Lipidic folding pathway of α-Synuclein via a toxic oligomer.

Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.

Liquid-infused nanostructured composite as a high-performance thermal interface material for effective cooling.

Effective heat dissipation remains a grand challenge for energy-dense devices and systems. As heterogeneous integration becomes increasingly inevitable in electronics, thermal resistance at interfaces has emerged as a critical bottleneck for thermal management. However, existing thermal interface solutions are constrained by either high thermal resistance or poor reliability.

Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.

The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.

Range shifts as drivers of niche breadth and dispersal ability in wild populations.

Research Highlight: Edwards, O. M., Zhai, L.

Soil Nitrogen Supply Exerts Largest Influence on Leaf Nitrogen in Environments with the Greatest Leaf Nitrogen Demand.

Accurately representing the relationships between nitrogen supply and photosynthesis is crucial for reliably predicting carbon-nitrogen cycle coupling in Earth System Models (ESMs). Most ESMs assume positive correlations amongst soil nitrogen supply, leaf nitrogen content, and photosynthetic capacity. However, leaf photosynthetic nitrogen demand may influence the leaf nitrogen response to soil nitrogen supply; thus, responses to nitrogen supply are expected to be the largest in environments where demand is the greatest.

How Pediatric Readiness can Impact Pediatric Trauma From Every Day to Mass Events.

Disaster events such as weather events and mass casualty events are increasing in frequency and severity. Caring for children during a surge requires a regional approach given limited pediatric inpatient capacity and expertise. During the 2024 American Academy of Pediatrics National Convention and Exhibition, the Section on Surgery and Council on Children and Disasters (COCD) partnered to present a joint symposium emphasizing importance of pediatric readiness and disaster preparedness and role of pediatric trauma surgeons in disaster preparedness and response in all communities.

Feline Aural Inflammatory Polyps.

Feline aural inflammatory polyps originate from the tympanic bulla and less frequently from the auditory tube, representing the most common benign tumor of the feline ear. Clinical signs may be compatible with otitis externa, media, and/or interna with rare occurrences involving meningoencephalitis or abscessation of periauricular tissue. Traction and avulsion is an effective treatment procedure with a relatively low recurrence rate, especially when systemic glucocorticoids are given after polyp removal.

Proliferative and Necrotizing Otitis Externa of Cats and Kittens.

Proliferative and necrotizing otitis externa (PNOE) is characterized by thick, adherent dark red, brown, or black crusts. It most commonly affects the concave pinnae and vertical ear canals bilaterally. Lesions may also be seen on the face, and it may rarely present in a generalized form.

Fun in the sun: ribosomes defend against UV irradiation.

The concept that ribosomes are sensors of translational distress has sparked significant interest, although much of the research has been conducted in vitro. A new study by Vind et al. provides in vivo evidence that the ribotoxic stress response (RSR) serves as the first line of defense against ultraviolet (UV) radiation.

Comparing the incidence of hypospadias across the United States: A contemporary analysis.

Introduction: Hypospadias is a common congenital malformation occurring in up to 80 in 10,00 live male births, with emerging evidence associating exogenous environmental exposures with increased disease incidence. Military personnel are at particularly higher risk for such exposures and indeed, the rate of hypospadias in infant males born to United States military servicewomen deployed during the Gulf War has been reported to be more than 5 times greater compared to undeployed female military personnel.

Objective: To characterize contemporary trends in hypospadias incidence in the general population as well as high risk groups such as males born from US servicewomen using the National Birth Defects Prevention Network.

Neocortical somatostatin neuron diversity in cognition and learning.

Somatostatin-expressing (SST) neurons are a major class of electrophysiologically and morphologically distinct inhibitory cells in the mammalian neocortex. Transcriptomic data suggest that this class can be divided into multiple subtypes that are correlated with morpho-electric properties. At the same time, availability of transgenic tools to identify and record from SST neurons in awake, behaving mice has stimulated insights about their response properties and computational function.

Genome-scale, functional screen of Plasmodium sexual replication.

