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7 recordsLinked to original sources
PubMed2026

Genome-Wide SNP Characterisation of Three Kazakh Sheep Breeds: Kazakh Fat-Tailed Coarse-Wool, Degeres, and Etti Merino.

Kazakhstan's sheep portfolio underpins much of the country's mutton and wool production, yet several of its principal breeds remain genomically uncharacterised. The aim of this study was to characterise the genomic diversity, population structure, and global phylogenetic placement of three economically important Kazakh breeds and to determine whether they constitute separate gene pools requiring independent management. We present the first genome-wide SNP characterisation to include the Degeres (DE), the Etti Merino (EM), and the Kazakh fat-tailed coarse-wool (KKG) breeds simultaneously. A total of 1497 animals (DE = 354, EM = 642, KKG = 501) sampled across seven production households were genotyped and, after quality control, analysed at 42,279 SNPs, of which 22,766 LD-pruned markers were used for principal component analysis and AMOVA. We applied principal component analysis (PCA), pairwise FST, analysis of molecular variance (AMOVA), neighbour-joining phylogenetics, model-based ancestry estimation (ADMIXTURE), and Hill-number diversity profiling, and projected the breeds against the global Ovine SNP50 HapMap panel (74 reference breeds, 2819 animals; 37,685 shared SNPs). All three breeds retained uniformly high within-breed diversity (expected heterozygosity 0.413-0.417) with fixation indices at or near zero. AMOVA partitioned 94.03% of variance within breeds (&#x3a6;ST = 0.060, p < 0.001). PCA, phylogeny, and ADMIXTURE concordantly resolved three breed-specific clusters at K = 3, with a maximum interbreed FST of 0.038 within the study dataset. Against the global panel, EM was genetically closest to Merino and Merino-derived reference breeds (pooled FST = 0.017) and substantially more distant from Southwest Asian sheep (FST = 0.045), whereas DE and KKG showed the reciprocal pattern (FST = 0.027 and 0.020 to Southwest Asia, 0.052 to the Merino group). DE additionally displayed the heterozygote excess and partial admixture expected of an incompletely consolidated composite. These results delineate three distinct gene pools and carry direct implications for breed management and the conservation of genomic diversity in Kazakhstani sheep.

ADMIXTURE↗
PubMed1979

[Endoscopic diagnosis and therapy of colorectal tumours (author's transl)].

1. If endoscopy leads to the suspicion of an exulcerated and/or polypous carcinoma of the colon, surgical intervention is the primary therapy. Histological classification of the tumour should be effected by means of endoscopic biopsy. 2. (Familial) adenomatosis of the colon requires colectomy. 3. Broad-based polypi resembling a lawn where a large wound area must be expected by electrocoagulation (risk of perforation), and pediculate polypi of the (rare) size of 3 cm and more (risk of haemorrhage) should not be resected via endoscopy but by surgery. 4. Solitary or multiple polypi of the colon not covered by points 1 to 3 above, are primarily for reasons of diagnosis an indication for endoscopic polypectomy. Biospy in the case of adenomas to clarify the histological structure and to obtain qualitative and quantitative information regarding malignant degeration, must be discouraged (""partial diagnosis''.) 5. Basing on the current state of knowledge it is assumed that effective prohylaxis of cancer is achieved by the endoscopic removal of benign adenomas of the colon. 6. It is also assumed that effective cancer therapy can be realised by the endoscopic removal of adenomas which have already undergone malignant degeration (adenoma with severe cellular atypia, invasive differntiated adenocarcinoma in the head of the adenoma.)

Adenocarcinoma↗
PubMed1977

Neocortical cholinergic neurons in elderly people.

Choline acetyltransferase activity (presynaptic cholinergic system) and high affinity binding of cholinergic antagonists (postsynaptic cholinergic system) were measured in brain tissue removed after death from both mentally normal and demented old people. Muscarinic receptor binding sites in frontal cortex decreased with advancing years only in old people without appreciable morphological evidence of senile degeration. Preliminary data for temporal lobe suggested that also in Pick's disease the density of receptor binding sites is reduced. The markers are not significantly reduced in cases of mixed senile and vascular dementia. However, in non-vascular senile dementia of the Alzheimer type, there were indications that the presynaptic marker is selectively depleted. Therefore, centrally acting anticholinesterases might be beneficial, particularly in the early stages of the disease.

Age Factors↗
PubMed1979

Chronic phenylmercuric acetate toxicity in a horse.

