Spatial hepatocyte plasticity of gluconeogenesis during the metabolic transitions between fed, fasted and starvation states.

The liver acts as a master regulator of metabolic homeostasis in part by performing gluconeogenesis. This process is dysregulated in type 2 diabetes, leading to elevated hepatic glucose output. The parenchymal cells of the liver (hepatocytes) are heterogeneous, existing on an axis between the portal triad and the central vein, and perform distinct functions depending on location in the lobule.

Crystal Packing Reveals a Potential Autoinhibited KRAS Dimer Interface and a Strategy for Small-Molecule Inhibition of RAS Signaling.

KRAS GTPases harbor oncogenic mutations in more than 25% of human tumors. KRAS is considered to be largely undruggable due to the lack of a suitable small-molecule binding site. Here, we report a unique crystal structure of His-tagged KRAS that reveals a remarkable conformational change.

Exploring Covalent Bond Formation at Tyr-82 for Inhibition of Ral GTPase Activation.

Ral RAS GTPases are directly activated by KRAS through a trimeric complex with a guanine exchange factor. Ral is considered undruggable and lacks an accessible cysteine for covalent drug development. Previously we had reported an aryl sulfonyl fluoride fragment that formed a covalent bond at Tyr-82 on Ral and created a deep and well-defined pocket.

Evaluation of Derivatives of (+)-Puupehenone against and Other Gram-Positive Bacteria.

Patients receiving healthcare are at higher risk of acquiring healthcare-associated infections, which cause a significant number of illnesses and deaths. Most pathogens responsible for these infections are highly resistant to multiple antibiotics, prompting the need for discovery of new therapeutics to combat these evolved threats. We synthesized structural derivatives of (+)-puupehenone, a marine natural product, and observed growth inhibition of several clinically relevant Gram-positive bacteria, particularly .

Synthesis and Evaluation of Marine Natural Product-Inspired Meroterpenoids with Selective Activity toward Dormant .

Tuberculosis is a disease caused primarily by the organism (), which claims about 1.5 million lives every year. A challenge that impedes the elimination of this pathogen is the ability of to remain dormant after primary infection, thus creating a reservoir for the disease in the population that reactivates under more ideal conditions.

Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes against Species.

Tetrahydrolipstatin (THL, ) has been shown to inhibit both mammalian and bacterial α/β hydrolases. In the case of bacterial systems, THL is a known inhibitor of several hydrolases involved in mycomembrane biosynthesis. Herein we report a highly efficient eight-step asymmetric synthesis of THL using a route that allows modification of the THL α-chain substituent to afford compounds through .

Photocatalytic Ozonation Performance In Landfill Leachate Treatment.

This work aims to identify the best treatment condition for removal of chemical oxigen demand (COD) and increase of biodegradability in an advanced oxidative process of photocatalytic ozonation with titanium dioxide (TiO2), applied to the remediation of the leachate produced at the municipal landfill of Campo Mourão, Paraná. The experiment was carried out using a photocatalytic chamber and an ozonation system based on the corona effect. A statistical model of the central composite rotatable design (CCRD) was elaborated and three variables (pH, TiO2 dose and airflow) were analyzed, to define the optimum condition that allows the highest perfomance of the treatment.

Predictive Modeling of 30-Day Emergency Hospital Transport of German Patients Using a Personal Emergency Response: Retrospective Study and Comparison with the United States.

Background: Predictive analytics based on data from remote monitoring of elderly via a personal emergency response system (PERS) in the United States can identify subscribers at high risk for emergency hospital transport. These risk predictions can subsequently be used to proactively target interventions and prevent avoidable, costly health care use. It is, however, unknown if PERS-based risk prediction with targeted interventions could also be applied in the German health care setting.

The Role of the Neighborhood Social Environment in Physical Activity among Hispanic Children: Moderation by Cultural Factors and Mediation by Neighborhood Norms.

Little is known about how the neighborhood social environment (e.g., safety, crime, traffic) impacts child physical activity.

Evaluating the Impact of a Risk Assessment System With Tailored Interventions in Germany: Protocol for a Prospective Study With Matched Controls.

Background: With a worldwide increase in the elderly population, and an associated increase in health care utilization and costs, preventing avoidable emergency department visits and hospitalizations is becoming a global priority. A personal emergency response system (PERS), consisting of an alarm button and a means to establish a live connection to a response center, can help the elderly live at home longer independently. Individual risk assessment through predictive modeling can help indicate what PERS subscribers are at elevated risk of hospital transport so that early intervention becomes possible.

Neuroprotective and Anti-neuroinflammatory Properties of Ebselen Derivatives and Their Potential to Inhibit Neurodegeneration.

Ebselen (EBS) is an organo-selenium-containing compound that has anti-inflammatory, antitumor, and antibacterial properties. EBS is being explored as a possible treatment for reperfusion injury and stroke and is under clinical trials as a mimetic of lithium for the treatment of bipolar disorder [Mota et al. 2020, 74 (7), 1-6] and noise-induced hearing loss as a result of these actives [Martini et al.

Chemical characterization of marijuana blunt smoke by non-targeted chemical analysis.

Marijuana blunts, which are tobacco cigar wrappers filled with marijuana, are commonly smoked in the US as a means of cannabis use. The use of marijuana blunts presents toxicity concerns because the smoke contains both marijuana-related and tobacco-related chemicals. Thus, it is important to understand the chemical composition of mainstream smoke (MSS) from marijuana blunts.

