Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder leading to end-stage renal disease. ADPKD arises from mutations in the and genes, which encode polycystin 1 (PC1) and polycystin 2 (PC2), respectively. PC2 is a nonselective cation channel, and disease-linked mutations disrupt normal cellular processes, including signaling and fluid secretion.

Universal Diffusion in Coulomb Crystals.

Diffusion coefficients for crystallized Coulomb plasmas are essential microphysics input for modeling white dwarf cores and neutron star crusts but are poorly understood. In this work we present a model for diffusion in Coulomb crystals. We show that melting and diffusion follow the same universal scaling such that diffusion is independent of screening.

CALHM2 is a mitochondrial protein import channel that regulates fatty acid metabolism.

For mitochondrial metabolism to occur in the matrix, multiple proteins must be imported across the two (inner and outer) mitochondrial membranes. Classically, two protein import channels, TIM/TOM, are known to perform this function, but whether other protein import channels exist is not known. Here, using super-resolution microscopy, proteomics, and electrophysiological techniques, we identify CALHM2 as the import channel for the ECHA subunit of the mitochondrial trifunctional protein (mTFP), which catalyzes β-oxidation of fatty acids in the mitochondrial matrix.

Incidence of Postsurgical Intraocular Inflammation 6 Months After Implantation with a Multifocal Intraocular Lens.

Purpose: This study assessed the incidence of postsurgical intraocular inflammation after cataract extraction by phacoemulsification and implantation with AcrySof IQ ReSTOR intraocular lenses (IOLs) produced using an updated manufacturing process. Incidence rates were compared with historical rates of postsurgical intraocular inflammation.

Methods: This was a prospective, multicenter, post-approval study at 34 sites.

Calcium signalling and transport in the kidney.

The kidney plays a pivotal role in regulating calcium levels within the body. Approximately 98% of the filtered calcium is reabsorbed in the nephron, and this process is tightly controlled to maintain calcium homeostasis, which is required to facilitate optimal bone mineralization, preserve serum calcium levels within a narrow range, and support intracellular signalling mechanisms. The maintenance of these functions is attributed to a delicate balance achieved by various calcium channels, transporters, and calcium-binding proteins in renal cells.

Ubiquitin E3 Ligase FBXO9 Regulates Pluripotency by Targeting DPPA5 for Ubiquitylation and Degradation.

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have unique characteristics where they can both contribute to all three germ layers in vivo and self-renewal indefinitely in vitro. Post-translational modifications of proteins, particularly by the ubiquitin proteasome system (UPS), control cell pluripotency, self-renewal, and differentiation. A significant number of UPS members (mainly ubiquitin ligases) regulate pluripotency and influence ESC differentiation with key elements of the ESC pluripotency network (including the "master" regulators NANOG and OCT4) being controlled by ubiquitination.

Impact of prone position on dead-space fraction in COVID-19 related acute respiratory distress syndrome.

Introduction: COVID-19 Related Acute Respiratory Syndrome (C-ARDS) is characterized by a mismatch between respiratory mechanics and hypoxemia, suggesting increased dead-space fraction (DSF). Prone position is a cornerstone treatment of ARDS under invasive mechanical ventilation reducing mortality. We sought to investigate the impact of prone position on DSF in C-ARDS in a cohort of patients receiving invasive mechanical ventilation.

Cardio-respiratory interactions in acute asthma.

Asthma encompasses of respiratory symptoms that occur intermittently and with varying intensity accompanied by reversible expiratory airflow limitation. In acute exacerbations, it can be life-threatening due to its impact on ventilatory mechanics. Moreover, asthma has significant effects on the cardiovascular system, primarily through heart-lung interaction-based mechanisms.

Does maternal vitamin D status influence placental weight or vascular and inflammatory pathology? Secondary analysis from the Kellogg Pregnancy Study.

Introduction: Positive effects of vitamin D (vitD) supplementation on comorbidities of pregnancy (COP) have been explored; however, few studies have elucidated the pathophysiology behind the development of these COP and the potential relationship with derangements in placental development and morphology. Additionally, it is known that placentas weighing 10th-90th % for gestational age are associated with better outcomes. Therefore, the objective of this study was to assess the impact of resulting circulating serum 25(OH)D concentrations associated with intake of high or low doses of supplementary vitD on placental development and morphology in women who participated in a randomized double blind, placebo-controlled trial of vitD supplementation.

Association of sickle cell trait with adverse pregnancy outcomes in a population-based cohort.

Introduction: Sickle cell trait (SCT) is common in African descendants. Its association with several adverse pregnancy outcomes (APOs) has been reported but remains inconsistent. The objectives of this study are to test associations of SCT with APOs in non-Hispanic Black women, including (1) validate the associations of SCT with previously reported APOs, (2) test novel associations of SCT with broad spectrum of APOs, and (3) estimate the attributable risk of SCT for implicated APOs.

Reverse Correlation Uncovers More Complete Tinnitus Spectra.

This study validates an approach to characterizing the sounds experienced by tinnitus patients via reverse correlation, with potential for characterizing a wider range of sounds than currently possible. Ten normal-hearing subjects assessed the subjective similarity of random auditory stimuli and target tinnitus-like sounds ("buzzing" and "roaring"). Reconstructions of the targets were obtained by regressing subject responses on the stimuli, and were compared for accuracy to the frequency spectra of the targets using Pearson's [Formula: see text].

Microbiota from Preterm Infants Who Develop Necrotizing Enterocolitis Drives the Neurodevelopment Impairment in a Humanized Mouse Model.

Necrotizing enterocolitis (NEC) is the leading basis for gastrointestinal morbidity and poses a significant risk for neurodevelopmental impairment (NDI) in preterm infants. Aberrant bacterial colonization preceding NEC contributes to the pathogenesis of NEC, and we have demonstrated that immature microbiota in preterm infants negatively impacts neurodevelopment and neurological outcomes. In this study, we tested the hypothesis that microbial communities before the onset of NEC drive NDI.

Minimally Invasive Treatment Options for Hepatic Uveal Melanoma Metastases.

Uveal melanoma is one of the most common primary intraocular malignancies that accounts for about 85% of all ocular melanomas. The pathophysiology of uveal melanoma is distinct from cutaneous melanoma and has separate tumor profiles. The management of uveal melanoma is largely dependent on the presence of metastases, which confers a poor prognosis with a one-year survival reaching only 15%.

Use of clinical phenotypes to characterize emergency department patients administered intravenous opioids for acute pain.

Objective: Individual experience with opioids is highly variable. Some patients with acute pain do not experience pain relief with opioids, and many report no euphoria or dysphoric reactions. In this study, we describe the clinical phenotypes of patients who receive intravenous opioids.

The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains.

Necrotizing enterocolitis in premature infants-A defect in the brakes? Evidence from clinical and animal studies.

A key aspect of postnatal intestinal adaptation is the establishment of symbiotic relationships with co-evolved gut microbiota. Necrotizing enterocolitis (NEC) is the most severe disease arising from failure in postnatal gut adaptation in premature infants. Although pathological activation of intestinal Toll-like receptors (TLRs) is believed to underpin NEC pathogenesis, the mechanisms are incompletely understood.

A randomized controlled trial of oropharyngeal therapy with mother's own milk for premature infants.

Objective: To determine if oropharyngeal therapy with mother's own milk (OPT-MOM) reduces late-onset sepsis (L-OS; primary outcome), NEC, death, length of stay, time to full enteral nutrition (FEN) and full oral feeds in preterm infants (BW < 1250 g).

Design: Infants (N = 220) were randomized to Group A (milk) or B (placebo) and received 0.2 mL every 2 h for 48 h, then every 3 h until 32 weeks CGA.

Prominent Intrapulmonary Shunt Vessels and Altered Lung Development in Infants With Sudden Unexplained Infant Death.

The purpose of this study was to evaluate intrapulmonary arteriovenous shunts in patients with and without sudden unexplained infant death. We identified open intrapulmonary bronchopulmonary anastomoses as potential pathways for right-to-left shunt in a subset of infants with sudden unexplained infant death.

Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR.

Transitioning from pluripotency to differentiated cell fates is fundamental to both embryonic development and adult tissue homeostasis. Improving our understanding of this transition would facilitate our ability to manipulate pluripotent cells into tissues for therapeutic use. Here, we show that membrane voltage (V) regulates the exit from pluripotency and the onset of germ layer differentiation in the embryo, a process that affects both gastrulation and left-right patterning.

Characterizing metastatic uveal melanoma patients who develop symptomatic brain metastases.

Metastatic uveal melanoma (mUM) is an advanced ocular malignancy characterized by a hepatotropic pattern of spread. As the incidence of brain metastases (BM) in mUM patients has been thought to be low, routine CNS surveillance has not been recommended. Notably, no formal assessment of BM incidence in mUM has to date been published to support this clinical practice.