Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Plasmodium falciparum transporters in drug resistance

Although the fight against malaria has achieved a remarkable progress during the last 15 years, there were still 214 million new cases and 438000 estimated deaths caused by malaria worldwide in 2015. Transporters play a crucial role in Plasmodium biology but they can also be considered as double edge swords: on the one hand, they are potential new antimalarial drug targets but on the other hand, they are the main players in the development of drug resistance. PFE0825w is a putative organic cation transporter that has been proposed as the target of the candidate antimalarial drug albitiazolium and the locus where it is localized has been linked to chloroquine transport. In this study, different PFE0825w isoforms were identified and studied using the X. laevis oocyte system. Two of the isoforms were expressed at the oocyte oolemma but no significant transport of putative organic cation substrates was detected, restricting further characterization of this transporter. A better characterized transporter that plays a significant role in resistance against chloroquine (CQ) and quinine (QN) is the chloroquine resistance transporter PfCRT. It is known that this transporter has at least three different phosphorylation sites and that the phosphorylation of one of these sites -T416- is essential for the correct trafficking of PfCRT to the food vacuolar membrane. In this study the role of phosphorylation in the drug-resistance-mediating function of PfCRT was investigated. CQ-resistant parasites treated with the kinase inhibitor ML-7 accumulated more CQ than untreated parasites and showed CQ and QN IC50 values comparable to those of sensitive strains. Along the same line, the mutagenesis of the phosphorylation site S33 to alanine in PfCRT led to reduced CQ and QN IC50 values although no increase in drug accumulation was observed. Furthermore, PfCRTS33A conferred a fitness advantage to the parasites in the absence of CQ and a fitness cost in the presence of the drug. Two protein kinases were analyzed regarding their roles in PfCRT phosphorylation, PfCK2 and PF11_0488, the latter being identified in a Y2H assay. The downregulation of PfCK2 did not have an effect on CQ accumulation, but the overexpression of the C-terminal part of PF11_0488 resulted in reduced levels of CQ accumulation. However, the same fragment did not show any catalytic activity when recombinantly expressed and used in in vitro phosphorylation assays. Downregulation of this kinase was not achievable, most likely due to its essential function. Altogether, these results point to the fact that the parasite susceptibility towards CQ and QN is regulated by phosphorylation, although the exact molecular mechanism needs to be further examined.
Tight Lower Complexity Bounds for Strongly Convex Finite-Sum Optimization

Finite-sum optimization plays an important role in the area of machine learning, and hence has triggered a surge of interest in recent years. To address this optimization problem, various randomized incremental gradient methods have been proposed with guaranteed upper and lower complexity bounds for their convergence. Nonetheless, these lower bounds rely on certain conditions: deterministic optimization algorithm, or fixed probability distribution for the selection of component functions. Meanwhile, some lower bounds even do not match the upper bounds of the best known methods in certain cases. To break these limitations, we derive tight lower complexity bounds of randomized incremental gradient methods, including SAG, SAGA, SVRG, and SARAH, for two typical cases of finite-sum optimization. Specifically, our results tightly match the upper complexity of Katyusha when each component function is strongly convex and smooth, and tightly match the upper complexity of SDCA without duality and of KatyushaX when the finite-sum function is strongly convex and the component functions are average smooth.
Minor collagens of the skin with not so minor functions

The structure and function of the skin relies on the complex expression pattern and organisation of extracellular matrix macromolecules, of which collagens are a principal component. The fibrillar collagens, types I and III, constitute over 90% of the collagen content within the skin and are the major determinants of the strength and stiffness of the tissue. However, the minor collagens also play a crucial regulatory role in a variety of processes, including cell anchorage, matrix assembly, and growth factor signalling. In this article, we review the expression patterns, key functions and involvement in disease pathogenesis of the minor collagens found in the skin. While it is clear that the minor collagens are important mediators of normal tissue function, homeostasis and repair, further insight into the molecular level structure and activity of these proteins is required for translation into clinical therapies.
Possible Return of the Driftwood Catfish, Trachelyopterus galeatus (Family: Auchenipteridae) to Trinidad, Trinidad and Tobago

