How Reproducible is the Synthesis of Zr-Porphyrin Metal-Organic Frameworks? An Interlaboratory Study.

Metal-organic frameworks (MOFs) are a rapidly growing class of materials that offer great promise in various applications. However, the synthesis remains challenging: for example, a range of crystal structures can often be accessed from the same building blocks, which complicates the phase selectivity. Likewise, the high sensitivity to slight changes in synthesis conditions may cause reproducibility issues.

Antigen-specific depletion of CD4 T cells by CAR T cells reveals distinct roles of higher- and lower-affinity TCRs during autoimmunity.

Both higher- and lower-affinity self-reactive CD4 T cells are expanded in autoimmunity; however, their individual contribution to disease remains unclear. We addressed this question using peptide-MHCII chimeric antigen receptor (pMHCII-CAR) T cells to specifically deplete peptide-reactive T cells in mice. Integration of improvements in CAR engineering with TCR repertoire analysis was critical for interrogating in vivo the role of TCR affinity in autoimmunity.

Adherence to the 2015 and 2020 British Society of Paediatric Endocrinology and Diabetes guidelines and outcomes in critically ill children with diabetic ketoacidosis: a retrospective cohort study.

Objectives: To compare clinical management and key outcomes of critically ill children with diabetic ketoacidosis (DKA) in two cohorts (2015 cohort: managed according to the 2015 British Society of Paediatric Endocrinology and Diabetes (BSPED) guidelines; 2020 cohort: managed according to the 2020 BSPED guidelines).

Design: Retrospective cohort study using prospectively collected data.

Setting: A critical care advice and transport service based in London, and referring hospitals within the critical care network.

Peripheral and Central/Intraosseous Vasoactive Infusions During and After Pediatric Critical Care Transport: Retrospective Cohort Study of Extravasation Injury.

Objectives: To compare the prevalence of adverse events related to vasoactive drug infusions administered via a peripheral venous catheter versus a central venous or intraosseous catheter.

Design: Retrospective observational study.

Setting: A pediatric critical care transport team, and the PICUs and regional hospitals within the North Thames and East Anglia regions of the United Kingdom.

Beyond online participant crowdsourcing: The benefits and opportunities of big team addiction science.

Participant crowdsourcing platforms (e.g., MTurk, Prolific) offer numerous advantages to addiction science, permitting access to hard-to-reach populations and enhancing the feasibility of complex experimental, longitudinal, and intervention studies.

Increasing availability of lower energy meals vs. energy labelling in virtual full-service restaurants: two randomized controlled trials in participants of higher and lower socioeconomic position.

Background: There are a range of interventions designed to promote healthier food choices in full-service restaurants. However, it is unclear how these interventions affect dietary choices in people of lower and higher socioeconomic position (SEP).

Methods: A total of 2091 US participants recruited online completed Study 1 (n = 1001) and Study 2 (n = 1090).

Respiratory Complex I in and Pumps Four Protons across the Membrane for Every NADH Oxidized.

Respiratory complex I couples electron transfer between NADH and ubiquinone to proton translocation across an energy-transducing membrane to support the proton-motive force that drives ATP synthesis. The proton-pumping stoichiometry of complex I ( the number of protons pumped for each two electrons transferred) underpins all mechanistic proposals. However, it remains controversial and has not been determined for any of the bacterial enzymes that are exploited as model systems for the mammalian enzyme.

The impact and efficacy of routine pulse oximetry screening for CHD in a local hospital.

Objectives: The objective of this study was to evaluate the impact and efficacy of pulse oximetry screening for CHD in a level-two neonatal unit without on-site access to paediatric echocardiography.

Methods: All neonatal unit admissions between 1 September, 2011 and 31 August, 2013 were reviewed to determine the outcomes of newborns identified by pulse oximetry screening. Record linkage with the National Congenital Heart Disease Audit allowed follow-up of newborns with a negative screening result.

Quantitative carbon detector for enhanced detection of molecules in foods, pharmaceuticals, cosmetics, flavors, and fuels.

Analysis of trace compounds, such as pesticides and other contaminants, within consumer products, fuels, and the environment requires quantification of increasingly complex mixtures of difficult-to-quantify compounds. Many compounds of interest are non-volatile and exhibit poor response in current gas chromatography and flame ionization systems. Here we show the reaction of trimethylsilylated chemical analytes to methane using a quantitative carbon detector (QCD; the Polyarc™ reactor) within a gas chromatograph (GC), thereby enabling enhanced detection (up to 10×) of highly functionalized compounds including carbohydrates, acids, drugs, flavorants, and pesticides.

A Self-Assembled Respiratory Chain that Catalyzes NADH Oxidation by Ubiquinone-10 Cycling between Complex I and the Alternative Oxidase.

