Miracle-dz/UniFAR-FTUs huggingface dataset:
Analgesic effect of leaf extract from Ageratina glabrata in the hot plate test

Ageratina glabrata (Kunth) R.M. King & H. Rob. , Asteraceae (syn. Eupatorium glabratum Kunth) is widely distributed throughout Mexico and popularly known as "chamizo blanco" and "hierba del golpe" for its traditional use as external analgesic remedy. Though glabrata species has been chemically studied, there are no experimentally asserted reports about possible analgesic effects which can be inferred from its genus Ageratina. To fill the gap, we evaluated A. glabrata extracts in an animal model of nociception exploiting thermal stimuli. NMR and mass analyses identified a new thymol derivative, 10-benzoiloxy-6,8,9-trihydroxy-thymol isobutyrate (1), which was computationally converted into a ring-closed structure to explain interaction with the COX-2 enzyme in a ligand-receptor docking study. The resulting docked pose is in line with reported crystal complexes of COX-2 with chromene ligands. Based on the present results of dichloromethane extracts from its dried leaves, it is safe to utter that the plant possesses analgesic effects in animal tests which are mediated through inhibition of COX-2 enzyme.
Fishermen Resistance to Exit Fisheries

Excessive harvesting pressure is an important force behind the decline of East Africa's Lake Victoria fisheries. The question of entry-exit is, therefore, crucial. This paper uses micro-data collected from the Kenyan side of Lake Victoria to analyze this issue. Results indicate that fishermen are in their current enterprise because alternatives are lacking. In spite of the "commons" nature of these fisheries, over two-thirds of the fishermen would welcome more fishermen, as the positive externalities of this exceed the negative ones. Opportunity cost of exiting, fishing experience, and whether the skipper of a fishing unit is its owner or an employee, are the significant determinants of resistance to exit from these Kenyan fisheries. Exit inertia usually associated with imperfect capital malleability and attachment to fishing is lacking, or minimal, in these fisheries.
The large subunit of bacteriophage λ’s terminase plays a role in DNA translocation and packaging termination 1 1 Edited by M. Gottesman

Abstract The DNA packaging enzyme of bacteriophage λ, terminase, is a heteromultimer composed of a small subunit, gpNu1, and a large subunit, gpA, products of the Nu1 and A genes, respectively. The role of terminase in the initial stages of packaging involving the site-specific binding and cutting of the DNA has been well characterized. While it is believed that terminase plays an active role in later post-cleavage stages of packaging, such as the translocation of DNA into the head shell, this has not been demonstrated. Accordingly, we undertook a generalized mutagenesis of λ’s A gene and found ten lethal mutations, nine of which cause post-cleavage packaging defects. All were located in the amino-terminal two-thirds of gpA, separate from the carboxy-terminal region where mutations affecting the protein’s endonuclease activity have been found. The mutants fall into five groups according to their packaging phenotypes: (1) two mutants package part of the λ chromosome, (2) one mutant packages the entire chromosome, but very slowly compared to wild-type, (3) two mutants do not package any DNA, (4) four mutants, though inviable, package the entire λ chromosome, and (5) one mutant may be defective in both early and late stages of DNA packaging. These results indicate that gpA is actively involved in late stages of packaging, including DNA translocation, and that this enzyme contains separate functional domains for its early and late packaging activities.
Role of NF-kappaB/Rel proteins in mediating innate immune responses in Drosophila melanogaster

