Autophagy in Plant Health and Disease.

Autophagy has emerged as an essential quality control pathway in plants that selectively and rapidly removes damaged or unwanted cellular components to maintain cellular homeostasis. It can recycle a broad range of cargoes, including entire organelles, protein aggregates, and even invading microbes. It involves the de novo biogenesis of a new cellular compartment, making it intimately linked to endomembrane trafficking pathways.

Beyond , Pharmaceutical Molecule Production in Cell-Free Systems and the Use of Noncanonical Amino Acids Therein.

Throughout history, we have looked to nature to discover and copy pharmaceutical solutions to prevent and heal diseases. Due to the advances in metabolic engineering and the production of pharmaceutical proteins in different host cells, we have moved from mimicking nature to the delicate engineering of cells and proteins. We can now produce novel drug molecules, which are fusions of small chemical drugs and proteins.

Mitochondria complex III-generated superoxide is essential for IL-10 secretion in macrophages.

Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mitochondria ETC complex III (CIII)-deficient macrophages exhibit increased susceptibility to influenza A virus (IAV) and LPS-induced endotoxic shock. Cultured bone marrow-derived macrophages (BMDMs) isolated from these mitochondria CIII-deficient mice released less IL-10 than controls following TLR3 or TLR4 stimulation.

Elucidating assembly and function of VirB8 cell wall subunits refines the DNA translocation model in Gram-positive T4SSs.

Bacterial type IV secretion systems (T4SSs) are widespread nanomachines specialized in the transport across the cell envelope of various types of molecules including mobile genetic elements during conjugation. Despite their prevalence in Gram-positive bacteria, including relevant pathogens, their assembly and functioning remain unknown. This study addresses these gaps by investigating VirB8 proteins, known to be central components of conjugative T4SSs in Gram-positive bacteria.

Stress responsiveness in a wild primate predicts survival across an extreme El Niño drought.

We know more about the costs of chronic stress than the benefits of the acute stress response-an adaptive response that buffers organisms from life-threatening challenges. As yet, no primate study has empirically identified how the stress response adaptively affects evolutionary fitness. Here, we take advantage of a natural experiment-an El Niño drought-that produced unprecedented mortality for wild white-faced capuchins.

Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST.

Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multiomic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in and mutants, where lysosomes accumulate cholesterol.

The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.

A change language for ontologies and knowledge graphs.

Ontologies and knowledge graphs (KGs) are general-purpose computable representations of some domain, such as human anatomy, and are frequently a crucial part of modern information systems. Most of these structures change over time, incorporating new knowledge or information that was previously missing. Managing these changes is a challenge, both in terms of communicating changes to users and providing mechanisms to make it easier for multiple stakeholders to contribute.

Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner.

Perinatal dysfunction of innate immunity in cystic fibrosis.

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.

Carbonation under Varying Humidity Conditions: A 3D Micro-Scale Kinetic Monte Carlo Approach.

This paper investigates the impact of varying humidity conditions on the carbonation depth in hardened cement paste using a 3-dimensional microscale kinetic Monte Carlo (kMC) approach. The kMC algorithm effectively simulates the carbonation process by capturing the interplay between CO diffusion and relative humidity at the microscale, providing insights into macro trends that align with historical models. The study reveals that the maximum carbonation depth is achieved at relative humidity levels between 55 and 65%, where the balance between water and CO diffusion is optimized.

Unfolding of von Willebrand Factor Type D Like Domains Promotes Mucin Adhesion.

Mucins are the macromolecular key components of mucus. On wet epithelia of mammals, mucin solutions and gels act as powerful biolubricants and reduce friction and wear by generating a sacrificial layer and establishing hydration lubrication. Yet the structure-function relationship of mucin adhesion and lubrication remains elusive.

Triiodothyronine treatment in mice improves stroke outcome and reduces blood-brain barrier damage.

Objective Thyroid hormones (TH) control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of 3,3',5-triiodo-L-thyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. Methods Stroke was induced in mice by transient middle cerebral artery occlusion (tMCAO) and T3 was administered at different doses and time points before and after stroke.

Advancing bat monitoring: Assessing the impact of unmanned aerial systems on bat activity.

With the increasing height and rotor diameter of wind turbines, bat activity monitoring within the risk area becomes more challenging. This study investigates the impact of Unmanned Aerial Systems (UAS) on bat activity and explores acoustic bat detection via UAS as a new data collection method in the vicinity of wind turbines. We tested two types of UAS, a multicopter and a Lighter Than Air (LTA) UAS, to understand how they may affect acoustically recorded and analyzed bat activity level for three echolocation groups: Pipistrelloid, Myotini, and Nyctaloid.

