Miracle-dz/UniFAR-FTUs huggingface dataset:
Análise de haplótipos intragênicos ao gene MJD1 em pacientes com doença de Machado-Joseph

Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA-3), is an autossomal dominant neurodegenerative disorder originally described in families of Portuguese-Azorean ancestries. Generalized incoordination of gait, speech and limb movements can be present in affected MJD patients.The disease onset occurs in general between 30 and 40 years of age, and symptoms progress slowly. Survival after onset is between 14 to 17 years. The disease-associated gene, named MJD1, was identified in 1994 and is located on chromosome 14. This gene is characterized by a CAG nucleotide repeat in the 5 end of exon 2. Number of repeats is polymorphic in the population; normal alleles vary from 12 to 37 CAG repeats, while expanded alleles vary between 61 to 84 repeats. A recent worldwide haplotype study demonstrated two different haplotypes in families of Azorean background which are specific to the island of origin. In families from the mainland of Portugal, both Azorean haplotypes can be found. The majority of the nonPortuguese families also share the same intragenic haplotype carried by families coming from Flores Island, but at least three others haplotypes can be determined. So far, the strongest hypothesis states that the spread of an original founder mutation is directly linked to the Portuguese-Azorean immigration. In the present study, we tested this hypothesis by linkage-disequilibrium analysis of three intragenic single-base-pair polymorphisms (ATG/GTG, CGG/GGG, TAA/TAC). Detection of the 669 polymorphism was carried out by PCR, followed by SSCP analysis and the confirmation of sequence variation was obtained by direct sequencing analysis. Detection of both 987 polymorphism and 1118 polymorphism was performed by allele-specific PCR. The results obtained indicated that the A-C-A intragenic haplotype was associated to the disease allele in the majority of patients (92%). These results are in agreement to previous studies. This indicates that a single MJD mutation was introduced in various populations, followed by a local founder effect; and this mutational event is probably very old. Based on findings presented here and comparing to data generated by the worldwide haplotype study, we can speculate that the origin of MJD associated-mutation in patients from South Brazil comes from Flores Island.
Knowledge, attitude and practice towards exclusive breast feeding among lactating mothers in a South Indian Hospital

Background: Exclusive breast feeding (EBF) isconsidered when the infant does not receive any additional food or nutriment other than breast milk. Aims and Objectives: The object of the study was to assess knowledge, attitude and practice towards EBF among lactating mothers in a south Indian hospital. Materials and Methods: Thiscross-sectionalstudy was conducted among 300 mothers, attending outpatient department of a tertiary care hospital, Karpaga Vinayaga Institute of Medical Sciences over a period of one year. They were administereda structured questionnaire which sought such information as age, educationalstatus, occupation, initiation of breast feeding, prelacteal feeding and knowledge and practice of exclusive breast feeding. Results: Exclusive breast feeding was given for six months by 77.3% of study population. Their knowledge to start early breast feeding wasgood (57.7%). Formula milk was the most commonly used top milk (25.7%). Not enough breast milk (38%) and baby didn’t drink well (15.3%) were the main reasons for stopping breastfeeding. Conclusion: Exclusive breastfeeding during approximately the first 6 months of life with continued breast feeding through at least the second half of infancy is associated with reduced risk of adverse outcomes in mother and infant.
Characterization and influence on virulence of the levansucrase gene from the fireblight pathogen Erwinia amylovora

Abstract Levan, a β-2,6-fructofuranan, produced by the fireblight pathogen Erwinia amylovora , is synthesized from sucrose by the extracellular enzyme levansucrase. Levansucrase mutants, created by Tn5 transposon mutagenesis, showed retarded development of necrotic symptoms on inoculated pear seedlings. By complementation experiments the levansucrase gene ( lsc ) was located in a 1·4 kb Pst I- Eco RV chromosomal DNA fragment, isolated from a genomic library of E. amylovora . An open reading frame of 415 amino acids, promotor sequences and a ribosome binding site were identified by DNA sequencing. The cloned lsc gene of E. amylovora was expressed in E. coli from its own promotor. The enzyme accumulated in E. coli in the periplasm and caused an altered colony morphology on sucrose containing solid media. When analysed by SDS-PAGE and isoelectric focusing, the enzyme purified from E. coli was found to be identical with the protein isolated from E. amylovora .
Differential cell surface expression of GABAA receptor α1, α6, β2 and β3 subunits in cultured mouse cerebellar granule cells – influence of cAMP‐activated signalling

