Expression of selected genes related to energy mobilization and insulin resistance in dairy cows

The physiological and metabolic adaptation characterizing the transition period in the dairy cows is developed by a complex modulation of different metabolic pathways as well as the expression of selected tissue-specific gene. The aim of this study was to evaluate the age effect on expression of selected genes in adipose, hepatic and muscle tissues in dairy cows during their dry period using the quantitative Real Time Polymerase Chain Reaction (qRT-PCR). Twenty-two pluriparous dairy cows were divided into 3 groups in relation to the age: Group A (38 \uc2\ub1 2 months); Group B (52 \uc2\ub1 2 months) and Group C (80 \uc2\ub1 8 months). Lower levels of peroxisome proliferator-activated receptor gamma (PPARG) and higher levels of adiponectin (ADIPOQ) were found in adipose tissue in Group C than Groups A and B (P < 0.05). Higher levels of solute carrier family 2/facilitated glucose transporter member 4 (SLC2A4) were found in muscle in Group C than Group A (P < 0.001) and Group B (P < 0.05). The present study showed in dairy cows that the expression of selected genes associated with mobilization of energy and with insulin resistance are influenced by age demonstrating and highlighting the importance of a genomics approach to assess the metabolic status of dairy cows during the transition period

Commitment of Autologous Human Multipotent Stem Cells on Biomimetic Poly-L-lactic Acid-Based Scaffolds Is Strongly Influenced by Structure and Concentration of Carbon Nanomaterial

Nanocomposite scaffolds combining carbon nanomaterials (CNMs) with a biocompatible matrix are able to favor the neuronal differentiation and growth of a number of cell types, because they mimic neural-tissue nanotopography and/or conductivity. We performed comparative analysis of biomimetic scaffolds with poly-L-lactic acid (PLLA) matrix and three different p-methoxyphenyl functionalized carbon nanofillers, namely, carbon nanotubes (CNTs), carbon nanohorns (CNHs), and reduced graphene oxide (RGO), dispersed at varying concentrations. qRT-PCR analysis of the modulation of neuronal markers in human circulating multipotent cells cultured on nanocomposite scaffolds showed high variability in their expression patterns depending on the scaffolds\u2019 inhomogeneities. Local stimuli variation could result in a multi- to oligopotency shift and commitment towards multiple cell lineages, which was assessed by the qRT-PCR profiling of markers for neural, adipogenic, and myogenic cell lineages. Less conductive scaffolds, i.e., bare poly-L-lactic acid (PLLA)-, CNH-, and RGO-based nanocomposites, appeared to boost the expression of myogenic-lineage marker genes. Moreover, scaffolds are much more effective on early commitment than in subsequent differentiation. This work suggests that biomimetic PLLA carbon-nanomaterial (PLLA-CNM) scaffolds combined with multipotent autologous cells can represent a powerful tool in the regenerative medicine of multiple tissue types, opening the route to next analyses with specific and standardized scaffold features

DNA methylation episignature testing improves molecular diagnosis of Mendelian chromatinopathies

Purpose: Chromatinopathies include more than 50 disorders caused by disease-causing variants of various components of chromatin structure and function. Many of these disorders exhibit unique genome-wide DNA methylation profiles, known as episignatures. In this study, the methylation profile of a large cohort of individuals with chromatinopathies was analyzed for episignature detection. Methods: DNA methylation data was generated on extracted blood samples from 129 affected individuals with the Illumina Infinium EPIC arrays and analyzed using an established bioinformatic pipeline. Results: The DNA methylation profiles matched and confirmed the sequence findings in both the discovery and validation cohorts. Twenty-five affected individuals carrying a variant of uncertain significance, did not show a methylation profile matching any of the known episignatures. Three additional variant of uncertain significance cases with an identified KDM6A variant were re-classified as likely pathogenic (n = 2) or re-assigned as Wolf-Hirschhorn syndrome (n = 1). Thirty of the 33 Next Generation Sequencing negative cases did not match a defined episignature while three matched Kabuki syndrome, Rubinstein-Taybi syndrome and BAFopathy respectively. Conclusion: With the expanding clinical utility of the EpiSign assay, DNA methylation analysis should be considered part of the testing cascade for individuals presenting with clinical features of Mendelian chromatinopathy disorders

