Comparison of pathological lesions in navicular bone (os sesamoideum distale) and analysis of remodelling capacity in warmblood and coldblood horses.

The problem of navicular bone lesions is better understood in warmblood horses. The aim of our research was to compare pathologic lesions of navicular bone of different types of horses divided into age groups. An extra goal was to compare radiographs with anatomical status of navicular bone dissected from the hoof capsule. The study group included 161 horses, out of which 100 individuals were warmbloods, and 61 - coldbloods. In total 280 navicular bones were analysed. The flexor surface, distal border fragments, enthesophytes and the process of obliteration of nutrient foramina were analysed. Some navicular bones were also subject to histology test. A greater tendency for the obliteration of nutrient foramina was observed in coldblood horses than in warmbloods. This fact can be explained as increased remodelling, covering the phenomenon of closure of synovial invaginations and canaliculi within the navicular bone. As a result, the synovial groove disappears and blood vessels cannot enter the distal border. New bone formation on the distal border is more frequently observed in coldblood horses. The development of enthesophytes both on the distal and proximal borders depends to a large extent on the age of horses of both types. Warmbloods, however, are more prone to have the lesions located on the flexor surface, leading as a consequence to deep erosions. They might be found even in very young horses in the form of grooves crossing the sagittal ridge. The frequency of lesions varies depending on the type of the horse. Post-mortem analysis of navicular bones helped interpret radiographs in a more precise manner.

Biallelic EPCAM deletions induce tissue-specific DNA repair deficiency and cancer predisposition.

We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAMdel iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter. This was associated with loss of MSH2 expression, increased mutational burden, MMRD signatures and MS-indel accumulation, the hallmarks of MMRD. In contrast, maturation into brain organoids and examination of blood and fibroblasts failed to show similar processes, preserving MMR proficiency. The combined use of iPSC, organoid technologies and functional genomics analyses highlights the potential of cutting-edge cellular and molecular analysis techniques to define processes controlling tumorigenesis and uncovers a new paradigm of tissue-specific MMRD, which affects the clinical management of these patients.

Transferrin, haematological indices and liver glycogen in field mice collected from a coal mining area and a control site in Poland.

A polymorphism for serum transferrin in field mice from polluted and control sites was compared with body-morphological and haematological parameters, and with liver glycogen concentration. The distribution of genotypes in the polluted area was not panmictic, due to higher frequencies of the rare allele Trf(c) occurring mainly in males. In the polluted area, transferrin-c was accompanied by slowly migrating, Fe-binding protein fractions. Since the Trf(c)/Trf(c) homozygote possessed higher red blood cell parameters, it is suggested that these extra proteins have an Fe-transport function. The morpho-physiology of heterozygotes from the polluted area did not differ significantly from those from the control site. The animals from the polluted area possessed a high concentration of liver glycogen, indicative of poor environmental conditions. Also, a generally lower level of red blood cell parameters suggests that non-oxygenic processes dominate over oxygenic ones in the polluted area.

K63-ubiquitylation of VHL by SOCS1 mediates DNA double-strand break repair.

DNA repair is essential for maintaining genomic stability, and defects in this process significantly increase the risk of cancer. Clear-cell renal cell carcinoma (CCRCC) caused by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is characterized by high genomic instability. However, the molecular mechanism underlying the association between the loss of VHL and genomic instability remains unclear. Here, we show that suppressor of cytokine signaling 1 (SOCS1) promotes nuclear redistribution and K63-ubiquitylation of VHL in response to DNA double-strand breaks (DSBs). Loss of VHL or VHL mutations that compromise its K63-ubiquitylation attenuates the DNA-damage response (DDR), resulting in decreased homologous recombination repair and persistence of DSBs. These results identify VHL as a component of the DDR network, inactivation of which contributes to the genomic instability associated with CCRCC.

Differences in exterior conformation between primitive, Half-bred, and Thoroughbred horses: anatomic-breeding approach.