In this study we have used mature, primary cultured mouse cerebellar granule cells (CGCs) to initiate our studies on the mechanisms governing neuronal trafficking of GABAA receptors (GABARs). Initially the steady‐state distribution of GABAR α1, α6, β2 and β3 subunits between the cell surface and cell interior was quantified. Cell surface proteins were modified with a membrane‐impermeable cross‐linking agent, bis(sulfosuccinimidyl)suberate (BS3) or the proteolytic enzyme, chymotrypsin. The proportion of unmodified (intracellular) and modified (cell surface) subunits was quantified by immunoblotting. We found that 51% of α6, 74% of α1, and 83% of β2/3 were expressed at the cell surface, thus identifying a sizeable intracellular pool of α6 in contrast to the low levels of intracellular α1 and β2/3. Chronic activation of protein kinase A (PKA) in CGCs in vitro, post‐transcriptionally up‐regulated expression of α1, β2 and β3 but not α6. This was paralleled by an increase in the BZ‐S subtype of [3H]Ro15–4513 binding sites. GABAR α1 was increased at the cell surface and in the cell interior, β2 was increased almost exclusively at the cell surface whilst β3 was increased almost exclusively in the cell interior. The intracellular pool of α6 was not affected. Thus, GABAR subunits are subject to differentially regulated trafficking, affording yet greater scope for GABAR diversity and plasticity.
Regression Methods for Analyzing Risk Factors Causing Cardiovascular Disease in Muzaffarabad AJ&K, Pakistan

Background: The aim of the study was to determine the most likely risk factor of cardiovascular disease (CVD) and to model the prevalence of CVD in patients arriving at Abbas Institute of Medical Sciences hospital, Muzaffarabad Azad Kashmir, Pakistan. Objective: This paper attempted to identify the significant risk factors associated with CVD in Muzaffarabad. A hospital-based, case- control study was conducted in Muzaffarabad Azad Kashmir, Pakistan, to identify the most significant risk factors that could expose the normal person to CVD as an individual and to predict the increased threat by mutual effect of risk factors like age, blood pressure, pulse rate, family history, diabetes and smoking. A total of 150 cases of coronary artery disease along with 250 controls were studied. Methodology: Descriptive analysis was done and binary logistic regression carried out with goodness of fit test such as cox and Snell’s test, likelihood ratio test and Chi-square test to detect the significant risk factors. Results: The present analysis shows that for age group 60 and above the risk of CVD is higher as compared to other age groups. It is also projected that people with blood pressure (systolic) >140, pulse rate >120, diabetic and with positive family history are more likely to have cardio-vascular disease. Conclusion: The present study concludes that in the presence of increased age, pulse rate, systolic blood pressure, diabetes and a family history of CVD there is 0.97 probability for a person to be a CVD patient.
Diseases in Orinoco crocodile (Crocodylus intermedius) and American crocodile (Crocodylus acutus) kept in Venezuelan farms.

El caimán del Orinoco Crocodylus intermedius habitaba en la cuenca del Río Orinoco de Venezuela y Colombia, el caimán de la costa Crocodylus acutus a lo largo de la costa, lagos, lagunas y rios afluentes del Mar Caribe. Después de la cacería comercial a principios y mediados del siglo XX, quedó el caimán del Orinoco en estado critico y en peligro de extinción; el caimán de la costa como una especie amenazada. En la década de los ochenta, comenzaron programas de recuperación de ambas especies por medio del censaje, monitoreo de poblaciones silvestres, protección de los hábitas, programas de cría en cautiverio para futuras liberaciones y recuperación de sus poblaciones. Con tal finalidad existian para 1998 cuatro zoocriaderos de caimán del Orinoco y uno de caimán de la costa. Las enfermedades ocurridas en estos zoocriaderos fueron: ETAPA DE NEONATOS (onfalitis, anomalías congénitas e intoxicaciones); ETAPA DE CR~AS Y JUVENILES (deficiencias nutricionales como avitaminosis A, E y B 1, escoliosis, osteodistrofia, enfermedades infecciosas bacterianas, micóticas, vírales, síndrome de las crías, casuística parasitaria por protozoario~, nemátodes y tremátodes, traumatismos y estados de shock) y ADULTOS (deficiencias nutricionales, xifosis, escoliosis, osteodistrofia, hiperparatiroidismo nutricional secundario, traumatismos, heridas y estados de shock). En la etapa de crias y juveniles el índice de mortalidad anual fue de un 70% por zoocriadero. Los datos de este trabajo fueron recopilados entre los años 85 y 98.
Landscape‐scale determinants of non‐native fish communities

Aim Predicting and preventing invasions depends on knowledge of the factors that make ecosystems susceptible to invasion. Current studies generally rely on non‐native species richness (NNSR) as the sole measure of ecosystem invasibility; however, species identity is a critical consideration, given that different ecosystems may have environmental characteristics suitable to different species. Our aim was to examine whether non‐native freshwater fish community composition was related to ecosystem characteristics at the landscape scale.
Regulation of Phenotypic Plasticity in Triple-Negative Breast Cancer

Regulation of Phenotypic Plasticity in Triple-Negative Breast Cancer by Nicholas Christopher D’Amato Department of Pharmacology and Cancer Biology Duke University Date:_______________________ Approved: ___________________________ Victoria Seewaldt, Supervisor ___________________________ Mark Dewhirst ___________________________ Mariano Garcia-Blanco ___________________________ Jeffrey Rathmell ___________________________ Xiao-fan Wang An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pharmacology and Cancer Biology in the Graduate School of Duke University 2011 Copyright by Nicholas Christopher D’Amato 2011 iv Abstract Breast cancers with a basal-like gene signature are primarily triple-negative, are frequently metastatic, and carry the worst prognosis. Basal-like breast cancers are also frequently enriched for markers of breast cancer stem cells as well as markers of epithelial-mesenchymal transition (EMT). While EMT is generally thought to be important in the process of metastasis, direct in vivo evidence of EMT in human disease remains rare. Here we report a novel model of human triplenegative breast cancer, the DKAT cell line, which was isolated from an aggressive, treatment-resistant triple-negative breast cancer that demonstrated morphological and biochemical evidence of epithelial-mesenchymal plasticity in the patient. In culture, the DKAT cell line exhibits a basal epithelial phenotype under normal culture conditions in serum-free MEGM, and can undergo a reversible EMT in response to serum-containing media, a unique property among the breast cancer cell lines we tested. This EMT is marked by increased expression of the transcription factor Zeb1, and Zeb1 is required for the enhanced migratory ability of DKAT cells in the mesenchymal state. Additionally, we find that expression of the cytokine IL-6 is dramatically increased in mesenchymal DKAT cells, and blocking IL-6 signaling reduces expression of Zeb1 in DKAT and MDA-MB-231 cells. We further show that
Functional innovation through vestigialization in a modular marine invertebrate

Few studies show how morphological vestigialization may facilitate functional innovation. Fewer still describe the co-occurrence of the derived and more ancestral structures in the same genetic individual. In the present study, we explore that rare instance in a modular (colonial) marine invertebrate. Using laser scanning confocal microscopy with fluorescent staining and behavioural observations, we describe homologous structures in polymorphic modules (zooids) in the bryozoan Bugula flabellata and document the occurrence of previously unreported retractor and circular muscles in the more derived module, the bird’s-head avicularium. In the evolution of a sessile feeding zooid to a moveable nonfeeding zooid with sensory and grasping functions, transformations were effected in the food-capture apparatus, orificial structures, musculature, and sensory structures. We expand on and clarify previous reports of homologies between ancestral and derived modules in bryozoans and argue that vestigialization and augmentation of homologous structures were coincident with functional innovations in the avicularium. The present study offers rare evidence for the evolution of functional innovation through vestigialization. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104, 63‐74.
FRoM MIcRobES To PEoPlE: TRAcTAblE bENEFITS oF No-TAkE AREAS FoR coRAl REEFS