The mean freshwater and riverine ichthyofaunal species richness for Trinidad and Tobago, according to Phillip (1998), was calculated to be 38.7 using a wide range of species richness estimators, with the recorded observed being 38 fish species. Since then there have been numerous taxonomic disputes causing this richness estimate to change. Mohammed et al . (2010) documented an additional species, the gouramy, Trichogaster trichopterus in the south-central Oropuche drainage of Trinidad. Prior to this, Kenny (1995) reported 43 freshwater fish species listed for Trinidad and Tobago. In this account, the historical occurrences of the elongate hatchetfish, Triportheus elongatus (Family: Characidae) and driftwood catfish, Trachelyopterus galeatus (Family: Auchenipteridae) were noted, but both were suspected to be extinct. Neither species were reported in Phillip’s (1998) account, and subsequently were absent in the taxonomic keys for freshwater fishes by Phillip and Ramnarine (2001). Recently, T. elongatus was reported in south-east Trinidad (Mohammed et al . 2010), and T. galeatus has been re-discovered in 2011 in the central drainages of the Caroni Plain.
The ability of antimicrobial peptides to migrate across the gastrointestinal epithelial and vascular endothelial barriers

The antibiotic resistance crisis has resulted in an urgent need for the development of new antimicrobial compounds that can be used in clinical settings. Bacteriocins have many properties which suggests they are viable alternatives to antibiotics. However, little research has been done regarding the pharmacodynamics and in situ delivery of bacteriocins. Migration of the lantibiotic, nisin A and class IIa bacteriocins, plantaricin 423 and bacST4SA across vascular endothelial and gastrointestinal epithelial cells was studied using in vitro simulations. Monolayers of human umbilical vein endothelial cells (HUVECs) and human colonic adenocarcinoma (Caco-2) cells were seeded onto transmigration inserts placed in a 24-well tissue culture plate with growth medium and exposed to fluorescently labelled nisin A, plantaricin 423 and bacST4SA. All three peptides diffused across HUVECs and Caco2 cells. A small percentage of the peptides (21% nisin A, 11% plantaricin 423 and 12% bacST4SA) remained attached to Caco-2 cells. Only 6% nisin A and 3% bacST4SA attached to the HUVECs, while plantaricin 423 did not attach. The viability of both cell types remained unchanged when exposed to 50 μM nisin A, 50 μM plantaricin 423 and 50 μM bacST4SA, respectively, as determined with XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulphenyl)2H-Tetrazolium-5-Carboxanilide) and neutral red assays, whereas a slight decrease in cell viability was observed when the cell lines were treated with 100 μM peptide. Furthermore, nisin A, a FDA food preservative, displayed significantly higher levels of cytotoxicity compared to plantaricin 423 and bacST4SA in both cell lines (P<0.05). The three peptides retained 60% of their antimicrobial activity when individually exposed to 80% human plasma for 24 h at a concentration of 25 μM, but with increasing concentrations, this loss of antimicrobial activity became less pronounced (68% and 79% activity retained at 50 μM and 100 μM respectively). The stability of the peptides in the presence of human blood plasma increased as exposure time increased from 24 h to 48 h to 72 h, as expected. This is the first report of nisin A, plantaricin 423 and bacST4SA migrating across simulated gastrointestinaland vascular barriers. In vivo studies are required to confirm these findings and determine the effect these peptides may have in the treatment of systemic infections.
Motility and chemotaxis in the Lyme disease spirochete Borrelia burgdorferi : role in pathogenesis

Lyme disease is the most prevalent vector-borne disease in United States and is caused by the spirochete Borrelia burgdorferi. The disease is transmitted from an infected Ixodes scapularis tick to a mammalian host. B. burgdorferi is a highly motile organism and motility is provided by flagella that are enclosed by the outer membrane and thus are called periplasmic flagella. Chemotaxis, the cellular movement in response to a chemical gradient in external environments, empowers bacteria to approach and remain in beneficial environments or escape from noxious ones by modulating their swimming behaviors. Both motility and chemotaxis are reported to be crucial for migration of B. burgdorferi from the tick to the mammalian host, and persistent infection of mice. However, the knowledge of how the spirochete achieves complex swimming is limited. Moreover, the roles of most of the B. burgdorferi putative chemotaxis proteins are still elusive. B. burgdorferi contains multiple copies of chemotaxis genes (two cheA, three cheW, three cheY, two cheB, two cheR, cheX, and cheD), which make its chemotaxis system more complex than other chemotactic bacteria. In the first project of this dissertation, we determined the role of a putative chemotaxis gene cheD. Our experimental evidence indicates that CheD enhances chemotaxis CheX phosphatase activity, and modulated its infectivity in the mammalian hosts. Although CheD is important for infection in mice, it is not required for acquisition or transmission of spirochetes during mouse-tick-mouse infection cycle experiments. However, it has an effect on the survivability of spirochetes in the arthropod vectors. This is the first report of the role of cheD in the host tissue colonization in any pathogenic bacterium. Delineating the role of cheD in B. burgdorferi will provide insights into not only the chemotaxis pathway of this spirochete, but also its asymmetric swimming and infectious life cycle of the spirochete. Chemotaxis signal transduction systems control bacterial motility. Aside from the chemotaxis pathway, the architectural structure of the flagellar apparatus is also intimately intertwined with motility and the morphology of B. burgdorferi. Unlike other externally flagellated bacteria, spirochetes possess periplasmic flagella with a unique structural component called the collar. This unique component is located in the periplasmic space and is linked to the flagellar basal body. However, there are no reports regarding the gene(s) encoding for the collar or its function in any bacterium. In the second project of this dissertation, we have identified for the first time a gene, flbB, in any spirochete, and defined its function in motility, cell morphology, periplasmic flagella orientation, and assembly of other flagellar structures. We also demonstrated the mechanism shown as to how the organism tilts their periplasmic flagella toward the cell pole.
C 4 GENE EXPRESSION

C4 plants, including maize, Flaveria, amaranth, sorghum, and an amphibious sedge Eleocharis vivipara, have been employed to elucidate the molecular mechanisms and signaling pathways that control C4 photosynthesis gene expression. Current evidence suggests that pre-existing genes were recruited for the C 4 pathway after acquiring potent and surprisingly diverse regulatory elements. This review emphasizes recent advances in our understanding of the creation of C4 genes, the activities of the C4 gene promoters consisting of synergistic and combinatorial enhancers and silencers, the use of 5 0 and 3 0 untranslated regions for transcriptional and posttranscriptional regulations, and the function of novel transcription factors. The research has also revealed new insights into unique or universal mechanisms underlying cell-type specificity, coordinate nuclear-chloroplast actions, hormonal, metabolic, stress and light responses, and the control of enzymatic activities by phosphorylation and reductive processes.
GST P1-1 polymorphisms do not affect the rate of TELCYTA™ (TLK286) prodrug activation.

Proc Amer Assoc Cancer Res, Volume 45, 2004 3825 TLK286 is a novel glutathione analog cancer prodrug that has shown significant antitumor activity and improved survival in multiple Phase 2 clinical trials in ovarian, breast, non-small cell lung and colorectal cancers. TLK286 is activated by glutathione S-transferase P1-1 (GST P1-1), an enzyme upregulated in many cancers and often over-expressed in tumor cells resistant to chemotherapeutic agents. The activation of TLK286 is catalyzed by GST P1-1 and involves the cleavage of the molecule to release two electophilic moieties, a vinyl sulfone and a phosphorodiamidate, that induce apoptosis mediated through the stress response pathway. Genetic polymorphism of the human GST P1-1 class exists in codons 105 and 114. Two GST P1-1 alleles, designated as GSTP1*A (Ile105/Ala114) and GSTP1*B (Val105/Ala114), account for over 90% occurrence of the polymorphism in the general population. We report the comparison of GST P1-1/Ile105 and GST P1-1/Val105 variants in the activation TLK286. Using HPLC to monitor and quantitate the cleavage of TLK286, both GST P1-1 variants were equally effective in catalyzing the cleavage. These results suggest that individuals with polymorphism at position 105 of GST P1-1 should have similar capability to activate TLK286 to its proapoptotic fragments.
Exposure to HIV-1 Altered CCR7-Mediated Migration of Monocytes: Regulation by PGE2

