PTPN2 Regulates Metabolic Flux to Affect β-Cell Susceptibility to Inflammatory Stress.

Protein tyrosine phosphatase N2 (PTPN2) is a type 1 diabetes (T1D) candidate gene identified from human genome-wide association studies. PTPN2 is highly expressed in human and murine islets and becomes elevated upon inflammation and models of T1D, suggesting that PTPN2 may be important for β-cell survival in the context of T1D. To test whether PTPN2 contributed to β-cell dysfunction in an inflammatory environment, we generated a β-cell-specific deletion of Ptpn2 in mice (PTPN2-β knockout [βKO]).

Ethical challenges of conducting and reviewing human genomics research in Malaysia: An exploratory study.

Even though there is a significant amount of scholarly work examining the ethical issues surrounding human genomics research, little is known about its footing in Malaysia. This study aims to explore the experience of local researchers and research ethics committee (REC) members in developing it in Malaysia. In-depth interviews were conducted from April to May 2021, and the data were thematically analysed.

A biomechanics dataset of healthy human walking at various speeds, step lengths and step widths.

The biomechanics of human walking are well documented for standard conditions such as for self-selected step length and preferred speed. However, humans can and do walk with a variety of other step lengths and speeds during daily living. The variation of biomechanics across gait conditions may be important for describing and determining the mechanics of locomotion.

Comprehensive proteomic quantification of bladder stone progression in a cystinuric mouse model using data-independent acquisitions.

Cystinuria is one of various disorders that cause biomineralization in the urinary system, including bladder stone formation in humans. It is most prevalent in children and adolescents and more aggressive in males. There is no cure, and only limited disease management techniques help to solubilize the stones.

TimTrack: A drift-free algorithm for estimating geometric muscle features from ultrasound images.

Ultrasound imaging is valuable for non-invasively estimating fascicle lengths and other features of pennate muscle, especially when performed computationally. Effective analysis techniques to date typically use optic flow to track displacements from image sequences, but are sensitive to integration drift for longer sequences. We here present an alternative algorithm that objectively estimates geometric features of pennate muscle from ultrasound images, without drift sensitivity.

Paradigmatic Relations Interact During the Production of Complex Words: Evidence From Variable Plurals in Dutch.

A growing body of work in psycholinguistics suggests that morphological relations between word forms affect the processing of complex words. Previous studies have usually focused on a particular type of paradigmatic relation, for example the relation between paradigm members, or the relation between alternative forms filling a particular paradigm cell. However, potential interactions between different types of paradigmatic relations have remained relatively unexplored.

Soft tissue deformations explain most of the mechanical work variations of human walking.

Humans perform mechanical work during walking, some by leg joints actuated by muscles, and some by passive, dissipative soft tissues. Dissipative losses must be restored by active muscle work, potentially in amounts sufficient to cost substantial metabolic energy. The most dissipative, and therefore costly, walking conditions might be predictable from the pendulum-like dynamics of the legs.

The high energetic cost of rapid force development in muscle.

Muscles consume metabolic energy for active movement, particularly when performing mechanical work or producing force. Less appreciated is the cost for activating muscle quickly, which adds considerably to the overall cost of cyclic force production. However, the cost magnitude relative to the cost of mechanical work, which features in many movements, is unknown.

The metabolic cost of constant muscle force production at zero net mechanical work.

The metabolic cost per unit force is generally thought to increase with the mechanical work done by the muscle fibres. It is currently unclear how the metabolic cost of doing alternating positive and negative muscle fibre mechanical work relates to the metabolic cost of doing zero muscle fibre mechanical work at similar muscle force. The current study aimed to investigate this issue by comparing metabolic power between a dynamic and an isometric near-constant force production task.

Mass Spectrometry-based Assay to Identify Drugs that Influence Cystine Solubility.

Cystinuria is a rare genetic disorder characterized by recurrent, painful kidney stones, primarily composed of cystine, the dimer of the amino acid cysteine (Sumorok and Goldfarb, 2013). Using a mouse model of cystinuria, we have recently shown that administration of drugs that increase cystine solubility in the urine can be a novel therapeutic strategy for the clinical management of the disease (Zee ., 2017).

Statistical heartburn: an attempt to digest four pizza publications from the Cornell Food and Brand Lab.

Background: We present the results of a reanalysis of four articles from the Cornell Food and Brand Lab based on data collected from diners at an Italian restaurant buffet.

