A Netrin-3 Like Protein is Secreted from \u3ci\u3eTetrahymena thermophila\u3c/i\u3e

Netrin proteins are a family of laminin-related secreted proteins that provide signals for axonal growth and cell migration during vertebrate development. Netrin homologs are expressed throughout the animal kingdom; however, some animals do not express a homolog of any known netrin receptors. We have previously found that the ciliated protozoan, Tetrahymena thermophila, responds to netrin-1 peptide by showing avoidance behavior. In addition, Tetrahymena secrete a protein that is immunologically similar to netrin-1 as detected by ELISA. Since netrin-3, like netrin-1, is a guidance molecule for axons and overlaps signaling pathways with netrin-1 in vertebrates, we hypothesized that netrin-3 may also act as a chemorepellent in Tetrahymena. While behavioral assays did not confirm this hypothesis, growth assays indicate that netrin-3 peptide inhibits cell division in Tetrahymena. In addition, ELISA and Western blots indicate that a netrin-3 like protein of approximately 48 kDa is secreted from Tetrahymena. Immunolocalization of this protein within the cell shows that it appears in widely distributed throughout the cell, and co-localizes with the netrin-1 like protein. Using ER tracker™, we found that some of the netrin-3-like protein co-localizes with the endoplasmic reticulum, as might be expected for a secreted protein. Further experimentation is necessary to determine the mechanism by which netrin-3 peptide inhibits growth in Tetrahymena

Glucose regulation in non-insulin-dependent diabetes mellitus: Interaction between pancreatic islets and the liver

The degree of fasting hyperglycemia in patients with non-insulin-dependent diabetes mellitus is dependent on the rate of hepatic glucose production. The basal rate of hepatic glucose production is increased in patients with non-insulin-dependent diabetes mellitus, and there is a positive correlation between hepatic glucose production and fasting glucose levels. Diminished secretion of insulin, impaired hepatic sensitivity to insulin's effects, or a combination of these factors could contribute to the elevated hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. The relationship between insulin secretion and hepatic glucose production is regulated by a closed feedback loop operating between glucose levels and pancreatic beta cells. Although fasting insulin levels are usually comparable between patients with non-insulin-dependent diabetes mellitus and normal subjects, insulin secretion is markedly impaired in non-insulin-dependent diabetes mellitus in relation to the degree of hyperglycemia present. In fact, the degree of fasting hyperglycemia in a given patient with non-insulin-dependent diabetes mellitus is closely related to the degree of impaired pancreatic beta-cell responsiveness to glucose. Such findings suggest that impaired insulin secretion leads to increased hepatic glucose production, which raises the plasma glucose level. The resulting hyperglycemia helps to maintain relatively normal basal insulin output. Chronic sulfonylurea drug therapy of patients with non-insulin-dependent diabetes mellitus enhances pancreatic islet sensitivity to glucose, leading to increased insulin secretion, suppression of hepatic glucose production, and a decline in the steady-state fasting glucose level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25595/1/0000139.pd

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

A circumpolar study unveils a positive non-linear effect oftemperature on arctic arthropod availability that may reduce therisk of warming-induced trophic mismatch for breeding shorebirds

Seasonally abundant arthropods are a crucial food source for many migratorybirds that breed in the Arctic. In cold environments, the growth and emergence ofarthropods are particularly tied to temperature. Thus, the phenology of arthropodsis anticipated to undergo a rapid change in response to a warming climate, potentiallyleading to a trophic mismatch between migratory insectivorous birds and their prey.Using data from 19 sites spanning a wide temperature gradient from the Subarcticto the High Arctic, we investigated the effects of temperature on the phenology andbiomass of arthropods available to shorebirds during their short breeding seasonat high latitudes. We hypothesized that prolonged exposure to warmer summertemperatures would generate earlier peaks in arthropod biomass, as well as higherpeak and seasonal biomass. Across the temperature gradient encompassed by ourstudy sites (>10°C in average summer temperatures), we found a 3-day shift inaverage peak date for every increment of 80 cumulative thawing degree-days.Interestingly, we found a linear relationship between temperature and arthropodbiomass only below temperature thresholds. Higher temperatures were associatedwith higher peak and seasonal biomass below 106 and 177 cumulative thawingdegree-days, respectively, between June 5 and July 15. Beyond these thresholds,no relationship was observed between temperature and arthropod biomass. Ourresults suggest that prolonged exposure to elevated temperatures can positivelyinfluence prey availability for some arctic birds. This positive effect could, in part,stem from changes in arthropod assemblages and may reduce the risk of trophicmismatch. Sarctic arthropods, arctic breeding shorebirds, climate warming, insectivorous birds,invertebrate biomass, phenology, trophic mismatcpublishedVersio

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections

Neuromatch Academy: a 3-week, online summer school in computational neuroscience

Neuromatch Academy (https://academy.neuromatch.io; (van Viegen et al., 2021)) was designed as an online summer school to cover the basics of computational neuroscience in three weeks. The materials cover dominant and emerging computational neuroscience tools, how they complement one another, and specifically focus on how they can help us to better understand how the brain functions. An original component of the materials is its focus on modeling choices, i.e. how do we choose the right approach, how do we build models, and how can we evaluate models to determine if they provide real (meaningful) insight. This meta-modeling component of the instructional materials asks what questions can be answered by different techniques, and how to apply them meaningfully to get insight about brain function