Sex-based Differences in C. elegans Responsiveness to Aversive Stimuli

Behavioral differences between sexes are evident across many species. The underlying mechanisms surrounding such differences are not fully elucidated, however, due to the complexities of animal behavior. The nematode Caenorhabditis elegans (C. elegans) is a well-characterized, genetically amenable species with two sexes, hermaphrodites (XX) and males (XO). This makes it an appropriate model system for investigating sex-based behavioral differences. Chemosensation in C. elegans is mediated by exposed ciliated sensory neurons, one of which is ASH. ASH is a polymodal nociceptor that elicits reversal when an animal encounters aversive stimuli. We hypothesized that hermaphrodite and male C. elegans worms respond differently to stimuli detected by ASH such as the bitter tastant quinine, the detergent sodium dodecyl sulfate (SDS), and the heavy metal copper (CuCl2). Wild-type assay-age hermaphrodites and males were picked from a nematode growth media (NGM) plate with E. coli OP50 and kept on an NGM plate without food for 10 minutes prior to assaying. A drop of aversive stimulus was placed in front of a forward-moving animal, and the animal’s response was recorded. A positive response is backwards movement within 4 seconds after contact with the stimulus. Our results reveal a quantifiable difference in how wild-type hermaphrodite and male C. elegans respond to aversive stimuli. Specifically, wild-type males are less responsive than hermaphrodites to quinine, SDS, and CuCl2. Further investigations will be conducted through experiments with C. elegans strains in which hermaphrodites have masculinized, and males have feminized nervous systems or subsets of neurons. Through these experiments, we aim to explore potential sites of difference that lead to these observable differences in responsiveness to aversive stimuli

Safety, dosing, and pharmaceutical quality for studies that evaluate medicinal products (including biological products) in neonates

The study of medications among pediatric patients has increased worldwide since 1997 in response to new legislation and regulations, but these studies have not yet adequately addressed the therapeutic needs of neonates. Additionally, extant guidance developed by regulatory agencies worldwide does not fully address the specificities of neonatal drug development, especially among extremely premature newborns who currently survive. Consequently, an international consortium from Canada, Europe, Japan, and the United States was organized by the Critical Path Institute to address the content of guidance. This group included neonatologists, neonatal nurses, parents, regulators, ethicists, clinical pharmacologists, specialists in pharmacokinetics, specialists in clinical trials and pediatricians working in the pharmaceutical industry. This group has developed a comprehensive, referenced White Paper to guide neonatal clinical trials of medicines-particularly early phase studies. Key points include: The need to base product development on neonatal physiology and pharmacology while making the most of knowledge acquired in other settings; the central role of families in research; and the value of the whole neonatal team in the design, implementation and interpretation of studies. This White Paper should facilitate successful clinical trials of medicines in neonates by informing regulators, sponsors, and the neonatal community of existing good practice

Enrollment of Neonates in More Than One Clinical Trial

Because the highest rates of morbidity and mortality in neonates are seen in those born at 1 clinical trial. Neonatal units that have the infrastructure and resources to engage in research frequently face the question of whether it is permissible to enroll a neonate in >1 trial. This article examines the pertinent scientific, ethical, regulatory, and industry issues that should be taken into account when considering enrolling neonates in multiple clinical studies

Toxicity of insecticides to insect pollinators

1 sheet; 28 cm

Pediatric Hypertension

XVI, 600 p. 67 illus., 22 illus. in color.online

Decreased low-density lipoprotein receptor function and mRNA levels in lymphocytes from uremic patients

Decreased low density lipoprotein receptor function and mRNA levels in lymphocytes from uremic patients. The mechanisms by which renal failure causes hyperlipoproteinemia remain unclear. To investigate the potential role of the low-density lipoprotein (LDL) receptor in lipoprotein metabolism in uremia we measured LDL receptor function in peripheral blood mononuclear cells (PBMC) from uremic patients and control subjects using a functional assay in which proliferation of lectin-stimulated PBMC in the presence of lovastatin was dependent upon internalization of exogenous cholesterol via a functional LDL receptor. The amount of LDL required to reverse 50% of lovastatin-induced inhibition of proliferation in PBMC from uremic patients was significantly greater (3.6 ± 1.8 µg/ml, N = 33, P < 0.05) than controls, (1.99 ± 0.6 µg/ml, N = 37). Abnormal LDL receptor function in four uremic patients normalized following renal transplantation. To investigate the molecular basis for LDL receptor dysfunction, we directly quantitated LDL receptor messenger RNA (mRNA) in PBMC from uremic patients and control subjects using a ribonuclease protection assay. LDL receptor mRNA expression in uremic patients was 0.42 ± 0.08 (N = 10), significantly lower (P < 0.015) than in normal subjects, 0.71 ± 0.08 (N = 14). These data suggest that an acquired defect in LDL receptor function in PBMC from uremic patients exists which may be due to decreased LDL receptor expression. These abnormalities, if present in other tissues, could contribute to the aberrant lipoprotein metabolism which is a consistent feature of uremia

Proteinuria in South Asian children: prevalence and determinants

Proteinuria in children is a marker of kidney disease and atherosclerosis, both which are known predictors of cardiovascular mortality. Recent evidence suggests that migrant South Asian populations living in the West may be at higher risk of kidney disease than native Caucasians. However, the determinants of proteinuria in South Asian children have not been explored. Previously, we reported ethnic variation in the prevalence of proteinuria in the adult population of Pakistan. However, it is not known whether ethnic predisposition to proteinuria appears during childhood or whether it is acquired later in life as a result of prolonged exposure to undiagnosed diabetes and hypertension. Analyses were based on a subset of data for 4977 children aged 5 to less than 15 years collected as part of the broad National Health Survey of Pakistan, conducted between 1990 and 1994. Proteinuria was defined as a dipstick positive for protein on a random urine sample. Ethnicity was reported as mother-tongue , which is specific for each of the five major ethnic subgroups of Pakistan: Muhajir, Punjabi, Sindhi, Pashtun, and Baluchi. The overall prevalence (95% CI) of proteinuria in the children was 3.3% (2.7-3.9%). It was 6.2% in Sindhis, 3.6% in Muhajirs, 2.8% in Punjabis, 2.8% in Baluchis, and 1.0% in Pashtuns (p\u3c0.001). In multivariable analyses, proteinuria was associated with greater height (p=0.007), urban dwelling (p=0.03), lower socioeconomic status (p=0.02), and certain ethnicities (p=0.005). The ethnic variation in proteinuria in South Asian children mirrors variation among ethnic groups in adults. This suggests variations in susceptibility or early exposure to causes of chronic kidney disease, rather than long-term exposure to undiagnosed diabetes or hypertension. Further studies are needed to determine factors in early life that may differentially predispose certain ethnic groups to proteinuria