Homeobox genes in normal and abnormal vasculogenesis

Homeobox containing genes are a family of transcription factors regulating normal development and controlling primary cellular processes (cell identity, cell division and differentiation) recently enriched by the discovery of their interaction with miRNAs and ncRNAs. Class I human homeobox genes (HOX genes) are characterized by a unique genomic network organization: four compact chromosomal loci where 39 sequence corresponding genes can be aligned with each other in 13 antero-posterior paralogous groups. The cardiovascular system is the first mesoderm organ-system to be generated during embryonic development; subsequently it generates the blood and lymphatic vascular systems. Cardiovascular remodelling is involved through homeobox gene regulation and deregulation in adult physiology (menstrual cycle and wound healing) and pathology (atherosclerosis, arterial restenosis, tumour angiogenesis and lymphangiogenesis). Understanding the role played by homeobox genes in endothelial and smooth muscle cell phenotype determination will be crucial in identifying the molecular processes involved in vascular cell differentiation, as well as to support future therapeutic strategies. We report here on the current knowledge of the role played by homeobox genes in normal and abnormal vasculogenesis and postulate a common molecular mechanism accounting for the involvement of homeobox genes in the regulation of the nuclear export of specific transcripts potentially capable of generating endothelial phenotype modification involved in new vessel formation

Preliminary genetic variability analysis of the native Garfagnina goats based on microsatellite polymorphism

For the development of an appropriate programme for conservation of animal genetic resources, genetic typifying is considered an important preliminary step. In this paper, we have done a preliminary genetic variability analysis of 48 adult Garfagnina goats belonging to a single flock of Tuscany using 12 STR markers (MAF065, SRCRSP05, INRA023, McM527, CSRD247, SRCRSP23, OarFCB20, TGLA53, INRA005, INRA063, ETH10, ILSTS87) some of which belonged to a markers panel validated by the International Society of Animal Genetics (ISAG) and others routinely used by the facilities of the Laboratorio di Genetica e Servizi (Associazione Italiana Allevatori, Migliaro, Italy). Garfagnina is an Italian native goat breed registered on the Tuscan regional repertory of genetic resources at risk of extinction and have a total of about 745 animals belonging to 17 flocks. Garfagnina breed is important for livestock biodiversity preservation, being a key animal for specialized cheese market in the Tuscan region. For each marker the following parameters were computed: number of alleles, effective allele size, observed heterozygosity and polymorphism information content (PIC). Allelic frequencies were estimated by direct counting. To analyze the genetic variability of the population, the following parameters were computed at population level: molecular co-ancestry coefficients (fij), kinship distance (Dk), and inbreeding coefficient (Fi). Moreover, genetic similarities (GS) among all animals were investigated using the Individual Multilocus Genotype. The number of alleles ranged from 3 to 9 (mean 5.92) whereas the expected heterozygosity ranged from 0.48 to 0.83 (mean 0.69). There was a high genetic similarity within the whole population (0.43) showing the great homogeneity of the sampled animals, as confirmed also by the small kinship distance (0.34). However inbreeding coefficient was low (0.32). The results of this research indicate that, despite the fact that animals are considered to belong to the same breeding, the genetic variability of this Garfagnina goat population is acceptable for a population with a reduced numerical value

Behavioural Signs and Neurological Disorders in Dogs and Cats

The boundary between neurological and behavioural disorders often is not clear, and they often coexist. As a matter of fact, many neurological conditions lead to behavioural changes, which can be the only sign and the first sign complained by the owners. Sometimes it is not possible to reach a diagnosis based only on neurology or on behavioural medicine. Finally, some behavioural problems can facilitate the onset or worsening of neurological conditions. A synergy between neurology and behavioural medicine would be beneficial for both of them, in the diagnostic procedure and in the treatment. Veterinarians of such disciplines should collaborate as much as possible

Canine Cerebral Intravascular Lymphoma: Neuropathological and Immunohistochemical Findings

