Protein dynamics underlies strong temperature dependence of heat receptors.

Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals.

Msh2-Msh3 DNA-binding is not sufficient to promote trinucleotide repeat expansions in Saccharomyces cerevisiae.

Mismatch repair (MMR) is a highly conserved DNA repair pathway that recognizes mispairs that occur spontaneously during DNA replication and coordinates their repair. In Saccharomyces cerevisiae, Msh2-Msh3 and Msh2-Msh6 initiate MMR by recognizing and binding insertion deletion loops (in/dels) up to ∼ 17 nucleotides (nt.) and base-base mispairs, respectively; the two complexes have overlapping specificity for small (1-2 nt.

Meta-Analysis of the Input and Disposition of Various Dosage Forms of Methylprednisolone in Healthy Subjects Utilizing a Physiologically Based Pharmacokinetic Model.

The study quantitatively analyzes and compares the pharmacokinetics (PK) of methylprednisolone (MPL) in humans upon administration of various dosage forms. The PK parameters and profiles of MPL in healthy subjects were collected from 22 literature sources. A minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue (lumped liver and kidney, remainder) compartments with nonlinear tissue partitioning was applied to describe MPL disposition.

Superstable lipid vacuoles endow cartilage with its shape and biomechanics.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis.

Denovo variants in POGZ and YY1 genes: The novel mega players for neurodevelopmental syndromes in two unrelated consanguineous families.

Novel denovo variants of exome sequences are major cause of pathogenic neurodevelopmental disorders with a dominant genetic mechanism that emphasize their heterogeneity and complex phenotypes. White Sutton syndrome and Gabriele-de-Vries syndrome are congenital neuro-impairments with overlap of severe intellectual disability, microcephaly, convulsions, seizures, delayed development, dysmorphism of faces, retinal diseases, movement disorders and autistic traits. POGZ gene codes for pogo transposable element-derived zinc-finger protein and YY1 gene regulates transcription, chromatin, and RNA-binding proteins that have been associated with White Sutton and Gabriele-de-Vries syndromes, in recent data.

Semisynthesis of Alkaloid Derivatives: Pyranoacridone-Hydroxamic Acid Cytotoxic Conjugates with HDAC and Topoisomerase II α Dual Inhibitory Activity.

Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.

Genetic Heterogeneity in Four Probands Reveals , , and Related Neurodevelopmental Disorders.

: Neurodevelopmental disorders of genetic etiology are a highly diverse set of congenital recurrent complications triggered by irregularities in the basic tenets of brain development. : We present whole exome sequencing analysis and expression characteristics of the probands from four unrelated Pakistani consanguineous families with facial dysmorphism, neurodevelopmental, ophthalmic, auditory, verbal, psychiatric, behavioral, dental, and skeletal manifestations otherwise unexplained by clinical spectrum. : Whole exome sequencing identifies a novel, bi-allelic, missense variant in the gene [NM_152419.

Impaired network organization in mild age-related hearing loss.

Age-related hearing loss (ARHL) is considered one of the most common neurodegenerative disorders in the elderly; however, how it contributes to cognitive decline is poorly understood. With resting-state functional magnetic resonance imaging from 66 individuals with ARHL and 54 healthy controls, group spatial independent component analyses, sliding window analyses, graph-theory methods, multilayer networks, and correlation analyses were used to identify ARHL-induced disturbances in static and dynamic functional network connectivity (sFNC/dFNC), alterations in global network switching and their links to cognitive performances. ARHL was associated with decreased sFNC/dFNC within the default mode network (DMN) and increased sFNC/dFNC between the DMN and central executive, salience (SN), and visual networks.

Historical redlining and clustering of present-day breast cancer factors.

Purpose: Historical redlining, a 1930s-era form of residential segregation and proxy of structural racism, has been associated with breast cancer risk, stage, and survival, but research is lacking on how known present-day breast cancer risk factors are related to historical redlining. We aimed to describe the clustering of present-day neighborhood-level breast cancer risk factors with historical redlining and evaluate geographic patterning across the US.

Methods: This ecologic study included US neighborhoods (census tracts) with Home Owners' Loan Corporation (HOLC) grades, defined as having a score in the Historic Redlining Score dataset; 2019 Population Level Analysis and Community EStimates (PLACES) data; and 2014-2016 Environmental Justice Index (EJI) data.

The gap between surgeon goal and achieved sagittal alignment in adult cervical spine deformity surgery.

Objective: Malalignment following cervical spine deformity (CSD) surgery can negatively impact outcomes and increase complications. Despite the growing ability to plan alignment, it remains unclear whether preoperative goals are achieved with surgery. The objective of this study was to assess how good surgeons are at achieving their preoperative goal alignment following CSD surgery.

Assessment of Craniofacial Growth Pattern Relative to Respiratory Mandibular Movement and Sleep Characteristics: A Pilot Study.

Objectives:  The primary objective was to evaluate the influence of sagittal skeletal pattern on mandibular movement (MM) during sleep in growing orthodontic populations. The secondary objective was to compare MM according to obstructive sleep apnea (OSA) status.

Materials And Methods:  This cross-sectional study included subjects between 6 and 17 years old, presenting with class I, II, and III skeletal patterns and no previous history of orthodontic treatment.

Bilateral Semicircular Canal Dehiscence Analyzed Using the International Classification of Functioning, Disability, and Health (ICF) Framework: Case Report.

