SEC-SAXS/MC Ensemble Structural Studies of the Microtubule Binding Protein Cdt1 Show Monomeric, Folded-Over Conformations.

Cdt1 is a mixed folded protein critical for DNA replication licensing and it also has a "moonlighting" role at the kinetochore via direct binding to microtubules and the Ndc80 complex. However, it is unknown how the structure and conformations of Cdt1 could allow it to participate in these multiple, unique sets of protein complexes. While robust methods exist to study entirely folded or unfolded proteins, structure-function studies of combined, mixed folded/disordered proteins remain challenging.

Economy-wide impact of a reduction in tobacco use in India.

Background: Public policy measures aimed at regulating tobacco use should consider the net gains for the nation, as the tobacco sector contributes to employment and tax revenue while also imposing substantial economic burden on the country. This study investigates the economy-wide impact of reducing tobacco consumption in India through the implementation of fiscal measures.

Methods: The study uses a computable general equilibrium model based on the Global Trade Analysis Project model and database and augments the same with several country-specific information on tobacco products, to examine the macroeconomic impact of a targeted reduction in the consumption of bidis, cigarettes and smokeless tobacco by 10% by the year 2026 through the adoption of fiscal measures.

Feasibility and efficacy of virtual reality rehabilitation compared with conventional physiotherapy for upper extremity impairment due to ischaemic stroke: protocol for a randomised controlled trial.

Introduction: Approximately half of all stroke survivors have persistent upper extremity functional impairment, leading to reduced self-care, independence and quality of life. High-intensity, task-oriented virtual reality rehabilitation improves motor recovery. However, its clinical efficacy over standard rehabilitation remains uncertain.

A Computational Model of Deep Brain Stimulation for Parkinson's Disease Tremor and Bradykinesia.

Parkinson's disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD.

How hydrophobicity, side chains, and salt affect the dimensions of disordered proteins.

Despite the generally accepted role of the hydrophobic effect as the driving force for folding, many intrinsically disordered proteins (IDPs), including those with hydrophobic content typical of foldable proteins, behave nearly as self-avoiding random walks (SARWs) under physiological conditions. Here, we tested how temperature and ionic conditions influence the dimensions of the N-terminal domain of pertactin (PNt), an IDP with an amino acid composition typical of folded proteins. While PNt contracts somewhat with temperature, it nevertheless remains expanded over 10-58°C, with a Flory exponent, ν, >0.

AI Can Improve the Economics of Blindness Prevention in Canada.

Diabetic retinopathy is a leading cause of vision loss in Canada and creates significant economic and social burden on patients. Diabetic retinopathy is largely a preventable complication of diabetes mellitus. Yet, hundreds of thousands of Canadians continue to be at risk and thousands go on to develop vision loss and disability.

SAXS/MC studies of the mixed-folded protein Cdt1 reveal monomeric, folded over conformations.

Cdt1 is a protein critical for DNA replication licensing and is well-established to be a binding partner of the minichromosome maintenance (MCM) complex. Cdt1 has also been demonstrated to have an emerging, "moonlighting" role at the kinetochore via direct binding to microtubules and to the Ndc80 complex. However, it is not known how the structure and conformations of Cdt1 could allow for these multiple, completely unique sets of protein complexes.

A Deep Learning Framework with an Intermediate Layer Using the Swarm Intelligence Optimizer for Diagnosing Oral Squamous Cell Carcinoma.

One of the most prevalent cancers is oral squamous cell carcinoma, and preventing mortality from this disease primarily depends on early detection. Clinicians will greatly benefit from automated diagnostic techniques that analyze a patient's histopathology images to identify abnormal oral lesions. A deep learning framework was designed with an intermediate layer between feature extraction layers and classification layers for classifying the histopathological images into two categories, namely, normal and oral squamous cell carcinoma.

Anti-obesity effects of olivetol in adult zebrafish model induced by short-term high-fat diet.

Obesity is a complex disease caused by various factors, and synthetic drugs used to treat it can have side effects. Natural compounds, such as olivetol, could be a promising alternative. Olivetol is a substance found in certain lichen species and has anti-inflammatory and anti-cancer properties.

Efficient community detection in multilayer networks using boolean compositions.

Networks (or graphs) are used to model the dyadic relations between entities in complex systems. Analyzing the properties of the networks reveal important characteristics of the underlying system. However, in many disciplines, including social sciences, bioinformatics, and technological systems, multiple relations exist between entities.

Use, misuse, and overuse of antenatal corticosteroids. A retrospective cohort study.

Objectives: To evaluate the timing of antenatal corticosteroids (ACS) administration in relation to the delivery timing based on indications and risk factors for preterm delivery.

Methods: We conducted a retrospective cohort study to understand what factors predict the optimal timing of ACS administration (ACS administration within seven days). We reviewed consecutive charts of adult pregnant women receiving ACS from January 1, 2011, to December 31, 2019.

Emergency obstetric referrals in public health facilities: A descriptive study from urban Maharashtra, India.

Background: An effective referral system is key to access timely emergency obstetric care. The criticality of referrals makes it necessary to understand its pattern at the health system level. This study aims to document the patterns and primary reasons of obstetric case referral and the maternal and perinatal outcome of the cases in public health institutions in select areas of urban Maharashtra, India.

Coupled Memristor Oscillators for Neuromorphic Locomotion Control: Modeling and Analysis.

