Apolipoprotein L1-Specific Antibodies Detect Endogenous APOL1 inside the Endoplasmic Reticulum and on the Plasma Membrane of Podocytes.

Background: APOL1 is found in human kidney podocytes and endothelia. Variants G1 and G2 of the gene account for the high frequency of nondiabetic CKD among African Americans. Proposed mechanisms of kidney podocyte cytotoxicity resulting from variant overexpression implicate different subcellular compartments.

TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.

Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies.

CD18 deficiency improves liver injury in the MCD model of steatohepatitis.

Neutrophils and macrophages are important constituents of the hepatic inflammatory infiltrate in non-alcoholic steatohepatitis. These innate immune cells express CD18, an adhesion molecule that facilitates leukocyte activation. In the context of fatty liver, activation of infiltrated leukocytes is believed to enhance hepatocellular injury.

Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis, steatosis and liver injury.

Diets containing excess carbohydrate and fat promote hepatic steatosis and steatohepatitis in mice. Little is known, however, about the impact of specific carbohydrate/fat combinations on liver outcome. This study was designed to determine whether high-energy diets with identical caloric density but different carbohydrate and fat composition have unique effects on the liver.

Differential hepatotoxicity of dietary and DNL-derived palmitate in the methionine-choline-deficient model of steatohepatitis.

Background: Saturated fatty acids are toxic to liver cells and are believed to play a central role in the pathogenesis of non-alcoholic steatohepatitis. In experimental steatohepatitis induced by feeding mice a methionine-choline-deficient (MCD) diet, the degree of liver damage is related to dietary sugar content, which drives de novo lipogenesis and promotes the hepatic accumulation of saturated fatty acids. The objective of this study was to determine whether dietary palmitate exerts the same toxicity as carbohydrate-derived palmitate in the MCD model of fatty liver disease.

An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females.

Estrogen-receptor alpha (ERα) neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL) control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire.

De novo neurogenesis in adult hypothalamus as a compensatory mechanism to regulate energy balance.

The ability to develop counter-regulatory mechanisms to maintain energy balance in response to environmental and physiologic insults is essential for survival, but the mechanisms underlying these compensatory regulations are poorly understood. Agouti-related peptide (AGRP) and Neuropeptide Y are potent orexigens and are coexpressed in neurons in the arcuate nucleus of the hypothalamus. Acute ablation of these neurons leads to severe anorexia and weight loss, whereas progressive degeneration of these neurons has minimal impact on food intake and body weight, suggesting that compensatory mechanisms are developed to maintain orexigenic drive.

Functional requirement of AgRP and NPY neurons in ovarian cycle-dependent regulation of food intake.

In female mammals including rodents and humans, feeding decreases during the periovulatory period of the ovarian cycle, which coincides with a surge in circulating estrogen levels. Ovariectomy increases food intake, which can be normalized by estrogen treatment at a dose and frequency mimicking those during the estrous cycle. Furthermore, administration of estrogen to rodents potently inhibits food intake.

Gonadal hormones modulate sex differences in judgments of relative numerousness in meadow voles, Microtus pennsylvanicus.

Animals in a variety of taxa discriminate between a greater quantity and a lesser quantity of the same object, an ability that is referred to as relative numerousness judgment. For example, meadow voles can distinguish between areas containing more over-marks by one opposite-sex scent donor and fewer over-marks by another opposite-sex scent donor. Females appear to be able to make better discriminations between more or less over-marks than do males.

Self discrimination in meadow voles, .

Particular features of the signaling characteristics of the scent marks of temperate-zone, seasonally breeding mammals may reflect differences in their reproductive state and, hence, be variable. Consequently, an individual's perception of self may depend more on the condition independent than on the condition-dependent signaling characteristics of the scent marks. Yet, we do not know whether an individual responds to changes in the signaling characteristics of its own scent marks, such as those associated with changes in an individual's reproductive state.

Meadow voles, Microtus pennsylvanicus, have the capacity to recall the "what", "where", and "when" of a single past event.

Some non-human animals may possess the ability to recall the "what", "where", and "when" of a single past event. We tested the hypothesis that male meadow voles possess the capacity to recall the "what", "where", and "when" of a single past event associated with mate selection in two experiments. Briefly, male voles were allowed to explore an apparatus that contained two chambers.

Food deprivation and the role of estradiol in mediating sexual behaviors in meadow voles.

Female mammals are particularly sensitive to changes in food availability. The mechanisms that affect sexual behavior and food intake are closely related to one another; chief among the mechanisms that control sexual behaviors in females is estradiol. In order to understand how food deprivation results in inhibition of sexual behavior (attractivity, proceptivity, and receptivity), we measured the effects of food deprivation on circulating concentrations of estradiol.

Re-feeding and the restoration of odor attractivity, odor preference, and sexual receptivity in food-deprived female meadow voles.

Food-deprived meadow voles were used to test predictions of two hypotheses associated with the recovery of sexual behaviors following re-feeding. Specifically, we tested between the body weight set point and metabolic fuels hypotheses. To do so, we determined whether the body weight of previously food-deprived female voles had to return to pre-food deprivation levels before they would recover their sexual behaviors.

Meadow voles, Microtus pennsylvanicus, can distinguish more over-marks from fewer over-marks.

Is it possible that voles have a sense of number? To address this question, we determined whether voles discriminate between two different scent-marking individuals and identify the individual whose scent marks was on top more often than the other individual. We tested whether voles show a preference for the individual whose scent marks was on top most often. If so, the simplest explanation was that voles can make a relative size judgement-such as distinguishing an area containing more of one individual's over-marks as compared to less of another individual's over-marks.