Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors.

Membrane-engineered cells displaying antigen-targeting ligands are useful as both scientific tools and clinical therapeutics. While genetically encoded artificial receptors have proven efficacious, their scope remains limited, as this approach is not amenable to all cell types and the modification is often permanent. Our group has developed a nongenetic method to rapidly, stably, and reversibly modify any cell membrane with a chemically self-assembled nanoring (CSAN) that can function as a prosthetic receptor.

Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions.

Mercury (Hg) emissions pose a global problem that requires global cooperation for a solution. However, neither emissions nor regulations are uniform world-wide, and hence the impacts of regulations are also likely to vary regionally. We report here an approach to model the effectiveness of regulations at different scales (local, regional, global) in reducing Hg deposition and fish Hg concentrations in the Laurentian Great Lakes (GL) region.

Potential roles of inorganic phosphate on the progression of initially bound glucopyranose toward the nonenzymatic glycation of human hemoglobin: mechanistic diversity and impacts on site selectivity.

Nonenzymatic glycation (NEG) begins with the non-covalent binding of a glucopyranose to a protein. The bound glucopyranose must then undergo structural modification to generate a bound electrophile that can reversibly form a Schiff base, which can then lead to Amadori intermediates, and ultimately to glycated proteins. Inorganic phosphate (Pi) is known to accelerate the glycation of human hemoglobin (HbA), although the specific mechanism(s) of Pi as an effector reagent have not been determined.

Carcinogenicity assessment of the Hedgehog pathway inhibitor, vismodegib in Tg.rasH2 mice and Sprague-Dawley rats.

Vismodegib (also known as GDC-0449) is a novel small molecule inhibitor of the Hedgehog (Hh) signaling pathway currently approved for the treatment of metastatic or locally advanced basal cell carcinoma (BCC) in humans. Its tumorigenic potential was assessed in dedicated carcinogenicity studies in rasH2 transgenic (Tg.rasH2) mice and Sprague Dawley (SD) rats.

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI.

The Potential of Past Tense Marking in Oral Reading as a Clinical Marker of Specific Language Impairment in School-Age Children.

Purpose: The purpose of this study was twofold. The first aim was to explore differences in profiles of past tense marking in oral reading of school-age children with specific language impairment (SLI). The second aim was to explore the potential of past tense marking in oral reading as a clinical marker of SLI in school-age children.

Sweat mechanisms and dysfunctions in atopic dermatitis.

Skin barrier dysfunction is inherent to atopic dermatitis (AD), causing dryness, irritation, and increased permeability to irritants, allergens and pathogens. Eccrine sweat functions as part of the skin's protective barrier. Variations in sweat responses have been observed in patients with AD, and altered sweat composition and dynamics are under-recognized as important factors in the disease cycle.

Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety.

Objective: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis.

Methods: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression.

Tau directs intracellular trafficking by regulating the forces exerted by kinesin and dynein teams.

Organelles, proteins, and mRNA are transported bidirectionally along microtubules by plus-end directed kinesin and minus-end directed dynein motors. Microtubules are decorated by microtubule-associated proteins (MAPs) that organize the cytoskeleton, regulate microtubule dynamics and modulate the interaction between motor proteins and microtubules to direct intracellular transport. Tau is a neuronal MAP that stabilizes axonal microtubules and crosslinks them into bundles.

Acetylated Microtubules Are Preferentially Bundled Leading to Enhanced Kinesin-1 Motility.

The motor proteins kinesin and dynein transport organelles, mRNA, proteins, and signaling molecules along the microtubule cytoskeleton. In addition to serving as tracks for transport, the microtubule cytoskeleton directs intracellular trafficking by regulating the activity of motor proteins through the organization of the filament network, microtubule-associated proteins, and tubulin posttranslational modifications. However, it is not well understood how these factors influence motor motility, and in vitro assays and live cell observations often produce disparate results.

Fully robotic da Vinci Ivor-Lewis esophagectomy in four-arm technique-problems and solutions.

The aim of this technical note is a step-by-step description of a fully robotic abdominothoracic esophagectomy with an intrathoracic esophagogastrostomy. We report on our technique and short-term results of 75 patients undergoing an Ivor-Lewis esophagectomy using a fully robotic 4-arm approach in the abdominal and thoracic phase with a hand-sewn intrathoracic anastomosis. There are several important steps and differences to consider compared to the conventional minimal invasive approach (patient's positioning, anaesthesiological set up, port placement, gastric conduit pull up, technique of esophagostrostomy).

