An incomplete unidentified work on inheritance : manuscript, undated

بسم الله الرحمن الرحيم وبه الاعانة فصل اعلم ان الناظم لم يتعرض. :Incipit

Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression

Centromeres form the site of chromosome attachment to microtubules during mitosis. Identity of these loci is maintained epigenetically by nucleosomes containing the histone H3 variant CENP-A. Propagation of CENP-A chromatin is uncoupled from DNA replication initiating only during mitotic exit. We now demonstrate that inhibition of Cdk1 and Cdk2 activities is sufficient to trigger CENP-A assembly throughout the cell cycle in a manner dependent on the canonical CENP-A assembly machinery. We further show that the key CENP-A assembly factor Mis18BP1(HsKNL2) is phosphorylated in a cell cycle-dependent manner that controls its centromere localization during mitotic exit. These results strongly support a model in which the CENP-A assembly machinery is poised for activation throughout the cell cycle but kept in an inactive noncentromeric state by Cdk activity during S, G2, and M phases. Alleviation of this inhibition in G1 phase ensures tight coupling between DNA replication, cell division, and subsequent centromere maturation.

Initial characterization of stiff skin-like syndrome in West Highland white terriers

BACKGROUND Stiff skin syndrome and systemic or localized scleroderma are cutaneous disorders characterized by dermal fibrosis and present clinically with induration of the skin, with or without joint, internal organ or vascular involvement. OBJECTIVES To provide clinical, histological and preliminary genetic analysis of two West Highland white terrier siblings presenting with indurated skin resembling stiff skin syndrome in humans. ANIMALS Two client owned full sibling West Highland white terriers from two different litters. METHODS Clinical examination, histopathological examination and whole genome sequencing analysis of affected and unaffected West Highland white terriers. RESULTS Affected dogs exhibited markedly indurated skin that was attached firmly to the underlying tissue and incomplete closure of the mouth and eyes. No abnormalities were found by neurological or orthopaedic examination, radiographs of the head or whole body computed tomography. Histologically, the dermis and pannicular septa were thickened by a marked increase in coarse collagen fibres and a mild to moderate increase in collagen fibre diameter. The syndrome most likely follows an autosomal recessive mode of inheritance. The sequence analysis did not reveal any obvious causative variant in the investigated candidate genes ADAMTSL2 and FBN1. CONCLUSION AND CLINICAL IMPORTANCE The clinical phenotype and histopathological features of two West Highland white terrier siblings resembled stiff skin syndrome in humans. Unlike in humans, or previously described beagles with stiff skin, there was no restriction of joint mobility. Genetic analysis did not detect a candidate causative variant and warrants further research.

Pulmonary hypoplasia and anasarca syndrome in Cika cattle

BACKGROUND: Hydrops foetalis is defined as excessive fluid accumulation within the foetal extravascular compartments and body cavities. It has been described in human and veterinary medicine, but despite several descriptive studies its aetiology is still not fully clarified. Pulmonary hypoplasia and anasarca (PHA) syndrome is a rare congenital abnormality in cattle that is characterised by hydrops foetalis including extreme subcutaneous oedema (anasarca) and undeveloped or poorly formed lungs (pulmonary hypoplasia). Until now, sporadic cases of PHA were reported in cattle breeds like Australian Dexter, Belted Galloway, Maine-Anjou, and Shorthorn. This report describes the first known cases of PHA syndrome in Slovenian Cika cattle. CASE PRESENTATION: A 13-year-old cow aborted a male calf in the seventh month of pregnancy, while a male calf was delivered by caesarean section on the due date from a 14-year-old cow. The pedigree analysis showed that the calves were sired by the same bull, the dams were paternal half-sisters and the second calf was the product of a dam-son mating. Gross lesions were similar in both cases and characterized by severe anasarca, hydrothorax, hydropericardium, ascites, hypoplastic lungs, absence of lymph nodes, and an enlarged heart. The first calf was also athymic. Histopathology of the second affected calf confirmed severe oedema of the subcutis and interstitium of the organs, and pulmonary hypoplasia. The lymph vessels in the subcutis and other organs were severely dilated. Histopathology of the second calf revealed also lack of bronchus associated lymphoid tissue and adrenal gland hypoplasia. CONCLUSIONS: The findings were consistent with known forms of the bovine PHA syndrome. This is the first report of the PHA syndrome occurring in the local endangered breed of Cika cattle. Observed inbreeding practice supports that this lethal defect most likely follows an autosomal recessive mode of inheritance. In the light of the disease phenotype it is assumed that a mutation causing an impaired development of lymph vessels is responsible for the hydrops foetalis associated malformations in bovine PHA.

Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle.

BACKGROUND Cholesterol deficiency (CD), a newly identified autosomal recessive genetic defect in Holstein cattle, is associated with clinical signs of diarrhea, failure to thrive, and hypocholesterolemia. HYPOTHESIS/OBJECTIVES The objective is to describe the clinicopathological phenotype of affected Holstein cattle homozygous for the causative apolipoprotein B gene (APOB) mutation. ANIMALS Six Holstein cattle, 5 calves with a clinical history of chronic diarrhea, and 1 heifer with erosions in the buccal cavity and neurologic symptoms were admitted to the Clinic for Ruminants. METHODS This case review included a full clinical examination, a complete blood count, blood chemistry, and measurements of cholesterol and triglycerides. The animals were euthanized and necropsied. A PCR-based direct gene test was applied to determine the APOB genotype. RESULTS All 6 animals were inbred, could be traced back to the sire Maughlin Storm, and were confirmed homozygous for the APOB mutation. The clinical phenotype included poor development, underweight, and intermittent diarrhea in the calves, and neurologic signs in the heifer included hypermetria and pacing. Hypocholesterolemia and low triglycerides concentrations were present in all animals. The pathological phenotype of all animals was steatorrhea with enterocytes of the small intestine containing intracytoplasmic lipid vacuoles. The peripheral nervous system of the heifer displayed degenerative changes. CONCLUSIONS AND CLINICAL IMPORTANCE Suspicion of CD in Holstein cattle is based on the presence of chronic diarrhea with no evidence of primary infections. Confirmation of the associated APOB gene mutation is needed. Additionally, the heifer demonstrated primarily signs of neurologic disease providing an unexpected phenotype of CD.

Lake-effect snow as the dominant control of mesic-forest distribution in Michigan, USA

1Recent studies demonstrated the sensitivity of northern forest ecosystems to changes in the amount and duration of snow cover at annual to decadal time scales. However, the consequences of snowfall variability remain uncertain for ecological variables operating at longer time scales, especially the distributions of forest communities. 2The Great Lakes region of North America offers a unique setting to examine the long-term effects of variable snowfall on forest communities. Lake-effect snow produces a three-fold gradient in annual snowfall over tens of kilometres, and dramatic edaphic variations occur among landform types resulting from Quaternary glaciations. We tested the hypothesis that these factors interact to control the distributions of mesic (dominated by Acer saccharum, Tsuga canadensis and Fagus grandifolia) and xeric forests (dominated by Pinus and Quercus spp.) in northern Lower Michigan. 3We compiled pre-European-settlement vegetation data and overlaid these data with records of climate, water balance and soil, onto Landtype Association polygons in a geographical information system. We then used multivariate adaptive regression splines to model the abundance of mesic vegetation in relation to environmental controls. 4Snowfall is the most predictive among five variables retained by our model, and it affects model performance 29% more than soil texture, the second most important variable. The abundance of mesic trees is high on fine-textured soils regardless of snowfall, but it increases with snowfall on coarse-textured substrates. Lake-effect snowfall also determines the species composition within mesic forests. The weighted importance of A. saccharum is significantly greater than of T. canadensis or F. grandifolia within the lake-effect snowbelt, whereas T. canadensis is more plentiful outside the snowbelt. These patterns are probably driven by the influence of snowfall on soil moisture, nutrient availability and fire return intervals. 5Our results imply that a key factor dictating the spatio-temporal patterns of forest communities in the vast region around the Great Lakes is how the lake-effect snowfall regime responds to global change. Snowfall reductions will probably cause a major decrease in the abundance of ecologically and economically important species, such as A. saccharum.