Methods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures.

Tryptophan mannosylation, the covalent addition of an α-ᴅ-mannose sugar to a tryptophan side chain, is a post-translational modification (PTM) that can affect protein stability, folding, and interactions. Compared to other forms of protein glycosylation, it is relatively uncommon but is affected by conformational anomalies and modeling errors similar to those seen in N- and O-glycans in the Protein Data Bank (PDB). In this work, we report methods for detecting, building, and improving mannose structures linked to tryptophans.

Definition of sinonasal and otological exacerbation in patients with primary ciliary dyskinesia: an expert consensus.

Background: Recurrent infections of the nose, sinuses and ears are common problems for people with primary ciliary dyskinesia. While pulmonary exacerbations in primary ciliary dyskinesia are defined, there is no definition for ear-nose-throat exacerbations, a potential outcome for research and clinical trials.

Methods: We set up an expert panel of 24 ear-nose-throat specialists, respiratory physicians, other healthcare professionals and patients to develop consensus definitions of sinonasal and otological exacerbations in children and adults with primary ciliary dyskinesia for research settings.

Post-translational modifications in the Protein Data Bank.

Proteins frequently undergo covalent modification at the post-translational level, which involves the covalent attachment of chemical groups onto amino acids. This can entail the singular or multiple addition of small groups, such as phosphorylation; long-chain modifications, such as glycosylation; small proteins, such as ubiquitination; as well as the interconversion of chemical groups, such as the formation of pyroglutamic acid. These post-translational modifications (PTMs) are essential for the normal functioning of cells, as they can alter the physicochemical properties of amino acids and therefore influence enzymatic activity, protein localization, protein-protein interactions and protein stability.

Reproductive Capabilities of Female Nilgai () in Southern Texas.

Free-ranging nilgai antelope () are an understudied species, both on their native ranges of India, Pakistan, and Nepal and on their introduced ranges in southern Texas. Basic data related to population sizes, survival, reproduction, and recruitment are needed throughout their range to inform management and conservation decisions. We collected nilgai fetuses from 3 ranches in southern Texas, including East Foundation's El Sauz and Santa Rosa ranches, and the Norias Division of the King Ranch from 2018-2021.

Importance of the (Pro)renin Receptor in Activating the Renin-Angiotensin System During Normotensive and Preeclamptic Pregnancies.

Purpose Of Review: For a healthy pregnancy to occur, a controlled interplay between the maternal circulating renin-angiotensin-aldosterone system (RAAS), placental renin-angiotensin system (RAS) and intrarenal renin-angiotensin system (iRAS) is necessary. Functionally, both the RAAS and iRAS interact to maintain blood pressure and cardiac output, as well as fluid and electrolyte balance. The placental RAS is important for placental development while also influencing the maternal circulating RAAS and iRAS.

Treatment of moderate acute malnutrition through community health volunteers is a cost-effective intervention: Evidence from a resource-limited setting.

Treatment outcomes for acute malnutrition can be improved by integrating treatment into community case management (iCCM). However, little is known about the cost-effectiveness of this integrated nutrition intervention. The present study investigates the cost-effectiveness of treating moderate acute malnutrition (MAM) through community health volunteer (CHV) and integrating it with routine iCCM.

Physiological carry-over effects of variable precipitation are mediated by reproductive status in a long-lived ungulate.

In the age of global climate change, extreme climatic events are expected to increase in frequency and severity. Animals will be forced to cope with these novel stressors in their environment. Glucocorticoids (i.

The crystal structure of methanogen McrD, a methyl-coenzyme M reductase-associated protein.

Methyl-coenzyme M reductase (MCR) is a multi-subunit (αβγ) enzyme responsible for methane formation via its unique F cofactor. The genes responsible for producing MCR (mcrA, mcrB and mcrG) are typically colocated with two other highly conserved genes mcrC and mcrD. We present here the high-resolution crystal structure for McrD from a human gut methanogen Methanomassiliicoccus luminyensis strain B10.

The impacts of task shifting on the management and treatment of malnourished children in Northern Kenya: a cluster-randomized controlled trial.

Treating children with acute malnutrition can be challenging, particularly regarding access to healthcare facilities during treatment. Task shifting, a strategy of transferring specific tasks to health workers with shorter training and fewer qualifications, is being considered as an effective approach to enhancing health outcomes in primary healthcare. This study aimed to assess the effectiveness of integrating the treatment of acute malnutrition by community health volunteers into integrated community case management in two sub-counties in northern Kenya (Loima and Isiolo).

Framework of the strengths and challenges of clinically integrated trials: An expert panel report.

The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems.

Perceptions towards management of acute malnutrition by community health volunteers in northern Kenya.

Child undernutrition is a persistent challenge in arid and semi-arid areas due to low and erratic rainfall, recurrent droughts and food insecurity. In these settings, caregivers face several challenges in accessing health services for sick and/or malnourished children, including long distances to health facilities, harsh terrain, and lack of money to pay for transportation costs to the health facilities, leading to low service coverage and sub-optimal treatment outcomes. To address these challenges and optimize treatment outcomes, the World Health Organization recommends utilizing community health volunteers (CHVs) to manage acute malnutrition in the community.

Monitoring carbohydrate 3D structure quality with the database.

