1,2,3,4-Tetrafluorobiphenylene: A Prototype Janus-Headed Scaffold for Ambipolar Materials.

The title compound was synthesized by Ullmann cross-coupling in low yield as the first representative of [n]phenylene containing hydrocarbon and fluorocarbon rings. Stille/Suzuki-Miyaura cross-coupling reactions, as well as substitution of fluorine in suitable starting compounds, failed to give the same product. The geometric and electronic structures of the title compound were studied by X-ray diffraction, cyclic voltammetry and density functional theory calculations, together with Hirshfeld surface and reduced density gradient analyses.

Validity and Reliability of a Site-Level Assessment Questionnaire to Assess Nutrition and Physical Activity Practices in Schools.

Schools are an ideal setting for policy, systems, and environmental approaches to obesity prevention. Although school health environment assessments exist for planning purposes, we developed and tested a comprehensive questionnaire that is suitable for both evaluation and planning. Reliability was measured by comparing data collected by school personnel from low-income elementary schools across California at two time points, an average of 2 months apart ( = 23).

A salvage pathway maintains highly functional respiratory complex I.

Regulation of the turnover of complex I (CI), the largest mitochondrial respiratory chain complex, remains enigmatic despite huge advancement in understanding its structure and the assembly. Here, we report that the NADH-oxidizing N-module of CI is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI arising from the inactivation of the N-module subunits due to attrition caused by its constant activity under physiological conditions.

Reducing Hematologic Toxicity With Short Course Postexposure Prophylaxis With Zidovudine for HIV-1 Exposed Infants With Low Transmission Risk.

Using retrospectively collected data from 383 infants born to HIV-1-infected mothers receiving antiretroviral therapy, we compared transmission rates and hematologic toxicity between infants receiving 2-week (short course) versus longer duration zidovudine postexposure prophylaxis. Short course resulted in lower hematologic toxicity without evidence of increased vertical transmission risk.

Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset.

Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 () gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid-associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease. Clinical and laboratory data of 38 patients (17 males, 21 females, from 29 families) with homozygous or (compound) heterozygous mutations were retrospectively collected.

Improvements in Physical Activity Opportunities: Results From a Community-Based Family Child Care Intervention.

Introduction: Reaching preschool-aged children to establish healthy lifestyle habits, including physical activity, is an important component of obesity prevention efforts. However, few studies have examined family child care homes where nearly 1 million children receive care.

Study Design: A pre- and post-intervention evaluation without a control group was conducted to evaluate what changes occurred in family child care homes that participated in the Healthy Eating and Active Living project, a multicomponent obesity prevention initiative, focused on community-driven policy and environmental change in neighborhoods within Kaiser Permanente service areas.

Changes in Nutrition Policies and Dietary Intake in Child Care Homes Participating in Healthy Eating and Active Living Initiative.

Introduction: From 2012 to 2014, a total of 17 family child care homes participated in a multisector, community-wide initiative to prevent obesity. Strategies included staff workshops, materials, site visits, and technical assistance regarding development and implementation of nutrition policies. The purpose of the evaluation was to examine the impact of the initiative on family child care home nutrition-related policies and practices and child dietary intake.

CLPP deficiency protects against metabolic syndrome but hinders adaptive thermogenesis.

Mitochondria are fundamental for cellular metabolism as they are both a source and a target of nutrient intermediates originating from converging metabolic pathways, and their role in the regulation of systemic metabolism is increasingly recognized. Thus, maintenance of mitochondrial homeostasis is indispensable for a functional energy metabolism of the whole organism. Here, we report that loss of the mitochondrial matrix protease CLPP results in a lean phenotype with improved glucose homeostasis.

[Frequency and Timing of Decisions to Limit Intensive Medical Care and Tumor-Specific Therapy in University Hematology and Oncology].

 Decisions to limit treatment (DLT) are important in order to prevent overtreatment at the end of life. However, they are not always discussed with the patient in advance or sufficiently documented. In a study to improve DLT in patients with an advanced hematological/ oncological disease we examined how often DLT precede deaths and how early they are determined.

Ascites' neutrophil function is significantly impaired in patients with decompensated cirrhosis but can be restored by autologous plasma incubation.

Systemic immune cell dysfunction is a typical feature of liver diseases and increases the risk of bacterial infection, especially spontaneous bacterial peritonitis. We evaluated functional properties of neutrophil granulocytes in blood and ascites of patients both with and without decompensated cirrhosis. We collected blood and ascites samples from 63 patients with cirrhosis and eight without cirrhosis.

CLPP coordinates mitoribosomal assembly through the regulation of ERAL1 levels.