The number of no-take marine protected areas (here referred to as no-take areas, NTAs) on coral reefs has increased considerably in recent decades. coincident with accelerating degradation of coral reefs, expectations of the benefits that NTAs can provide for coastal societies and sustainability of marine ecosystems has grown. These include increasing abundance of reef organisms both inside and outside NTAs, protecting key ecosystem functions, and providing social and economic benefits through improved fisheries and tourism. However, there is a lack of convincing evidence for many of these expectations. This is the first attempt to synthesize all potential costs and benefits of coral reef NTAs and critically examine evidence of their impacts on both ecosystems and societies. NTAs with high compliance consistently increase the diversity, density and biomass of exploited reef fishes and certain groups of motile invertebrates within their boundaries and have benefits for reef-associated tourism. Some NTAs provide small increases in the abundance of corals and decreases in macroalgal cover. The effects of NTAs on genetic diversity and connectivity among meta-populations are variable or as yet unquantified. There is limited evidence of NTAs providing social benefits through increased fishery yields and tourism revenue. There are examples of both positive and negative effects on social well-being. Finally, sharks, marine megafauna and microbial communities showed few tangible benefits from NTAs. Substantial gaps in the science of NIcHolAS A.J. GRAHAM ET Al. 106 coral reef NTAs remain, especially in their capacity to provide socioeconomic benefits. A crucial research priority is understanding how the cumulative effects of climate change will influence the various benefits that NTAs provide. To be effective, NTAs must be used in conjunction with a range of other management tools and applied according to local environmental and societal contexts.
Genetic Variation and Molecular Evolution

The comparison of DNA sequences of genes and entire genomes offers interesting insights into the possible evolutionary relatedness of genetic information of living organisms. Together with a relatively rich database from experimental microbial genetics, conclusions can be drawn on the molecular mechanisms by which genetic variations are spontaneously generated. A number of different specific mechanisms contribute to the overall mutagenesis. These mechanisms are here grouped into three natural strategies of the spontaneous generation of genetic variations: local changes of DNA sequences, intragenomic rearrangement of DNA segments, and acquisition of foreign DNA by horizontal gene transfer. These three strategies have different qualities with regard to their contributions to the evolutionary process. As a general rule, none of the known mechanisms producing genetic variants is clearly directed. Rather, the resulting alterations in the inherited genomes are more random. In addition, usually only a minority of resulting variants provide a selective advantage. Interestingly, in most of the molecular mechanisms involved, the products of so-called evolution genes are involved as generators of genetic variation and/or as modulators of the frequencies of genetic variation. Products of evolution genes work in tight collaboration with nongenetic factors such as structural flexibilities and chemical instabilities of molecules, chemical and physical mutagens, and random encounter. All of these aspects contributing to the spontaneous generation of genetic variations together form the core of the theory of molecular evolution. This theory brings neo-Darwinism to the molecular level. In view of the increasing evidence coming particularly from microbial genetics, knowledge of molecular evolution can be seen as a confirmation of Darwinism at the level of biologically active molecules, in particular, nucleic acids and proteins. Philosophical and practical implications of this knowledge will be briefly discussed. Keywords: Biological Evolution; DNA Rearrangement; Evolution Gene; Gene Acquisition; Natural Selection; Spontaneous Mutation; Transposition; Variation Generator
Genomic methods for studying the post-translational regulation of transcription factors

