Chronic low-level Pb exposure during development alters proteins involved in energy metabolism in auditory neurons of the brainstem

Low level lead (Pb) exposure is a risk factor for neurological dysfunction including ADHD. How Pb produces these behavioral deficits is unknown, but low-level exposure during development is associated with auditory temporal processing deficits, even though hearing remains normal. Pb disrupts cellular energy metabolism and efficient energy production is crucial for auditory neurons to maintain their high rates of synaptic activity. The voltage dependent ion channel (VDAC) is an ion channel involved in the regulation of mitochondrial physiology and is a critical component in controlling mitochondrial energy production. No studies to date have investigated the effect of Pb on VDAC, therefore the current series of studies examines the interactions between Pb and VDAC. In-vitro studies were used to delineate the effects of Pb on VDAC expression. Both differentiated SH-SY5Y cells and PC-12 cells exposed to 10 μM Pb for 48 h result in a significant decrease in VDAC expression. Exposure to 24 h of hypoxia fails to decrease VDAC expression, suggesting this is a specific effect of Pb. In addition, a corresponding decrease in cellular ATP that is correlated with decreased VDAC expression occurs with Pb. Real-time RT-PCR demonstrated a significant decrease in mRNA levels for VDAC1 isoform, suggesting that Pb decreases VDAC protein expression through decreased transcription. A proteomics approach was then used to confirm that Pb exposure during development results in changes in proteins involved in energy metabolism in auditory regions of the brainstem. CBA mice were exposed to 0 mM (control), 0.01 mM (low), or 2 mM (high) Pb acetate during development. At P21, the ventral brainstem region containing several auditory nuclei, including the Medial Nucleus of the Trapezoid Body, and the medial and lateral superior olivary nuclei, was separated from the total brainstem. Proteomic analysis (isolation and separation of proteins by 2D-PAGE; analysis by MALDI-MS) revealed that chronic Pb exposure alters the expression of proteins involved in the regulation of cellular energy metabolism including VDAC and creatine kinase B. Immunohistochemistry confirms that Pb exposure results in decreased expression of VDAC in auditory nuclei, supporting the hypothesis that Pb disrupts energy metabolism in auditory neurons

Clinical review: Adiponectin biology and its role in inflammation and critical illness

Adiponectin is an adipokine first described just over a decade ago. Produced almost exclusively by adipocytes, adiponectin circulates in high concentrations in human plasma. Research into this hormone has revealed it to have insulin-sensitizing, anti-inflammatory and cardioprotective roles. This review discusses the history, biology and physiological role of adiponectin and explores its role in disease, with specific focus on adiponectin in inflammation and sepsis. It appears that an inverse relationship exists between adiponectin and inflammatory cytokines. Low levels of adiponectin have been found in critically ill patients, although data are limited in human subjects at this stage. The role of adiponectin in systemic inflammation and critical illness is not well defined. Early data suggest that plasma levels of adiponectin are decreased in critical illness. Whether this is a result of the disease process itself or whether patients with lower levels of this hormone are more susceptible to developing a critical illness is not known. This observation of lower adiponectin levels then raises the possibility of therapeutic options to increase circulating adiponectin levels. The various options for modulation of serum adiponectin (recombinant adiponectin, thiazolidinediones) are discussed

Automated Indexing and Tool Cleaning for Tapping Torque Test Device

ME450 Capstone Design and Manufacturing Experience: Winter 2010Professor Gordon Krauss is interested in testing various lubricants for metal work. To do this a tapping torque tester is utilized. The test results can possibly be extended to other metal forming operations and be used to heighten production rates. We have been asked to automate this process by modifying the machine so that a software program can perform the testing with minimal operator involvement and adequate accuracy and repeatability. The machine must also have the ability to clean the tap after each hole is threaded and a mount for convenient supercritical CO2 application.http://deepblue.lib.umich.edu/bitstream/2027.42/109383/1/me450w10project25_report.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109383/2/me450w10project25_photo.jp

Planning to Fairly Allocate: Probabilistic Fairness in the Restless Bandit Setting

