Alien Registration- Clark, Kathleen (Fort Fairfield, Aroostook County)

https://digitalmaine.com/alien_docs/35727/thumbnail.jp

Candidate Sequence Variants and Fetal Hemoglobin in Children with Sickle Cell Disease Treated with Hydroxyurea

Fetal hemoglobin level is a heritable complex trait that strongly correlates with the clinical severity of sickle cell disease. Only few genetic loci have been identified as robustly associated with fetal hemoglobin in patients with sickle cell disease, primarily adults. The sole approved pharmacologic therapy for this disease is hydroxyurea, with effects largely attributable to induction of fetal hemoglobin. In a multi-site observational analysis of children with sickle cell disease, candidate single nucleotide polymorphisms associated with baseline fetal hemoglobin levels in adult sickle cell disease were examined in children at baseline and induced by hydroxyurea therapy. For baseline levels, single marker analysis demonstrated significant association with BCL11A and the beta and epsilon globin loci (HBB and HBE, respectively), with an additive attributable variance from these loci of 23%. Among a subset of children on hydroxyurea, baseline fetal hemoglobin levels explained 33% of the variance in induced levels. The variant in HBE accounted for an additional 13% of the variance in induced levels, while variants in the HBB and BCL11A loci did not contribute beyond baseline levels. These findings clarify the overlap between baseline and hydroxyurea-induced fetal hemoglobin levels in pediatric disease. Studies assessing influences of specific sequence variants in these and other genetic loci in larger populations and in unusual hydroxyurea responders are needed to further understand the maintenance and therapeutic induction of fetal hemoglobin in pediatric sickle cell disease

Reframing conservation physiology to be more inclusive, integrative, relevant and forward-looking: Reflections and a horizon scan

Applying physiological tools, knowledge and concepts to understand conservation problems (i.e. conservation physiology) has becomecommonplace and confers an ability to understand mechanistic processes,develop predictive models and identify cause-and-effect relationships. Conservation physiology is making contributions to conservation solutions; the number of \u27success stories\u27 is growing, but there remain unexplored opportunities for which conservation physiology shows immense promise and has the potential to contribute to major advances in protecting and restoring biodiversity. Here, we consider howconservation physiology has evolved with a focus on reframing the discipline to be more inclusive and integrative.Using a \u27horizon scan\u27,we further exploreways in which conservation physiology can be more relevant to pressing conservation issues of today (e.g. addressing the Sustainable Development Goals; delivering science to support the UN Decade on Ecosystem Restoration), aswell as more forward-looking to inform emerging issues and policies for tomorrow. Our horizon scan provides evidence that, as the discipline of conservation physiology continues to mature, it provides a wealth of opportunities to promote integration, inclusivity and forward-thinking goals that contribute to achieving conservation gains. To advance environmentalmanagementand ecosystemrestoration,we need to ensure that the underlying science (such as that generated by conservation physiology) is relevant with accompanying messaging that is straightforward and accessible to end users

One hundred research questions in conservation physiology for generating actionable evidence to inform conservation policy and practice

Environmental change and biodiversity loss are but two of the complex challenges facing conservation practitioners and policy makers. Relevant and robust scientific knowledge is critical for providing decision-makers with the actionable evidence needed to inform conservation decisions. In the Anthropocene, science that leads to meaningful improvements in biodiversity conservation, restoration and management is desperately needed. Conservation Physiology has emerged as a discipline that is well-positioned to identify the mechanisms underpinning population declines, predict responses to environmental change and test different in situ and ex situ conservation interventions for diverse taxa and ecosystems. Here we present a consensus list of 10 priority research themes. Within each theme we identify specific research questions (100 in total), answers to which will address conservation problems and should improve the management of biological resources. The themes frame a set of research questions related to the following: (i) adaptation and phenotypic plasticity; (ii) human-induced environmental change; (iii) human-wildlife interactions; (iv) invasive species; (v) methods, biomarkers and monitoring; (vi) policy, engagement and communication; (vii) pollution; (viii) restoration actions; (ix) threatened species; and (x) urban systems. The themes and questions will hopefully guide and inspire researchers while also helping to demonstrate to practitioners and policy makers the many ways in which physiology can help to support their decisions

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Reframing conservation physiology to be more inclusive, integrative, relevant and forward-looking: reflections and a horizon scan

Applying physiological tools, knowledge and concepts to understand conservation problems (i.e. conservation physiology) has become common place and confers an ability to understand mechanistic processes, develop predictive models and identify cause-and-effect relationships. Conservation physiology is making contributions to conservation solutions; the number of 'success stories' is growing, but there remain unexplored opportunities for which conservation physiology shows immense promise and has the potential to contribute to major advances in protecting and restoring biodiversity. Here, we consider howconservation physiology has evolved with a focus on reframing the discipline to be more inclusive and integrative. Using a 'horizon scan', we further exploreways in which conservation physiology can be more relevant to pressing conservation issues of today (e.g. addressing the Sustainable Development Goals; delivering science to support the UN Decade on Ecosystem Restoration), as well as more forward-looking to inform emerging issues and policies for tomorrow. Our horizon scan provides evidence that, as the discipline of conservation physiology continues to mature, it provides a wealth of opportunities to promote integration, inclusivity and forward-thinking goals that contribute to achieving conservation gains. To advance environmenta lmanagement and ecosystem restoration, we need to ensure that the underlying science (such as that generated by conservation physiology) is relevant with accompanying messaging that is straightforward and accessible to end users

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries