Out of Florida: mtDNA reveals patterns of migration and Pleistocene range expansion of the Green Anole lizard (Anolis carolinensis)

Anolis carolinensis is an emerging model species and the sole member of its genus native to the United States. Considerable morphological and physiological variation has been described in the species, and the recent sequencing of its genome makes it an attractive system for studies of genome variation. To inform future studies of molecular and phenotypic variation within A. carolinensis, a rigorous account of intraspecific population structure and relatedness is needed. Here, we present the most extensive phylogeographic study of this species to date. Phylogenetic analyses of mitochondrial DNA sequence data support the previous hypothesis of a western Cuban origin of the species. We found five well-supported, geographically distinct mitochondrial haplotype clades throughout the southeastern United States. Most Florida populations fall into one of three divergent clades, whereas the vast majority of populations outside Florida belong to a single, shallowly diverged clade. Genetic boundaries do not correspond to major rivers, but may reflect effects of Pleistocene glaciation events and the Appalachian Mountains on migration and expansion of the species. Phylogeographic signal should be examined using nuclear loci to complement these findings.Organismic and Evolutionary Biolog

Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation

Background Allergic disease affects 30% to 40% of the world's population, and its development is determined by the interplay between environmental and inherited factors. Air pollution, primarily consisting of diesel exhaust emissions, has increased at a similar rate to allergic disease. Exposure to diesel exhaust may play a role in the development and progression of allergic disease, in particular allergic respiratory disease. One potential mechanism underlying the connection between air pollution and increased allergic disease incidence is DNA methylation, an epigenetic process with the capacity to integrate gene-environment interactions. Objective We sought to investigate the effect of allergen and diesel exhaust exposure on bronchial epithelial DNA methylation. Methods We performed a randomized crossover-controlled exposure study to allergen and diesel exhaust in humans, and measured single-site (CpG) resolution global DNA methylation in bronchial epithelial cells. Results Exposure to allergen alone, diesel exhaust alone, or allergen and diesel exhaust together (coexposure) led to significant changes in 7 CpG sites at 48 hours. However, when the same lung was exposed to allergen and diesel exhaust but separated by approximately 4 weeks, significant changes in more than 500 sites were observed. Furthermore, sites of differential methylation differed depending on which exposure was experienced first. Functional analysis of differentially methylated CpG sites found genes involved in transcription factor activity, protein metabolism, cell adhesion, and vascular development, among others. Conclusions These findings suggest that specific exposures can prime the lung for changes in DNA methylation induced by a subsequent insult

Rationale, Study Design, and Cohort Characteristics for the Markers for Environmental Exposures (MEE) Study.

Environmental factors have been linked to many diseases and health conditions, but reliable assessment of environmental exposures is challenging. Developing biomarkers of environmental exposures, rather than relying on self-report, will improve our ability to assess the association of such exposures with disease. Epigenetic markers, most notably DNA methylation, have been identified for some environmental exposures, but identification of markers for additional exposures is still needed. The rationale behind the Markers for Environmental Exposures (MEE) Study was to (1) identify biomarkers, especially epigenetic markers, of environmental exposures, such as pesticides, air/food/water contaminants, and industrial chemicals that are commonly encountered in the general population; and (2) support the study of potential relationships between environmental exposures and health and health-related factors. The MEE Study is a cross-sectional study with potential for record linkage and follow-up. The well-characterized cohort of 400 postmenopausal women has generated a repository of biospecimens, including blood, urine, and saliva samples. Paired data include an environmental exposures questionnaire, a breast health questionnaire, dietary recalls, and a food frequency questionnaire. This work describes the rationale, study design, and cohort characteristics of the MEE Study. In addition to our primary research goals, we hope that the data and biorepository generated by this study will serve as a resource for future studies and collaboration

Complete genome sequences of two Helicobacter pylori strains from a Canadian Arctic Aboriginal community

We report here the complete genome sequences of two Amerind Helicobacter pylori strains from Aklavik, Northwest Territories, Canada. One strain contains extra iron-cofactored urease genes and ~140 rearrangements in its chromosome relative to other described strains (typically differing from one another by <10 rearrangements), suggesting that it represents a novel lineage of H. pylori

MHC-I genotype and tumor mutational burden predict response to immunotherapy.

