207 research outputs found

    Gestating at altitude: How do maternal physiology and evolutionary adaptation influence fetal growth?

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    Lowland mammals, including humans, experience an increased risk for fetal growth restriction (FGR) at high altitudes. FGR is associated with a range of adverse lifetime risks, including lower infant survival. Maternal physiology, such as cardiopulmonary function and nutrient provisioning, has been hypothesized to play an important role in driving altitude-dependent FGR, but strong associations between specific aspects of maternal physiology and FGR at altitude have been difficult to establish. One approach has been to study populations adapted to altitude; highland populations of humans, sheep, and deer mice (Peromyscus maniculatus) mitigate altitude-induced reductions in fetal growth and may thus offer insight into the relevant underlying physiology. We assessed the relationship between measures of maternal physiology and fetal growth outcomes using deer mice derived from highland-adapted and lowland populations that gestated under normoxia or hypobaric hypoxia. At late pregnancy, we measured fetal mass along with an array of physiological measures from dams (e.g., body and organ masses, and blood hematocrit and glucose). Using linear modeling, we assessed the relationships between maternal physiology and fetal growth phenotypes. To investigate the possibility that fetal growth is a function of many incremental changes in physiology, we compressed dimensionality of the maternal physiology data using PCA and then used the reduced dimensions in a linear modeling framework. The results from our study will add to our broader understanding of how maternal physiology shapes fetal growth, and they will help expand our understanding of the physiological systems that contribute to altitude adaptation across mammals

    Competing biosecurity and risk rationalities in the Chittagong poultry commodity chain, Bangladesh

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    This paper anthropologically explores how key actors in the Chittagong live bird trading network perceive biosecurity and risk in relation to avian influenza between production sites, market maker scenes and outlets. They pay attention to the past and the present, rather than the future, downplaying the need for strict risk management, as outbreaks have not been reported frequently for a number of years. This is analysed as ‘temporalities of risk perception regarding biosecurity’, through Black Swan theory, the idea that unexpected events with major effects are often inappropriately rationalized (Taleb in The Black Swan. The impact of the highly improbable, Random House, New York, 2007). This incorporates a sociocultural perspective on risk, emphasizing the contexts in which risk is understood, lived, embodied and experienced. Their risk calculation is explained in terms of social consent, practical intelligibility and convergence of constraints and motivation. The pragmatic and practical orientation towards risk stands in contrast to how risk is calculated in the avian influenza preparedness paradigm. It is argued that disease risk on the ground has become a normalized part of everyday business, as implied in Black Swan theory. Risk which is calculated retrospectively is unlikely to encourage investment in biosecurity and, thereby, points to the danger of unpredictable outlier events

    The Structural Basis for the Increased Immunogenicity of Two HIV-Reverse Transcriptase Peptide Variant/Class I Major Histocompatibility Complexes

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    Designing altered peptide ligands to generate specific immunological reactivity when bound to class I major histocompatibility complexes is important for both therapeutic and prophylactic reasons. We have previously shown that two altered peptides, derived from human immunodeficiency virus (HIV)-reverse transcriptase (RT) residues 309-317, are more immunogenic in vitro than the wild-type peptide. One peptide variant, I1Y, was able to stimulate RT-specific cytotoxic T cells from the blood of three HIV-infected individuals better than the wild-type RT peptide. Both I1Y and I1F peptide variants increase the cell surface half-life of the peptide-class I complex approximately 3-fold over that of the RT peptide but have different immunological activities. These peptides are candidates for the design of vaccines for HIV due to their increased immunogenicity. To understand the basis for the increased cell surface stability compared with wild-type peptide and to understand the differences in T cell recognition between I1Y and I1F, we determined the x-ray crystal structures of the two class I MHC-peptide complexes. These structures indicate that the increased cell surface half-life is due to pi-pi stacking interactions between Trp-167 of HLA-A2.1 and the aromatic P1 residues of I1F and I1Y. Comparison of the structures and modeling potential T cell receptor (TCR) interactions suggests that T cell interactions and immunogenicity are different between I1Y and I1F for two reasons. First, subtle changes in the steric and polar properties of the I1Y peptide affect TCR engagement. Second, water-mediated hydrogen bond interactions between the P1-Tyr and the P4-Glu peptide residues increase peptide side chain rigidity of residues critical for TCR engagement

