Benchmarking residue-resolution protein coarse-grained models for simulations of biomolecular condensates.

Intracellular liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a fundamental mechanism by which cells compartmentalize their components and perform essential biological functions. Molecular simulations play a crucial role in providing microscopic insights into the physicochemical processes driving this phenomenon. In this study, we systematically compare six state-of-the-art sequence-dependent residue-resolution models to evaluate their performance in reproducing the phase behaviour and material properties of condensates formed by seven variants of the low-complexity domain (LCD) of the hnRNPA1 protein (A1-LCD)-a protein implicated in the pathological liquid-to-solid transition of stress granules.

Nucleosome Spacing Can Fine-Tune Higher Order Chromatin Assembly.

Cellular chromatin displays heterogeneous structure and dynamics, properties that control diverse nuclear processes. Models invoke phase separation of conformational ensembles of chromatin fibers as a mechanism regulating chromatin organization . Here we combine biochemistry and molecular dynamics simulations to examine, at single base-pair resolution, how nucleosome spacing controls chromatin phase separation.

A novel and efficient digital image steganography technique using least significant bit substitution.

Steganography is used to hide sensitive types of data including images, audio, text, and videos in an invisible way so that no one can detect it. Image-based steganography is a technique that uses images as a cover media for hiding and transmitting sensitive information over the internet. However, image-based steganography is a challenging task due to transparency, security, computational efficiency, tamper protection, payload, etc.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.

Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.

Immunohistochemical expression of TLR1, TLR2, TLR4, and TLR9 in the different types of lesions associated with bovine paratuberculosis.

The factors that determine the appearance of the different pathologic forms associated with bovine paratuberculosis are not fully understood, but new research suggests a critical role of innate immunity. Toll-like receptors (TLRs) trigger the recognition of invading pathogens by innate immune cells and the onset of specific immune responses. The aim of this work was to assess, immunohistochemically, the expression of TLR1, TLR2, TLR4, and TLR9 in intestinal samples of 20 cows showing different types of paratuberculous lesions: uninfected controls, focal lesions, paucibacillary, and multibacillary diffuse forms.

Comorbidities, long-term outcome and poststroke epilepsy associated with ischemic stroke - A multicenter observational study of 125 dogs.

Background: Little is known regarding the comorbidities and prognostic factors associated with the long-term outcome of ischemic stroke in dogs. Although poststroke epilepsy is a well-recognized syndrome in people, it is unclear if this phenomenon also occurs in dogs.

Hypothesis/objective: Document comorbidities, long-term outcome (survival and stroke recurrence), and occurrence of epileptic seizures associated with ischemic stroke.

Integrated analysis of immunometabolic interactions in Down syndrome.

Down syndrome (DS), caused by trisomy 21 (T21), results in immune and metabolic dysregulation. People with DS experience co-occurring conditions at higher rates than the euploid population. However, the interplay between immune and metabolic alterations and the clinical manifestations of DS are poorly understood.

Evaluation of alternative vaccination routes against paratuberculosis in goats.

Paratuberculosis is a chronic granulomatous enteritis, caused by subspecies (), that affects ruminants worldwide. Vaccination has been considered the most cost-effective method for the control of this disease in infected dairy herds. However, currently available vaccines do not provide complete protection and interfere with the diagnosis of both paratuberculosis and bovine tuberculosis, limiting its use.

Outcomes of the Subsequent Periprosthetic Joint Infection Revisions after a Failed Debridement, Antibiotics and Implant Retention: A Multicentric Study of 197 Patients.

The impact of prior unsuccessful debridement, antibiotics, and implant retention (DAIR) procedures on subsequent revisions is uncertain, with conflicting evidence. Despite 85% consensus against the second DAIR procedure following the 2018 International Consensus Meeting, a 2020 study reported high success rates for the aforementioned second DAIR procedure. We conducted a multicenter observational study reviewing data from patients with failed DAIR procedures between 2005 and 2021.

Genomics reveal local skin immune response key to control sarcoptic mange in Iberian ibex (Capra pyrenaica).

Background: Sarcoptic mange is an emerging and neglected contagious skin disease caused by the mite Sarcoptes scabiei, affecting humans, domestic animals, and wildlife. Mange is the main disease and a major concern for the management and conservation of populations of Iberian ibex (Capra pyrenaica), a medium-sized mountain ungulate endemic to the Iberian Peninsula and Northern Pyrenees. Differences in host-parasite interaction and host immune response determine mange clinical outcome, but little is known about the related differences in gene expression.

Zoonotic Potential of Chronic Wasting Disease after Adaptation in Intermediate Species.

Chronic wasting disease (CWD) is an emerging disease in Europe. We report an increase in interspecies transmission capacity and zoonotic potential of a moose CWD isolate from Europe after passage in an ovine prion protein-expressing host. Those results indicated some CWD prions could acquire enhanced zoonotic properties following adaptation in an intermediate species.

Mechano-dependent sorbitol accumulation supports biomolecular condensate.

Condensed droplets of protein regulate many cellular functions, yet the physiological conditions regulating their formation remain largely unexplored. Increasing our understanding of these mechanisms is paramount, as failure to control condensate formation and dynamics can lead to many diseases. Here, we provide evidence that matrix stiffening promotes biomolecular condensation in vivo.

Stakeholder perceptions of mangrove ecosystem services across scales of conservation focus.

Conservation faces a chronic shortage of resources, including time, funding, mental capacity, and human capital. Efforts to make the expenditure of these resources more efficient should, therefore, support more equitable and effective conservation prioritization. To achieve this, it is necessary to ensure the integration of the knowledge and perceptions of local stakeholders into larger scale conservation decisions.

Predictions of the interfacial free energy along the coexistence line from single-state calculations.

The calculation of the interfacial free energy between two thermodynamic phases is crucial across various fields, including materials science, chemistry, and condensed matter physics. In this study, we apply an existing thermodynamic approach, the Gibbs-Cahn integration method, to determine the interfacial free energy under different coexistence conditions, relying on data from a single-state calculation at specified pressure and temperature. This approach developed by Laird et al.

A Phase 2 Sensitivity and Selectivity Study of High-Dose 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent Glioblastoma.

Background And Objectives: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented, but the problem of false-negative observations remains. This study compares high-grade glioma visualization with low/standard dose 5-ALA (<30 mg/kg) to high-dose 5-ALA (>40 mg/kg) to see if by using this higher dose, it is possible to reduce the rate of false-negative observations without increasing the rate of false-positive (FP) observations and therefore increase the sensitivity.

Methods: This is a prospective study of consecutive patients with radiological evidence of presumed high-grade glioma.

A Patient With Unilateral Vocal Cord Paralysis Presenting to the Emergency Department With Voice Changes and Dyspnea.

Unilateral vocal cord paralysis can cause a change in phonation and dyspnea and can be a cause of distress for a patient. The causes are varied and include post-surgical and post-intubation causes, malignancy, and other etiologies. Here, we present the case of a 72-year-old female who presented to the ED with a new onset of a "raspy voice" and dyspnea and had undergone an L4-L5 laminectomy with associated endotracheal intubation two weeks prior to ED presentation.

A Case of Purple Urine Bag Syndrome (PUBS) in a Patient With a Chronic Indwelling Foley Catheter.

Purple urine bag syndrome (PUBS) is a medical condition characterized by the appearance of purple discoloration in the urine collection bag of patients who use catheters for urinary drainage. PUBS is primarily seen in elderly, female, and institutionalized patients who have chronic indwelling catheters. The discoloration occurs due to the presence of certain bacteria that can produce indigo (which has a blue hue) and indirubin (with a red hue) leading to the formation of a purple color.

JAK inhibition in Down Syndrome Regression Disorder.

Down Syndrome Regression Disorder (DRSD) is an uncommon but devastating condition affecting primarily adolescents and young adults with Down syndrome (DS). Individuals with DS display a dysregulated immune system associated with hyperactive interferon signaling, which is associated with a high incidence of autoimmune conditions. While the cause of DSRD is unknown, increasing evidence indicates that it may have an immune basis, and some individuals with DSRD have responded to intravenous immunoglobulin therapy.

Metabolic dysfunction mediated by HIF-1α contributes to epithelial differentiation defects in eosinophilic esophagitis.

Background: Investigating the contributory role that epithelial cell metabolism plays in allergic inflammation is a key factor to understanding what influences dysfunction and the pathogenesis of the allergic disease eosinophilic esophagitis (EoE). We previously highlighted that the absence of hypoxia signaling through hypoxia-inducible factor (HIF)-1α in EoE contributes to esophageal epithelial dysfunction. However, metabolic regulation by HIF-1α has not been explored in esophageal allergy.

Wellens Syndrome in a 28-Year-Old With Pleuritic Chest Pain.

We report a case of a 28-year-old African American male with months of diffuse, pleuritic, intermittent, non-exertional chest pain with elevated troponin and an ECG showing Wellens syndrome; he was found to have myocardial infarction with 80% proximal left anterior descending (LAD) coronary artery occlusion and 100% distal LAD occlusion. This patient's age and symptoms were not typical for cardiac ischemia, although the ECG was typical. Identification and proper management of Wellens syndrome rely on familiarity with its ECG patterns.