Phenylmercuric acetate (PMA) was administered orally to a horse over a period of 27 weeks (190 days) at a dose rate of 0.4 mg Hg/kg per day. The effects produced were consistent with those of chronic inorganic mercury intoxication. The clinical features included masseter muscle atrophy, difficulty in prehension and mastication, malodorous breath, reduced appetite and weight loss, and reflected significant pathological changes involving the buccal, mandibular and dental tissues. Renal dysfunction was evident terminally and there was degeration and necrosis of the proximal tubular epithelium. Necrotic and mineralized foci were found in facial and masticatory msucles, splenic trabecuale and the myocardium. The central nervous system and the intestinal tract were unaffected. The approximate mean plasma inorganic mercury concentration was 500 ng/ml whereas organic mercury levels in blood were much lower. The renal cortex had the highest inorganic mercury content, three times greater than in the liver and cecum, while organic mercury was highest in those tissues and absent from the kidney. The difference in the effects produced in this horse as compared to those in a horse receiving mercuric chloride at the same mercury dose rate, could be attributed to the more rapid and complete absorption of PMA from the gastrointestinal tract.

Animals↗
PubMed2025

Cell-free DNA aneuploidy score as a dynamic early response marker in prostate cancer.

Cell-free circulating tumor DNA (ctDNA) has emerged as a promising biomarker for response evaluation in metastatic castration-resistant prostate cancer (mCRPC). The current study evaluated the modified fast aneuploidy screening test-sequencing system (mFast-SeqS), a quick, tumor-agnostic and affordable ctDNA assay that requires a small input of DNA, to generate a genome-wide aneuploidy (GWA) score in mCRPC patients, and correlated this to matched metastatic tumor biopsies. In this prospective multicenter study, GWA scores were evaluated from blood samples of 196 mCRPC patients prior to treatment (baseline) with taxanes (docetaxel and cabazitaxel) and androgen receptor signaling inhibitors (ARSI; abiraterone and enzalutamide), and from 74 mCRPC patients at an early timepoint during treatment (early timepoint; median 21&#x2009;days). Z-scores per chromosome arm were tested for their association with tumor tissue genomic alterations. We found that a high tumor load in blood (GWAhigh) at baseline was associated with poor response to ARSI [HR: 2.63 (95% CI: 1.86-3.72) P&#x2009;<&#x2009;0.001] but not to taxanes. Interestingly, GWAhigh score at the early timepoint was associated with poor response to both ARSIs [HR: 6.73 (95% CI: 2.60-17.42) P&#x2009;<&#x2009;0.001] and taxanes [2.79 (95% CI: 1.34-5.78) P&#x2009;=&#x2009;0.006]. A significant interaction in Cox proportional hazards analyses was seen when combining GWA status and type of treatment (at baseline P&#x2009;=&#x2009;0.008; early timepoint P&#x2009;=&#x2009;0.018). In summary, detection of ctDNA in blood by mFast-SeqS is cheap, fast and feasible, and could be used at different timepoints as a potential predictor for outcome to ARSI and taxane treatment in mCRPC.

Humans↗
PubMed2026

A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.

Hemostasis and thrombosis are strongly dependent on the unique ability of platelets to rapidly activate integrin receptors and to firmly adhere to sites of injury under shear stress conditions. Central to integrin activation is the small GTPase RAP1, which itself is activated by guanine nucleotide exchange factors (GEFs). CalDAG-GEFI (RASGRP2) is the highest expressed and functionally dominant platelet RAP-GEF. However, a genome-wide association study also suggested a significant role for RAPGEF2 (PDZ-GEFI), a low-expressed RAP-GEF, in human platelet aggregation. Here, we used mice deficient in RAPGEF2 (megakaryocyte-specific, Rapgef2mKO), CalDAG-GEFI (Caldaggef1-/-), or both RAPGEF2 and CalDAG-GEFI (DKO) to characterize the contribution of RAPGEF2 signaling to platelet function, hemostasis, and thrombosis. RAPGEF2 protein was detected in murine and human platelets. Compared with control or Caldaggef1-/- platelets, both RAP1 activation and integrin &#x3b1;IIb&#x3b2;3-mediated aggregation were significantly diminished in DKO platelets. When compared with controls, Rapgef2mKO platelets exhibited reduced integrin activation, a more reversible aggregation response, and impaired adhesion under conditions of shear stress ex vivo and in vivo. Mechanistic studies strongly suggest that RAPGEF2 operates downstream of receptors coupled to the heterotrimeric G protein G13 (GNA13), such as &#x3b1;IIb&#x3b2;3 and the thromboxane receptor. Together, our studies provide genetic evidence that RAPGEF2 in platelets operates downstream of G13 as an important regulator of RAP1 signaling and integrin activation, especially under conditions of elevated shear stress. These findings markedly improve our understanding of G protein signaling and integrin function in platelets, with potential implications for the development of improved platelet-targeted therapies for cardiovascular disease.

Animals↗