Tubuloreticular Inclusions in the Absence of Systemic Lupus Erythematosus and HIV Infection: A Report of Three Pediatric Cases.

Tubuloreticular inclusions (TRIs) are subcellular structures located within the cisternae of endoplasmic reticulum. Formation of TRIs has been linked to the exposure of excess interferon (IFN), either from endogenous or exogenous sources. In renal disease, TRIs have been most commonly associated with systemic lupus erythematosus (SLE), and human immunodeficiency virus-associated nephropathy (HIVAN).

Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants.

Iron supplementation may have adverse health effects in infants, probably through manipulation of the gut microbiome. Previous research in low-resource settings have focused primarily on anemic infants. This was a double blind, randomized, controlled trial of home fortification comparing multiple micronutrient powder (MNP) with and without iron.

Language Assessment With Children Who Speak Nonmainstream Dialects: Examining the Effects of Scoring Modifications in Norm-Referenced Assessment.

Purpose: We compared outcomes from 2 measures of language ability in children who displayed a range of dialect variation: 1 using features that do not contrast between mainstream American English (MAE) and nonmainstream dialects (NMAE), and 1 using contrastive features. We investigated how modified scoring procedures affected the diagnostic accuracy of the measure with contrastive features.

Method: Second-grade students (N = 299; 167 White, 106 African American, 26 other) completed measures of language variation and ability (the Diagnostic Evaluation of Language Variation-Screening Test and the Clinical Evaluation of Language Fundamentals-Fourth Edition [CELF-4]).

Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity.

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously.

Small-molecule stabilization of the p53 - 14-3-3 protein-protein interaction.

14-3-3 proteins are positive regulators of the tumor suppressor p53, the mutation of which is implicated in many human cancers. Current strategies for targeting of p53 involve restoration of wild-type function or inhibition of the interaction with MDM2, its key negative regulator. Despite the efficacy of these strategies, the alternate approach of stabilizing the interaction of p53 with positive regulators and, thus, enhancing tumor suppressor activity, has not been explored.

Renal-Limited "Lupus-Like" Nephritis: How Much of a Lupus?

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by development of autoantibodies to nuclear and cytoplasmic antigens. A small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative antinuclear antibody tests. Our report describes a 5-year-old male who presented with histopathological findings suggestive of lupus nephritis with no clinical signs or symptoms of SLE and negative autoantibodies.

Local inhibition of microtubule dynamics by dynein is required for neuronal cargo distribution.

Abnormal axonal transport is associated with neuronal disease. We identified a role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo distribution.

Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor Maintenance Therapy.

Background: Neurological disorders due to calcineurin inhibitor (CNI) treatment pose a well-known problem after liver transplantation (LTx). In this study, the impact of CNIs on cognitive functioning during maintenance therapy was analyzed. A possible improvement of cognitive functioning, compliance and health-related quality of life (HRQoL) after conversion to a once-daily tacrolimus formulation was prospectively assessed.

Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients - a prospective study.

Background: Detection of circulating (CTC) or disseminated tumor cells (DTC) has been associated with negative prognosis and outcome in patients with colorectal cancer, though testing for these cells is not yet part of clinical routine. There are several different methodological approaches to detect tumor cells but standardized detection assays are not implemented so far.

Methods: In this prospective monocentric study 299 patients with colon cancer were included.

Clinical and pathological features of hair coat abnormalities in curly coated retrievers from UK and Sweden.

Objectives: To gain information on hair loss amongst curly coated retrievers by questionnaire and to define the clinical and pathological features of hair coat abnormalities in affected dogs in the United Kingdom and Sweden.

Materials And Methods: Questionnaires were completed by members of the Curly Coated Retriever Clubs. Fourteen dogs (six in the United Kingdom, eight in Sweden) were clinically examined and skin/hair samples collected for microscopy and histopathology.

Measuring Molecular Forces Using Calibrated Optical Tweezers in Living Cells.

Optical tweezers have been instrumental in uncovering the mechanisms motor proteins use to generate and react to force. While optical traps have primarily been applied to purified, in vitro systems, emerging methods enable measurements in living cells where the actively fluctuating, viscoelastic environment and varying refractive index complicate calibration of the instrument. Here, we describe techniques to calibrate optical traps in living cells using the forced response to sinusoidal oscillations and spontaneous fluctuations, and to measure the forces exerted by endogenous ensembles of kinesin and dynein motor proteins as they transport cargoes in the cell.