Monocytes play critical roles in human immunodeficiency virus type1 (HIV-1) pathogenesis. During HIV-1 infection, proinflammatory molecules such as prostaglandin E2 (PGE2) are observed at elevated levels in infected individuals. Mono-Mac-1 cells as well as freshly isolated monocytes were exposed to pseudotyped, R5 or dual tropic HIV-1 particles. CCR7 expression was determined by FACS analysis while chemotaxis assays were performed to show CCR7 functionality. We demonstrated that PGE2 enhanced CCR7 surface expression on monocytes. However, monocytes exposition to R5 or dual tropic HIV-1 particles did not highly modulate surface expression of CCR7. On the other hand, monocytes exposition to HIV-1 impaired the CCR7 dependent migratory capacity to CCL19. The addition of PGE2 to HIV-1-exposed monocytes restored the CCR7 dependent migration to levels similar to PGE2 treated unexposed monocytes. Monocytes acquired a functional responsiveness to CCL19 after exposure to PGE2 only when gp120 is expressed on viral particles. Finally, HIV-1-exposed monocytes that migrated in a Transwell system efficiently transmitted the infection to sensible cells. Collectively, we show that PGE2 is essential for the CCR7-dependent migration of monocytes exposed to HIV-1.
Développement d'une approche markovienne pour l'analyse de l'organisation spatiale des génomes.

Le sequencage a grande echelle a permis d'acceder aux genomes complets de nombreux organismes. Les modeles de Markov caches sont une des methodes probabilistes les plus utilisees pour l'analyse des sequences. L'objectif de ces travaux est de participer a l'analyse de l'organisation et a la comprehension de l'evolution des genomes. Une methode de prediction des isochores adaptee au genome humain a ete developpee. L'originalite de cette approche consiste a identifier des ruptures d'homogeneite des sequences mais surtout leurs causes biologiques, comme l'influence des regions UTRs lors du classement des genes dans un isochore. Cette methode a ensuite ete appliquee au genome du tetraodon, pour lequel l'existence d'une structure en mosaique nouvelle le long de son genome a ete mise en evidence.
Plant‐based compounds with potential as push‐pull stimuli to manage behavior of leaf‐cutting ants

Leaf‐cutting ants are a serious pest of young forestry plantations. Currently, the main control method is the use of broad‐spectrum insecticides, which have a negative effect on non‐target organisms and the environment. In this work, plant‐based compounds were evaluated in laboratory assays with Acromyrmex ambiguus Emery (Hymenoptera: Formicidae) for their potential use as repellent and attractant stimuli to be used in a push‐pull strategy. Farnesol, a sesquiterpene present in many essential oils, was tested as a repellent at doses of 10, 50, and 100 mg. Its distance of action was studied by comparing the repellent effect of farnesol in a situation in which ants had to touch the farnesol in order to reach the food source in comparison to when ants could reach the food source without getting into direct contact with it. Different parts of the orange fruit (pulp and peel) were evaluated and compared as attractants, given that citrus‐based baits are among the most popular attractants used. Results from laboratory bioassays indicated that farnesol is repellent at doses of 50 mg and acts upon contact or at a very short distance. Furthermore, orange pulp was more attractive than the peel, and volatile compounds were highly responsible for the attraction. When both stimuli were tested simultaneously in a laboratory experiment, repellency of farnesol was enhanced in the presence of orange pulp odor. When tested in a field push‐pull experiment, the results also showed a good repellent effect of farnesol as well as an attractant effect of the orange pulp. These results encourage long‐term studies with these substances in a field setting and suggest that repellents can be enhanced by the use of attractants to manage leaf‐cutting ants behavior.
Nucleic acid tests for toxic phytoplankton in Irish waters-phytotest: Marine Strategic RTDI project AT/04/02/02 - research update

