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101.
Reik Löser Jiri Gut Philip J. Rosenthal Maxim Frizler Michael Gütschow Katherine T. Andrews 《Bioorganic & medicinal chemistry letters》2010,20(1):252-255
Azadipeptide nitriles—novel cysteine protease inhibitors—display structure-dependent antimalarial activity against both chloroquine-sensitive and chloroquine-resistant lines of cultured Plasmodium falciparum malaria parasites. Inhibition of parasite’s hemoglobin-degrading cysteine proteases was also investigated, revealing the azadipeptide nitriles as potent inhibitors of falcipain-2 and -3. A correlation between the cysteine protease-inhibiting activity and the antimalarial potential of the compounds was observed. These first generation azadipeptide nitriles represent a promising new class of compounds for antimalarial drug development. 相似文献
102.
Royo H Polikiewicz G Mahadevaiah SK Prosser H Mitchell M Bradley A de Rooij DG Burgoyne PS Turner JM 《Current biology : CB》2010,20(23):2117-2123
The mammalian X and Y chromosomes share little homology and are largely unsynapsed during normal meiosis. This asynapsis triggers inactivation of X- and Y-linked genes, or meiotic sex chromosome inactivation (MSCI). Whether MSCI is essential for male meiosis is unclear. Pachytene arrest and apoptosis is observed in mouse mutants in which MSCI fails, e.g., Brca1(-/-), H2afx(-/-), Sycp1(-/-), and Msh5(-/-). However, these also harbor defects in synapsis and/or recombination and as such may activate a putative pachytene checkpoint. Here we present evidence that MSCI failure is sufficient to cause pachytene arrest. XYY males exhibit Y-Y synapsis and Y chromosomal escape from MSCI without accompanying synapsis/recombination defects. We find that XYY males, like synapsis/recombination mutants, display pachytene arrest and that this can be circumvented by preventing Y-Y synapsis and associated Y gene expression. Pachytene expression of individual Y genes inserted as transgenes on autosomes shows that expression of the Zfy 1/2 paralogs in XY males is sufficient to phenocopy the pachytene arrest phenotype; insertion of Zfy 1/2 on the X chromosome where they are subject to MSCI prevents this response. Our findings show that MSCI is essential for male meiosis and, as such, provide insight into the differential severity of meiotic mutations' effects on male and female meiosis. 相似文献
103.
104.
Wouter Everaerts Bernd Nilius Grzegorz Owsianik 《Progress in biophysics and molecular biology》2010,103(1):2-17
The Transient Receptor Potential Vanilloid 4 channel, TRPV4, is a Ca2+ and Mg2+ permeable non-selective cation channel involved in many different cellular functions. It is activated by a variety of physical and chemical stimuli, including heat, mechano-stimuli, endogenous substances such as arachidonic acid and its cytochrome P450-derived metabolites (epoxyeicosatrienoic acids), endocannabinoids (anandamide and 2-arachidonoylglycerol), as well as synthetic α-phorbol derivatives. Recently, TRPV4 has been characterized as an important player modulating osteoclast differentiation in bone remodelling and as a urothelial mechanosensor that controls normal voiding. Several TRPV4 gain-of-function mutations are shown to cause autosomal-dominant bone dysplasias such as brachyolmia and Koszlowski disease. In this review we comprehensively describe the structural, biophysical and (patho)physiological properties of the TRPV4 channel and we summarize the current knowledge about the role of TRPV4 in the pathogenesis of several diseases. 相似文献
105.
Zbigniew Szybiński Stanisław Walas Paweł Zagrodzki Grzegorz Sokołowski Filip Gołkowski Halina Mrowiec 《Biological trace element research》2010,138(1-3):28-41
The purpose of this work was to determine trace element levels in urine and evaluate possible associations between urinary iodine concentration (UIC), other trace elements (Cr, Cu, Fe, Mn, Na, Se, Zn), toxic elements (Cd, Pb), anthropometrical measures (body weight and height), glycemic indices (serum insulin and glucose), and several parameters related to thyroid function (thyroid stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, thyroid volume, and thyroid echogenicity) in pregnant women. One hundred sixty-nine participants were recruited. The whole study group, originating from Krakow region, comprised three subgroups belonging to three trimesters: I trimester (n?=?28), II trimester (n?=?83), and III trimester (n?=?58). Trace elements were determined using inductively coupled plasma mass/(atomic emission) spectrometry. Partial least square model was used to reveal correlation structure between parameters investigated, as well as a possible causal relationship between dependent parameters and potentially explanatory parameters. Results obtained for trace and toxic elements in urine were comparable with results of other authors, although the study group was not homogenous. We confirmed (1) low iodine excretion in pregnant women, (2) the existence of statistically significant correlation between UIC and urinary selenium, and (3) lack of correlation between latter parameter and typical indices of thyroid function. Urinary selenium correlated with other urinary trace elements, but physiological significance of this finding remains uncertain. The fact that a large number of pregnant women fail to meet dietary recommendations for iodine is the major reason for concern. 相似文献
106.
