Molecular puzzle of insulin: structural assembly pathways and their role in diabetes.

Properly folded proteins are essential for virtually all cellular processes including enzyme catalysis, signal transduction, and structural support. The cells have evolved intricate mechanisms of control, such as the assistance of chaperones and proteostasis networks, to ensure that proteins mature and fold correctly and maintain their functional conformations. Here, we review the mechanisms governing the folding of key hormonal regulators or glucose homeostasis.

ETVs dictate hPSC differentiation by tuning biophysical properties.

Stem cells maintain a dynamic dialog with their niche, integrating biochemical and biophysical cues to modulate cellular behavior. Yet, the transcriptional networks that regulate cellular biophysical properties remain poorly defined. Here, we leverage human pluripotent stem cells (hPSCs) and two morphogenesis models - gastruloids and pancreatic differentiation - to establish ETV transcription factors as critical regulators of biophysical parameters and lineage commitment.

Impact of socioeconomic status on cancer care in Southeast Texas: a retrospective population-based cohort study.

Background: Gastrointestinal (GI) cancers are the third leading cause of cancer-related mortality worldwide. Disparities in healthcare frequently stem from variations in socioeconomic status (SES). This study investigated the influence of socioeconomic factors such as gender, race, age, and geography on time to treatment initiation (TTI) and survival outcomes.

The Acquisition of Complement-Dependent Cytotoxicity by the Type II Anti-CD20 Therapeutic Antibody Obinutuzumab.

Rituximab, a prototypic anti-CD20 mAb, and the third-generation anti-CD20 mAb obinutuzumab differ in their ability to activate the complement system. According to recent studies, this contrast stems from the architecture of the antigen-antibody complex formed by these two mAbs that facilitates (rituximab) or disables (obinutuzumab) further oligomerization, leading to engagement of the initial classical complement pathway component C1q. We examined whether a gain-of-function C2 variant that acts downstream of C1q and enforces the formation of complement convertase resistant to physiological decay can impact complement activation by obinutuzumab.

Neuroblast migration along cellular substrates in the developing porcine brain.

In the past decade it has become evident that neuroblasts continue to supply the human cortex with interneurons via unique migratory streams shortly following birth. Owing to the size of the human brain, these newborn neurons must migrate long distances through complex cellular landscapes to reach their final locations. This process is poorly understood, largely because of technical difficulties in acquiring and studying neurotypical postmortem human samples along with diverging developmental features of well-studied mouse models.

Early Influences of Microbiota on White Matter Development in Germ-Free Piglets.

Abnormalities in the prefrontal cortex (PFC), as well as the underlying white matter (WM) tracts, lie at the intersection of many neurodevelopmental disorders. The influence of microorganisms on brain development has recently been brought into the clinical and research spotlight as alterations in commensal microbiota are implicated in such disorders, including autism spectrum disorders, schizophrenia, depression, and anxiety the gut-brain axis. In addition, gut dysbiosis is common in preterm birth patients who often display diffuse WM injury and delayed WM maturation in critical tracts including those within the PFC and corpus callosum.

Enhancing the credibility of decisions based on scientific conclusions: transparency is imperative.

Transparency and documentation of the decision process are at the core of a credible risk assessment and, in addition, are essential in the presentation of a weight of evidence (WoE)-based approach. Lack of confidence in the risk assessment process (as the basis for a risk management decision), beginning with evaluation of raw data and continuing through the risk decision process, is largely because of issues surrounding transparency. There is a critical need to implement greater transparency throughout the risk assessment process, and although doing so will not guarantee the correctness of the risk assessment or that all risk assessors come up with the same conclusions, it will provide essential information on how a particular conclusion or decision was made, thereby increasing confidence in the conclusions.

Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity.

The discovery of acrylamide (AA) in many common cooked starchy foods has presented significant challenges to toxicologists, food scientists, and national regulatory and public health organizations because of the potential for producing neurotoxicity and cancer. This paper reviews some of the underlying experimental bases for AA toxicity and earlier risk assessments. Then, dietary exposure modeling is used to estimate probable AA intake in the U.

Workgroup report: public health strategies for reducing aflatoxin exposure in developing countries.

Consecutive outbreaks of acute aflatoxicosis in Kenya in 2004 and 2005 caused > 150 deaths. In response, the Centers for Disease Control and Prevention and the World Health Organization convened a workgroup of international experts and health officials in Geneva, Switzerland, in July 2005. After discussions concerning what is known about aflatoxins, the workgroup identified gaps in current knowledge about acute and chronic human health effects of aflatoxins, surveillance and food monitoring, analytic methods, and the efficacy of intervention strategies.

Aflatoxin, hepatitis and worldwide liver cancer risks.

Aflatoxins are among the most potent mutagenic and carcinogenic substances known. Differential potency of aflatoxin among species can be partially attributed to differences in metabolism; however, current information on competing aspects of metabolic activation and detoxification of aflatoxin in various species does not identify an adequate animal model for humans. Risk of liver cancer is influenced by a number of factors, most notably carriage of hepatitis B virus as determined by the presence in serum of the hepatitis B surface antigen (HBsAg+ or HBsAg-).