Crotaphytus reticulatus

Number of Pages: 2Integrative BiologyGeological Science

MARCADORES PARASITOLÓGICOS E HEMATOLÓGICOS PARA A SELEÇÃO DE BOVINOS RESISTENTES À DERMATOBIOSE

O presente trabalho foi desenvolvido na UFPR - Campus Palotina e em três propriedades rurais do município de Palotina, Paraná, durante o período de setembro de 1997 a agosto de 1999. O experimento foi delineado com o objetivo de estudar possíveis marcadores (parasitológicos e hematológicos) que refletem a habilidade do gado de leite (raça Holandesa Preto e Branco) em resistir à parasitose por larvas de Dermatobia hominis (Linnaeus Jr., 1781). Um total de 1050 larvas de D. hominis foram expulsas por meio de compressão digital. Os maiores valores de contagem total de leucócitos foram observados nos animais que apresentaram o menor número de nódulos de larvas de D. hominis. Study of parasitological and hematological markers for the selection of dermatobiose resistant bovines Abstract The present research work has been carried out from September 1997 through August 1999 at Federal University of Paraná Palotina Campus and in three farms from the same County. The main aim of this study was to analyze the possible parasitological and hematological markers that reflect Black and White Holstein dairy cattle resistance towards parasitism by Dermatobia hominis (Linnaeus Jr, 1781) larvae. From the group of 14 experimental animals a total of 1050 D. hominis were collected by manual compression during the period of time of the experiment. From the hematological data it was possible to conclude that there was an inverse relationship between the total leucocytes counting values and the number of larvae nodules, so that the highest the number of leucocytes per l of blood, the lowest the number of larvae nodules

A comparison of lysosomal enzymes expression levels in peripheral blood of mild- and severe-Alzheimer’s disease and MCI patients: implications for regenerative medicine approaches

The association of lysosomal dysfunction and neurodegeneration has been documented in several neurodegenerative diseases, including Alzheimer’s Disease (AD). Herein, we investigate the association of lysosomal enzymes with AD at different stages of progression of the disease (mild and severe) or with mild cognitive impairment (MCI). We conducted a screening of two classes of lysosomal enzymes: glycohydrolases (β-Hexosaminidase, β-Galctosidase, β-Galactosylcerebrosidase, β-Glucuronidase) and proteases (Cathepsins S, D, B, L) in peripheral blood samples (blood plasma and PBMCs) from mild AD, severe AD, MCI and healthy control subjects. We confirmed the lysosomal dysfunction in severe AD patients and added new findings enhancing the association of abnormal levels of specific lysosomal enzymes with the mild AD or severe AD, and highlighting the difference of AD from MCI. Herein, we showed for the first time the specific alteration of β-Galctosidase (Gal), β-Galactosylcerebrosidase (GALC) in MCI patients. It is notable that in above peripheral biological samples the lysosomes are more sensitive to AD cellular metabolic alteration when compared to levels of Aβ-peptide or Tau proteins, similar in both AD groups analyzed. Collectively, our findings support the role of lysosomal enzymes as potential peripheral molecules that vary with the progression of AD, and make them useful for monitoring regenerative medicine approaches for AD

EFICÁCIA DE NÚCLEO HOMEOPÁTICO NA PREVENÇÃO DA INFESTAÇÃO POR Dermatobia hominis E Haematobia irritans EM BOVINOS

O presente trabalho foi desenvolvido na UFPR - Campus Palotina - Paraná e em uma propriedade rural do município de Mundo Novo - Mato Grosso do Sul, durante o período de maio de 2002 a abril de 2003. O experimento foi delineado com os objetivos de avaliar: a) a eficácia do núcleo homeopático (nosódicos CH12, sacarose e Bixa orelhana) na prevenção da infestação natural por larvas de D. hominis e H. irritans em bovinos de corte e b) a dinâmica populacional de D. homins e H. irritans ao longo do ano. Para sua realização foram utilizados 24 vacas, de aproximadamente 15 meses de idade, distribuídas em dois grupos de 12 animais, com pesos médios semelhantes. Os animais do grupo A foram tratados com núcleo homeopático adicionado à suplementação mineral na proporção de 400 g de núcleo adicionado em 25 Kg da mesma. Os animais do grupo B receberam suplementação mineral (sem adição de núcleo homeopático). Foram contadas um total de 451 larvas de D. hominis. A análise de variância demonstrou diferença estatística significativa (

CNV-ClinViewer: Enhancing the clinical interpretation of large copy-number variants online

Purpose Large copy number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV pathogenicity classification, genotype-phenotype analyses, and therapeutic target identification are challenging and time-consuming tasks that require the integration and analysis of information from multiple scattered sources by experts. Methods We developed a web-application combining >250,000 patient and population CNVs together with a large set of biomedical annotations and provide tools for CNV classification based on ACMG/ClinGen guidelines and gene-set enrichment analyses. Results Here, we introduce the CNV-ClinViewer (https://cnv-ClinViewer.broadinstitute.org), an open-source web-application for clinical evaluation and visual exploration of CNVs. The application enables real-time interactive exploration of large CNV datasets in a user-friendly designed interface. Conclusion Overall, this resource facilitates semi-automated clinical CNV interpretation and genomic loci exploration and, in combination with clinical judgment, enables clinicians and researchers to formulate novel hypotheses and guide their decision-making process. Subsequently, the CNV-ClinViewer enhances for clinical investigators patient care and for basic scientists translational genomic research

Therapeutic Efficacy of a Potent Anti-venezuelan Equine Encephalitis Virus Antibody Is Contingent on FC Effector functionslc6a1 Variant Pathogenicity, Molecular Function and Phenotype: A Genetic and Clinical Analysis

Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.1% lp/p). Clinical and functional data were available for a subset of 126 individuals. We explored the potential associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered molecular function and phenotype severity using bioinformatic approaches. The GAT1 transmembrane domains 1, 6 and extracellular loop 4 (EL4) were enriched for patient over population variants. Across functionally tested missense variants (n = 156), the spatial proximity from the ligand was associated with loss-of-function in the GAT1 transporter activity. For variants with complete loss of in vitro GABA uptake, we found a 4.6-fold enrichment in patients having severe disease versus non-severe disease (P = 2.9 × 10−3, 95% confidence interval: 1.5–15.3). In summary, we delineated associations between the 3D structure and variant pathogenicity, variant function and phenotype in SLC6A1-related disorders. This knowledge supports biology-informed variant interpretation and research on GAT1 function. All our data can be interactively explored in the SLC6A1 portal (https://slc6a1-portal.broadinstitute.org/)

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12- q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice