EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.

DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data.

Laser Doppler measurements of the vocal fold blood micro-circulation.

The authors have developed a laser Doppler method, referred to as LDF+LS (laser Doppler flowmetry by laryngostereometry), for measuring the vocal fold micro-circulation. The vocal folds of 103 patients were examined during general anesthesia. A laser Doppler probe was placed on defined positions at the vocal fold edge: midmembranous position (MP), 2 mm and 4 mm behind, and 1 mm anterior to MP.

TCR signaling inhibits glucocorticoid-induced apoptosis in murine thymocytes depending on the stage of development.

Signaling by either the TCR or glucocorticoid receptor (GR) induces apoptosis in thymocytes. Interestingly, it has been shown previously that hybridoma T cells escape apoptosis induced by either TCR or GR when both of these receptors signal simultaneously. Whether such mutual antagonism is present in primary thymocytes was the subject of the present study.

[Treatment of vitally endangered anorexia nervosa patients based on guardianship laws].

Anorexia nervosa is a psychiatric disorder occurring primarily in young women. Especially when chronic or the body mass index is less than 12 kg/m(2), it has a mortality of up to 20%. Often these patients are admitted to emergency units and treated internistically.

A partial BRCA1 sequence homology mapping to 4q28.

Using a BRCA1 cDNA probe in Southern analysis, we detected a sequence of 348 bp on 4q28 that is homologous to the 3' end of BRCA1. A 28-kb sequence contig has been assembled spanning the homologous region, which we designated BRCA1-h. An open reading frame was identified encoding a sequence of 82 amino acids; 22 of the last 23 amino acids are identical to the last 23 residues of BRCA1.

WHSC1L1, on human chromosome 8p11.2, closely resembles WHSC1 and maps to a duplicated region shared with 4p16.3.

We have identified and characterized a gene (60% on protein level) and a pseudogene (93% on DNA level) that show high similarity to the Wolf-Hirschhorn syndrome candidate gene-1 (WHSC1). These genes, WHSC1L1 and WHSC1L2P, map to human chromosomes 8p11.2 and 17q21, respectively.

Bidirectional effects of corticosterone on splenic T-cell activation: critical role of cell density and culture time.

Glucocorticoids inhibit stimulus-induced T-cell proliferation, an early and essential parameter of cellular immunity. It was recently found however that physiological concentrations of glucocorticoids can also accelerate, not only inhibit, rat T-cell mitogenesis. We investigated mechanism(s) underlying mitogenic actions of glucocorticoids on anti-T-cell receptor (TCR)- and concanavalin A (Con A)-induced T-cell proliferation.

The brain mineralocorticoid receptor: greedy for ligand, mysterious in function.

Glucocorticoids exert their regulatory effects on the hypothalamic-pituitary-adrenocortical axis via two types of corticosteroid receptors: the glucocorticoid receptor and the mineralocorticoid receptor. Whereas the glucocorticoid receptor has a broad distribution in the brain, highest levels of mineralocorticoid receptor are found in the hippocampus. Based on the differential occupancy profile by endogenous glucocorticoids, glucocorticoid receptors are thought to mediate negative feedback signals of elevated glucocorticoid levels, whereas mineralocorticoid receptors control the inhibitory tone of the hippocampus on hypothalamic-pituitary-adrenocortical axis activity.

Glucocorticoids regulate TCR-induced elevation of CD4: functional implications.

CD4 serves as a coreceptor during Ag recognition by the TCR. This interaction results in a marked increase in the sensitivity of a T cell to Ag presented by MHC class II molecules. Here we report that activation of T cells either by plate-bound mAb (anti-TCR, anti-CD3) or soluble activators (staphylococcal enterotoxin A, Con A) is associated with an (up to 3-fold) increase in CD4 cell surface expression on CD25+ cells, which was maximal after 72-96 h.

The PWWP domain: a potential protein-protein interaction domain in nuclear proteins influencing differentiation?

Upon characterization of WHSC1, a gene mapping to the Wolf-Hirschhorn syndrome critical region and at its C-terminus similar to the Drosophila ASH1/trithorax group proteins, we identified a novel protein domain designated PWWP domain. To gain insight into its structure, evolutionary conservation and its potential functional role, we performed database searches to identify other PWWP domain-containing proteins. We retrieved 39 proteins, and a multiple alignment shows that the domain spans some 70 amino acids.

WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.

Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The smallest region of overlap between WHS patients, the WHS critical region, has been confined to 165 kb, of which the complete sequence is known.

Endocrine profile and neuroendocrine challenge tests in transgenic mice expressing antisense RNA against the glucocorticoid receptor.

A transgene expressing antisense RNA complementary to a fragment of the glucocorticoid receptor cDNA was incorporated into the mouse genome and resulted in a transgenic animal that has decreased glucocorticoid receptor function. The transgenic mice showed basal plasma ACTH and corticosterone levels similar to those of the normal control animals. We have further investigated changes in HPA axis regulation by use of different neuroendocrine challenge tests including a dexamethasone suppression test (DST).

Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p 16.3.

Recently, a deletion of chromosome 4pter was found in three patients with Pitt-Rogers-Danks syndrome. We investigated two of these patients, by means of DNA and FISH studies, together with two additional patients with Pitt-Rogers-Danks syndrome, to determine the critical region of the deletion in these patients and to compare this with the critical region in Wolf-Hirschhorn syndrome. All four patients showed terminal deletions of chromosome 4p of different sizes.

Increased stress-induced adrenocorticotropin response after long-term intracerebroventricular treatment of rats with antisense mineralocorticoid receptor oligodeoxynucleotides.

Brain corticosteroid receptors, the type 1 mineralocorticoid receptor (MR) and the type 2 glucocorticoid receptor (GR), are involved in the regulation of neuroendocrine and behavioral responses during ongoing and stressful conditions. To further investigate the role of MR in these responses, we treated male Wistar rats intracerebroventricularly (icv) for 1 week with an 18-base end-capped phosphorothioate-protected antisense oligodeoxynucleotide (ODN) directed against MR mRNA (MR-AS). A mixed bases sequence (MR-MB) and vehicle (0.

Nephropathic cystinosis (CTNS-LSB): construction of a YAC contig comprising the refined critical region on chromosome 17p13.

A yeast artificial chromosome (YAC) contig was constructed encompassing the entire region on chromosome 17p13 where the autosomal recessive disorder infantile nephropathic cystinosis (MIM 21980, CTNS-LSB) has been genetically mapped. It comprises seven clones ordered by their content of a series of six sequence-tagged sites (STSs). Fluorescence in situ hybridisation (FISH) revealed two chimaeric clones.

Yeast artificial chromosome mapping of the cystinosis locus on chromosome 17p by fluorescence in situ hybridization.

The gene locus for cystinosis has been mapped between markers D17S1583 and D17S1584 on the short arm of chromosome 17. Using markers encompassing the cystinosis region, we assigned different yeast artificial chromosome (YAC) clones previously identified by sequence tagged site (STS) screening to 17p13.3.

Estimate of severe autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D) among sporadic muscular dystrophy males: a study of 415 familes.

Ninety-five percent of cases of severe muscular dystrophy with early childhood onset result from mutations in the dystrophin region of the human X chromosome (DMD, McKusick 310200), whereas 5% are thought to result from mutations in autosomal genes. We examined a total of 415 families with at least one living patient whose clinical features suggested DMD. Based on formal genetics, haplotype analysis, and dystrophin determinations, we estimate that one in eight (11.

Long-term antidepressant treatment reduces behavioural deficits in transgenic mice with impaired glucocorticoid receptor function.

Impaired cognitive function and enhanced activity of the hypothalamic-pituitary-adrenocortical system are among the cardinal symptoms of major depression in humans that resolve after successful antidepressant treatment. We used a transgenic mouse model expressing antisense RNA complementary to that of glucocorticoid receptor (GR) mRNA to test the hypothesis that reduced GR function can cause these clinical disturbances. The transgenic mice show profound behavioural changes in a number of animal tests that are indicative of cognitive impairment.

Glucocorticoids accelerate anti-T cell receptor-induced T cell growth.

To study steroid regulation of cell-mediated immunity, we used anti-TCR-stimulated rat splenic lymphocyte mitogenesis as our experimental paradigm. Surprisingly, we found that the principal glucocorticoid of the rat, corticosterone (CORT), potently enhanced anti-TCR-induced lymphocyte proliferation after 2 to 3 days in culture, followed by inhibited cell growth after 5 to 7 days. Thus, glucocorticoids appeared to accelerate anti-TCR-induced lymphocyte mitogenesis.

Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats.

We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical (HPA) axis functioning when adult. To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge, 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10(8) human red blood cells (HRBC) or gram-negative bacterial endotoxin (Escherichia coli LPS: 30 micrograms/kg). The adult male progeny (3 mo old) of both experimental groups showed increased basal plasma corticosterone levels.

Dexamethasone nonsuppression in transgenic mice expressing antisense RNA to the glucocorticoid receptor.

Transgenic mice with impaired glucocorticoid receptor (GR) function produced by partially knocking out GR gene expression with antisense RNA were treated with increasing dosages of dexamethasone. In these mice, ten-fold higher dexamethasone dosages were required to induce full suppression of plasma corticosterone than in normal mice. This relative dexamethasone insensitivity adds to the evidence that these transgenic mice could serve as an appropriate model to study the negative feedback disturbance of the hypothalamic-pituitary-adrenocortical system in affective disorders.

Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system.

The effects of the tricyclic antidepressant amitriptyline on the rat hypothalamic-pituitary-adrenocortical (HPA) system were studied. The time-course experiments showed that amitriptyline, given via the drinking water (4.5 mg/kg.