Malaria mortality remains above 500 000 people annually, demonstrating the need for new and innovative control approaches. Using a genome-scale, functional screen of Plasmodium sexual replication, Sayers et al. identified over 300 genes essential for malaria transmission through the mosquito, providing many new candidates for drug and vaccine development.

The role of community pharmacists in point-of-care testing and treatment for influenza and Group A Streptococcus -a narrative review using Ecological Systems Theory.

Background: Point-of-care testing (POCT) is a valuable diagnostic approach for identifying pathogens such as Group A Streptococcus (GAS) and influenza. Early detection through POCT allows for timely initiation of appropriate treatments improving public health outcomes and minimizing antibiotic misuse. Community pharmacists are well positioned to offer POCT and treatment, but they face significant system level barriers to widespread implementation and reach.

Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.

Innovative biomaterials and tissue engineering strategies show great promise in regenerating periodontal tissues. This guidance provides an overview and detailed recommendations for evaluating the biological functionality of these new biomaterials in vitro, focusing on mineralization, immunomodulatory effects, cellular differentiation, and angiogenesis. Additionally, it discusses the use of in vivo experimental models that mimic periodontitis and scrutinizes methods such as osteogenic differentiation, immunomodulation, and anti-inflammatory responses to assess the effectiveness of these biomaterials in promoting periodontal tissue reconstruction.

Racial disparities in lung transplantation for cystic fibrosis in the era of highly effective modulator therapy.

Background: Highly effective modulator therapies (HEMT) including ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) have transformed treatment for people with cystic fibrosis (pwCF). However, non-HEMT-responsive mutations are more common in pwCF of non-White race/ethnicity; introduction of HEMT might have exacerbated racial/ethnic disparities in CF care.

Methods: Using the Scientific Registry of Transplant Recipients, we identified all lung transplant candidates and recipients 05/2005-12/2022 and categorized them by diagnosis (CF/non-CF), race/ethnicity (non-Hispanic White/Black/Hispanic) and era [Pre-HEMT (2005-1/30/2012), IVA (1/31/2012-10/30/2019), ETI (10/31/2019-12/31/2022)].

Clinical Applications of Microbiome in Renal Cell Carcinoma.

Advancements in microbiome research reveal its impact on cancer treatment outcomes, particularly in renal cell carcinoma (RCC). While immune checkpoint inhibitors (ICIs) have improved survival in metastatic RCC, composition of the gut microbiome has the potential to influence their efficacy. Antibiotic-induced microbiome disruptions correlate with diminished outcomes, while strains such as Akkermansia muciniphila, Clostridium butyricum, and others enhance immune responses and progression-free survival.

IRAK4: potential therapeutic target for airway disease exacerbations.

Inflammatory lung diseases represent a significant healthcare burden. There is an unmet need for identifying therapeutic targets for inflammatory lung diseases, such as asthma, and chronic obstructive pulmonary disease (COPD). In a recent study, Sayers et al.

The case of a woman with bilateral Dupuytren's contractures who developed CRPS-1 after fasciectomy with no relapse on subsequent collagenase clostridium histolyticum injection and manipulation of the other hand: Considerations for implementing a Budapest criteria checklist and assessing vasomotor instability by measuring differences in skin temperature.

Background: For patients who experience atypical neurogenic pain thought to be complex regional pain syndrome (CRPS) after Dupuytren's fasciectomy early recognition has been reported to improve outcomes. Furthermore, given the progressive nature of Dupuytren's, individuals with a history of CRPS have been "at risk" for further surgical intervention.

Purpose: To familiarize therapists with a Budapest criteria (BC) checklist for early diagnosis of CRPS, describe how tracking sudomotor/vasomotor signs alongside differences in skin temperature were used to monitor vasomotor instability and intervention effectiveness for a patient with atypical pain after fasciectomy and to detail management of the same patient with a CRPS history who had collagenase clostridium histolyticum (CCH) injection of her other hand without exacerbating CRPS.