Pressure Protein Denaturation Compared to Thermal and Chemical Unfolding: Analyses with Cooperative Models.

The thermodynamics of pressure-induced protein denaturation could so far not be directly compared with protein denaturation induced by temperature or chemical agents. Here, we provide a new cooperative model for pressure-induced protein denaturation that allows the quantitative comparison of all three denaturing processes based on their free energy, enthalpy, entropy, and cooperativity. As model proteins, we use apolipoprotein A-1 and lysozyme.

Fate of persistent and mobile chemicals in the water cycle: From municipal wastewater discharges to river bank filtrate.

Persistent and mobile (PM) chemicals are considered detrimental for drinking water resources as they may pass through all barriers protecting these resources against pollution. However, knowledge on the occurrence of PM chemicals in the water cycle, that make their way into drinking water resources, is still limited. The effluents of six municipal wastewater treatment plants (WWTPs, n = 38), surface water of two rivers (n = 32) and bank filtrate of one site (n = 15) were analyzed for 127 suspected PM chemicals.

Sources of persistent and mobile chemicals in municipal wastewater: a sewer perspective in Leipzig, Germany.

Persistent and mobile (PM) chemicals spread in the water cycle and have been widely detected, yet information about their sources is still scarce. In this study, 67 PM chemicals were analyzed in 19 wastewater samples taken in the sewer system of the city of Leipzig, Germany, covering different industrial, clinical, and domestic discharges. A total of 37 of these analytes could be detected, with highly variable median concentrations between substances (median: 0.

Posttraumatic stress disorder, Veterans Health Administration use, and care-seeking among recent-era U.S. veterans.

The current study investigated the associations among probable posttraumatic stress disorder (PTSD), recent Veterans Health Administration (VHA) health care use, and care-seeking for PTSD in U.S. military veterans.

Diffusion of excellence: evaluating a system to identify, replicate, and spread promising innovative practices across the Veterans health administration.

Introduction: The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program provides a system to identify, replicate, and spread promising practices across the largest integrated healthcare system in the United States. DoE identifies innovations that have been successfully implemented in the VHA through a Shark Tank style competition. VHA facility and regional directors bid resources needed to replicate promising practices.

Chemical Protein Unfolding - A Simple Cooperative Model.

Chemical unfolding with guanidineHCl or urea is a common method to study the conformational stability of proteins. The analysis of unfolding isotherms is usually performed with an empirical linear extrapolation method (LEM). A large positive free energy is assigned to the native protein, which is usually considered to be a minimum of the free energy.

Individual and Military Factors That Modify the Association Between Recent Sexual Trauma and Health Outcomes Among U.S. Service Members and Veterans.

Sexual trauma (ST), which includes both sexual harassment and sexual assault, is associated with a variety of adverse mental and physical health outcomes in military and civilian populations. However, little is known about whether certain individual or military attributes or prior experiences may modify the relationship between recent ST and mental or physical health outcomes. Data from a longitudinal cohort study of current and former military members were used to examine whether individual and military factors modify the association between recent ST and health outcomes (posttraumatic stress disorder, depression, multiple somatic symptoms, and insomnia).

Efficacy of activated carbon filtration and ozonation to remove persistent and mobile substances - A case study in two wastewater treatment plants.

Persistent and mobile (PM) substances are able to spread quickly in the water cycle and were thus identified as potentially problematic for the environment and water quality. If also toxic (PMT) or very persistent and very mobile (vPvM) their regulation under REACH as substances of very high concern is foreseen. Yet, knowledge on the effectiveness of advanced wastewater treatment in removing PM-substances from WWTP effluents is limited to few rather well-known chemicals.

P-glycoprotein (ABCB1) - weak dipolar interactions provide the key to understanding allocrite recognition, binding, and transport.

P-glycoprotein (ABCB1) is the first discovered mammalian member of the large family of ATP binding cassette (ABC) transporters. It facilitates the movement of compounds (called allocrites) across membranes, using the energy of ATP binding and hydrolysis. Here, we review the thermodynamics of allocrite binding and the kinetics of ATP hydrolysis by ABCB1.

Protein Stability─Analysis of Heat and Cold Denaturation without and with Unfolding Models.

Protein stability is important in many areas of life sciences. Thermal protein unfolding is investigated extensively with various spectroscopic techniques. The extraction of thermodynamic properties from these measurements requires the application of models.

Protein Unfolding-Thermodynamic Perspectives and Unfolding Models.

We review the key steps leading to an improved analysis of thermal protein unfolding. Thermal unfolding is a dynamic cooperative process with many short-lived intermediates. Protein unfolding has been measured by various spectroscopic techniques that reveal structural changes, and by differential scanning calorimetry (DSC) that provides the heat capacity change C(T).

Molecular understanding of calorimetric protein unfolding experiments.

Testing and predicting protein stability gained importance because proteins, including antibodies, became pharmacologically relevant in viral and cancer therapies. Isothermal scanning calorimetry is the principle method to study protein stability. Here, we use the excellent experimental heat capacity C(T) data from the literature for a critical inspection of protein unfolding as well as for the test of a new cooperative model.

The Millennium Cohort Study: The first 20 years of research dedicated to understanding the long-term health of US Service Members and Veterans.