Modeling of lifetime scenarios with non-monotonic failure rates.

The Weibull distribution is an important continuous distribution that is cardinal in reliability analysis and lifetime modeling. On the other hand, it has several limitations for practical applications, such as modeling lifetime scenarios with non-monotonic failure rates. However, accurate modeling of non-monotonic failure rates is essential for achieving more accurate predictions, better risk management, and informed decision-making in various domains where reliability and longevity are critical factors.

The climate impact and land use of cultivated meat: Evaluating agricultural feedstock production.

As global demand for meat continues to rise, alternative and sustainable methods of production are being explored. Cultivated meat (CM) is one such alternative that holds potential for sustainable production with less environmental impact. This study develops an approach to evaluate CM production based on agricultural feedstock.

Life satisfaction around the world: Measurement invariance of the Satisfaction With Life Scale (SWLS) across 65 nations, 40 languages, gender identities, and age groups.

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions.

Enhancing Insight in Patients With Obsessive Compulsive Disorder: A Case Study on Avatar Therapy Using Virtual Reality.

Treatment efficacy for patients with obsessive-compulsive disorder (OCD) with poor insight is low. Insight refers to a patient's ability to recognize that their obsessions are irrational and that their compulsions are futile attempts to reduce anxiety. This case study presents the first application of virtual reality-assisted avatar therapy for OCD (VRT-OCD) in a patient with contamination OCD and ambivalent insight.

Interpretation of Viscoelastic Hemostatic Assays in Cardiac Surgery Patients: Importance of Clinical Context.

Background: Rotational thromboelastometry (ROTEM) is widely used for point-of-care coagulation testing to reduce blood transfusions. Accurate interpretation of ROTEM data is crucial and requires substantial training. This study investigates the inter- and intrarater reliability of ROTEM interpretation among experts and compares their interpretations with a ROTEM-guided algorithm.

PSC and colitis: A complex relationship.

Primary sclerosing cholangitis is one of the most challenging conditions in hepatology, and due to our limited understanding of its pathogenesis, no causal therapies are currently available. While it was long assumed that a minority of people with IBD also develop PSC, which is sometimes labeled an extraintestinal manifestation of IBD, the clinical phenotype, genetic and intestinal microbiota associations strongly argue for PSC-IBD being a distinct form of IBD, existing alongside ulcerative colitis and Crohn's disease. In fact, the liver itself could contribute to intestinal pathology, clinically overt in 60 - 80 % of patients.

Clinical Evaluation of 3D Motion-Correction Via Scout Accelerated Motion Estimation and Reduction Framework Versus Conventional T1-Weighted MRI at 1.5 T in Brain Imaging.

Objectives: The aim of this study was to investigate the occurrence of motion artifacts and image quality of brain magnetic resonance imaging (MRI) T1-weighted imaging applying 3D motion correction via the Scout Accelerated Motion Estimation and Reduction (SAMER) framework compared with conventional T1-weighted imaging at 1.5 T.

Materials And Methods: A preliminary study involving 14 healthy volunteers assessed the impact of the SAMER framework on induced motion during 3 T MRI scans.

Demographic Characteristics and Relational Coordination in ICU Teams: Implications for Building Diverse and Effective Healthcare Collaboration.

Objective: To determine if professional roles and demographic characteristics predict relational coordination (RC) among healthcare professionals in the ICU.

Background: Race, age, and sex diversity are increasing in the medical and nursing workforce, raising questions regarding how well healthcare professionals are collaborating. RC is a validated model for coordinating interdependent work among healthcare professionals.

Assessment of Geriatric Problems and Risk Factors for Delirium in Surgical Medicine: Protocol for Multidisciplinary Prospective Clinical Study.

Background: An aging population in combination with more gentle and less stressful surgical procedures leads to an increased number of operations on older patients. This collectively raises novel challenges due to higher age heavily impacting treatment. A major problem, emerging in up to 50% of cases, is perioperative delirium.

Racial and Ethnic Disparities in Use of Helicopter Transport After Severe Trauma in the US.

Importance: In the US, traumatic injuries are a leading cause of mortality across all age groups. Patients with severe trauma often require time-sensitive, specialized medical care to reduce mortality; air transport is associated with improved survival in many cases. However, it is unknown whether the provision of and access to air transport are influenced by factors extrinsic to medical needs, such as race or ethnicity.

Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia.

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.