Complex I is a crucial respiratory enzyme that conserves the energy from NADH oxidation by ubiquinone-10 (Q10) in proton transport across a membrane. Studies of its energy transduction mechanism are hindered by the extreme hydrophobicity of Q10, and they have so far relied on native membranes with many components or on hydrophilic Q10 analogues that partition into membranes and undergo side reactions. Herein, we present a self-assembled system without these limitations: proteoliposomes containing mammalian complex I, Q10, and a quinol oxidase (the alternative oxidase, AOX) to recycle Q10H2 to Q10.

Kinetic evidence against partitioning of the ubiquinone pool and the catalytic relevance of respiratory-chain supercomplexes.

In mitochondria, four respiratory-chain complexes drive oxidative phosphorylation by sustaining a proton-motive force across the inner membrane that is used to synthesize ATP. The question of how the densely packed proteins of the inner membrane are organized to optimize structure and function has returned to prominence with the characterization of respiratory-chain supercomplexes. Supercomplexes are increasingly accepted structural entities, but their functional and catalytic advantages are disputed.

Kinetic, spectroscopic, and theoretical assessment of associative and dissociative methanol dehydration routes in zeolites.

Mechanistic interpretations of rates and in situ IR spectra combined with density functionals that account for van der Waals interactions of intermediates and transition states within confining voids show that associative routes mediate the formation of dimethyl ether from methanol on zeolitic acids at the temperatures and pressures of practical dehydration catalysis. Methoxy-mediated dissociative routes become prevalent at higher temperatures and lower pressures, because they involve smaller transition states with higher enthalpy, but also higher entropy, than those in associative routes. These enthalpy-entropy trade-offs merely reflect the intervening role of temperature in activation free energies and the prevalence of more complex transition states at low temperatures and high pressures.

Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria.

The biguanide metformin is widely prescribed for Type II diabetes and has anti-neoplastic activity in laboratory models. Despite evidence that inhibition of mitochondrial respiratory complex I by metformin is the primary cause of its cell-lineage-specific actions and therapeutic effects, the molecular interaction(s) between metformin and complex I remain uncharacterized. In the present paper, we describe the effects of five pharmacologically relevant biguanides on oxidative phosphorylation in mammalian mitochondria.

A spectrophotometric coupled enzyme assay to measure the activity of succinate dehydrogenase.

Respiratory complex II (succinate:ubiquinone oxidoreductase) connects the tricarboxylic acid cycle to the electron transport chain in mitochondria and many prokaryotes. Complex II mutations have been linked to neurodegenerative diseases and metabolic defects in cancer. However, there is no convenient stoichiometric assay for the catalytic activity of complex II.

A guide for integration of proteomic data standards into laboratory workflows.

The development of the HUPO-Proteomics Standards Initiative standard data formats and Minimum Information About a Proteomics Experiment guidelines facilitate coordination within the scientific community. The data standards provide a framework to exchange and share data regardless of the source instrument or software. Nevertheless there remains a view that Proteomics Standards Initiative standards are challenging to use and integrate into routine laboratory pipelines.

A clue to the diagnosis of TAPVD.

Total anomalous pulmonary venous drainage (TAPVD) is a rare form of congenital heart disease where all four pulmonary veins drain to the systemic venous circulation. A term infant was found to have low oxygen saturations on the neonatal check and he was admitted to the neonatal intensive care unit. An increasing oxygen requirement necessitated invasive ventilation.

An analytical system for the characterization of highly heterogeneous mixtures of N-linked oligosaccharides.

A novel system for characterizing complex N-linked oligosaccharide mixtures that uses a combination of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), capillary electrophoresis (CE), and high-performance liquid chromatography (HPLC) has been developed. In this study, oligosaccharides released from recombinant TNK-tPA (tissue plasminogen activator) were derivatized with 5-amino-2-naphthalenesulfonic acid (ANSA). The negative charge imparted by the ANSA label facilitated the analysis of the oligosaccharides by MALDI-TOF MS by allowing the observation of both neutral and sialylated oligosaccharides in a single negative ion mode spectrum.

Selective clearance of glycoforms of a complex glycoprotein pharmaceutical caused by terminal N-acetylglucosamine is similar in humans and cynomolgus monkeys.

To understand how the carbohydrate moieties of a recombinant glycoprotein affected its pharmacokinetic (PK) properties, the glycan distribution was directly assessed from serial blood samples taken during PK studies in cynomolgus monkeys and humans. The protein studied was an immunoadhesin (lenercept), containing an Fc domain from human immunoglobulin G (IgG-1) and two copies of the extensively glycosylated extra cellular domain of tumor necrosis factor receptor p55. The protein was recovered in pure form using a dual column, immunoaffinity-reversed-phase high-performance liquid chromatography method.