Improving the Clinical Diagnostic Criteria for Genetically Confirmed Adult-Onset Huntington Disease: Considering Nonmotor Presentations.

Background: Huntington disease (HD) is a genetic neurodegenerative disorder. Given the focus on motor manifestations, nonmotor symptoms are frequently underappreciated in clinical evaluations, despite frequently contributing to primary functional impairment.

Recent Findings: A diagnosis of motor-onset as the definition of manifest symptoms misrepresents the complex nature of HD presentation.

[Psychiatric symptoms of Huntington's disease].

Huntington's disease (HD) is an autosomal dominant inherited disease, which leads to motor, cognitive and psychiatric symptoms. The diagnosis can be confirmed by genetic testing for extended CAG repeats in the Huntingtin gene. Mental and behavioral symptoms are common in HD and can appear several years before the onset of motor symptoms.

Differential diagnosis of chorea (guidelines of the German Neurological Society).

Introduction: Choreiform movement disorders are characterized by involuntary, rapid, irregular, and unpredictable movements of the limbs, face, neck, and trunk. These movements often initially go unnoticed by the affected individuals and may blend together with seemingly intended, random motions. Choreiform movements can occur both at rest and during voluntary movements.

Symptomatic treatment options for Huntington's disease (guidelines of the German Neurological Society).

Introduction: Ameliorating symptoms and signs of Huntington's disease (HD) is essential to care but can be challenging and hard to achieve. The pharmacological treatment of motor signs (e.g.

[Recommendations for the Strategic Development of Health Care for People with Autism Spectrum Disorder (ASD) in Bavaria].

As mental illnesses Autism spectrum disorders (ASD) in DSM-V and ICD - 11 are classified under the category of neuronal and mental disorders. ASD manifests itself them selves in early childhood. A valid, early diagnosis is a basic prerequisite for the provision of appropriate treatment and support services as well as any care planning in all relevant areas such as therapy and early intervention.

Tcf-1 promotes genomic instability and T cell transformation in response to aberrant β-catenin activation.

Understanding the mechanisms promoting chromosomal translocations of the rearranging receptor loci in leukemia and lymphoma remains incomplete. Here we show that leukemias induced by aberrant activation of β-catenin in thymocytes, which bear recurrent translocations, depend on Tcf-1. The DNA double strand breaks (DSBs) in the site of the translocation are Rag-generated, whereas the DSBs are not.

TCF-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4CD8 thymocytes.

Thymocyte development requires a complex orchestration of multiple transcription factors. Ablating either TCF-1 or HEB in CD4CD8 thymocytes elicits similar developmental outcomes including increased proliferation, decreased survival, and fewer late Tcra rearrangements. Here, we provide a mechanistic explanation for these similarities by showing that TCF-1 and HEB share ~7,000 DNA-binding sites genome wide and promote chromatin accessibility.

[The diagnostics of autism spectrum disorder in children, adolescents and adults: Overview of the key questions and main results of the first part of the German AWMF-S3 - clinical guideline].

The diagnostics of autism spectrum disorder in children, adolescents and adults: Overview of the key questions and main results of the first part of the German AWMF-S3 - clinical guideline Autism spectrum disorders (ASD) include ICD-10 diagnoses of childhood autism, Asperger syndrome, and atypical autism; there is a lifetime prevalence of ~1 %. The aim of the evidence-based clinical guideline (AWMF-S3-Guideline) is to summarize the current evidence concerning diagnostic and therapeutic processes for professionals working in healthcare and social welfare and to provide consensus on clinical recommendations. The present study summarizes the most important results of the diagnostic part of this guideline.

Genome-wide Identification of Structure-Forming Repeats as Principal Sites of Fork Collapse upon ATR Inhibition.

DNA polymerase stalling activates the ATR checkpoint kinase, which in turn suppresses fork collapse and breakage. Herein, we describe use of ATR inhibition (ATRi) as a means to identify genomic sites of problematic DNA replication in murine and human cells. Over 500 high-resolution ATR-dependent sites were ascertained using two distinct methods: replication protein A (RPA)-chromatin immunoprecipitation (ChIP) and breaks identified by TdT labeling (BrITL).