The study included 249 horses belonging to 3 horse breeds. Konik horses, comprising the first group, is an example of a breed similar to the extinct Tarpan. In our study, these horses were taken to be a primitive anatomical model of the horse body. The other groups comprised the Polish Half-bred horse and Thoroughbred horse. The biometric characteristics of the horses were compared based on 24 indices. The aim of the paper was to find a reduced set of indices that can be used to determine group membership of the horses. To do this, we used statistical methods to find the most important indices that best discriminate breeds from each other. Chi-squared statistics, linear discriminant analysis, logistic regression, and 1-way ANOVA showed that the discrimination among groups of horses is connected with these 5 indices: scapula, smaller trunk (distance between tubercle of humerus and coxal tuber), greater trunk (distance between tubercle of humerus and ischial tuberosity), metacarpus circumference, and hind autopodium-smaller trunk. Thoroughbred and Half-bred horses are clearly different in exterior conformation from Konik horses. The differences between Thoroughbred and Half-bred horses are more subtle. The conformation of Thoroughbreds is jointly determined by relatively small differences in a range of features.

Konik and Hucul horses: a comparative study of exterior measurements.

An exterior comparison was made between 2 primitive horse breeds: the Konik and the Hucul breeds. Each animal was characterized using 25 measurements and 24 indices. Statistical methods employed in this study were principal components analysis and the Student's t-test. It was found that in spite of both breeds being included in the group of horses with a primitive exterior, the Konik and the Hucul possess completely different metric properties of their body conformations. Although the mean height for the Hucul breed slightly exceeds that of the Konik, the latter has longer scapulae and metacarpi. The hind limb also features different proportions among its segments in the 2 breeds. The observed differences seem to be connected with different habitats for these breeds. In particular, mountainous conditions may have had an effect on the specific body conformation of the Hucul breed.

Influence of pregnancy and lactation on diurnal and seasonal changes in lactic acid and pyruvic acid levels and in values of pH, pCO2 and pO2 in the mare blood.

1. The diurnal changes in the levels of lactic (LA) and pyruvic (PA) acids and in values of pH, pO2 and pCO2 were studied in the blood of barren and later on in pregnant and lactating mares, throughout three subsequent years. 2. Blood samples were taken every 4 hr, for one day, each month, throughout 3 years. 3. The mares were kept and fed in the same conditions, lighting was natural. 4. In barren mares, diurnal rhythm in LA, PA, pO2 and pCO2 was found. 5. The pregnancy as well as lactation masked diurnal rhythms in parameters studied, except the LA level during lactation but then the acrophase was shifted by 3-4 hr. 6. Seasonal cyclicity was found in the values of LA, PA and pCO2 in barren mares. The pregnancy abolished cyclicity in LA level and modified the behaviour of PA and pCO2 values causing a shift of acrophases and lowering the amplitudes of the indices. 7. In the pO2 tensions no seasonal cycles were observed. 8. In the values of pH neither diurnal rhythms nor seasonal cycles throughout study years were observed.

Influence of pregnancy on diurnal and seasonal changes in cortisol, T3 and T4 levels in the mare blood serum.

1. The diurnal changes in the level of total protein, cortisol, T3 and T4 were studied in four barren and four pregnant standard-bred mares, kept and examined under the same conditions. 2. Blood samples were taken every 4 hr. for one day each month, throughout one year. 3. In barren mares, a diurnal rhythm in cortisol level (acrophase at 0530 hr in summer and at 0830 hr in winter) and in T3 level (acrophase at 1330 hr in summer and at 1800 hr in winter) was found. 4. In pregnant mares, a diurnal rhythm in cortisol level only till 5th month of pregnancy was observed. 5. A diurnal rhythm in T3 level was found throughout the pregnancy, with acrophase always at 1400 hr. 6. No diurnal rhythm in the total protein content and in the T4 level was observed. 7. In both groups of mares the seasonal cyclicity in T3 and T4 levels were found. A seasonal cyclicity in cortisol level was found only in pregnant mares. 8. Pregnancy abolished seasonal cyclicity in total protein and showed it in cortisol level. 9. Pregnancy in mares modifies diurnal rhythms as well as seasonal cycles in secretion and metabolism of the hormones studied.

Influence of pregnancy on diurnal and seasonal changes in glucose level and activity of FDPA, AlAT and AspAT in mares.

