DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

The Redesigned American Board of Radiology 16-month Pathway in Nuclear Radiology: Initial Outcomes (2017-2022).

Launched on July 1, 2017, the redesigned American Board of Radiology 16-month Pathway in Nuclear Radiology is flourishing. The original goal of this accelerated training pathway was to help meet the ever-growing demand for nuclear radiology subspecialists in academic and community practices. As of March 1, 2024, 125 graduates of the 16-month pathway had achieved specialty certification in either diagnostic radiology or interventional radiology/diagnostic radiology; nearly 60% had also attained advanced certification in nuclear radiology and/or nuclear medicine.

Shedding Light on the Origin of ^{204}Pb, the Heaviest s-Process-Only Isotope in the Solar System.

Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the r-process contribution by their stable isobars are defined as s-only nuclei. For a long time the abundance of ^{204}Pb, the heaviest s-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance.

Radiosynthesis and Preclinical Evaluation of -[F]FET and [F]FET-OMe as Novel [F]FET Analogs for Brain Tumor Imaging.

-([F]Fluoroethyl)-l-tyrosine ([F]FET) is actively transported into the brain and cancer cells by LAT1 and possibly other amino acid transporters, which enables brain tumor imaging by positron emission tomography (PET). However, tumor delivery of this probe in the presence of competing amino acids may be limited by a relatively low affinity for LAT1. The aim of the present work was to evaluate the -substituted [F]FET analog -[F]FET and the methyl ester [F]FET-OMe, which were designed to improve tumor delivery by altering the physicochemical, pharmacokinetic, and/or transport properties.

Clinical heterogeneity within the ALS-FTD spectrum in a family with a homozygous optineurin mutation.

Objective: Mutations in the gene encoding for optineurin (OPTN) have been reported in the context of different neurodegenerative diseases including the amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum. Based on single case reports, neuropathological data in OPTN mutation carriers have revealed transactive response DNA-binding protein 43 kDa (TDP-43) pathology, in addition to accumulations of tau and alpha-synuclein. Herein, we present two siblings from a consanguineous family with a homozygous frameshift mutation in the OPTN gene and different clinical presentations.

Genome Sequencing for Cases Unsolved by Exome Sequencing: Identifying a Single-Exon Deletion in TBCK in a Case from 30 Years Ago.

In patients with neurodevelopmental disorders (NDDs), exome sequencing (ES), the diagnostic gold standard, reveals an underlying monogenic condition in only approximately 40% of cases. We report the case of a female patient with profound NDD who died 30 years ago at the age of 3 years and for whom genome sequencing (GS) now identified a single-exon deletion in previously missed by ExomeDepth, the copy number variation (CNV) detection algorithm in ES.Deoxyribonucleic acid (DNA) was extracted from frozen muscle tissue of the index patient and the parents' blood.

Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.

The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8.

Joint Linkage and Association Analysis Using GENEHUNTER-MODSCORE with an Application to Familial Pancreatic Cancer.

Introduction: Joint linkage and association (JLA) analysis combines two disease gene mapping strategies: linkage information contained in families and association information contained in populations. Such a JLA analysis can increase mapping power, especially when the evidence for both linkage and association is low to moderate. Similarly, an association analysis based on haplotypes instead of single markers can increase mapping power when the association pattern is complex.

Next-generation sequencing and comprehensive data reassessment in 263 adult patients with neuromuscular disorders: insights into the gray zone of molecular diagnoses.

Background: Neuromuscular disorders (NMDs) are heterogeneous conditions with a considerable fraction attributed to monogenic defects. Despite the advancements in genomic medicine, many patients remain without a diagnosis. Here, we investigate whether a comprehensive reassessment strategy improves the diagnostic outcomes.

NeuroCellCentreDB: Exploring a Novel Dataset for Neuron-like Cell Centre Detection with Deep Neural Networks.

The manipulation and stimulation of cell growth is invaluable for neuroscience research such as brain-machine interfaces or applications of neural tissue engineering. For the implementation of such research avenues, in particular the analysis of cells' migration behaviour, and accordingly, the determination of cell positions on microscope images is essential, causing a current need for labour-intensive, manual annotation efforts of the cell positions. In an attempt towards automation of the required annotation efforts, we i) introduce NeuroCellCentreDB, a novel dataset of neuron-like cells on microscope images with annotated cell centres, ii) evaluate a common (bounding box-based) object detector, faster region-based convolutional neural network (FRCNN), for the task at hand, and iii) design and test a fully convolutional neural network, with the specific goal of cell centre detection.

Exome sequencing (ES) of a pediatric cohort with chronic endocrine diseases: a single-center study (within the framework of the TRANSLATE-NAMSE project).

Background: Endocrine disorders are heterogeneous and include a significant number of rare monogenic diseases.

Methods: We performed exome sequencing (ES) in 106 children recruited from a single center within the TRANSLATE‑NAMSE project. They were categorized into subgroups: proportionate short stature (PSS), disproportionate short stature (DSS), hypopituitarism (H), differences in sexual development (DSD), syndromic diseases (SD) and others.

Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members.

The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here, we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation.

The diverse nature of intestinal fibroblasts in development, homeostasis, and disease.

Only in recent years have we begun to appreciate the involvement of fibroblasts in intestinal development, tissue homeostasis, and disease. These insights followed the advent of single-cell transcriptomics that allowed researchers to explore the heterogeneity of intestinal fibroblasts in unprecedented detail. Since researchers often defined cell types and their associated function based on the biological process they studied, there are a plethora of partially overlapping markers for different intestinal fibroblast populations.

De novo missense variants in RRAGC lead to a fatal mTORopathy of early childhood.

Purpose: Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) regulates cell growth in response to nutritional status. Central to the mTORC1 function is the Rag-GTPase heterodimer. One component of the Rag heterodimer is RagC (Ras-related GTP-binding protein C), which is encoded by the RRAGC gene.