BackgroundImmune checkpoint blockade (ICB) with antibodies inhibiting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) (or its ligand (PD-L1)) can stimulate immune responses against cancer and have revolutionized the treatment of tumors. The influence of host germline genetics and its interaction with tumor neoantigens remains poorly defined. We sought to determine the interaction between tumor mutational burden (TMB) and the ability of a patient's major histocompatibility complex class I (MHC-I) to efficiently present mutated driver neoantigens in predicting response ICB.MethodsComprehensive genomic profiling was performed on 83 patients with diverse cancers treated with ICB to determine TMB and human leukocyte antigen-I (HLA-I) genotype. The ability of a patient's MHC-I to efficiently present mutated driver neoantigens (defined by the Patient Harmonic-mean Best Rank (PHBR) score (with lower PHBR indicating more efficient presentation)) was calculated for each patient.ResultsThe median progression-free survival (PFS) for PHBR score &lt; 0.5 vs. ≥ 0.5 was 5.1 vs. 4.4 months (P = 0.04). Using a TMB cutoff of 10 mutations/mb, the stable disease &gt; 6 months/partial response/complete response rate, median PFS, and median overall survival (OS) of TMB high/PHBR high vs. TMB high/PHBR low were 43% vs. 78% (P = 0.049), 5.8 vs. 26.8 months (P = 0.03), and 17.2 months vs. not reached (P = 0.23), respectively. These findings were confirmed in an independent validation cohort of 32 patients.ConclusionsPoor presentation of driver mutation neoantigens by MHC-I may explain why some tumors (even with a high TMB) do not respond to ICB

Association of interleukin-6 with suicidal ideation in veterans: a longitudinal perspective

IntroductionStudies showing associations between inflammation in suicide are typically cross-sectional. Present study investigated how cytokine levels track with suicidal ideation and severity longitudinally.MethodsVeterans with a diagnosis of major depressive disorder (MDD) with or without suicide attempt history (MDD/SA n = 38, MDD/NS n = 41) and non-psychiatric non-attempter controls (HC n = 33) were recruited, MDD/SA and HC groups were followed longitudinally at 3 months and 6 months. Blood plasma was collected and processed using Luminex Immunology Multiplex technology.ResultsSignificant differences in depression severity (BDI) and suicidal ideation severity (SSI) were observed across all groups at study entry, wherein MDD/SA group had the highest scores followed by MDD/NS and HC, respectively. Cytokines IL-1β, IL-4, TNF-α, IFN-γ, and IL-6 were examined at study entry and longitudinally, with IL6 levels differing significantly across the groups (p = 0.0123) at study entry. Significant differences in changes in cytokine levels between depressed attempters and the control group were detected for IL-6 (interaction F1,91.77 = 5.58, p = 0.0203) and TNF-α (F1,101.73 = 4.69, p = 0.0327). However, only depressed attempters showed a significant change, in IL-6 and TNF-α levels, decreasing over time [IL-6: b = −0.04, 95% CI = (−0.08, −0.01), p = 0.0245 and TNF-α: b = −0.02, 95% CI = (−0.04, −0.01), p = 0.0196]. Although IL-6 levels were not predictive of suicidal ideation presence [OR = 1.34, 95% CI = (0.77, 2.33), p = 0.3067], IL-6 levels were significantly associated with suicidal ideation severity (b = 0.19, p = 0.0422).DiscussionIL-6 was not associated with presence of suicidal ideation. IL-6 however, was associated with severity of ideation, suggesting that IL-6 may be useful in clinical practice, as an objective marker of heightened suicide risk

Primary peritoneal and ovarian cancers: an epidemiological comparative analysis

We performed case–control analyses using data from the North Carolina Ovarian Cancer Study to determine risk factors that distinguish primary peritoneal cancer (PPC) from epithelial ovarian cancer (EOC). Our risk factor analyses were restricted to invasive serous cancers including 495 EOC cases, 62 PPC cases and 1,086 control women. Logistic regression analyses were used to calculate adjusted odds ratios and 95% confidence intervals for risk factor associations. Although many case–control associations for the invasive serous PPC cases were similar to those of the invasive serous EOC cases, some differences were observed including a twofold increase in risk of invasive serous PPC in women who were ≥35 years at last pregnancy, whereas a decreased risk was observed for invasive serous EOC risk. We could not confirm a previous report of an association between tubal ligation and PPC, a factor consistently associated with a decreased risk of EOC. The difference in the risk factor associations between invasive serous PPC and EOC cancers suggests divergent molecular development of peritoneal and ovarian cancers. A larger study to determine risk factors for invasive serous PPC is warranted