Title of Document: ROLE OF NF-κB/REL PROTEINS IN MEDIATING INNATE IMMUNE RESPONSES IN DROSOPHILA MELANOGASTER Subhamoy Pal, Doctor of Philosophy, 2006 Directed By: Dr. Louisa Wu, Associate Professor, Center for Biosystems Research, University of Maryland Biotechnology Institute In order to survive, the fruit fly Drosophila melanogaster needs to have a robust immune system to protect itself from numerous pathogenic microorganisms that are ubiquitous in its natural habitat. In two related projects, we studied the role of Rel transcription factors in mediating these immune responses. There are three Rel transcription factors, closely related to mammalian NF-κB: Dorsal, Dif, and Relish. They play an important role in mounting aspects of this response, including the inducible expression of antimicrobial peptides. To study the roles of these transcription factors in vivo, we used microarrays to determine the effect of null mutations in individual transcription factors on larval immune gene expression. Of the 188 genes that were significantly up-regulated in wildtype larvae upon bacterial challenge, overlapping but distinct groups of genes were affected in the Rel mutants. We also ectopically expressed Dorsal or Dif and used cDNA microarrays to determine the genes that were up-regulated in the presence of these transcription factors. Combining this data, we also identified novel genes that may be specific targets of Dif. In a related project, we observed that injection of a fungal secondary metabolite, Destruxin A reduced expression of various antimicrobial peptide genes. This reduction appeared to be mediated through suppression of the IMD pathway, through Relish. Destruxins are a class of cyclic depsipeptides produced by various fungi including the entomopathogen Metarhizium anisopliae. Though a direct relationship has been established between Destruxin production and fungal virulence, their in vivo mode of action during pathogenesis remained largely uncharacterized. To explore these effects, we looked at changes in gene expression following injection of Destruxin A into Drosophila. Microarray results revealed reduced expression of various AMPs that play a major role in the fly’s humoral immune response. Flies coinjected with Destruxin A and the Gram-negative bacteria E.coli, showed increased mortality and an accompanying increase in bacterial titers. This mortality was rescued through ectopic activation of IMD pathway components upstream of Relish that are responsible for AMP induction. Together, these results suggest a novel role for Destruxin A in specific suppression of the humoral immune response in insects. ROLE OF NF-κB/REL PROTEINS IN MEDIATING INNATE IMMUNE RESPONSES IN DROSOPHILA MELANOGASTER
Dissecting the genotype to phenotype relationships of genomic disorders

Over the last decade, major advances in the development and application of microarray-based comparative genomic hybridisation (aCGH) technology have significantly contributed to our understanding of Genomic Disorders. My aims here were to provide insight into the genotype to phenotype relationships of three Genomic Disorders; CUL4B-deleted X-Linked Mental Retardation (XLMR), Wolf-Hirschhorn Syndrome (WHS) and 16p11.2 Copy Number Variant Disorder. CUL4B encodes a structural component of the Cullin-RING-ligase 4-containing class of E3 ubiquitin ligases. CUL4B-deleted XLMR represents a syndromal form of mental retardation whereby patients exhibit other clinical features aside from the MR, such as seizures, growth retardation and disrupted sexual development. I used CUL4B-deleted patient-derived cell lines to investigate the impacts of CUL4B loss on mitochondrial function. I have shown that loss of CUL4B is associated with a distinct set of mitochondrial phenotypes, identifying CUL4B-deleted XLMR as a disorder associated with mitochondrial dysfunction. Furthermore, I have uncovered a reciprocal relationship between CUL4B and Cereblon, providing evidence of a potential role for the CUL4-CRBN E3 ligase complex in maintaining mitochondrial function. Deletion or duplication of the 16p11.2 region is associated with macro-/microcephaly respectively. Here, I have evaluated the cellular consequences of 16p11.2 CNV, specifically with regards KCTD13 expression, DNA replication and checkpoint activation. WHS is typically caused by a small hemizygous telomeric deletion of the 4p16.1 region. Haploinsufficiency of 4p16.1 is associated with microcephaly, growth retardation and complex developmental abnormalities. I investigated the impacts of LETM1 copy number change in WHS patient-derived cells. Here, I have shown that copy number change of LETM1 specifically segregates with mitochondrial dysfunction, likely underlying the seizure phenotype exhibited by the large subgroup of WHS patients whose deletions incorporate LETM1 as well as the rarer instances of the reciprocal duplication. In this thesis I use patient-derived cell lines from three Genomic Disorders as a fundamental tool providing new pathomechanistic insight into the clinical presentation of these conditions.
Contribution à l’émergence de nouvelles méthodes parallèles et réparties intelligentes utilisant un paradigme de programmation multi-niveaux pour le calcul extrême