Restless and collapsing bandits are commonly used to model constrained resource allocation in settings featuring arms with action-dependent transition probabilities, such as allocating health interventions among patients [Whittle, 1988; Mate et al., 2020]. However, state-of-the-art Whittle-index-based approaches to this planning problem either do not consider fairness among arms, or incentivize fairness without guaranteeing it [Mate et al., 2021]. Additionally, their optimality guarantees only apply when arms are indexable and threshold-optimal. We demonstrate that the incorporation of hard fairness constraints necessitates the coupling of arms, which undermines the tractability, and by extension, indexability of the problem. We then introduce ProbFair, a probabilistically fair stationary policy that maximizes total expected reward and satisfies the budget constraint, while ensuring a strictly positive lower bound on the probability of being pulled at each timestep. We evaluate our algorithm on a real-world application, where interventions support continuous positive airway pressure (CPAP) therapy adherence among obstructive sleep apnea (OSA) patients, as well as simulations on a broader class of synthetic transition matrices.Comment: 27 pages, 19 figure

Changes in serum adiponectin concentrations in critical illness: a preliminary investigation

Introduction Adiponectin plays an important role in the regulation of tissue inflammation and insulin sensitivity. Perturbations in adiponectin concentration have been associated with obesity and the metabolic syndrome. Data on adiponectin pathophysiology in critical illness are limited

The War on Terror

Presents comments (from the EPIIC Symposium at Tufts University, February 2004) concerning the war on terror; concern on the problem about terrorism; elaboration on the claim that the world is not in a global war on terror; and problems of the use and abuse of the word terrorism

Adiponectin is associated with cardiovascular disease in male renal transplant recipients: baseline results from the LANDMARK 2 study

BACKGROUND: Adiponectin is a major adipocyte-derived protein with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. Adiponectin levels correlate inversely with renal function and higher levels are predictive of lower cardiovascular disease (CVD) in patients with normal renal function and chronic kidney disease. No data exists on the association between adiponectin and CVD in renal transplant recipients (RTR). METHODS: Standard biochemistry, clinical data and adiponectin were collected from 137 RTR recruited to the LANDMARK 2 study at baseline. The LANDMARK 2 study is an ongoing randomized controlled study that compares the outcome of aggressive risk factor modification for cardiovascular disease versus standard post-transplant care in renal transplant recipients with impaired glucose tolerance or diabetes mellitus. RESULTS: Mean patient age was 53.4 +/- 12 years and the median post-transplantation period was 5 (0.5-31.9) years. Mean serum adiponectin level was 12.3 +/- 7.1 microg/mL. On univariate analysis, adiponectin was positively associated with female gender (P = 0.01) and serum high-density lipoprotein (HDL) concentration (P < 0.001), and inversely with body mass index (P = 0.009), metabolic syndrome (P = 0.047), abnormal glucose tolerance (P = 0.01), C-reactive protein (P = 0.001) and serum triglyceride (P < 0.001). On stepwise multivariate analysis, adiponectin in males was negatively correlated with combined baseline CVD (P = 0.03), waist-hip ratio (P = 0.003) and glomerular filtration rate (P = 0.046), and positively with HDL (P < 0.001). In contrast, in females adiponectin was inversely associated with C-reactive protein (P = 0.001) and serum triglyceride. CONCLUSION: In conclusion, adiponectin is positively correlated with inflammation, dyslipidemia and abnormal glucose tolerance in RTR. Furthermore, hypoadiponectinemia correlated with increased baseline CVD in male RTR

Ecosystem-Based Management Indicators for a Marine Planning Process in BC\u27s North Coast - Marine Planning Partnership (MaPP)

The Marine Planning Partnership for the North Pacific Coast (MaPP) is a collaborative planning process for coastal and marine areas in the north coast of British Columbia, Canada. MaPP is a co-led partnership between the Province of British Columbia and First Nations governments, represented by the Coastal First Nations-Great Bear Initiative, the North Coast-Skeena First Nations Stewardship Society, and the Nanwakolas Council. Marine plans are being developed for four sub-regions: Haida Gwaii, North Coast, Central Coast, and Northern Vancouver Island. MaPP is using an ecosystem-based management (EBM) framework and developing indicators for ecological integrity, human well-being, and governance. This talk will briefly outline the methodology and present draft indicators for monitoring EBM in the North Pacific Coast of British Columbia. These indicators are forming the basis of a MaPP EBM Indicator Toolbox to monitor the regional frameworks and sub-regional plans including objectives and strategies for climate change adaptation, marine uses and activities, marine pollution, and marine protected areas. It is too early for us to present on the results of using the indicators because the marine planning process is still underway, however we will discuss the potential use of indicators in connection with our work to analyse the vulnerability of ecosystem types to marine stressors, as well as in the context of a draft cumulative effects assessment framework. Finally, we will briefly discuss ideas for implementation of a monitoring program for the indicators in the toolkit

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

Estrogen Receptor-α Mediates Diethylstilbestrol-Induced Feminization of the Seminal Vesicle in Male Mice

Background: Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV)