Genetic suppression features ABHD18 as a Barth syndrome therapeutic target.

Cardiolipin (CL) is the signature phospholipid of the inner mitochondrial membrane, where it stabilizes electron transport chain protein complexes. The final step in CL biosynthesis relates to its remodelling: the exchange of nascent acyl chains with longer, unsaturated chains. However, the enzyme responsible for cleaving nascent CL (nCL) has remained elusive.

Uridine phosphorylase-1 supports metastasis by altering immune and extracellular matrix landscapes.

Understanding mechanisms that facilitate early events in metastatic seeding is key to developing therapeutic approaches to reduce metastasis. Here we identify uracil as a metastasis-associated metabolite in genetically engineered mouse models of cancer and in patients with metastatic breast cancer. Uracil is generated by the enzyme uridine phosphorylase-1 (UPP1), and we find that neutrophils are a significant source of UPP1 in metastatic cancer.

Multicenter evaluation of the safety and efficacy of varying doses of cangrelor used in acute cerebrovascular stenting in patients with acute ischemic stroke.

Background: Acute ischemic stroke often necessitates neuroendovascular interventions such as thrombectomy and, occasionally, stenting for large vessel occlusions or intracranial atherosclerotic disease. Effective antiplatelet therapy is essential during stenting to mitigate thrombosis risks, but consensus on optimal cangrelor dosing remains elusive. This study evaluates the safety and efficacy of various cangrelor doses used in acute cerebrovascular stenting.

Tafazzin regulates neutrophil maturation and inflammatory response.

Barth syndrome (BTHS) is a rare genetic disease caused by mutations in the TAFAZZIN gene. It is characterized by neutropenia, cardiomyopathy and skeletal myopathy. Neutropenia in BTHS is associated with life-threatening infections, yet there is little understanding of the molecular and physiological causes of this phenomenon.

Clinical outcomes of heart transplantation using hepatitis c-viremic donors: A systematic review with meta-analysis.

Background: Heart transplantation (HTx) from hepatitis C virus (HCV)-viremic donors to nonviremic recipients decreases mortality and costs. Consequently, many transplant centers have reported their results using this strategy. Hence, there is a need for an outcome analysis.

Efficacy of Bivalirudin for Therapeutic Anticoagulation in COVID-19 Patients Requiring ECMO Support.

Objectives: The Coronavirus Disease 2019 (COVID-19) pandemic has been associated with cases of refractory acute respiratory distress syndrome (ARDS) sometimes requiring support with extracorporeal membrane oxygenation (ECMO). Bivalirudin can be used for anticoagulation in patients on ECMO support, but its efficacy and safety in patients with COVID-19 is unknown. The authors set out to compare the pharmacologic characteristics and dosing requirements of bivalirudin in patients requiring ECMO support for ARDS due to COVID-19 versus ARDS from other etiologies.

Developmentally regulated expression is robust to TAD perturbations.

Topologically associating domains (TADs) have been proposed to both guide and constrain enhancer activity. is located within a TAD known to contain all its enhancers. To investigate the importance of chromatin conformation and TAD integrity on developmental gene regulation, we have manipulated the TAD - creating internal deletions, deleting CTCF sites, and deleting and inverting sequences at TAD boundaries.

Rapid and strong de novo donor-specific antibody development in a lung transplant recipient: Short communication/case report.

A 66-yo female patient (typed B*39:01, 44:02) underwent first left single lung transplant (typed B*81:01, 15:17) on 02/07/2016 with negative for DSA in current and historical samples. On 02/17/2016 strong de novo DSA (MFI=15,200, C1q+) to B81 were detected. The recipient has two children typed B*07:02, 44:02 B*27:03, 39:01, and had received multiple vaccinations.

Intestinal Graft Failure: Should We Perform the Allograft Enterectomy Before or With Retransplantation?

Background: Intestinal graft dysfunction is sometimes irreversible and requires allograft enterectomy with or without retransplantation. There is no comprehensive assessment of allograft enterectomy regarding indications and outcomes. The aim of this study was to evaluate management of patients with intestinal graft failure with special reference to indications and outcomes of allograft enterectomy and the procedure's validity as a bridge to retransplantation.

Cytomegalovirus Infection After Intestinal/Multivisceral Transplantation: A Single-Center Experience With 210 Cases.

Background: Cytomegalovirus (CMV) infection is the most prevalent infectious complication after solid organ transplantation, and recipients of isolated intestinal transplantation (IIT)/multivisceral transplantation (MVT) are among those at the highest risk. Limited clinical data exist regarding CMV infection after IIT/MVT. The aim of this study is to analyze risk factors for posttransplant CMV infection and to assess the efficacy and validity of our prophylaxis and treatment regimens in intestinal transplantation.

Post-transplant persistent lymphopenia is a strong predictor of late survival in isolated intestine and multivisceral transplantation.

Absolute lymphocyte count (ALC) has been identified as a prognostic factor in liver transplantation. We hypothesized that a lower ALC may be linked to poor outcomes in isolated intestinal/multivisceral transplantation (IIT/MVT). The aim of this study was to investigate the prognostic impact of ALC in IIT/MVT.

Mapping the Shh long-range regulatory domain.

Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity.

Long range regulation of the sonic hedgehog gene.

The regulatory architecture that controls developmental genes is often a collection of enhancers that, in combination, generate a complex spatial and temporal pattern of expression. These enhancers populate domains operating at long distances and, in the case of the sonic hedgehog (Shh) locus, this regulatory domain covers ∼900-1000kb. Within this context each embryonic tissue that expresses Shh has acquired its own regulatory apparatus which may require the activity from several distinct enhancers.

Miller (Genee-Wiedemann) syndrome represents a clinically and biochemically distinct subgroup of postaxial acrofacial dysostosis associated with partial deficiency of DHODH.

Biallelic mutations in the gene encoding DHOdehase [dihydroorotate dehydrogenase (DHODH)], an enzyme required for de novo pyrimidine biosynthesis, have been identified as the cause of Miller (Genée-Weidemann or postaxial acrofacial dysostosis) syndrome (MIM 263750). We report compound heterozygous DHODH mutations in four additional families with typical Miller syndrome. Complementation in auxotrophic yeast demonstrated reduced pyrimidine synthesis and in vitro enzymatic analysis confirmed reduced DHOdehase activity in 11 disease-associated missense mutations, with 7 alleles showing discrepant activity between the assays.

Human limb abnormalities caused by disruption of hedgehog signaling.

Human hands and feet contain bones of a particular size and shape arranged in a precise pattern. The secreted factor sonic hedgehog (SHH) acts through the conserved hedgehog (Hh) signaling pathway to regulate the digital pattern in the limbs of tetrapods (i.e.