The remediation of the carbohydrate data of the Protein Data Bank (PDB) has brought numerous enhancements to the findability and interpretability of deposited glycan structures, yet crucial quality indicators are either missing or hard to find on the PDB pages. Without a way to access wider glycochemical context, problematic structures may be taken as fact by keen but inexperienced scientists. The software is a validation and analysis tool that provides access to a number of metrics and links to external experimental resources, allowing users to evaluate structures using carbohydrate-specific methods.

The soluble (pro)renin receptor promotes a preeclampsia-like phenotype both in vitro and in vivo.

Preeclampsia is classified as new-onset hypertension coupled with gross endothelial dysfunction. Placental (pro)renin receptor ((P)RR) and plasma soluble (P)RR (s(P)RR) are elevated in patients with preeclampsia. Thus, we aimed to interrogate the role (P)RR may play in the pathogenesis of preeclampsia.

Measuring Cognitive Function and Cognitive Decline With Response Time Data in the National Social Life, Health, and Aging Project.

Objectives: Scholarly, clinical, and policy interest in cognitive function has grown over the last several decades in part due to large increases in Alzheimer's disease and related dementias as populations age. However, adequate measures of cognitive function have not been available in many research data sets. We argue that a wealth of previously unexploited survey data exists to model cognition and cognitive decline.

Online carbohydrate 3D structure validation with the Privateer web app.

Owing to the difficulties associated with working with carbohydrates, validating glycan 3D structures prior to deposition into the Protein Data Bank has become a staple of the structure-solution pipeline. The Privateer software provides integrative methods for the validation, analysis, refinement and graphical representation of 3D atomic structures of glycans, both as ligands and as protein modifiers. While Privateer is free software, it requires users to install any of the structural biology software suites that support it or to build it from source code.

Crystal Structures of Bacterial Pectin Methylesterases Pme8A and PmeC2 from Rumen .

Pectin is a complex polysaccharide that forms a substantial proportion of the plant's middle lamella of forage ingested by grazing ruminants. Methanol in the rumen is derived mainly from methoxy groups released from pectin by the action of pectin methylesterase (PME) and is subsequently used by rumen methylotrophic methanogens that reduce methanol to produce methane (CH). Members of the genus are key pectin-degrading rumen bacteria that contribute to methanol formation and have important roles in fibre breakdown, protein digestion, and the biohydrogenation of fatty acids.

Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity.

The (pro)renin receptor ((P)RR; also known as ) is a multifunctional receptor. The (P)RR activates the tissue renin-angiotensin system (RAS) and is also involved in regulating integral intracellular pathways such as V-ATPase and Wnt/β-catenin signalling. Given this, the (P)RR may be associated with essential pathways in placentation, however its role within the context of pregnancy remains poorly characterised.

Lessons From COVID-19 for Pandemic Preparedness: Proceedings From a Multistakeholder Think Tank.

While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic.

Personalising airway clearance in chronic suppurative lung diseases: a scoping review.

Background: Personalised airway clearance techniques are commonly recommended to augment mucus clearance in chronic suppurative lung diseases. It is unclear what current literature tells us about how airway clearance regimens should be personalised. This scoping review explores current research on airway clearance technique in chronic suppurative lung diseases, to establish the extent and type of guidance in this area, identify knowledge gaps and determine the factors which physiotherapists should consider when personalising airway clearance regimens.

Analysis and validation of overall N-glycan conformation in Privateer.

The oligosaccharides in N-glycosylation provide key structural and functional contributions to a glycoprotein. These contributions are dependent on the composition and overall conformation of the glycans. The Privateer software allows structural biologists to evaluate and improve the atomic structures of carbohydrates, including N-glycans; this software has recently been extended to check glycan composition through the use of glycomics data.

Myofibroblast senescence promotes arrhythmogenic remodeling in the aged infarcted rabbit heart.

Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and accelerate age-associated diseases.

Utility of 3D Printed Models Versus Cadaveric Pathology for Learning: Challenging Stated Preferences.

Introduction: 3D printing has recently emerged as an alternative to cadaveric models in medical education. A growing body of research supports the use of 3D printing in this context and details the beneficial educational outcomes. Prevailing studies rely on participants' stated preferences, but little is known about actual student preferences.

Development of a low resource exercise rehabilitation application for musculoskeletal disorders to help underserved patients in a primary care setting.

Objective: We set out to create a Family Medicine EHR (electronic health record) embedded exercise application. This was done to evaluate the utility of the exercise app for providers and to understand the usefulness of the exercise app from the perspective of patients.

Methods: This exercise application was developed through an iterative process with repeated pre-testing and feedback from an interprofessional team and embedded into the EHR at an academic family medicine clinic.

Structural characterisation of methanogen pseudomurein cell wall peptide ligases homologous to bacterial MurE/F murein peptide ligases.

Archaea have diverse cell wall types, yet none are identical to bacterial peptidoglycan (murein). Methanogens and possess cell walls of pseudomurein, a structural analogue of murein. Pseudomurein differs from murein in containing the unique archaeal sugar -acetyltalosaminuronic acid instead of -acetylmuramic acid, β-1,3 glycosidic bonds in place of β-1,4 bonds and only l-amino acids in the peptide cross-links.

The Impact on Parents of Diagnosing PCD in Young Children.

Primary ciliary dyskinesia (PCD) is an incurable, rare, inherited, chronic condition. Treatment includes the regular clearing of airway mucus, aggressive treatment of infections and management of hearing loss. Caregiver burden has not been explored, hence we interviewed 18 mothers and 6 fathers of children under 6 years to understand the impact of diagnostic testing and implications of a positive diagnosis.