Purpose: The Millennium Cohort Study, the US Department of Defense's largest and longest running study, was conceived in 1999 to investigate the effects of military service on service member health and well-being by prospectively following active duty, Reserve, and National Guard personnel from all branches during and following military service. In commemoration of the Study's 20th anniversary, this paper provides a summary of its methods, key findings, and future directions.

Methods: Recruitment and enrollment of the first 5 panels occurred between 2001 and 2021.

Islet vascularization is regulated by primary endothelial cilia via VEGF-A-dependent signaling.

Islet vascularization is essential for intact islet function and glucose homeostasis. We have previously shown that primary cilia directly regulate insulin secretion. However, it remains unclear whether they are also implicated in islet vascularization.

P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers.

P-glycoprotein or multidrug resistance protein (MDR1) is an adenosine triphosphate (ATP) binding cassette transporter (ABCB1) intensely investigated because it is an obstacle to successful pharmacotherapy of cancers. P-glycoprotein prevents cellular uptake of a large number of structurally and functionally diverse compounds, including most cancer therapeutics and in this way causes multidrug resistance (MDR). To overcome MDR, and thus improve cancer treatment, an understanding of P-glycoprotein inhibition at the molecular level is required.

Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing.

Diabetes mellitus affects one in eleven adults worldwide. Most suffer from Type 2 Diabetes which features elevated blood glucose levels and an inability to adequately secrete or respond to insulin. Insulin producing β-cells have primary cilia which are implicated in the regulation of glucose metabolism, insulin signaling and secretion.

Longitudinal Investigation of Military-specific Factors Associated With Continued Unhealthy Alcohol Use Among a Large US Military Cohort.

Objective: To examine whether military separation (Veteran), service component (active duty, Reserve/National Guard), and combat deployment are prospectively associated with continuing unhealthy alcohol use among US military service members.

Methods: Millennium Cohort Study participants were evaluated for continued or chronic unhealthy alcohol use, defined by screening positive at baseline and the next consecutive follow-up survey for heavy episodic, heavy weekly, or problem drinking. Participants meeting criteria for chronic unhealthy alcohol use were followed for up to 12 years to determine continued unhealthy use.

Phosphoproteomics Reveals the GSK3-PDX1 Axis as a Key Pathogenic Signaling Node in Diabetic Islets.

Progressive decline of pancreatic beta cell function is central to the pathogenesis of type 2 diabetes. Protein phosphorylation regulates glucose-stimulated insulin secretion from beta cells, but how signaling networks are remodeled in diabetic islets in vivo remains unknown. Using high-sensitivity mass spectrometry-based proteomics, we quantified 6,500 proteins and 13,000 phosphopeptides in islets of obese diabetic mice and matched controls, revealing drastic remodeling of key kinase hubs and signaling pathways.

Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans.

An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with diabetes-resistant B6-ob/ob mice.

Posttraumatic Stress Disorder Symptom Association With Subsequent Risky and Problem Drinking Initiation.

Objectives: Posttraumatic stress disorder (PTSD) and unhealthy alcohol use are commonly associated conditions. It is unknown whether specific symptoms of PTSD are associated with subsequent initiation of unhealthy alcohol use.

Methods: Data from the first 3 enrollment panels (n = 151,567) of the longitudinal Millennium Cohort Study of military personnel were analyzed (2001-2012).

Longitudinal Examination of the Influence of Individual Posttraumatic Stress Disorder Symptoms and Clusters of Symptoms on the Initiation of Cigarette Smoking.

Objectives: The aim of this study was to determine whether specific individual posttraumatic stress disorder (PTSD) symptoms or symptom clusters predict cigarette smoking initiation.

Methods: Longitudinal data from the Millennium Cohort Study were used to estimate the relative risk for smoking initiation associated with PTSD symptoms among 2 groups: (1) all individuals who initially indicated they were nonsmokers (n = 44,968, main sample) and (2) a subset of the main sample who screened positive for PTSD (n = 1622). Participants were military service members who completed triennial comprehensive surveys that included assessments of smoking and PTSD symptoms.

Limb- and Person-Level Risk Factors for Lower-Limb Amputation in the Prospective Seattle Diabetic Foot Study.

Objective: Diabetes is the leading cause of nontraumatic lower-limb amputations in the U.S., but no research has prospectively examined associations between limb-specific measurements and amputation risk among patients without foot ulcer.

Smoking and drinking behaviors of military spouses: Findings from the Millennium Cohort Family Study.

Introduction: The associations between stressful military experiences and tobacco use and alcohol misuse among Service members are well documented. However, little is known about whether stressful military experiences are associated with tobacco use and alcohol misuse among military spouses.

Methods: Using 9872 Service member-spouse dyads enrolled in the Millennium Cohort Family Study, we employed logistic regression to estimate the odds of self-reported cigarette smoking, risky drinking, and problem drinking among spouses by Service member deployment status, communication regarding deployment, and stress associated with military-related experiences, while adjusting for demographic, mental health, military experiences, and Service member military characteristics.

Patterns of Smoking and Unhealthy Alcohol Use Following Sexual Trauma Among U.S. Service Members.

In the first known longitudinal study of the topic, we examined whether experiencing sexual assault or sexual harassment while in the military was associated with increased risk for subsequent unhealthy alcohol use and smoking among U.S. service members in the Millennium Cohort Study (2001-2012).