Rationale for the project: The Phytotest project is a 3 year collaborative project funded through the Marine Strategic Programme in Advanced Technologies as part of the National Development plan 2000-2006. The project partners include the National Diagnostics Centre at NUI Galway and MI. The overall objective of the project is the development of nucleic acid tests (molecular methods) for the identification of key toxic phytoplankton species in Irish waters. In the final year of the programme the aim is to transfer the molecular methods developed in the project into MI to support their monitoring service. Currently, the monitoring for phytoplankton species in Irish waters is performed by light microscopy which can easily identify some plankton species based on distinctive morphological traits. Other species in particular, Pseudonitzschia spp. and Alexandrium spp. cannot be identified to species level by light microscopy. Identification of these species requires more sophisticated microscopic techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM). These techniques cannot easily be integrated into a routine testing environment. Molecular methods utilise unique information contained within an organism’s genome in order to identify it. This genetic information can be exploited in a range of molecular test platforms enabling microorganisms to be identified to species level. Additionally, there has been a major drive towards the development of highly automated platforms to support molecular tests for high-throughput testing in routine laboratory settings.
Étude du mécanisme de photoprotection lié à l’Orange Carotenoid Protein et ses homologues chez les cyanobactéries

La lumiere est essentielle pour les organismes photosynthetiques qui convertissent l'energie solaire en energie chimique. Cependant, la lumiere devient dangereuse lorsque l'energie qui arrive aux centres reactionnels de l'appareil photosynthetique, est en exces par rapport a l’energie consommee. Dans ce cas, la chaine de transport d'electrons photosynthetiques se reduit et les especes reactives de l'oxygene (ROS) sont accumulees, notamment au niveau des deux photosystemes, PSI et PSII. Les cyanobacteries ont developpe des mecanismes photoprotecteurs qui diminuent l'energie transferee au PSII attenuant ainsi l'accumulation de ROS et les dommages cellulaires, comme l’extinction non-photochimique (NPQcya) induite par la lumiere bleue-verte. La soluble Orange Carotenoide Proteine (OCPo) est essentielle pour ce mecanisme de photoprotection. L'OCP agit comme un senseur de l’intensite lumineuse et un inducteur de la dissipation d'energie des phycobilisomes (PBS), l'antenne extra-membranaire des cyanobacteries. L'OCP est la premiere proteine photo-active a carotenoide connue comme senseur. Une forte lumiere bleue-verte declenche des changements structurels dans l'OCPo qui induisent une forme active, rouge (OCPr). Le domaine N-terminal de l’OCPr, en s’intercalant entre les trimeres externes d’un des cylindres basaux du cœur du PBS, augmente la dissipation thermique de l'energie au niveau de l'antenne. L'OCP possede aussi une autre fonction : l’extinction de l’oxygene singulet, qui protege les cellules du stress oxydatif. Pour recuperer pleinement la capacite de l’antenne en faible lumiere, une deuxieme proteine est necessaire, la "Fluorescence Recovery Protein" (FRP), dont le role est de detacher l’OCPr des PBS et d’accelerer sa reconversion en OCPo inactive. Ce manuscrit est un etat des lieux des connaissances et des dernieres avancees sur le mecanisme de NPQ associe a l'OCP dans les cyanobacteries.
A Study on the Career Aspirations of Undergraduates in Sri Lanka.

Study of career aspirations among undergraduates has become an important topic since undergraduates have been facing numerous challenges after completing their university degree. This study examined the determinants of career aspirations among undergraduates and the key challenges faced by them in choosing one. This study employed the mono method approach in the mixed method and so qualitative data were collected from 20 undergraduates from 04 universities and from 03 graduates who had passed out to conduct case studies based on their success stories; the findings from the semi-structured interviews were then analyzed and validated through thematic analysis. This study found that subjective norms, behaviour, and individual attitude were the factors that determined the career aspirations of undergraduates in Sri Lanka. Thus, the key issues that influenced the career aspirations of undergraduates were identified. This research provides significant insights into this matter for policymakers and decision makers working on reforms to the university education system of the Island so that the universities can contribute more meaningfully towards the career development of undergraduates.