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81.
Kethika Kulleperuma Susan M.E. Smith Deri Morgan Boris Musset John Holyoake Nilmadhab Chakrabarti Vladimir V. Cherny Thomas E. DeCoursey Régis Pomès 《The Journal of general physiology》2013,141(4):445-465
The topological similarity of voltage-gated proton channels (HV1s) to the voltage-sensing domain (VSD) of other voltage-gated ion channels raises the central question of whether HV1s have a similar structure. We present the construction and validation of a homology model of the human HV1 (hHV1). Multiple structural alignment was used to construct structural models of the open (proton-conducting) state of hHV1 by exploiting the homology of hHV1 with VSDs of K+ and Na+ channels of known three-dimensional structure. The comparative assessment of structural stability of the homology models and their VSD templates was performed using massively repeated molecular dynamics simulations in which the proteins were allowed to relax from their initial conformation in an explicit membrane mimetic. The analysis of structural deviations from the initial conformation based on up to 125 repeats of 100-ns simulations for each system reveals structural features consistently retained in the homology models and leads to a consensus structural model for hHV1 in which well-defined external and internal salt-bridge networks stabilize the open state. The structural and electrostatic properties of this open-state model are compatible with proton translocation and offer an explanation for the reversal of charge selectivity in neutral mutants of Asp112. Furthermore, these structural properties are consistent with experimental accessibility data, providing a valuable basis for further structural and functional studies of hHV1. Each Arg residue in the S4 helix of hHV1 was replaced by His to test accessibility using Zn2+ as a probe. The two outermost Arg residues in S4 were accessible to external solution, whereas the innermost one was accessible only to the internal solution. Both modeling and experimental data indicate that in the open state, Arg211, the third Arg residue in the S4 helix in hHV1, remains accessible to the internal solution and is located near the charge transfer center, Phe150. 相似文献
82.
Nil Rahola Jér?me Depaquit Boris Kevin Makanga Christophe Paupy 《Memórias do Instituto Oswaldo Cruz》2013,108(7):845-849
During a research project aimed at the study of the Culicinae fauna of Gabon and
carried out in the National Park of La Lopé, we captured an unknown sandfly male
specimen (genus Phlebotomus) by CDC miniature light trap
belonging to a new species for Science. Furthermore, the originality of his
genitalia does not allow us to include this species in one of the existing
subgenus, thus in this paper we propose the creation of a new subgenus, as
Phlebotomus (Legeromyia) multihamatus sp. nov., subg. nov.
described from the National Park of La Lopé, through one male captured with CDC
miniature light trap. A new species and a new subgenus of sandfly is
characterised by a short style with three spines, a paramere wearing a basal
hook as well as a basal pouch and the absence of basal lobe on the coxite. The
originality of the genitalia of the male gives way to discussion about potential
primary homologies between P. multihamatus sp. nov. and
Phlebotomus (Abonnencius) fortunatarum, Phlebotomus
(Anaphlebotomus) stantoni and Phlebotomus (Euphlebotomus)
argentipes, which should be verified for future studies. The
discovery of this new species in Gabon must encourage the study of sandflies in
this country. 相似文献
83.
Pedro X. Astudillo Gabriela M. Samaniego Pedro J. Machado Juan M. Aguilar Boris A. Tinoco Catherine H. Graham 《Studies on Neotropical Fauna and Environment》2013,48(3):204-212
National parks are an important tool for conserving biodiversity, particularly in areas of high biodiversity and endemism such as the tropical Andes. However, national parks often face a variety of stressors related to recreation, road construction and illegal extraction of natural resources. Unfortunately, the influence of these stressors for biodiversity is rarely well documented. Cajas National Park in Ecuador is no exception. Despite being traversed by the Cuenca-Molleturo-Naranjal road, effects of the road construction on biodiversity have not been determined. We therefore assessed the influence of road proximity on bird species richness and abundance as well as composition of bird habitat groups in Cajas National Park using transect walks at 25 m and 250 m distance to the road (overall 18 transects, each 1 km length). In total, we recorded 1110 individuals of 28 páramo bird species. Overall species richness did not differ between transects near and far from the road. Nevertheless, the average abundance of shrubby páramo species was significantly higher far from the road than near the road (Far = 36, Near = 25). Moreover, we found a tendency towards differences in the composition of bird habitat groups between transects near and far from the road. One aspect potentially driving the observed patterns was the increasing proportion of planted non-native woody tree species within páramo grassland near the road, which may have caused reduced abundances of shrubby páramo bird species there. While roads represented a clear impact on the composition of bird species in the páramo, the major effect seems to be driven by the introduction of non-native plant species along the roadside. In order to reduce the impact of roads to a minimum, we suggest that park managers should control the introduction of such plant species. 相似文献
84.