1. The diurnal changes in the glucose level and in activity of FDPA, A1AT and AspAT in four pregnant standard-bred mares were studied. 2. As a control four barren mares, were kept and examined in the same conditions. 3. Blood samples were taken every 4 hr for one day, each month, throughout pregnancy, or one year. 4. A diurnal rhythm in activity of A1AT and AspAT in barren mares was found. The pregnancy masked diurnal rhythm in activities of both transaminases. 5. No diurnal rhythm in glucose level and FDPA activity in both groups of mares was observed. 6. Seasonal cyclicity was found in all indices studied, in both groups of mares. 7. The pregnancy did not abolish cyclicity in parameters studied but modified their behaviour--causing a shift of acrophases (glucose, FDPA, AspAT) and lowering the amplitudes (FDPA, A1AT, AspAT).

Diurnal changes in lactic and pyruvic acid levels and pH values in foals during the first 13 weeks of their life and in their lactating mothers.

1. The diurnal changes in the levels of lactic (LA) and pyruvic (PA) acids and values of pH were studied in standard-bred mares and their foals, for 13 weeks of foal life, throughout 2 years. 2. The studies began when a foal was 7 days old and were repeated every 2 weeks until foals reached 13 weeks of age. 3. Blood samples were taken every 4 hr for one day, each second week. 4. In the LA, PA levels and pH values no diurnal rhythm was stated in lactating mares during study periods. 5. In foals the diurnal rhythm in LA and PA occurred in the 3rd month of their life, with the acrophase at night hours. 6. The significant correlations between foal and their mother metabolites studied were observed. 7. The environmental factors (air temperature, humidity) influence fluctuations of the amplitude in parameters studied in the horse blood.

Diurnal changes in the haemoglobin level, red blood cell number and mean corpuscular haemoglobin in foals during the first 13 weeks of life and in their lactating mothers.

1. In six foals and their mothers (of Standard breed) diurnal changes in the haemoglobin level, red blood cell number and mean corpuscular haemoglobin during the first 13 weeks of foal life were studied. 2. Studies begun when a foal reached 7 days of age and were repeated every two weeks till 13 weeks of foal life. Blood was taken every 6 hr in foals and every 4 hr in mares. 3. No diurnal rhythmicity in parameters studied either in foals or in mares was found. 4. Decrease of haemoglobin level in lactating mares (14.0-12.5 g/100 ml) without changes in red blood cell number were observed. Mean corpuscular haemoglobin changed distinctly from one study day to another. 5. In foals were stated: significantly higher haemoglobin level and erythrocyte number and lower mean corpuscular haemoglobin than in mares.

Development of diurnal rhythm in some metabolic parameters in foals.

1. The development of diurnal rhythm activity of FDPA, AspAT and A1AT and in levels of cortisol, T3 and T4 was observed in the blood serum of six foals. 2. The studies began when a foal was 7 days old and were repeated every month until foals reached 1 year of age. Blood samples were taken every 4 hr for one day each month. 3. As a control group four barren mares were used, kept and examined in the same conditions. 4. In mature mares, diurnal rhythms in activity of A1AT (acrophase at 2200 hr), AspAt (2400 hr) and cortisol (0630 hr) but in T3 only in summer months (acrophase at 0100 hr) were observed. 5. During the first 6 months of foal life, significantly higher mean levels of FDPA, A1AT, T3 and T4 than in control mares were found. 6. The cortisol level in foals was half as much as that of mature mares throughout the year. 7. In foals the diurnal rhythm in A1AT activity occurred in the 5th month and in AspAt--in the 12th month (acrophase at 2400 hr), but in cortisol levels it was developed already in the second month of foal life (acrophase at 0830 hr).

A study of diurnal changes in cortisol and glucose levels and FDPA activity in foals during the first 13 weeks of life and in their lactating mothers.

1. In six standard-bred mares and their foals diurnal changes in the cortisol and glucose levels and in FDPA activity were studies for 13 weeks of foal life. 2. In the cortisol level diurnal rhythm was found in the 3rd, 7th and 11th week of foal life and in the 11th week of lactation in mares. 3. In mares the mean diurnal cortisol level changed from 32 ng/ml in the first week to 57 in the 11th week and in foals from 24 in the first week to 16 ng/ml in the 11th week. 4. In the glucose level no diurnal rhythm was observed. 5. In mares the mean diurnal glucose level after parturition was about 58 mg/100 ml and increased to 83-85 mg/100 ml. In foals it changed from 105 to 128 mg/100 ml. 6. In the activity of FDPA no diurnal rhythm was observed. 7. The mean activity of FDPA changed in mares from 3.3 to 4.4 U and in foals from 5.7 to 7.5 U.