Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.

Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.

The complex landscape of immune dysregulation in multisystem inflammatory syndrome in children with COVID-19.

The immune responses following SARS-CoV-2 infection in children are still under investigation. While coronavirus disease 2019 (COVID-19) is usually mild in the paediatric population, some children develop severe clinical manifestations or multisystem inflammatory syndrome in children (MIS-C) after infection. MIS-C, typically emerging 2-6 weeks after SARS-CoV-2 exposure, is characterized by a hyperinflammatory response affecting multiple organs.

Exposomics: a review of methodologies, applications, and future directions in molecular medicine.

The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses.

How can we make sound replication decisions?

Replication and the reported crises impacting many fields of research have become a focal point for the sciences. This has led to reforms in publishing, methodological design and reporting, and increased numbers of experimental replications coordinated across many laboratories. While replication is rightly considered an indispensable tool of science, financial resources and researchers' time are quite limited.

The present and future of peer review: Ideas, interventions, and evidence.

What is wrong with the peer review system? Is peer review sustainable? Useful? What other models exist? These are central yet contentious questions in today's academic discourse. This perspective critically discusses alternative models and revisions to the peer review system. The authors highlight possible changes to the peer review system, with the goal of fostering further dialog among the main stakeholders, including producers and consumers of scientific research.

Initiation of primary T cell-B cell interactions and extrafollicular antibody responses in an organized microphysiological model of the human lymph node.

Antibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response.

Characterization of 3D printed micro-blades for cutting tissue-embedding material.

Cutting soft materials on the microscale has emerging applications in single-cell studies, tissue microdissection for organoid culture, drug screens, and other analyses. However, the cutting process is complex and remains incompletely understood. Furthermore, precise control over blade geometries, such as the blade tip radius, has been difficult to achieve.

Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.

Hematopoietic stem cells (HSCs) generate blood and immune cells. Here, we present a protocol to differentiate human pluripotent stem cells (hPSCs) into hematopoietic progenitors that express the signature HSC transcription factors HLF, HOXA5, HOXA7, HOXA9, and HOXA10. hPSCs are dissociated, seeded, and then sequentially differentiated into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and hematopoietic progenitors through the sequential addition of defined, serum-free media.

High-temperature structural disorders stabilize hydrous aluminosilicates in the mantle transition zone.

Hydrous aluminosilicates are important deep water-carriers in sediments subducting into the deep mantle. To date, it remains enigmatic how hydrous aluminosilicates withstand extremely high temperatures in the mantle transition zone. Here we systematically investigate the crystal structures and chemical compositions of typical hydrous aluminosilicates using single-crystal X-ray diffraction, electron probe microanalyzer, and nanoscale secondary ion mass spectrometry.

The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots.

The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function.

MAPK1IP1L::TFE3-rearranged renal cell carcinoma: a novel fusion adding to the differential diagnosis of oncocytic renal neoplasms.

Beyond the more common TFE3 fusion partners PRCC, ASPSCR1, and SFPQ, additional less common fusion partners of TFE3-rearranged renal cell carcinoma (RCC) have been described. Herein, we present an example of TFE3-rearranged renal cell carcinoma harboring fusion partner MAPK1IP1L, a rare rearrangement with only one other reported tumor found in the literature. The currently reported TFE3-rearranged RCC demonstrates unique histological features compared to the previously reported tumor including dense eosinophilic cytoplasm and nuclear pseudoinclusions (corroborated by electron microscopic evaluation), with features not typically seen in other TFE3-rearranged RCCs.

Substitution load revisited: a high proportion of deaths can be selective.

Haldane's Dilemma refers to the concern that the need for many "selective deaths" to complete a substitution (i.e. selective sweep) creates a speed limit to adaptation.

Perspective on the 65-Year Anniversary of the Discovery of Cytomegalovirus.

This volume presents research and reviews bringing forward new insights into cytomegalovirus (CMV) pathogenesis and biology; CMV is a herpesvirus that has long been recognized as being medically significant [...

Investigations of Long-Acting Formulations in Children, Adolescents, and Pregnant Women: A Systematic Review.

Long-acting and extended-release drug delivery strategies have greatly improved treatment for a variety of medical conditions. Special populations, specifically infants, children, young people, and pregnant and postpartum women, could greatly benefit from access to these strategies but are often excluded from clinical trials. We conducted a systematic review of all clinical studies involving the use of a long-acting intramuscular injection or implant in infants, children, young people, and pregnant and postpartum people.

Evolutionary Trajectories of Shoots vs. Roots: Plant Volatile Metabolomes Are Richer but Less Structurally Diverse Belowground in the Tropical Tree Genus .

The breadth and depth of plant leaf metabolomes have been implicated in key interactions with plant enemies aboveground. In particular, divergence in plant species chemical composition-amongst neighbors, relatives, or both-is often suggested as a means of escape from insect herbivore enemies. Plants also experience strong pressure from enemies such as belowground pathogens; however, little work has been carried out to examine the evolutionary trajectories of species' specialized chemistries in both roots and leaves.

Latent Structure and Profiles of Emotion Regulation: Reappraisal and Suppression Patterns with the Polish Version of the Emotion Regulation Questionnaire.

: The Emotion Regulation Questionnaire (ERQ) is a 10-item self-report measure of two emotion regulation strategies, cognitive reappraisal (CR) and expressive suppression (ES). This study aimed to (1) examine the latent structure of the Polish version of the ERQ, and (2) use it to explore different profiles of emotion regulation strategy use and their links with mental health outcomes. : Our sample was 1197 Polish-speaking adults from the general community in Poland.

A Critical Reappraisal of Haloperidol for Delirium Management in the Intensive Care Unit: Perspective from Psychiatry.

Delirium is a complex neuropsychiatric syndrome with multifactorial pathophysiology, encompassing a wide range of neuropsychiatric symptoms, and its management remains a significant challenge in critical care. Although often managed with antipsychotics, like haloperidol, current research has predominantly focused on dopamine dysregulation as the primary driver of delirium, overlooking its broader neuroanatomical and neurochemical underpinnings. This has led to a majority of research focusing on haloperidol as a treatment for intensive care unit (ICU) delirium.

Highly Sensitive Non-Dispersive Infrared Gas Sensor with Innovative Application for Monitoring Carbon Dioxide Emissions from Lithium-Ion Battery Thermal Runaway.

The safety of power batteries in the automotive industry is of paramount importance and cannot be emphasized enough. As lithium-ion battery technology continues to evolve, the energy density of these batteries increases, thereby amplifying the potential risks linked to battery failures. This study explores pivotal safety challenges within the electric vehicle sector, with a particular focus on thermal runaway and gas emissions originating from lithium-ion batteries.

Post-discharge complications and follow-up timing after hospitalization for traumatic rib fractures.

Purpose: To evaluate frequency and timing of post-discharge complications in patients with traumatic rib fractures undergoing operative or nonoperative management.

Methods: We retrospectively reviewed adult patients with rib fractures admitted to a Level 1 trauma center from 1/2020 to 12/2021. Outcomes included rib-related complications, pneumonia within 1 month, new diagnosis of opioid- or alcohol-use disorder, and all-cause mortality.

In-situ probing of the Fischer-Tropsch reaction on Co single crystal surfaces up to 1 bar.

The surface chemistry of the Fischer-Tropsch catalytic reaction over Co has still several unknows. Here, we report an in-situ X-ray photoelectron spectroscopy study of Co and Co( ), and in-situ high energy surface X-ray diffraction of Co during the Fischer-Tropsch reaction at 0.15 bar - 1 bar and 406 K - 548 K in a H/CO gas mixture.

The Circulatory Arrest Recovery Ammonia Problem (CARAP) Hypothesis: a H-MRS study of brain metabolism during neonatal cardiopulmonary bypass surgery.

Objective: Congenital heart disease affects 1% of US births, with many babies requiring major cardiothoracic surgery under cardiopulmonary bypass (CPB), exposing the more critical patients to neurodevelopmental impairment. Optimal surgical parameters to minimize neuronal injury are unknown. We used H MRS and blood ammonia assays in a neonatal pig model of CPB to compare two approaches, complete circulatory arrest (CA) versus antegrade cerebral perfusion (ACP).

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported.

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

Role of tRNA-Derived Fragments in Protozoan Parasite Biology.

tRNA molecules are among the most fundamental and evolutionarily conserved RNA types, primarily facilitating the translation of genetic information from mRNA into proteins. Beyond their canonical role as adaptor molecules during protein synthesis, tRNAs have evolved to perform additional functions. One such non-canonical role for tRNAs is through the generation of tRNA-derived fragments via specific cleavage processes.