Les methodes iteratives de Krylov sont utilisees sur les plate-formes de Calcul Haute Performance (CHP) pour resoudre les grands systemes lineaires issus des domaines de la science et de l’ingenierie. Avec l’augmentation du nombre de cœurs et de l’heterogeneite des superordinateurs, le temps consacre a la communication et synchronisation globales nuit gravement aux leurs performances paralleles. La programmation tend a etre distribuee et parallele. Le developpement d’algorithmes devrait prendre en compte les principes: 1) parallelisme avec multi-granularite; 2) memoire hierarchique; 3) minimisation de la communication globale; 4) promotion de l’asynchronicite; 5) proposition de strategies d’ordonnancement et de moteurs de gestion pour gerer les trafics et la tolerance aux pannes. En reponse a ces objectifs, nous presentons un paradigme de programmation multi-niveaux distribues et paralleles pour les methodes de Krylov sur les plates-formes de CHP. La premiere partie porte sur la mise en œuvre d’un generateur de matrices avec des valeurs propres prescrites pour la reference des methodes iteratives. Dans la deuxieme partie, nous etudions les performances numeriques et paralleles de la methode iterative proposee. Son implementation avec un moteur de gestion peut gerer la communication, la tolerance aux pannes et la reutilisabilite. Dans la troisieme partie, un schema de reglage automatique est introduit pour la selection intelligente de ses parametres lors de l’execution. Enfin, nous etudions la possibilite d’implementer ce paradigme dans un environnement d’execution de flux de travail.
Intestinal parasitosis, undernutrition and socio-environmental factors in schoolchildren from Clorinda Formosa, Argentina.

OBJECTIVE To evaluate intestinal parasitosis, undernutrition and socio-environmental factors in schoolchildren from Clorinda (Formosa, Argentina). MATERIALS AND METHODS Serial fecal samples and anal swabs of 114 schoolchildren, canine feces and soil samples were analyzed. Body weight and height of 215 schoolchildren were measured and undernutrition was estimated according to the World Health Organization criteria. Socio-environmental variables were assessed by means of a semi-structured questionnaire. RESULTS 78.1% of children were infected by at least one of the 12 species identified and 70.8% had multiple parasitic infections. Blastocystis sp. , Giardia lamblia and Enterobius vermicularis were the most prevalent. Additionally, 17.5% of children were infected by at least one geohelminth (e.g. Ascarislumbricoides, Trichuris trichiura, hookworms). 64.3% of canine of canine feces were positive and six parasitic species were found; the most frequent were Ancylostoma caninum, Uncinaria stenocephala and G. lamblia. Furthermore, 37.5% of soil samples showed zoonotic parasites (i.e. Ascaris sp., Toxocara sp.). Finally, 10.0% of the children were undernourished and 85.7% of them had parasites. The risk for parasitosis was higher in children that lived in houses with inadequate solid waste disposal and whose parents were unemployed or had temporary jobs. CONCLUSIONS The lack of environmental sanitation, unstable employment of parents and the presence of zoonotic species were the most relevant factors observed. Consequently, these conditions result in an increase of parasitic infections and negatively influence the growth of children.
Echidna: Extraordinary Egg-Laying Mammal

The echidna is one of the world’s most extraordinary creatures. It is a living fossil whose relatives were walking the earth over 100 million years ago. Like the platypus, it is a mammal that lays eggs. And, like all mammals, it has fur and produces milk. This book describes the echidna’s lifestyle and the adaptations that have made it so successful. It draws on the latest research into these strange creatures, covering their evolution, anatomy, senses, reproduction, behaviour, feeding habits and metabolism. The authors reveal some fascinating new findings, showing how echidnas are masters of their environment, and not simply some sort of mammal ‘test model’ that went wrong. A final chapter on conservation includes information on captive diet and management.
Viral and Cellular Targets for the Varicella-Zoster Virus ORF66 Protein Kinase

