Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).

Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years. Many monogenic forms have been discovered due to comprehensive genetic testing like exome sequencing. However, disease-causing variants in known disease-associated genes only explain a proportion of cases.

AOX delays the onset of the lethal phenotype in a mouse model of Uqcrh (complex III) disease.

The alternative oxidase, AOX, provides a by-pass of the cytochrome segment of the mitochondrial respiratory chain when the chain is unavailable. AOX is absent from mammals, but AOX from Ciona intestinalis is benign when expressed in mice. Although non-protonmotive, so does not contribute directly to ATP production, it has been shown to modify and in some cases rescue phenotypes of respiratory-chain disease models.

Knockout mouse models as a resource for the study of rare diseases.

Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestations and low prevalence. There is a lack of specific treatments and only a few hundred of the approximately 7,000 RDs have an approved regime. Rapid technological development in genome sequencing enables the mass identification of potential candidates that in their mutated form could trigger diseases but are often not confirmed to be causal.

Implication of dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below 30 years of age. Many monogenic forms have been discovered mainly due to comprehensive genetic testing like exome sequencing (ES). However, disease-causing variants in known disease-associated genes still only explain a proportion of cases.

New C3H Kit cancer mouse model develops late-onset malignant mammary tumors with high penetrance.

Gastro-intestinal stromal tumors and acute myeloid leukemia induced by activating stem cell factor receptor tyrosine kinase (KIT) mutations are highly malignant. Less clear is the role of KIT mutations in the context of breast cancer. Treatment success of KIT-induced cancers is still unsatisfactory because of primary or secondary resistance to therapy.

Biallelic loss-of-function variants in RABGAP1 cause a novel neurodevelopmental syndrome.

Purpose: RABGAP1 is a GTPase-activating protein implicated in a variety of cellular and molecular processes, including mitosis, cell migration, vesicular trafficking, and mTOR signaling. There are no known Mendelian diseases caused by variants in RABGAP1.

Methods: Through GeneMatcher, we identified 5 patients from 3 unrelated families with homozygous variants in the RABGAP1 gene found on exome sequencing.

Monitoring longitudinal disease progression in a novel murine Kit tumor model using high-field MRI.

Animal models are an indispensable platform used in various research disciplines, enabling, for example, studies of basic biological mechanisms, pathological processes and new therapeutic interventions. In this study, we applied magnetic resonance imaging (MRI) to characterize the clinical picture of a novel N-ethyl-N-nitrosourea-induced Kit-mutant mouse in vivo. Seven C3H Kit mutant animals each of both sexes and their littermates were monitored every other month for a period of twelve months.

X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer's disease.

Purpose: Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease.

Methods: We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia.

Post-synaptic scaffold protein TANC2 in psychiatric and somatic disease risk.

Understanding the shared genetic aetiology of psychiatric and medical comorbidity in neurodevelopmental disorders (NDDs) could improve patient diagnosis, stratification and treatment options. Rare tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2 (TANC2)-disrupting variants were disease causing in NDD patients. The post-synaptic scaffold protein TANC2 is essential for dendrite formation in synaptic plasticity and plays an unclarified but critical role in development.

Establishing sample-preparation protocols for X-ray phase-contrast CT of rodent spinal cords: Aldehyde fixations and osmium impregnation.

Background: Dense and unbiased cellular-resolution representations of extended volumetric central nervous system soft-tissue anatomy are difficult to obtain, even in experimental post-mortem settings. Interestingly, X-ray phase-contrast computed tomography (X-PCI-CT), an emerging soft-tissue-sensitive volumetric imaging technique, can provide multiscale organ- to cellular-level morphological visualizations of neuroanatomical structure.

New Method: Here, we tested different nervous-tissue fixation procedures, conventionally used for transmission electron microscopy, to better establish X-PCI-CT-specific sample-preparation protocols.

The rRNA mA methyltransferase METTL5 is involved in pluripotency and developmental programs.

Covalent chemical modifications of cellular RNAs directly impact all biological processes. However, our mechanistic understanding of the enzymes catalyzing these modifications, their substrates and biological functions, remains vague. Amongst RNA modifications N-methyladenosine (mA) is widespread and found in messenger (mRNA), ribosomal (rRNA), and noncoding RNAs.

