116 research outputs found

    UÄŤinkovitost u zadacima fine motorike i prostornih odnosa tijekom menstrualnog ciklusa

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    Various studies have shown fl uctuations in task performance during the menstrual cycle. The aim of this study was to see the effects of the menstrual cycle on performing fi ne motor and spatial tasks of different level of complexity in twenty students aged 18 to 21 years, with regular menstrual cycle (28 to 30 days). The students performed O’Connor Finger Dexterity Test and mental rotation test during the menstrual, late follicular, and midluteal phase. Before the tests were performed, we administered Spielberger’s State-Trait Anxiety Inventory for each phase. After the tasks were completed, the subjects ranked their diffi culty on Borg’s scale. The results showed the best performance in both tests in the midluteal phase (with sex hormones at their peak). The anxiety level and task diffi culty ranking were the highest in the menstrual phase, when the hormone levels were the lowest.Različita su istraživanja pokazala promjene učinkovitosti tijekom menstrualnog ciklusa. U zadacima u kojima su uspješnije žene, najveća učinkovitost događa se tijekom kasne folikularne ili srednje lutealne faze. U zadacima u kojima su pak uspješniji muškarci najveća je učinkovitost nađena u menstrualnoj fazi. Na osnovi uporabe zadataka fi ne motorike i prostornih zadataka različitih razina kompleksnosti, cilj ovog istraživanja bio je ispitati utjecaj menstrualnog ciklusa na kognitivne funkcije. U istraživanju je sudjelovalo dvadeset ispitanica, dobi od 18 do 21 godinu, s redovitim menstrualnim ciklusima (28 do 30 dana). Ispitanice su izvodile O’Connorov deksterimetar i zadatke mentalne rotacije tijekom menstrualne, kasne folikularne i srednje lutealne faze. Prije izvođenja zadataka, u svakoj fazi ciklusa primijenjen je Spielbergerov upitnik stanja anksioznosti. Nakon izvođenja zadataka, ispitanice su procjenjivale njihovu težinu na Borgovoj skali. Rezultati su pokazali najbolju učinkovitost u oba zadatka u fazi visokih razina spolnih hormona (srednja lutealna faza). Stanje anksioznosti i procijenjene težine zadataka bili su najviši u menstrualnoj fazi, kada su razine spolnih hormona najniže

    miR-125b Promotes Early Germ Layer Specification through Lin28/let-7d and Preferential Differentiation of Mesoderm in Human Embryonic Stem Cells

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    Unlike other essential organs, the heart does not undergo tissue repair following injury. Human embryonic stem cells (hESCs) grow indefinitely in culture while maintaining the ability to differentiate into many tissues of the body. As such, they provide a unique opportunity to explore the mechanisms that control human tissue development, as well as treat diseases characterized by tissue loss, including heart failure. MicroRNAs are small, non-coding RNAs that are known to play critical roles in the regulation of gene expression. We profiled the expression of microRNAs during hESC differentiation into myocardial precursors and cardiomyocytes (CMs), and determined clusters of human microRNAs that are specifically regulated during this process. We determined that miR-125b overexpression results in upregulation of the early cardiac transcription factors, GATA4 and Nkx2-5, and accelerated progression of hESC-derived myocardial precursors to an embryonic CM phenotype. We used an in silico approach to identify Lin28 as a target of miR-125b, and validated this interaction using miR-125b knockdown. Anti-miR-125b inhibitor experiments also showed that miR-125b controls the expression of miRNA let-7d, likely through the negative regulatory effects of Lin28 on let-7. We then determined that miR-125b overexpression inhibits the expression of Nanog and Oct4 and promotes the onset of Brachyury expression, suggesting that miR-125b controls the early events of human CM differentiation by inhibiting hESC pluripotency and promoting mesodermal differentiation. These studies identified miR-125b as an important regulator of hESC differentiation in general, and the development of hESC-derived mesoderm and cardiac muscle in particular. Manipulation of miR-125b-mediated pathways may provide a novel approach to directing the differentiation of hESC-derived CMs for cell therapy applications

    Validation of <i>N</i>-myristoyltransferase as Potential Chemotherapeutic Target in Mammal-Dwelling Stages of <i>Trypanosoma cruzi</i>

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    BACKGROUND:Trypanosoma cruzi causes Chagas disease, an endemic and debilitating illness in Latin America. Lately, owing to extensive population movements, this neglected tropical disease has become a global health concern. The two clinically available drugs for the chemotherapy of Chagas disease have rather high toxicity and limited efficacy in the chronic phase of the disease, and may induce parasite resistance. The development of new anti-T. cruzi agents is therefore imperative. The enzyme N-myristoyltransferase (NMT) has recently been biochemically characterized, shown to be essential in Leishmania major, Trypanosoma brucei, and T. cruzi¸ and proposed as promising chemotherapeutic target in these trypanosomatids. METHODOLOGY/PRINCIPAL FINDINGS:Here, using high-content imaging we assayed eight known trypanosomatid NMT inhibitors, against mammal-dwelling intracellular amastigote and trypomastigote stages and demonstrated that three of them (compounds 1, 5, and 8) have potent anti-proliferative effect at submicromolar concentrations against T. cruzi, with very low toxicity against human epithelial cells. Moreover, metabolic labeling using myristic acid, azide showed a considerable decrease in the myristoylation of proteins in parasites treated with NMT inhibitors, providing evidence of the on-target activity of the inhibitors. CONCLUSIONS/SIGNIFICANCE:Taken together, our data point out to the potential use of NMT inhibitors as anti-T. cruzi chemotherapy

    Zebrafish: a vertebrate tool for studying basal body biogenesis, structure, and function.