Intra-abdominal hypertension due to heparin - induced retroperitoneal hematoma in patients with ventricle assist devices: report of four cases and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Elevated intra-abdominal pressure (IAP) has been identified as a cascade of pathophysiologic changes leading in end-organ failure due to decreasing compliance of the abdomen and the development of abdomen compartment syndrome (ACS). Spontaneous retroperitoneal hematoma (SRH) is a rare clinical entity seen almost exclusively in association with anticoagulation states, coagulopathies and hemodialysis; that may cause ACS among patients in the intensive care unit (ICU) and if treated inappropriately represents a high mortality rate.</p> <p>Case Presentation</p> <p>We report four patients (a 36-year-old Caucasian female, a 59-year-old White-Asian male, a 64-year-old Caucasian female and a 61-year-old Caucasian female) that developed an intra-abdominal hypertension due to heparin-induced retroperitoneal hematomas after implantation of ventricular assist devices because of heart failure. Three of the patients presented with dyspnea at rest, fatigue, pleura effusions in chest XR and increased heart rate although b-blocker therapy. A 36-year old female (the forth patient) presented with sudden, severe shortness of breath at rest, 10 days after an "acute bronchitis". At the time of the event in all cases international normalized ratio (INR) was <3.5 and partial thromboplastin time <65 sec. The patients were treated surgically, the large hematomas were evacuated and the systemic manifestations of the syndrome were reversed.</p> <p>Conclusion</p> <p>Identifying patients in the ICU at risk for developing ACS with constant surveillance can lead to prevention. ACS is the natural progression of pressure-induced end-organ changes and develops if IAP is not recognized and treated in a timely manner. Failure to recognize and appropriately treat ACS is fatal while timely intervention - if indicated - is associated with improvements in organ function and patient survival. Means for surgical decision making are based on clinical indicators of adverse physiology, rather than on a single measured parameter.</p

Nuovo approccio per il trattamento dello Xeroderma Pigmentoso: case report

Xeroderma Pigmentosum (XP) is a rare genetic syndrome characterized by an enzymatic defection in the DNA-repair pathway known as nucleotide excision repair (NER). Patients show extreme sensitivity to sun exposure and a high incidence of skin tumours that strongly invalidate their lifestyle, reducing the life expectancy to a maximum 40 years old. To date, no curative treatments are available for XP patients. Throughout the years, numerous therapeutic approaches have been proposed as an alternative to surgical resection of skin cancers, however, they showed to induce nonspecific mild/severe adverse effects. With the introduction of personalized medicine, alternative methods have been proposed. Among them, the gene therapy and delivery of an exogenous DNA repair enzyme, T4 endonuclease 5 (T4N5), mediated by lipidic nanoparticles. The last approach demonstrated to exert the best performance and to be well tolerated, without inducing any nonspecific/adverse effects. Nevertheless, their efficacy resulted limited by the structural composition of the carrier. The present Ph.D. thesis is based on the characterization of the molecular mechanisms underlying the clinically demonstrated efficacy of an optimized T4N5 liposomal formulation, used in vivo as an alternative treatment for one XPC patient. This analysis showed that the proposed formulation is efficient to rescue many of the intracellular pathways that are recognized as altered by the pathologic status (i.e., P53, Notch1, NF-κB, EGFR) and that are involved in the cancer onset, guaranteeing a safety condition. Moreover, in order to further improve this medical approach, an analogue liposomal formulation has been manufactured to vehicle a newly synthetized peptide (XP-1), corresponding to the sequence of T4N5 able to bind the damaged DNA. The responsiveness of both T4N5 and XP-1 liposomal formulations to UV exposure was in vitro evaluated through the assessment of a cellular model using fibroblasts obtained from the XPC patient. This study allowed to demonstrate that the enzyme and the peptide efficiently rescue XPC cells from UV-induced DNA lesions and restore intracellular checkpoints that are pivotal in the maintenance of skin homeostasis (i.e., cell cycle control, oxidative stress, inflammation, fibrosis and extracellular matrix integrity). Overall, this work suggests that improved liposomal formulations containing T4N5 or XP-1 could be suggested as successful medical devices to counteract the molecular basis of a disease that was incurable for many years.Xeroderma Pigmentosum (XP) is a rare genetic syndrome characterized by an enzymatic defection in the DNA-repair pathway known as nucleotide excision repair (NER). Patients show extreme sensitivity to sun exposure and a high incidence of skin tumours that strongly invalidate their lifestyle, reducing the life expectancy to a maximum 40 years old. To date, no curative treatments are available for XP patients. Throughout the years, numerous therapeutic approaches have been proposed as an alternative to surgical resection of skin cancers, however, they showed to induce nonspecific mild/severe adverse effects. With the introduction of personalized medicine, alternative methods have been proposed. Among them, the gene therapy and delivery of an exogenous DNA repair enzyme, T4 endonuclease 5 (T4N5), mediated by lipidic nanoparticles. The last approach demonstrated to exert the best performance and to be well tolerated, without inducing any nonspecific/adverse effects. Nevertheless, their efficacy resulted limited by the structural composition of the carrier. The present Ph.D. thesis is based on the characterization of the molecular mechanisms underlying the clinically demonstrated efficacy of an optimized T4N5 liposomal formulation, used in vivo as an alternative treatment for one XPC patient. This analysis showed that the proposed formulation is efficient to rescue many of the intracellular pathways that are recognized as altered by the pathologic status (i.e., P53, Notch1, NF-κB, EGFR) and that are involved in the cancer onset, guaranteeing a safety condition. Moreover, in order to further improve this medical approach, an analogue liposomal formulation has been manufactured to vehicle a newly synthetized peptide (XP-1), corresponding to the sequence of T4N5 able to bind the damaged DNA. The responsiveness of both T4N5 and XP-1 liposomal formulations to UV exposure was in vitro evaluated through the assessment of a cellular model using fibroblasts obtained from the XPC patient. This study allowed to demonstrate that the enzyme and the peptide efficiently rescue XPC cells from UV-induced DNA lesions and restore intracellular checkpoints that are pivotal in the maintenance of skin homeostasis (i.e., cell cycle control, oxidative stress, inflammation, fibrosis and extracellular matrix integrity). Overall, this work suggests that improved liposomal formulations containing T4N5 or XP-1 could be suggested as successful medical devices to counteract the molecular basis of a disease that was incurable for many years

