In Pursuit of Indigenous Intellectual Justice: The Cultural and Health Institutional Review Boards of the Eastern Band of Cherokee Indians

Since the inception of Cultural and Health Tribal institutional review boards (IRBs) for the Eastern Band of Cherokee Indians (EBCI) in 1998, formal proposals for academic research among the Tribe has averaged about 50 per year. The EBCI needed a formal process to accomplish three things: 1) review requests to protect the Tribe’s interests, 2) ensure the research was culturally appropriate and respectful, and 3) to ensure data control by the Tribe, exercising their right to intellectual sovereignty. Also, this formal review process was necessary due to receipt of federal grant funds to conduct research involving human subjects. It is expected by the IRB members that researchers whose research has been approved by the respective EBCI IRB would fully comply with tribal expectations that reflect the goals of sovereignty and self-determination

The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10^{-8}; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely mediator of intergenerational effects of metabolic traits

Creatures Great and SMAL: Recovering the Shape and Motion of Animals from Video

We present a system to recover the 3D shape and motion of a wide variety of quadrupeds from video. The system comprises a machine learning front-end which predicts candidate 2D joint positions, a discrete optimization which finds kinematically plausible joint correspondences, and an energy minimization stage which fits a detailed 3D model to the image. In order to overcome the limited availability of motion capture training data from animals, and the difficulty of generating realistic synthetic training images, the system is designed to work on silhouette data. The joint candidate predictor is trained on synthetically generated silhouette images, and at test time, deep learning methods or standard video segmentation tools are used to extract silhouettes from real data. The system is tested on animal videos from several species, and shows accurate reconstructions of 3D shape and pose.GlaxoSmithKlin

Carbon and climate system coupling on timescales from the Precambrian to the Anthropocene

Author Posting. © Annual Reviews, 2007. This is the author's version of the work. It is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 32 (2007): 31-66, doi:10.1146/annurev.energy.32.041706.124700.The global carbon and climate systems are closely intertwined, with biogeochemical processes responding to and driving climate variations. Over a range of geological and historical time-scales, warmer climate conditions are associated with higher atmospheric levels of CO2, an important climate-modulating greenhouse gas. The atmospheric CO2-temperature relationship reflects two dynamics, the planet’s climate sensitivity to a perturbation in atmospheric CO2 and the stability of non-atmospheric carbon reservoirs to evolving climate. Both exhibit non-linear behavior, and coupled carbon-climate interactions have the potential to introduce both stabilizing and destabilizing feedback loops into the Earth System. Here we bring together evidence from a wide range of geological, observational, experimental and modeling studies on the dominant interactions between the carbon cycle and climate. The review is organized by time-scale, spanning interannual to centennial climate variability, Holocene millennial variations and Pleistocene glacial-interglacial cycles, and million year and longer variations over the Precambrian and Phanerozoic. Our focus is on characterizing and, where possible quantifying, the emergent behavior internal to the coupled carbon-climate system as well as the responses of the system to external forcing from tectonics, orbital dynamics, catastrophic events, and anthropogenic fossil fuel emissions. While there are many unresolved uncertainties and complexity in the carbon cycle, one emergent property is clear across time scales: while CO2 can increase in the atmosphere quickly, returning to lower levels through natural processes is much slower, so the consequences of the human perturbation will far outlive the emissions that caused them.S. Doney acknowledges support from the NSF Geosciences Carbon and Water program (NSF ATM-0628582) and the WHOI W. Van Alan Clark Sr. Chair. D. Schimel acknowledges support from the NSF Biocomplexity in the Environment program (NSF EAR-0321918)

The intestinal expulsion of the roundworm Ascaris suum is associated with eosinophils, intra-epithelial T cells and decreased intestinal transit time

Ascaris lumbricoides remains the most common endoparasite in humans, yet there is still very little information available about the immunological principles of protection, especially those directed against larval stages. Due to the natural host-parasite relationship, pigs infected with A. suum make an excellent model to study the mechanisms of protection against this nematode. In pigs, a self-cure reaction eliminates most larvae from the small intestine between 14 and 21 days post infection. In this study, we investigated the mucosal immune response leading to the expulsion of A. suum and the contribution of the hepato-tracheal migration. Self-cure was independent of previous passage through the liver or lungs, as infection with lung stage larvae did not impair self-cure. When animals were infected with 14-day-old intestinal larvae, the larvae were being driven distally in the small intestine around 7 days post infection but by 18 days post infection they re-inhabited the proximal part of the small intestine, indicating that more developed larvae can counter the expulsion mechanism. Self-cure was consistently associated with eosinophilia and intra-epithelial T cells in the jejunum. Furthermore, we identified increased gut movement as a possible mechanism of self-cure as the small intestinal transit time was markedly decreased at the time of expulsion of the worms. Taken together, these results shed new light on the mechanisms of self-cure that occur during A. suum infections