Varicella-zoster virus (VZV) is a human alphaherpesvirus that causes two important diseases, chickenpox and herpes zoster, separated by a prolonged period of latent infection in which no disease occurs. VZV remains a serious public health concern despite the availability of licensed vaccines for the prevention of chickenpox during childhood and zoster in the elderly. The VZV ORF66 protein kinase is a well-established mediator of VZV tropism and pathogenesis in vivo, but information regarding the molecular mechanisms of ORF66 function is limited. ORF66 is orthologous to the alphaherpesvirus US3 kinase family, which is involved in regulating diverse aspects of the host environment. ORF66 has been implicated in nuclear exclusion of the VZV principle transcriptional regulator and tegument protein, IE62, during late-stage VZV infection; and in downmodulation of class I major histocompatibility complex surface expression, which is critical for the identification and elimination of infected cells by the adaptive immune system. However, the mechanisms underlying these processes are not well-resolved. In this work, I have significantly extended our understanding of known ORF66 functions during VZV infection, and I have established novel functions for both ORF66 and the IE62 protein. Purification of ORF66 allowed the development of an in vitro kinase assay, and I used this to prove that ORF66 directly phosphorylates IE62 adjacent to its nuclear localization signal to mediate nuclear exclusion. Additional investigations of IE62 nucleocytoplasmic trafficking revealed a novel nuclear export activity, which was multi-dimensionally regulated by intrinsic IE62 nuclear retention and phosphorylation by kinase(s) other than ORF66. With regard to the ORF66 role in the regulation of MHC-I surface presentation, I developed assays with recombinant VZV expressing enhanced green fluorescent protein-tagged ORF66 to establish that ORF66 affects the cellular environment such that early MHC-I biogenesis is delayed, resulting in a reduction in total surface MHC-I. MHC-I studies indicated highly novel ORF66 nuclear distribution patterns, and a further examination of these revealed that ORF66 may regulate nucleocapsid morphogenesis or trafficking in VZV-infected nuclei. In sum, this work represents a major contribution to VZV biology and provides insights into a multi-functional mediator of VZV persistence and pathogenesis.
Dynamical reduction of metabolic networks by singular perturbation theory : application to microalgae

Lipids from microalgae and carbohydrates from cyanobacteria can be transformed into biodiesel and bioethanol, respectively. Enhancing the production of these molecules must account for the periodic inputs (mainly light) forcing the metabolic network of these photosynthetic organisms. It is therefore necessary to account for the dynamics of the metabolic network, while reducing its dimension to ensure mathematical tractability. The aim of this work is to design an original approach to reduce dynamic metabolic networks while keeping the core dynamics. This method is based on time-scale separation. For a class of metabolic network models described by ODE, the dynamics of the reduced systems are computed using the theorem of Tikhonov for singularly perturbed systems. This Quasi Steady State Approximation accurately coincides with the original network dynamics, with a bounded error. The approach is first developed for reaction systems that can be linearized around a working point and that are forced by external continuous inputs. Then, a generalization of this method is given for networks with fast reactions of Michaelis-Menten kinetics and any type of slow kinetics, also considering a finite number of external continuous inputs. The reduction method highlights a relation between the concentration magnitude of the metabolites and the range of the reaction rates: the metabolites that are consumed by fast reactions have concentration one order of magnitude lower than metabolites consumed at slow rates. This property is satisfied for metabolites with fast dynamics that are not in a flux trap, a concept introduced in this work. The reduced system can be calibrated with experimental data using a dedicated identification procedure based on minimization. The approach is illustrated with an autotrophic microalgae metabolic network, including the core metabolism and representing the carbohydrates and lipids dynamics. The approach efficiently fits the experimental data from Lacour et al. (2012) with the microalgae Tisochrysis lutea. Finally, a scheme to optimize the production of target molecules is proposed using the reduced system.
The role of histone Htz1 in nucleotide excision repair inSaccharomyces cerevisiae