A severe case of bilateral superior semicircular dehiscence was presented in Instituto de Neurorrehabilitación y Balance, Chile. The patient reports hearing and vestibular problems in certain situations; a complete analysis is carried out from the clinical history to neurological laboratory studies and imaging to diagnose bilateral semicircular canal dehiscence finally. Health condition management is under the ICF model, which will allow for determining and classifying the problems and possible interventions for this interesting clinical case.

CD38 Coordinates with NF-κB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.

Noise exposure is one of the most common causes of sensorineural hearing loss. Although many studies considered inflammation to be a major contributor to noise-induced hearing loss, the process of cochlear inflammation is still unclear. Studies have found that activation of the NF-κB signaling pathway results in the accumulation of macrophages in the inner ear plays an important role in hair cell damage.

Pediatric neck injuries associated with trampoline use.

Objective: Trampolines are popular among children, but trampoline injuries constitute a large number of emergency department visits. The purpose of this study was to determine how often neck injuries occur among children with trampoline-related injuries and to identify the mechanism of injury.

Methods: We analyzed the National Electronic Injury Surveillance System (NEISS) database to characterize patient demographics, injury types, injury subsite, and emergency department disposition status associated with trampoline related neck injuries between 2012 and 2021 in the United States.

PK/PD Evaluation of Antibody-Drug Conjugates with Enhanced Immune Effector Functions.

Optimizing the interaction between antibody (mAb)-based therapeutics and immune effector functions (EFs) offers opportunities to improve the therapeutic window of these molecules. However, the role of EFs in antibody-drug conjugate (ADC) efficacy and toxicity remains unknown, with limited studies that have investigated how modulation of EF affects the pharmacology of ADCs. This study aimed to evaluate the effect of EF modulation on ADC efficacy using trastuzumab-vc-MMAE as a model ADC.

Atomistic Simulations and Analysis of Peripheral Membrane Proteins with Model Lipid Bilayers.

All-atom molecular dynamics (AAMD) is a computational technique that predicts the movement of particles based on the intermolecular forces acting on the system. It enables the study of biological systems at atomic detail, complements observations from experiments, and can help the selection of experimental targets. Here, we describe the applications of MD simulations to study the interaction between peripheral membrane proteins and lipid bilayers.

A multimodal axial array resonator and its application in radiofrequency (RF) volume coil designs for low-field open magnetic resonance imaging (MRI).

Background: Low-field open magnetic resonance imaging (MRI) systems, typically operating at magnetic field strengths below 1 Tesla, has greatly expanded the accessibility of MRI technology to meet a wide range of patient needs. However, the inherent challenges of low-field MRI, such as limited signal-to-noise ratios and limited availability of dedicated radiofrequency (RF) coils, have prompted the need for innovative coil designs that can improve imaging quality and diagnostic capabilities. In this work, we introduce a multimodal axial array resonator and its implementation in a volume coil, or referred to as a coupled stack-up volume coil, to address these challenges in low-field open MRI.

Perfluorooctanesulfonic acid (PFOS) removal from aqueous solution through N-doped porous copper-carbon composite derived from recycled copper obtained from fly ash incinerator: Water decontamination via municipal waste remnants.

Invincible growth in waste production is the consequence of overpopulation, which should be addressed to reduce the occupied landfill surface needed for their disposal and to alleviate the leachate of extremely hazardous material into the soil and water bodies. In this study, copper (Cu) was extracted from fly ash of a municipal solid waste incinerator by an electro-chemical method, which was optimized to recover the highest amount of Cu, and then it was chelated with 4-aminobenzoic acid (AM) and terephthalic acid (TM) in an aqueous phase. The obtained composites were then heated to form a porous calcinated copper-carbon composite and utilized to adsorb the forever contaminant of PFOS from aqueous solutions.

Association of Cognitive Symptoms and Abnormal Oculomotor Signs With Recovery in Adolescents After Sport-Related Concussion.

Objective: Sport-related concussion (SRC) affects cognitive and oculomotor function. We evaluated recovery from SRC in athletes with cognitive symptoms and/or oculomotor impairments who were prescribed early aerobic exercise treatment.

Design: Secondary exploratory analysis of a randomized controlled trial.

Differing clinical characteristics among individuals with concussions sustained at work, in motor vehicle collisions, and sport.

Purpose: To compare clinical characteristics in patients with concussions sustained by prevalent, but understudied, mechanisms (work-related concussion [WRC] and motor vehicle collision [MVC]-related concussion) to sport-related concussion (SRC).

Methods: Retrospective review of 281 electronic medical records from an outpatient concussion clinic. Time since injury (days), duration of care (days), amount of care (number of visits), and perceived health (Short-Form 12) were collected.

The Clinical Utility of Assessing Orthostatic Intolerance in Adolescents with Sport-Related Concussion, a Retrospective Study.

Background/objective: Assessing Orthostatic Intolerance (OI, symptoms upon standing from supine) is recommended in athletes with sport-related concussions (SRCs), as this is caused by impairments in the cardiovascular autonomic nervous system (cANS). Early Exercise Intolerance (Early EI, symptoms on light physical exertion) is also due to impairments in the cANS but is difficult to incorporate into outpatient clinical practice (cost of personnel, time, equipment). The purpose of this study was to determine if we could use OI to screen for Early EI, as well as understand differences between adolescents who do and do not report OI.

Magnetic resonance imaging-based biomarkers of multiple sclerosis and neuromyelitis optica spectrum disorder: a systematic review and meta-analysis.

Background/objective: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are neuroinflammatory conditions with overlapping clinical and imaging features. Distinguishing between these diseases is crucial for appropriate diagnosis and management. Magnetic resonance imaging (MRI) may have the potential to differentiate these disorders.