Micro-imaging of Brain Cancer Radiation Therapy Using Phase-contrast Computed Tomography.

Purpose: Experimental neuroimaging provides a wide range of methods for the visualization of brain anatomic morphology down to subcellular detail. Still, each technique-specific detection mechanism presents compromises among the achievable field-of-view size, spatial resolution, and nervous tissue sensitivity, leading to partial sample coverage, unresolved morphologic structures, or sparse labeling of neuronal populations and often also to obligatory sample dissection or other sample invasive manipulations. X-ray phase-contrast imaging computed tomography (PCI-CT) is an experimental imaging method that simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity, and ex vivo full organ rodent brain coverage without any need for sample dissection, staining or labeling, or contrast agent injection.

Understanding gene functions and disease mechanisms: Phenotyping pipelines in the German Mouse Clinic.

Since decades, model organisms have provided an important approach for understanding the mechanistic basis of human diseases. The German Mouse Clinic (GMC) was the first phenotyping facility that established a collaboration-based platform for phenotype characterization of mouse lines. In order to address individual projects by a tailor-made phenotyping strategy, the GMC advanced in developing a series of pipelines with tests for the analysis of specific disease areas.

Spatio-temporal TGV denoising for ASL perfusion imaging.

In arterial spin labeling (ASL) a perfusion weighted image is achieved by subtracting a label image from a control image. This perfusion weighted image has an intrinsically low signal to noise ratio and numerous measurements are required to achieve reliable image quality, especially at higher spatial resolutions. To overcome this limitation various denoising approaches have been published using the perfusion weighted image as input for denoising.

The vertebral trabecular model revisited: magnetic field distribution in the vicinity of osseous disconnections.

In the current paper a vertebral bone model is introduced that can be used for studying trabecular thinning and the formation of trabecular disconnections. Magnetostatic simulations are applied in MR-osteodensitometry to deduce the quality of trabecular bone from experimentally obtained susceptibility effects. The course of trabecular bone loss, which results in distinct interruptions and consequently severe mechanical impairment, is not assessable in the majority of such applied models.

A fully automated trabecular bone structural analysis tool based on T2* -weighted magnetic resonance imaging.

One major source affecting the precision of bone structure analysis in quantitative magnetic resonance imaging (qMRI) is inter- and intraoperator variability, inherent in delineating and tracing regions of interest along longitudinal studies. In this paper an automated analysis tool, featuring bone marrow segmentation, region of interest generation, and characterization of cancellous bone of articular joints is presented. In evaluation studies conducted at the knee joint the novel analysis tool significantly decreased the standard error of measurement and improved the sensitivity in detecting minor structural changes.

Quantification of direct current in electrically active implants using MRI methods.

The aim of this study was to evaluate a variety of phase- and magnitude-based MRI methods at 1.5 T and 3 T regarding their sensitivity and accuracy with respect to the quantification of electrical direct current via the induced magnetic field inhomogeneity. For this, a phantom was constructed which was specially designed to reduce RF effects and which provided a one-dimensional electrical direct current in a thin copper conductor perpendicular to the static magnetic field of the scanner.

MR temperature monitoring applying the proton resonance frequency method in liver and kidney at 0.2 and 1.5 T: segment-specific attainable precision and breathing influence.

Object: The objective of this study was to evaluate breathing influence on precision in temperature determination by using the proton resonance frequency (PRF) shift method depending on the location in abdominal organs at 0.2 and 1.5 T.

[Contrast optimisation of musculoskeletal tissues in the knee region using spinecho and spoiled gradientecho MR imaging].

In this study the contrast behaviour of five different musculoskeletal tissues of the knee (muscle, cartilage, bone marrow, synovial fluid and the Hoffa's fat body) were analysed for spinecho-and spoiled gradientecho sequences by means of computer simulations On the basis of tissue properties (spin density, T1, T2 and T2*) obtained from three healthy subjects optimal imaging parameters TR, TE and the flip angle (the latter only for GRE) were derived for separation between two tissue types. As a criterion for the ability to separate two tissues the ratio between signal intensity difference regarding the two tissues of interest and the used measuring time was applied. The paper presents the sequence type and parameters for optimal tissue contrast regarding all possible pairs of tissue.