Despite being one of the most studied proteases in bacteria, very little is known about the role of ClpXP in mitochondria. We now present evidence that mammalian CLPP has an essential role in determining the rate of mitochondrial protein synthesis by regulating the level of mitoribosome assembly. Through a proteomic approach and the use of a catalytically inactive CLPP, we produced the first comprehensive list of possible mammalian ClpXP substrates involved in the regulation of mitochondrial translation, oxidative phosphorylation, and a number of metabolic pathways.

Impact of the Berkeley Excise Tax on Sugar-Sweetened Beverage Consumption.

Objectives: To evaluate the impact of the excise tax on sugar-sweetened beverage (SSB) consumption in Berkeley, California, which became the first US jurisdiction to implement such a tax ($0.01/oz) in March 2015.

Methods: We used a repeated cross-sectional design to examine changes in pre- to posttax beverage consumption in low-income neighborhoods in Berkeley versus in the comparison cities of Oakland and San Francisco, California.

Loss of CLPP alleviates mitochondrial cardiomyopathy without affecting the mammalian UPRmt.

The mitochondrial matrix protease CLPP plays a central role in the activation of the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans Far less is known about mammalian UPR(mt) signaling, although similar roles were assumed for central players, including CLPP To better understand the mammalian UPR(mt) signaling, we deleted CLPP in hearts of DARS2-deficient animals that show robust induction of UPR(mt) due to strong dysregulation of mitochondrial translation. Remarkably, our results clearly show that mammalian CLPP is neither required for, nor it regulates the UPR(mt) in mammals. Surprisingly, we demonstrate that a strong mitochondrial cardiomyopathy and diminished respiration due to DARS2 deficiency can be alleviated by the loss of CLPP, leading to an increased de novo synthesis of individual OXPHOS subunits.

Hepatitis B surface antigen genetic elements critical for immune escape correlate with hepatitis B virus reactivation upon immunosuppression.

Unlabelled: Hepatitis B virus (HBV) reactivation during immunosuppression can lead to severe acute hepatitis, fulminant liver failure, and death. Here, we investigated hepatitis B surface antigen (HBsAg) genetic features underlying this phenomenon by analyzing 93 patients: 29 developing HBV reactivation and 64 consecutive patients with chronic HBV infection (as control). HBsAg genetic diversity was analyzed by population-based and ultradeep sequencing (UDS).

Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity.

Although mitochondrial dysfunction is often accompanied by excessive reactive oxygen species (ROS) production, we previously showed that an increase in random somatic mtDNA mutations does not result in increased oxidative stress. Normal levels of ROS and oxidative stress could also be a result of an active compensatory mechanism such as a mild increase in proton leak. Uncoupling protein 2 (UCP2) was proposed to play such a role in many physiological situations.

Protein expression from exogenous mRNA: uptake by receptor-mediated endocytosis and trafficking via the lysosomal pathway.

Insertional mutagenesis and the inherent risk of malignancy compromise the clinical use of DNA-based therapies. Being a transient copy of genetic material, mRNA is a safe alternative, overcoming this limitation. As a prerequisite for the development of efficient mRNA-based therapies, we investigated the cellular uptake and intracellular fate of mRNA for the first time.

Identification of an aliphatic epoxide and the corresponding dihydrodiol as novel congeners of zearalenone in cultures of Fusarium graminearum.

The mycotoxin zearalenone (ZEN) is produced by various Fusarium fungi and frequently found as a contaminant in food and feed. There are reports in the literature that several closely related analogues of ZEN are also formed in cultures of Fusarium species. We have therefore analyzed the organic extract from a 40 day culture of Fusarium graminearum by LC-DAD-MS and detected 15 compounds, which could be congeners of ZEN because of their ultraviolet, mass spectroscopy, and tandem mass spectroscopy spectra.

Lack of HLA class II antigen expression in microsatellite unstable colorectal carcinomas is caused by mutations in HLA class II regulatory genes.

Colorectal cancers (CRCs) develop on the basis of a deficient DNA mismatch repair (MMR) system in about 15% of cases. MMR-deficient CRC lesions show high-level microsatellite instability (MSI-H) and accumulate numerous mutations located at coding microsatellite loci that lead to the generation of immunogenic neopeptides. Consequently, the host's antitumoral immune response is of high importance for the course of the disease in MSI-H CRC patients.

Immunoselective pressure and human leukocyte antigen class I antigen machinery defects in microsatellite unstable colorectal cancers.

In colorectal cancer, the immune response is particularly pronounced against tumors displaying the high microsatellite instability (MSI-H) phenotype. MSI-H tumors accumulate mutations affecting microsatellites located within protein encoding regions (coding microsatellites, cMS), which lead to translational shifts of the respective reading frames. Consequently, novel tumor-specific frameshift-derived neopeptides (FSP) are generated and presented by MSI-H tumor cells, thus eliciting effective cytotoxic immune responses.