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    Understanding the role of basal bodies (BBs) during development and disease has been largely overshadowed by research into the function of the cilium. Although these two organelles are closely associated, they have specific roles to complete for successful cellular development. Appropriate development and function of the BB are fundamental for cilia function. Indeed, there are a growing number of human genetic diseases affecting ciliary development, known collectively as the ciliopathies. Accumulating evidence suggests that BBs establish cell polarity, direct ciliogenesis, and provide docking sites for proteins required within the ciliary axoneme. Major contributions to our knowledge of BB structure and function have been provided by studies in flagellated or ciliated unicellular eukaryotic organisms, specifically Tetrahymena and Chlamydomonas. Reproducing these and other findings in vertebrates has required animal in vivo models. Zebrafish have fast become one of the primary organisms of choice for modeling vertebrate functional genetics. Rapid ex-utero development, proficient egg laying, ease of genetic manipulation, and affordability make zebrafish an attractive vertebrate research tool. Furthermore, zebrafish share over 80 % of disease causing genes with humans. In this article, we discuss the merits of using zebrafish to study BB functional genetics, review current knowledge of zebrafish BB ultrastructure and mechanisms of function, and consider the outlook for future zebrafish-based BB studies

    Membrane Cholesterol Regulates Lysosome-Plasma Membrane Fusion Events and Modulates Trypanosoma cruzi Invasion of Host Cells

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    Trypanosoma cruzi, is the etiological agent of a neglected tropical malady known as Chagas' disease, which affects about 8 million people in Latin America. 30–40% of affected individuals develop a symptomatic chronic infection, with cardiomyopathy being the most prevalent condition. T. cruzi utilizes an interesting strategy for entering cells: T. cruzi enhances intracellular calcium levels, which in turn trigger the exocytosis of lysosomal contents. Lysosomes then donate their membrane for the formation of the parasitophorous vacuole. Membrane rafts, cholesterol-enriched microdomains in the host cell plasma membrane, have also been implicated in T. cruzi invasion process. Since both plasma membrane and lysosomes collaborate in parasite invasion, we decided to study the importance of these membrane domains for lysosomal recruitment and fusion during T. cruzi invasion into host cells. Our results show that drug dependent depletion of plasma membrane cholesterol changes raft organization and induces excessive lysosome exocytosis in the earlier stages of treatment, leading to a depletion of lysosomes near the cell cortex, which in turn compromises T. cruzi invasion. Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events of pre-docked lysosomes, reducing lysosome availability at the cell cortex and consequently compromising T. cruzi infection

    Isolation and Characterization of Novel Murine Epiphysis Derived Mesenchymal Stem Cells

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    BACKGROUND: While bone marrow (BM) is a rich source of mesenchymal stem cells (MSCs), previous studies have shown that MSCs derived from mouse BM (BMMSCs) were difficult to manipulate as compared to MSCs derived from other species. The objective of this study was to find an alternative murine MSCs source that could provide sufficient MSCs. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we described a novel type of MSCs that migrates directly from the mouse epiphysis in culture. Epiphysis-derived MSCs (EMSCs) could be extensively expanded in plastic adherent culture, and they had a greater ability for clonogenic formation and cell proliferation than BMMSCs. Under specific induction conditions, EMSCs demonstrated multipotency through their ability to differentiate into adipocytes, osteocytes and chondrocytes. Immunophenotypic analysis demonstrated that EMSCs were positive for CD29, CD44, CD73, CD105, CD166, Sca-1 and SSEA-4, while negative for CD11b, CD31, CD34 and CD45. Notably, EMSCs did not express major histocompatibility complex class I (MHC I) or MHC II under our culture system. EMSCs also successfully suppressed the proliferation of splenocytes triggered by concanavalin A (Con A) or allogeneic splenocytes, and decreased the expression of IL-1, IL-6 and TNF-α in Con A-stimulated splenocytes suggesting their anti-inflammatory properties. Moreover, EMSCs enhanced fracture repair, ameliorated necrosis in ischemic skin flap, and improved blood perfusion in hindlimb ischemia in the in vivo experiments. CONCLUSIONS/SIGNIFICANCES: These results indicate that EMSCs, a new type of MSCs established by our simple isolation method, are a preferable alternative for mice MSCs due to their better growth and differentiation potentialities

    Revitalisierung von Fliessgewässern in Grundwasserschutzgebieten - ein Oxymoron

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    Renaturierung der Wiese im Gebiet Lange Erlen in Riehen/Base

    Masquerading acidosis after cardiopulmonary bypass: a case of propionic acidemia and congenital heart disease.

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    We report the case of a child with both propionic acidemia and cyanotic congenital heart disease. The presence of an underlying inborn error of metabolism confounded the management of this patient in the postoperative period, resulting in therapeutic misdirection until the true etiology of hyperlactemia was recognized
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