    “It’s Like the Elephant in the Room” A Qualitative Analysis of Racism in a U.S. High School

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    Identifying and addressing systemic racial oppression in the education system is a key component in confronting pervasive health and economic disparities for Black students. In this qualitative study, we conducted secondary analysis of existing data. Transcripts of interviews and focus group discussions belonged to 21 Black students in a charter school in Michigan in the year 2013. Open access data were downloaded from University of Michigan’s Inter-university Consortium for Political and Social Research (ICPSR) database in 2022. We used an inductive analytic approach to analyze the qualitative data for constructs related to experiences of structural racism. Three constructs that characterized students’ experiences of structural racism in the U.S. education system were found: (a) Lack of Color-conscious Curriculum; (b) Selective Cultural Erasure; and (c) The Demonstration of Racialized Power. For researchers, these data highlight a need for more studies on the effects of structural racism in the U.S. education system on educational, economic, and health outcomes. For administrative and policy makers, the results emphasize the need for educational initiatives that address deeply-rooted structural inequalities in the U.S. education system. This may include adoption of color-conscious curriculum and culturally responsive pedagogy, the utilization of restorative justice practices, and reparations for Black Americans

    Written information about individual medicines for consumers.

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    Medicines are the most common intervention in most health services. As with all treatments, those taking medicines need sufficient information: to enable them to take and use the medicines effectively, to understand the potential harms and benefits, and to allow them to make an informed decision about taking them. Written medicines information, such as a leaflet or provided via the Internet, is an intervention that may meet these purposes

    Engagement with Care, Substance Use, and Adherence to Therapy in HIV/AIDS

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    Engagement with care for those living with HIV is aimed at establishing a strong relationship between patients and their health care provider and is often associated with greater adherence to therapy and treatment (Flickinger, Saha, Moore, and Beach, 2013). Substance use behaviors are linked with lower rates of engagement with care and medication adherence (Horvath, Carrico, Simoni, Boyer, Amico, and Petroli, 2013). This study is a secondary data analysis using a cross-sectional design from a larger randomized controlled trial (n = 775) that investigated the efficacy of a self-care symptom management manual for participants living with HIV. Participants were recruited from countries of Africa and the US. This study provides evidence that substance use is linked with lower self-reported engagement with care and adherence to therapy. Data on substance use and engagement are presented. Clinical implications of the study address the importance of utilizing health care system and policy factors to improve engagement with care

    Geothermal Heat Recovery Complex: Large-Scale, Deep Direct-Use System in a Low-Temperature Sedimentary Basin

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    This feasibility study is the first assessment of geothermal resources in the Illinois Basin (ILB). The breadth of previous, geologic-based research in the ILB supported this thorough determination of geothermal resources in the Mt. Simon Sandstone (MSS) and the techno-economics of establishing a geothermal energy system (GES) at the University of Illinois at Urbana-Champaign (U of IL). An integrated, multi-disciplinary scientific and engineering approach allowed simulations for both the belowground and aboveground components of the GES that would meet the required baseload of 2 MMBtu/hr at the end-user agricultural research facilities (ARFs). This assessment contributes to the broader discussion surrounding the U of IL’s goal to achieve net-zero carbon emissions by 2050. Furthermore, a rigorous evaluation of the ILB’s geological, hydrological, and thermal frameworks facilitated a broader assessment of the feasibility of applying deep direct-use (DDU) technologies at facilities (e.g., military installations, hospitals, and school campuses) in other geographical areas in the ILB, and in other sedimentary basins in midcontinent of the US.U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy, Geothermal Technologies Office Award Number DE-EE0008106Ope

    The Role of Zinc in the Modulation of Neuronal Proliferation and Apoptosis

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    Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G0/G1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis
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