Tuna Longline Fishing around West and Central Pacific Seamounts

BACKGROUND: Seamounts have been identified as aggregating locations for pelagic biodiversity including tuna; however the topography and prevailing oceanography differ between seamounts and not all are important for tuna. Although a relatively common feature in oceanic ecosystems, little information is available that identifies those that are biologically important. Improved knowledge offers opportunities for unique management of these areas, which may advance the sustainable management of oceanic resources. In this study, we evaluate the existence of an association between seamounts and tuna longline fisheries at the ocean basin scale, identify significant seamounts for tuna in the western and central Pacific Ocean, and quantify the seamount contribution to the tuna longline catch. METHODOLOGY/PRINCIPAL FINDINGS: We use data collected for the Western and Central Pacific Ocean for bigeye, yellowfin, and albacore tuna at the ocean basin scale. GLMs were applied to a coupled dataset of longline fisheries catch and effort, and seamount location information. The analyses show that seamounts may be associated with an annual longline combined catch of 35 thousand tonnes, with higher catch apparent for yellowfin, bigeye, and albacore tuna on 17%, 14%, and 14% of seamounts respectively. In contrast 14%, 18%, and 20% of seamounts had significantly lower catches for yellowfin, bigeye and albacore tuna respectively. Studying catch data in relation to seamount positions presents several challenges such as bias in location of seamounts, or lack of spatial resolution of fisheries data. Whilst we recognize these limitations the criteria used for detecting significant seamounts were conservative and the error in identification is likely to be low albeit unknown. CONCLUSIONS/SIGNIFICANCE: Seamounts throughout the study area were found to either enhance or reduce tuna catch. This indicates that management of seamounts is important Pacific-wide, but management approaches must take account of local conditions. Management of tuna and biodiversity resources in the region would benefit from considering such effects

Reducing bias through directed acyclic graphs

<p>Abstract</p> <p>Background</p> <p>The objective of most biomedical research is to determine an unbiased estimate of effect for an exposure on an outcome, i.e. to make causal inferences about the exposure. Recent developments in epidemiology have shown that traditional methods of identifying confounding and adjusting for confounding may be inadequate.</p> <p>Discussion</p> <p>The traditional methods of adjusting for "potential confounders" may introduce conditional associations and bias rather than minimize it. Although previous published articles have discussed the role of the causal directed acyclic graph approach (DAGs) with respect to confounding, many clinical problems require complicated DAGs and therefore investigators may continue to use traditional practices because they do not have the tools necessary to properly use the DAG approach. The purpose of this manuscript is to demonstrate a simple 6-step approach to the use of DAGs, and also to explain why the method works from a conceptual point of view.</p> <p>Summary</p> <p>Using the simple 6-step DAG approach to confounding and selection bias discussed is likely to reduce the degree of bias for the effect estimate in the chosen statistical model.</p

The interaction between a sexually transferred steroid hormone and a female protein regulates oogenesis in the malaria mosquito anopheles gambiae

Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that the mating-dependent pathway of egg development in these mosquitoes is regulated by the interaction between the steroid hormone 20-hydroxy-ecdysone (20E) transferred by males during copulation and a female Mating-Induced Stimulator of Oogenesis (MISO) protein. RNAi silencing of MISO abolishes the increase in oogenesis caused by mating in blood-fed females, causes a delay in oocyte development, and impairs the function of male-transferred 20E. Co-immunoprecipitation experiments show that MISO and 20E interact in the female reproductive tract. Moreover MISO expression after mating is induced by 20E via the Ecdysone Receptor, demonstrating a close cooperation between the two factors. Male-transferred 20E therefore acts as a mating signal that females translate into an increased investment in egg development via a MISO-dependent pathway. The identification of this male–female reproductive interaction offers novel opportunities for the control of mosquito populations that transmit malaria

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures