Glial controls systemic mitochondrial function, oxidative stress, and neuronal viability via copper ion homeostasis.

Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly reliant on mitochondrial production of ATP, with many neurodegenerative diseases, including Parkinson's disease, associated with diminished mitochondrial function. The gene encodes a ribonuclease that targets pre-mRNA of replication-dependent histones, proteins recently found in yeast to reduce Cu(II) to Cu(I), and when mutated disrupt ATP production, elevates oxidative stress, and severely impacts cell growth.

Forward genetic screen of the C. elegans million mutation library reveals essential, cell-autonomous contributions of BBSome proteins to dopamine signaling.

The nematode Caenorhabditis elegans is well known for its ability to support forward genetic screens to identify molecules involved in neuronal viability and signaling. The proteins involved in C. elegans dopamine (DA) regulation are highly conserved across evolution, with prior work demonstrating that the model can serve as an efficient platform to identify novel genes involved in disease-associated processes.

Association between precipitation and mortality due to diarrheal diseases by climate zone: A multi-country modeling study.

Background: Precipitation could affect the transmission of diarrheal diseases. The diverse precipitation patterns across different climates might influence the degree of diarrheal risk from precipitation. This study determined the associations between precipitation and diarrheal mortality in tropical, temperate, and arid climate regions.

Optical Imaging Demonstrates Tissue-Specific Metabolic Perturbations in Mblac1 Knockout Mice.

Objective: Metabolic changes have been extensively documented in neurodegenerative brain disorders, including Parkinson's disease and Alzheimer's disease (AD). Mutations in the C. elegans swip-10 gene result in dopamine (DA) dependent motor dysfunction accompanied by DA neuron degeneration.

Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?

Receiving a neurodegenerative disease (NDD) diagnosis, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis, is devastating, particularly given the limited options for treatment. Advances in genetic technologies have allowed for efficient modeling of NDDs in animals and brought hope for new disease-modifying medications. The complexity of the mammalian brain and the costs and time needed to identify and develop therapeutic leads limits progress.

Mortality Associated with Ambient Exposure in India: Results from the Million Death Study.

Background: Studies on the extent to which long-term exposure to ambient particulate matter (PM) with aerodynamic diameter () contributes to adult mortality in India are few, despite over 99% of Indians being exposed to levels that the World Health Organization (WHO) considers unsafe.

Objective: We conducted a retrospective cohort study within the Million Death Study (MDS) to provide the first-ever quantification of national mortality from exposure to in India from 1999 to 2014.

Methods: We calculated relative risks (RRs) by linking a total of ten 3-y intervals of satellite-based estimated exposure to deaths 3 to 5 y later in over 7,400 small villages or urban blocks covering a total population of .

Assessment of SARS-CoV-2 Seropositivity During the First and Second Viral Waves in 2020 and 2021 Among Canadian Adults.

Importance: The incidence of infection during SARS-CoV-2 viral waves, the factors associated with infection, and the durability of antibody responses to infection among Canadian adults remain undocumented.

Objective: To assess the cumulative incidence of SARS-CoV-2 infection during the first 2 viral waves in Canada by measuring seropositivity among adults.

Design, Setting, And Participants: The Action to Beat Coronavirus study conducted 2 rounds of an online survey about COVID-19 experience and analyzed immunoglobulin G levels based on participant-collected dried blood spots (DBS) to assess the cumulative incidence of SARS-CoV-2 infection during the first and second viral waves in Canada.

Is Malaria an Important Cause of Death among Adults?

A long-held assumption has been that nearly all malaria deaths in high-transmission areas are of children younger than 5 years and pregnant women. Most global malaria mortality estimates incorporate this assumption in their calculations. In 2010, the Indian Million Death Study, which assigns cause of death by verbal autopsy (VA), challenged the reigning perception, producing a U-shaped mortality age curve, with rates rising after age 45 years in areas of India with substantial malaria transmission.

Mortality attributable to hot and cold ambient temperatures in India: a nationally representative case-crossover study.

Background: Most of the epidemiological studies that have examined the detrimental effects of ambient hot and cold temperatures on human health have been conducted in high-income countries. In India, the limited evidence on temperature and health risks has focused mostly on the effects of heat waves and has mostly been from small scale studies. Here, we quantify heat and cold effects on mortality in India using a nationally representative study of the causes of death and daily temperature data for 2001-2013.

Glial loss of the metallo β-lactamase domain containing protein, SWIP-10, induces age- and glutamate-signaling dependent, dopamine neuron degeneration.

Across phylogeny, glutamate (Glu) signaling plays a critical role in regulating neural excitability, thus supporting many complex behaviors. Perturbed synaptic and extrasynaptic Glu homeostasis in the human brain has been implicated in multiple neuropsychiatric and neurodegenerative disorders including Parkinson's disease, where theories suggest that excitotoxic insults may accelerate a naturally occurring process of dopamine (DA) neuron degeneration. In C.

Renal failure deaths and their risk factors in India 2001-13: nationally representative estimates from the Million Death Study.

Background: Renal failure represents a growing but mostly undocumented cause of premature mortality in low-income and middle-income countries. We investigated changes in adult renal failure mortality and its key risk factors in India using the nationally representative Million Death Study.

Methods: In this cross-sectional analysis of population-based data, two trained physicians independently assigned underlying causes to 150 018 deaths at ages 15-69 years from a nationally-representative mortality survey in India for 2001-03 and 2010-13, using the International Classification of Diseases, 10th version (ICD-10).

Age-specific and sex-specific adult mortality risk in India in 2014: analysis of 0·27 million nationally surveyed deaths and demographic estimates from 597 districts.

Background: As child mortality decreases rapidly worldwide, premature adult mortality is becoming an increasingly important contributor to global mortality. Any possible worldwide reduction of premature adult mortality before the age of 70 years will depend on progress in India. Indian districts increasingly have responsibility for implementing public health programmes.

Deaths from acute abdominal conditions and geographic access to surgical care in India: a nationally representative population-based spatial analysis.

Background: Acute abdominal conditions have high case-fatality rates in the absence of timely surgical care. In India, and many other low-income and middle-income countries, few population-based studies have quantified mortality from surgical conditions and related mortality to access to surgical care. We aimed to describe the spatial and socioeconomic distributions of deaths from acute abdomen (DAA) in India and to quantify potential access to surgical facilities in relation to such deaths.

Deaths from acute abdominal conditions and geographical access to surgical care in India: a nationally representative spatial analysis.

Background: Few population-based studies quantify mortality from surgical conditions and relate mortality to access to surgical care in low-income and middle-income countries.

Methods: We linked deaths from acute abdominal conditions within a nationally representative, population-based mortality survey of 1·1 million households in India to nationally representative facility data. We calculated total and age-standardised death rates for acute abdominal conditions.

Snakebite mortality in India: a nationally representative mortality survey.

Background: India has long been thought to have more snakebites than any other country. However, inadequate hospital-based reporting has resulted in estimates of total annual snakebite mortality ranging widely from about 1,300 to 50,000. We calculated direct estimates of snakebite mortality from a national mortality survey.

Adult and child malaria mortality in India: a nationally representative mortality survey.

Background: National malaria death rates are difficult to assess because reliably diagnosed malaria is likely to be cured, and deaths in the community from undiagnosed malaria could be misattributed in retrospective enquiries to other febrile causes of death, or vice-versa. We aimed to estimate plausible ranges of malaria mortality in India, the most populous country where the disease remains common.

Methods: Full-time non-medical field workers interviewed families or other respondents about each of 122,000 deaths during 2001-03 in 6671 randomly selected areas of India, obtaining a half-page narrative plus answers to specific questions about the severity and course of any fevers.

The Summary Index of Malaria Surveillance (SIMS): a stable index of malaria within India.

Background: Malaria in India has been difficult to measure. Mortality and morbidity are not comprehensively reported, impeding efforts to track changes in disease burden. However, a set of blood measures has been collected regularly by the National Malaria Control Program in most districts since 1958.