Method: We calculated whether the means, standard deviations, and test statistics were compatible with the sample size. Test statistics and values were recalculated.

Are you mind-wandering, or is your mind on task? The effect of probe framing on mind-wandering reports.

The last decade has seen a dramatic rise in the number of studies that utilize the probe-caught method of collecting mind-wandering reports. This method involves stopping participants during a task, presenting them with a thought probe, and asking them to choose the appropriate report option to describe their thought-state. In this experiment we manipulated the framing of this probe, and demonstrated a substantial difference in mind-wandering reports as a function of whether the probe was presented in a mind-wandering frame compared with an on-task frame.

α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria.

Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1 mouse model of cystinuria by increasing the solubility of urinary cystine.

How Can People Be so Good at Intercepting Accelerating Objects if They Are so Poor at Visually Judging Acceleration?

People are known to be very poor at visually judging acceleration. Yet, they are extremely proficient at intercepting balls that fall under gravitational acceleration. How is this possible? We previously found that people make systematic errors when trying to tap on targets that move with different constant accelerations or decelerations on interleaved trials.

Why patients' disruptive behaviours impair diagnostic reasoning: a randomised experiment.

Background: Patients who display disruptive behaviours in the clinical encounter (the so-called 'difficult patients') may negatively affect doctors' diagnostic reasoning, thereby causing diagnostic errors. The present study aimed at investigating the mechanisms underlying the negative influence of difficult patients' behaviours on doctors' diagnostic performance.

Methods: A randomised experiment with 74 internal medicine residents.

Do patients' disruptive behaviours influence the accuracy of a doctor's diagnosis? A randomised experiment.

Background: Literature suggests that patients who display disruptive behaviours in the consulting room fuel negative emotions in doctors. These emotions, in turn, are said to cause diagnostic errors. Evidence substantiating this claim is however lacking.

A Drosophila model identifies a critical role for zinc in mineralization for kidney stone disease.

Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs.

The transcription factor early B-cell factor 1 regulates bone formation in an osteoblast-nonautonomous manner.

Early B-cell factor 1 (Ebf1) is a transcription factor whose inactivation in all cells results in high bone mass because of an increase in bone formation. This observation suggests Ebf1 may be an inhibitor of osteoblast differentiation. To test this contention, we analyzed Ebf1 pattern of expression and function in osteoblasts ex vivo and in vivo through osteoblast-specific inactivation in the mouse.

Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma.

Impaired lung function caused by decreased airway diameter (bronchoconstriction) is frequently observed whether body weight is abnormally high or low. That these opposite conditions affect the airways similarly suggests that the regulation of airway diameter and body weight are intertwined. We show here that, independently of its regulation of appetite, melanocortin pathway, or sympathetic tone, leptin is necessary and sufficient to increase airway diameter by signaling through its cognate receptor in cholinergic neurons.

T-cell protein tyrosine phosphatase regulates bone resorption and whole-body insulin sensitivity through its expression in osteoblasts.

Insulin signaling in osteoblasts contributes to whole-body glucose homeostasis in the mouse and in humans by increasing the activity of osteocalcin. The osteoblast insulin signaling cascade is negatively regulated by ESP, a tyrosine phosphatase dephosphorylating the insulin receptor. Esp is one of many tyrosine phosphatases expressed in osteoblasts, and this observation suggests that other protein tyrosine phosphatases (PTPs) may contribute to the attenuation of insulin receptor phosphorylation in this cell type.

The eliciting dose of peanut in double-blind, placebo-controlled food challenges decreases with increasing age and specific IgE level in children and young adults.

Background: Several risk factors for severe anaphylactic reactions to food in daily life are known. However, to date, it is not possible to predict the severity of allergic reactions to food in the individual patient with accuracy. Some studies show that a history of severe reactions is associated with a lower eliciting dose in double-blind, placebo-controlled food challenges (DBPCFCs).

Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population.

Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Delta4E4, R59Op, A337V, and L256P) in this population.

Analysis of pipecolic acid in biological fluids using capillary gas chromatography with electron-capture detection and [2H11]pipecolic acid as internal standard.

A sensitive and accurate stable isotope dilution assay was developed for the measurement of pipecolic acid in body fluids using capillary gas chromatography with electron-capture detection. The method utilizes [2H11]pipecolic acid as the internal standard. Sample preparation consisted of derivatization in aqueous solution (pH 11.