Nucleotide excision repair (NER) is critical for maintaining genome integrity. How chromatin dynamics are regulated to facilitate this process in chromatin is still under exploration. Htz1 (H2A.Z), a highly conserved histone H2A variant, is incorporated into the nucleosomes around the promoters of many genes in S. cerevisiae. Htz1 is involved in the maintenance of genome stability, DNA transcription activation, DNA replication and DNA repair. In this study, I employed Saccharomyces cerevisiae, as a model organism. In this thesis, I examined the role of histone Htz1 in the response to UV light at specific regions using a high resolution approach and throughout the entire yeast genome using chromatin-immunoprecipitation coupled to microarrays. htz1Δ and its deposition related mutants are more sensitive to UV and CPD removal was impaired in total DNA from both htz1Δ and swr1Δ strains. Acetylation of Htz1 at K3, 8, 10, 14 does not contribute to UV sensitivity or CPD removal from total DNA. CPD removal experiments at the MFA2 promoter and the HMRa1 coding region have showed that Htz1 has a role in NER and it likely only affects repair at local nucleosomes containing Htz1. My ChIP experiments at MFA2 and HMRa1 indicate that Htz1 enhances the binding of the HAT Gcn5 to Htz1 containing chromatin and this promotes histone H3 hyperacetylation in Htz1 nucleosomes in the MFA2 promoter after UV irradiation. As a result of this optimal level of histone H3 acetylation occur and the binding of Rad14 to damaged DNA is also enhanced at this region. My genome-wide study shows that UV does not influence the localization of Htz1 as it still resides at the pre-UV sites. Htz1 and H3 K9K14 acetylation is found to be associated with each other genome-wide. This is believed to be via the interaction between Htz1 and Gcn5. These results show that there is a positive role of Htz1 in promoting efficient GG-NER.
Antifungal properties of some plant-extracts against Chaetomium globosum.

The efficacy of aqueous extracts of twenty plants was observed for their antifungal activity against Chaetomium globosum, causal organism of decay of cotton and other cellulose materials. The maximum inhibitory effect was shown by stem extracts of Aloe vera (85.72%), while leaf extracts of Camellia sinensis (79.69%), bark extracts of Acacia arabicae (79.06%) and bark extracts of Callistemon lanceolatus (58.34%) showed strong inhibitory effect. Some of the other plants showed moderate inhibition against the mycelium growth of test fungi i.e. Azadirachta indica> Albizia lebbeck> Aegle marmelos> Acacia catechu.
Modeling Mortality of Related Populations via Parameter Shrinkage

Parameter shrinkage is known to reduce fitting and prediction errors in linear models. When the variables are dummies for age, period, etc. shrinkage is more commonly applied to differences between adjacent parameters, perhaps by fitting cubic splines or piecewise-linear curves (linear splines) across the parameters. A common problem in mortality is modeling related populations where some commonality is desired. We do this by shrinking slope changes of linear splines for the largest population, then shrinking differences from those slope changes for the other populations. There are frequentist and Bayesian approaches to shrinkage, and they have a good deal of similarity. Here we use a unified approach that compromises a bit with both of these paradigms. It uses Bayesian tools without some of the historical Bayesian concepts, and pushes the random-effects framework slightly to accommodate. Modeling Swedish and Danish male mortality data is used as an illustration.
Organization and Expression of tRNA Genes in Saccharomyces cerevisiae

INTRODUCTION Transfer RNAs have traditionally been among the favorite tools of molecular biologists. By virtue of their small size and relative abundance, tRNAs have long been the RNA molecules of choice for determination of primary, secondary, and tertiary structure. Their pivotal and multifaceted roles in cellular metabolism have made them the focus of biochemists’ attention for more than three decades; as a result, probably as much is known about their functional interactions as about any other class of macromolecules. The piece-de-resistance of their appeal stems from their amenability to genetic analysis. Once converted to a suppressor, a tRNA gene is no longer anonymous; its distinctive phenotype is readily identified and easily tracked. Given the appropriate genetic background, phenotypic loss of suppression can be used to identify each of the elements essential for transcription, maturation, and activity of the tRNA gene product. The power of these complementary approaches has already been amply demonstrated in both phage and bacterial systems. The ultimate goal of knowing not only the physical relationships among each of the nucleotides in the three-dimensional structure, but also of understanding how each of these structural features relates to the synthesis and function of the mature tRNA, is now conceivably within reach. As the details of this picture have become more refined, the need for comparable information in eukaryotes has become more apparent. Although contemporary methodology has now made it possible to rapidly accumulate primary sequence data from a variety of higher organisms, results of this kind are of only.