Intravascular lymphoma (IVL) is a rare angiotropic large-cell lymphoma in which neoplastic lymphocytes proliferate within the lumina of small blood vessels in the absence of a primary extravascular mass or leukemia. This study included 10 cases of canine IVL restricted to the CNS. Dogs had an average age of 8 years and neurological signs mainly referred to brain involvement such as depression, seizures, and ambulatory deficits. Gross examination at necropsy showed focal extensive or multiple hemorrhagic areas mainly distributed in the telencephalon and diencephalon. Histopathologically, numerous veins and capillaries were filled with neoplastic lymphoid cells, accompanied by edema, hemorrhage, and thrombosis. Immunohistochemistry (IHC) for CD3, CD20, and PAX5 was performed to phenotype the neoplastic lymphocytes. IHC for CD44 and CD29 were used to investigate the pathogenetic mechanism leading to the intravascular aggregation of the neoplastic lymphocytes. The same IHC panel was applied to 8 cases of primary and metastatic canine CNS lymphoma in order to compare IVL immunoreactivity. Three IVLs were typified as T-cell, 3 as B-cell, and 4 as non-T non-B. Neoplastic lymphocytes showed marked expression of CD44 in all IVL cases, and CD29-immunolabeled cells were observed in 4 IVLs. CD44 immunoreactivity was consistent with the findings reported in human IVL, suggesting a predisposition to the formation of lymphocyte aggregates. CD29 was inconsistently immunonegative in canine IVL, confirming only partially the pathogenetic mechanism suggested for the human counterpart

Pinch-induced behavioural inhibition (clipthesia) as a restraint method for cats during veterinary examinations: preliminary results on cat susceptibility and welfare.

Cats are often subjected to minimally painful or forced procedures during routine clinical practice, which can be poorly tolerated, leading veterinary surgeons to need to offer physical restraint, usually aided by an assistant. The aim of this study was to assess the effectiveness and ultimate welfare implications of using clipthesia as a method of restraint during veterinary examination. This was carried out in a real clinical setting and compared to manual scruffing. Twenty-seven cats were restrained, during a veterinary examination, using two stationery clips placed on the skin along the cervical dorsal midline, whilst a group of 13 cats were restrained through gentle manual scruffing. Susceptibility to clipthesia (ie a positive clip score) was observed in 81.5% of cats, while a complete response was found in 40.7% of subjects. The presence or absence of a disease/condition did not affect the susceptibility. Heart rate and the number of cats showing mydriasis (pupillary dilation) was statistically higher during manual scruffing, whilst plasma cortisol did not differ between the two groups. The more responsive the cats were to clipthesia, the more they displayed kneading and purring. These preliminary findings suggest that clipthesia is not more stressful than manual scruffing in restraining cats during a veterinary examination. However, not all cats were found to be susceptible to this method of restraint. Further research is needed to clarify whether clipthesia should be implementated as a matter of course in veterinary practice from the point of view of welfare and safety

Neuropathology of Central and Peripheral Nervous System Lymphoma in Dogs and Cats: A Study of 92 Cases and Review of the Literature

The literature about nervous system lymphoma (NSL) in dogs and cats is fragmentary, based on a few case series and case reports with heterogeneous results. The aim of our study was to retrospectively analyze 45 cases of canine and 47 cases of feline NSL and compare our results with previously reported data, also providing an extensive literature review. Breed, age, gender, clinical signs, type, and neurolocalization were recorded for each case. The pathological patterns and phenotype were assessed by histopathology and immunohistochemistry. The occurrence of central and peripheral NSL was similar between the two species in both primary and secondary types. NSL occurred with a slightly higher prevalence in Labrador Retrievers, and spinal cord lymphoma (SCL) was associated with young age in cats. The most frequent locations were the forebrain in dogs and the thoracolumbar segment in cats. Primary central nervous system lymphoma (CNSL) in cats most frequently involved the forebrain meninges, particularly as a B-cell phenotype. Peripheral NSL mostly affected the sciatic nerve in dogs and had no preferred location in cats. Nine different pathological patterns were identified, with extradural as the most prevalent SCL pattern in both species. Finally, lymphomatosis cerebri was described for the first time in a dog

RpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment

5-FU is a chemotherapy drug commonly used for the treatment of human cancers; however drug resistance represents a major challenge for its clinical application. In the present study, we reporte that rpL3 induced by 5-FU treatment in Calu-6 cells represses CBS transcription and reduces CBS protein stability leading to a decrease of CBS protein levels. rpL3 also regulates negatively the activation of NFκB by preventing NFκB nuclear translocation through IκB-α up-regulation. Furthermore, we demonstrate that rpL3 significantly enhances the apoptosis of 5-FU treated Calu-6 cells promoting the overexpression of the pro-apoptotic proteins Bax and the inhibition of the anti-apoptotic protein Bcl-2. We finally demonstrate that rpL3 potentiates 5-FU efficacy inhibiting cell migration and invasion. Our results suggest that combination of rpL3 and 5-FU is a promising strategy for chemotherapy of lung cancers lacking functional p53 that are resistant to 5-FU