The Energetics and Physiological Impact of Cohesin Extrusion.

Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases.

Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation.

50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially regulated steps.

The cell cycle restricts activation-induced cytidine deaminase activity to early G1.

Activation-induced cytidine deaminase (AID) converts cytosine into uracil to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of antibody genes. In addition, this enzyme produces DNA lesions at off-target sites that lead to mutations and chromosome translocations. However, AID is mostly cytoplasmic, and how and exactly when it accesses nuclear DNA remains enigmatic.

Naturally occurring radioactivity in some Swedish concretes and their constituents - Assessment by using I-index and dose-model.

The reference level for effective dose due to gamma radiation from building materials and construction products used for dwellings is set to 1 mSv per year (EC, 1996, 1999), (CE, 2014). Given the specific conditions presented by the EC in report 112 (1999) considering building and construction materials, an I-index of 1 may generate an effective dose of 1 mSv per year. This paper presents a comparison of the activity concentrations of (4)(0)K, (226)Ra and (232)Th of aggregates and when these aggregates constitute a part of concrete.

Autism beyond diagnostic categories: characterization of autistic phenotypes in schizophrenia.

Background: Behavioral phenotypical continua from health to disease suggest common underlying mechanisms with quantitative rather than qualitative differences. Until recently, autism spectrum disorders and schizophrenia were considered distinct nosologic entities. However, emerging evidence contributes to the blurring of symptomatic and genetic boundaries between these conditions.

Substantia nigra hyperechogenicity in hypokinetic Huntington's disease patients.

Substantia nigra (SN) hyperechogenicity can be detected by transcranial sonography (TCS) to assist the early diagnosis of idiopathic Parkinson's disease (IPD). This study prospectively investigated whether SN hyperechogenicity is also present in Huntington's disease (HD) patients with symptoms of hypokinesia and/or rigidity. All patients recruited to the study (n = 15) were characterised by hypokinesia and/or rigidity while nine of these patients also displayed chorea and/or dystonia.

B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity.

The antibody gene mutator activation-induced cytidine deaminase (AID) promiscuously damages oncogenes, leading to chromosomal translocations and tumorigenesis. Why nonimmunoglobulin loci are susceptible to AID activity is unknown. Here, we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome.

β-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells.

The density and type of lymphocytes that infiltrate colon tumors are predictive of the clinical outcome of colon cancer. High densities of T helper 17 (T(H)17) cells and inflammation predict poor outcome, whereas infiltration by T regulatory cells (Tregs) that naturally suppress inflammation is associated with longer patient survival. However, the role of Tregs in cancer remains controversial.

β-Catenin induces T-cell transformation by promoting genomic instability.

Deregulated activation of β-catenin in cancer has been correlated with genomic instability. During thymocyte development, β-catenin activates transcription in partnership with T-cell-specific transcription factor 1 (Tcf-1). We previously reported that targeted activation of β-catenin in thymocytes (CAT mice) induces lymphomas that depend on recombination activating gene (RAG) and myelocytomatosis oncogene (Myc) activities.

Transcriptional regulation of the Ikzf1 locus.

Ikaros is a critical regulator of lymphocyte development and homeostasis; thus, understanding its transcriptional regulation is important from both developmental and clinical perspectives. Using a mouse transgenic reporter approach, we functionally characterized a network of highly conserved cis-acting elements at the Ikzf1 locus. We attribute B-cell and myeloid but not T-cell specificity to the main Ikzf1 promoter.

A far downstream enhancer for murine Bcl11b controls its T-cell specific expression.

Bcl11b is a T-cell specific gene in hematopoiesis that begins expression during T-lineage commitment and is required for this process. Aberrant expression of BCL11B or proto-oncogene translocation to the vicinity of BCL11B can be a contributing factor in human T-ALL. To identify the mechanism that controls its distinctive T-lineage expression, we corrected the identified Bcl11b transcription start site and mapped a cell-type-specific differentially methylated region bracketing the Bcl11b promoter.