Living in High-SES Neighborhoods Is Protective against Obesity among Higher-Income Children but Not Low-Income Children: Results from the Healthy Communities Study.

Numerous studies have focused on the role of neighborhood socioeconomic status in childhood obesity and physical activity, but few studies have examined the effect of neighborhood socioeconomic changes over time and the interaction between family and neighborhood SES on childhood obesity and physical activity. This study measured neighborhood socioeconomic histories between 2000 and 2010 and examined the associations between neighborhood socioeconomic histories and childhood obesity, as well as physical activity. The moderating role of family poverty status was also examined.

Biochemical and microbiological evaluation of -aryl urea derivatives against mycobacteria and mycobacterial hydrolases.

A focused library of 24 -aryl urea derivatives was prepared and evaluated against serine esterases of () Rv3802c and Ag85C. The members of the library were evaluated for both selectivity and mode of inhibition. Furan-based urea derivative was found to be the most potent non-covalent inhibitor of Rv3802c with a value of 5.

Associations of community programs and policies with children's dietary intakes: the Healthy Communities Study.

Background: The impact of community-based obesity prevention efforts on child nutrition has not been adequately studied.

Objective: Examine relationships between number, type and intensity of community programs and policies (CPPs) and child nutrition.

Methods: An observational study of 5138 children (grades K-8) in 130 U.

Community characteristics modify the relationship between obesity prevention efforts and dietary intake in children: the Healthy Communities Study.

Background: The influence of community characteristics on the effectiveness of childhood obesity prevention efforts is not well understood.

Objective: Examine the interaction of community characteristics with the relationship between community programmes and policies (CPPs) and dietary intake.

Methods: An observational study of 5138 children in grades K-8 in 130 US communities was conducted in 2013-2015.

Objectives of community policies and programs associated with more healthful dietary intakes among children: findings from the Healthy Communities Study.

Background: Rational planning of community policies and programs (CPPs) to prevent obesity requires an understanding of CPP objectives associated with dietary behaviours.

Objective: The objective of the study is to identify objectives of CPPs associated with healthful dietary behaviours.

Methods: An observational study identified 4026 nutrition CPPs occurring in 130 communities in the prior 6 years.

Association between community characteristics and implementation of community programmes and policies addressing childhood obesity: the Healthy Communities Study.

Background: Little is known about whether characteristics of communities are associated with differential implementation of community programmes and policies to promote physical activity and healthy eating. This study examines associations between community characteristics (e.g.

Associations between community programmes and policies and children's physical activity: the Healthy Communities Study.

Background: Community initiatives to promote physical activity in children are common, but evidence supporting their effectiveness is limited.

Objectives: The objective of this study is to examine the relationships between community programmes and policies and children's physical activity in a large and diverse sample of US communities.

Methods: Programmes and policies to promote children's physical activity were assessed in 130 communities by key informant interviews, and physical activity behaviours were measured by self-report and parental report in samples of children in each community (total n = 5138).

The longitudinal relationship between community programmes and policies to prevent childhood obesity and BMI in children: the Healthy Communities Study.

Background: Although a national epidemic of childhood obesity is apparent, how community-based programmes and policies (CPPs) affect this outcome is not well understood.

Objectives: This study examined the longitudinal relationship between the intensity of CPPs in 130 communities over 10 years and body mass index (BMI) of resident children. We also examined whether these relationships differ by key family or community characteristics.

Neuroprosthetic-enabled control of graded arm muscle contraction in a paralyzed human.

Neuroprosthetics that combine a brain computer interface (BCI) with functional electrical stimulation (FES) can restore voluntary control of a patients' own paralyzed limbs. To date, human studies have demonstrated an "all-or-none" type of control for a fixed number of pre-determined states, like hand-open and hand-closed. To be practical for everyday use, a BCI-FES system should enable smooth control of limb movements through a continuum of states and generate situationally appropriate, graded muscle contractions.

Community Policies and Programs to Prevent Obesity and Child Adiposity.

Introduction: Evidence regarding impact of community policies and programs (CPPs) to prevent child obesity is limited, and which combinations of strategies and components are most important is not understood. The Healthy Communities Study was an observational study to assess relationships of characteristics and intensity of CPPs with adiposity, diet, and physical activity in children, taking advantage of variation across the U.S.

Mechanical Ventilation and Cytopathological Changes in the Oral Mucosa.

Background: The oral mucosa is an important defense barrier to penetration of microorganisms. Thus, changes in the oral epithelium might indicate risk for infection in intensive care patients receiving mechanical ventilation.

Objective: To evaluate the oral mucosa of intensive care patients who did or did not receive mechanical ventilation by using liquid-base exfoliative cytology.

Community-based HCV screening: knowledge and attitudes in a high risk urban population.

Background: In an attempt to curtail the rising morbidity and mortality from undiagnosed HCV (hepatitis C virus) in the United States, screening guidelines have been expanded to high-risk individuals and persons born 1945-1965. Community-based screening may be one strategy in which to reach such persons; however, the acceptance of HCV testing, when many high-risk individuals may not have access to HCV specific medications, remains unknown.

Methods: We set out to assess attitudes about HCV screening and knowledge about HCV disease at several community-based testing sites that serve high-risk populations.