The recent surge of interest in brain-inspired architectures along with the development of nonlinear dynamical electronic devices and circuits has enabled energy-efficient hardware realizations of several important neurobiological systems and features. Central pattern generator (CPG) is one such neural system underlying the control of various rhythmic motor behaviors in animals. A CPG can produce spontaneous coordinated rhythmic output signals without any feedback mechanism, ideally realizable by a system of coupled oscillators.

GRB2 dimerization mediated by SH2 domain-swapping is critical for T cell signaling and cytokine production.

GRB2 is an adaptor protein required for facilitating cytoplasmic signaling complexes from a wide array of binding partners. GRB2 has been reported to exist in either a monomeric or dimeric state in crystal and solution. GRB2 dimers are formed by the exchange of protein segments between domains, otherwise known as "domain-swapping".

A round-robin approach provides a detailed assessment of biomolecular small-angle scattering data reproducibility and yields consensus curves for benchmarking.

Through an expansive international effort that involved data collection on 12 small-angle X-ray scattering (SAXS) and four small-angle neutron scattering (SANS) instruments, 171 SAXS and 76 SANS measurements for five proteins (ribonuclease A, lysozyme, xylanase, urate oxidase and xylose isomerase) were acquired. From these data, the solvent-subtracted protein scattering profiles were shown to be reproducible, with the caveat that an additive constant adjustment was required to account for small errors in solvent subtraction. Further, the major features of the obtained consensus SAXS data over the q measurement range 0-1 Å are consistent with theoretical prediction.

Novel interaction interfaces mediate the interaction between the NEIL1 DNA glycosylase and mitochondrial transcription factor A.

The maintenance of human mitochondrial DNA (mtDNA) is critical for proper cellular function as damage to mtDNA, if left unrepaired, can lead to a diverse array of pathologies. Of the pathways identified to participate in DNA repair within the mitochondria, base excision repair (BER) is the most extensively studied. Protein-protein interactions drive the step-by-step coordination required for the successful completion of this pathway and are important for crosstalk with other mitochondrial factors involved in genome maintenance.

In Ovo and Ex Ovo Methods to Study Avian Inner Ear Development.

The inner ear perceives sound and maintains balance using the cochlea and vestibule. It does this by using a dedicated mechanosensory cell type known as the hair cell. Basic research in the inner ear has led to a deep understanding of how the hair cell functions, and how dysregulation can lead to hearing loss and vertigo.

Radiological Diagnosis of a Rare Prepontine Lesion: Ecchordosis Physaliphora.

Ecchordosis physaliphora (EP) is a notochordal remnant tissue rarely encountered during routine clinical practice. These lesions usually do not produce any significant symptoms as they are slow-growing and mostly small in size. Symptoms are due to mass effects on adjacent structures when they are large or extra-tumoral hemorrhage.

Mycobiomes of the Ocular Surface in Bacterial Keratitis Patients.

Inflammation of the cornea is known as keratitis, and bacteria, fungi, protozoans, and viruses are the etiological agents of this disease. Delayed treatment of keratitis could result in loss of vision and, under certain severity conditions, the removal of an eye and its associated structures. In the current study, the ocular surface (conjunctiva and cornea) mycobiomes of individuals with bacterial keratitis were compared with the ocular mycobiome (conjunctiva) of healthy individuals, free of any ocular morbidity.

Long promoter sequences form higher-order G-quadruplexes: an integrative structural biology study of c-Myc, k-Ras and c-Kit promoter sequences.

We report on higher-order G-quadruplex structures adopted by long promoter sequences obtained by an iterative integrated structural biology approach. Our approach uses quantitative biophysical tools (analytical ultracentrifugation, small-angle X-ray scattering, and circular dichroism spectroscopy) combined with modeling and molecular dynamics simulations, to derive self-consistent structural models. The formal resolution of our approach is 18 angstroms, but in some cases structural features of only a few nucleotides can be discerned.

Solution structure and dynamics of the mitochondrial-targeted GTPase-activating protein (GAP) VopE by an integrated NMR/SAXS approach.

The bacterial pathogen Vibrio cholerae use a type III secretion system to inject effector proteins into a host cell. Recently, a putative Toxic GTPase Activating Protein (ToxGAP) called Vibrio outer protein E (VopE) was identified as a T3SS substrate and virulence factor that affected host mitochondrial dynamics and immune response. However, biophysical and structural characterization has been absent.

The Risk of Readmission after Early Postpartum Discharge during the COVID-19 Pandemic.

Objective: To determine whether early postpartum discharge during the coronavirus disease 2019 (COVID-19) pandemic was associated with a change in the odds of maternal postpartum readmissions.

Study Design: This is a retrospective analysis of uncomplicated postpartum low-risk women in seven obstetrical units within a large New York health system. We compared the rate of postpartum readmissions within 6 weeks of delivery between two groups: low-risk women who had early postpartum discharge as part of our protocol during the COVID-19 pandemic (April 1-June 15, 2020) and similar low-risk patients with routine postpartum discharge from the same study centers 1 year prior.

Valorization of red macroalgae biomass via hydrothermal liquefaction using homogeneous catalysts.

Hydrothermal liquefaction of red macroalgae species, Kappaphycus alvarezii (KA) and Eucheuma denticulatum (ED), was performed at 350 °C in the presence of 5 wt% neutral and alkali catalysts like NaCO, KCO, CaCO, NaSO, NaOH, and KOH. The maximum bio-crude yield of 26.7 wt% and 18.