The spatiotemporal coordination of gene expression is a fundamental process in cellular biology. Gene expression is regulated, in large part, by sequence-specific transcription factors that bind to DNA regions in the proximity of each target gene. Transcription factor activity and specificity are, in turn, regulated posttranslationally by protein-modifying enzymes. High-throughput methods exist to probe specific steps of this process, such as protein-protein and protein-DNA interactions, but few computational tools exist to integrate this information in a principled, model-oriented manner. In this work, I develop several computational tools for studying the functional implications of transcription factor modification. I establish the first publicly accessible database for known and predicted regulatory circuits that encompass modifying enzymes, transcription factors, and transcriptional targets. I also develop a model-based method for integrating heterogeneous genomic and proteomic data for the inference of modification-dependent transcriptional regulatory networks. The model-based method is thoroughly validated as a reliable and accurate computational genomic tool. Additionally, I propose and demonstrate fundamental improvements to computational proteomic methods for identifying modified protein forms. In summary, this work contributes critical methodological advances to the field of regulatory network inference. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Genomics & Computational Biology First Advisor Sridhar Hannenhalli Second Advisor Stephen R. Master
TFLPL: Programación con lógica de términos

Resumen. A partir del sistema l´ogico Term Functor Logic ( TFL ) y del concepto de base de datos aristot´elica, en esta contribuci´on presentamos los avances de un lenguaje de programaci´on l´ogica que hemos denomi-nado Term Functor Logic Programming Language ( TFL PL ).
Antibacterial free fatty acids from the marine diatom, Phaeodactylum tricornutum

The aim of this thesis was to isolate the compounds responsible for the antibacterial activity of cell extracts of the marine diatom, Phaeodactylum tricornutum. Marine microalgae are not only important primary producers but, due to their phylogenetic diversity, they are also a potential source of novel bioactive compounds. The marine diatom, P. tricornutum, was selected for study because its cell extracts are known to be antibacterial but the compounds responsible have not been isolated. In this thesis, the compounds responsible for the antibacterial activity are isolated from aqueous methanol P. tricornutum cell extracts by column chromatography and reverse phase high-performance liquid chromatography using a bioassay-guided approach. The compounds in three active fractions were identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the unsaturated fatty acids (5Z, 8Z, 11Z, 14Z, 17Z)-eicosapentaenoic acid, (9Z)-hexadecenoic acid and (6Z, 9Z, 12Z)-hexadecatrienoic acid. The fatty acids were found to be antibacterial against Staphylococcus aureus at micromolar concentrations. P. tricornutum exists in different cell morphs and, interestingly, extracts prepared from cultures in the fusiform morph were found to have greater antibacterial activity than extracts from oval cultures. This is explained by greater levels of the three antibacterial fatty acids in the fusiform cell extracts. The antibacterial fatty acids are proposed to be released by enzyme action when the diatom cells lose their integrity. The release of free fatty acids by diatoms is suggested to be a simple, very low cost population-level activated defence mechanism against potential pathogenic bacteria triggered when the cell loses its integrity. Further, this pathway may act against multiple threats to the microalga, including grazers, as fatty acids exhibit activity in diverse
Global and National Trends of HIV/AIDS

HIV/AIDS is one of the worst pandemics, the world has ever known and the entire world has been combating with it. Objective of the study is to analyze the global and national trend of HIV/AIDS regarding the indices PLHIV, New infections and AIDS-related death and coverage of ART. This is a quantitative research completely based on the secondary data. The data is analyzed by simple statistical representations. Regression analysis is used to analyze the trends and to make some predictions. The number of PLHIV is increased by 19.9 percent from 1997 to 2015 and by 69.6 percent from 2000 to 2015 in Nepal. In this same duration, the new HIV infection is reduced by 63.8 percent and 82.6 percent, AIDS related death by 52.2 percent and 411.1 percent respectively in the global and Nepal. The initial coverage of ART in both regions was negligible and by the end of 2015 it reached to 46.4 percent and 30.6 percent in the global and Nepal respectively. Nepal along with the global achieves some positive results in the combating of this health problem. By analyzing the trends, it is not worth to say that we are not far from the achievement of SDGs.