Andrzej Bunio Renata Szygula Slawomir Tubek Grzegorz Krasowski 《Biological trace element research》2010,136(2):149-156
Environmental factors significantly influence the incidence and course of metabolic syndrome diseases such as diabetes and
obesity. The content of elements in rainwater is an indirect indicator of their presence in dust suspended in the air. In
this paper we present the relationships between the content of selected elements in rainwater and hospitalization frequencies
due to diabetes (E10–E13) and obesity (E66). It was assumed that the hospitalization frequency could be taken as a measure
of deterioration of the metabolic process in the course of diabetes and its complications. The observations concerned the
population of Opole Voivodeship, Poland (one million inhabitants), distributed in small communities of 44,000 to 151,000 inhabitants
during the years 2000–2002. In cases of diabetes E10–E13 for all subjects relevant correlation indicators were found for chromium
(r = 0.71), cadmium (r = 0.65), and lead (r = 0.66). Borderline relevance was seen for copper (r = 0.57) and zinc (r = 056). For diabetic men the statistically relevant correlations were chromium (r = 0.79), lead (r = 0.77), cadmium (r = 0.74), copper (r = 0.70), chloride (r = 0.69), zinc (r = 0.68), and iron (r = 0.64). For women the only relevant correlations were chromium (r = 0.62) and cadmium (r = 0.55). No significant correlations were found in obese individuals of both sexes. 相似文献
107.
Grzegorz Lesiński 《Biologia》2010,65(4):749-753
Percentage of bats in tawny owls’ diet was compared in three periods: I — before 1976, II — 1976–1992, III — 1993–2009, by
using the published and unpublished material from Poland (only samples over 100 vertebrate prey items). This species of owl
showed an opportunistic predation on bats and took them more frequently in periods of higher abundance. Before the mass use
of toxic pesticides in Poland, in the period I bats constituted more than 2% of vertebrates in four out of five diet samples
(median 2.4%). The lowest bat abundance occurred in Poland in the 1980s and resulted in the lowest percentage of bats taken
by owls in the period II (n = 11, median 0.2%). Due to the recovery of bat populations in the period III, the percentage of bats in tawny owls’ diet
increased (n = 23, median 0.7%). In large samples (over 200 vertebrate items, n = 21) collected in central and north-eastern Poland the percentage of bats increased from 1980 to 2009 (the estimated average
value at the end of that period slightly exceeded 1%). Samples collected at the same five sites in 1975–1992 and again in
2000–2009, confirmed the increasing trend in percentage of bats captured by tawny owls noted in last years. 相似文献
108.
Bielawska-Drózd A Niemcewicz M Gaweł J Bartoszcze M Graniak G Joniec J Kołodziej M 《Medycyna do?wiadczalna i mikrobiologia》2010,62(4):351-360
Tularemia is highly infectious and fatal zoonotic disease caused by Gram negative bacteria Francisella tularensis. The necessity to undergo medical treatment in early phase of illness in humans and possibility of making use of bacterial aerosol by terrorists in an attack create an urgent need to implement a rapid and effective method which enables to identify the agent. In our study two primers FopA F/R and hybridization probes FopA S1/S2 designed from fopA gene sequence, were tested for their potential applicability to identify F. tularensis. In this research 50 strains of F. tularensis were used and the test gave positive results. Reaction specificity was confirmed by using of non-Francisella tularensis bacterial species. The results obtained in the real-time PCR reaction with primers Tul4 F/R and hybridization probes Tul4 S1/S2, designed from tul4 gene, were comparable to the results from previous experiment with fopA - primers set. Investigation of fopA and tul4 primers and hybridization probes properties revealed characteristic Tm (melting temperature) value of the products--61 degrees C and 60 degrees C, respectively. Detection sensitivity was remarkably higher when fopA primers set was used 1 fg/microl, and for tul4 primers set, minimal detectable concentration is 10 fg/microl. 相似文献
109.
Dennis R LaJeunesse Brooke Johnson Jason S Presnell Kathleen Kay Catignas Grzegorz Zapotoczny 《BMC physiology》2010,10(1):14
Background
The underlying cellular and molecular mechanisms that coordinate the physiological processes in digestion are complex, cryptic, and involve the integration of multiple cellular and organ systems. In all intestines, peristaltic action of the gut moves food through the various stages of digestion from the anterior end towards the posterior, with the rate of flow dependent on signals, both intrinsic and extrinsic to the gut itself. 相似文献110.
Adrian Doroszko Thomas S Hurst Dorota Polewicz Jolanta Sawicka Justyna Fert-Bober David H Johnson Grzegorz Sawicki 《Proteome science》2010,8(1):3