Dez anos de SINAES:: um mapeamento de teses e dissertações defendidas no período 2004 – 2014

O Sistema Nacional de Avaliação da Educação Superior (SINAES) foi instituído em 2004, no lugar do Exame Nacional de Cursos (ENC) conhecido, à época, como “Provão”. Em dez anos de vigência, o SINAES passou por várias mudanças e tornou-se objeto de pesquisa de inúmeros programas de pós graduação no país. O presente estudo é um inventário das teses e dissertações sobre o SINAES defendidas no período entre 2004 e 2014. Utilizamo-nos da Biblioteca Digital de Teses e Dissertações (BDTD) e do Banco de Teses e Dissertações da CAPES. Resultados demonstram que foram produzidas, no período, 101 obras, sendo a maioria sobre o eixo ‘avaliação institucional’ e a minoria sobre ‘avaliação de curso’. Universidade de Brasília é a instituição que mais produziu sobre o SINAES, sendo o professor José Vieira o que orientou o maior número de pesquisas, seguido da Universidade Federal do Ceará e professor Wagner Andriola, respectivamente.&nbsp; Por fim, tal mapeamento permite uma visão panorâmica do que se produziu sobre o SINAES na primeira década de sua existência: tendências, recorrências, silêncios, lugares e pessoas envolvidas com essa temática no país

Dez anos de SINAES: um mapeamento de teses e dissertações defendidas no período 2004 - 2014

O Sistema Nacional de Avaliação da Educação Superior (SINAES) foi instituído em 2004, no lugar do Exame Nacional de Cursos (ENC) conhecido, à época, como “Provão”. Em dez anos de vigência, o SINAES passou por várias mudanças e tornou-se objeto de pesquisa de inúmeros programas de pós-graduação no país. O presente estudo é um inventário das teses e dissertações sobre o SINAES defendidas no período entre 2004 e 2014. Utilizamo-nos da Biblioteca Digital de Teses e Dissertações (BDTD) e do Banco de Teses e Dissertações da CAPES. Resultados demonstram que foram produzidas, no período, 101 obras, sendo a maioria sobre o eixo ‘avaliação institucional’ e a minoria sobre ‘avaliação de curso’. Universidade de Brasília é a instituição que mais produziu sobre o SINAES, sendo o professor José Vieira o que orientou o maior número de pesquisas, seguido da Universidade Federal do Ceará e professor Wagner Andriola, respectivamente. Por fim, tal mapeamento permite uma visão panorâmica do que se produziu sobre o SINAES na primeira década de sua existência: tendências, recorrências, silêncios, lugares e pessoas envolvidas com essa temática no país