Veronika Slancarova Jana Zdanska Bohuslav Janousek Martina Talianova Christian Zschach Jitka Zluvova Jiri Siroky Viera Kovacova Hana Blavet Jiri Danihelka Bengt Oxelman Alex Widmer Boris Vyskot 《Evolution; international journal of organic evolution》2013,67(12):3669-3677
The plant genus Silene has become a model for evolutionary studies of sex chromosomes and sex‐determining mechanisms. A recent study performed in Silene colpophylla showed that dioecy and the sex chromosomes in this species evolved independently from those in Silene latifolia, the most widely studied dioecious Silene species. The results of this study show that the sex‐determining system in Silene otites, a species related to S. colpophylla, is based on female heterogamety, a sex determination system that is unique among the Silene species studied to date. Our phylogenetic data support the placing of S. otites and S. colpophylla in the subsection Otites and the analysis of ancestral states suggests that the most recent common ancestor of S. otites and S. colpophylla was most probably dioecious. These observations imply that a switch from XX/XY sex determination to a ZZ/ZW system (or vice versa) occurred in the subsection Otites. This is the first report of two different types of heterogamety within one plant genus of this mostly nondioecious plant family. 相似文献
85.
Jan Zima Atilla Arslan Petr Benda Miloš Macholán Boris Kryštufek 《Acta theriologica》2013,58(3):255-265
The study reports on chromosomes in several populations of social voles from south-eastern Europe and the Middle East. The standard karyotypes of individuals of Microtus hartingi and Microtus guentheri originating from both south-eastern Europe and Asia Minor comprised 54 mostly acrocentric chromosomes. However, variation between populations was found in the amount and distribution of C-heterochromatin in certain autosomes and the sex chromosomes. Furthermore, a specific pattern of argyrophilic nucleolar organizer region distribution was recorded in different geographic populations. In a population from Asia Minor, a heterozygous centric fusion of two autosomes was found. The G-banded karyotypes of M. guentheri and Microtus socialis were compared, and tandem fusions of autosomes were suggested as possible mechanism of the divergence. The karyotypes of the nine currently recognized species of social voles are reviewed, and implications of chromosomal data for systematics are evaluated. 相似文献
86.
Primož Treven Kristyna Turkova Aljoša Trmčić Tanja Obermajer Irena Rogelj Bojana Bogovič Matijašić 《Folia microbiologica》2013,58(6):623-630
Lactobacillus gasseri K7 is a probiotic strain that produces bacteriocins gassericin K7 A and K7 B. In order to develop a real-time quantitative PCR assay for the detection of L. gasseri K7, 18 reference strains of the Lactobacillus acidophilus group and 45 faecal samples of adults who have never consumed strain K7 were tested with PCR using 14 pairs of primers specific for gassericin K7 A and K7 B gene determinants. Incomplete gassericin K7 A or K7 B gene clusters were found to be dispersed in different lactobacilli strains as well as in faecal microbiota. One pair of primers was found to be specific for the total gene cluster of gassericin K7A and one for gassericin K7B. The real-time PCR analysis of faecal samples spiked with K7 strain revealed that primers specific for the gene cluster of the gassericin K7 A were more suitable for quantitative determination than those for gassericin K7 B, due to the lower detection level. Targeting of the gassericin K7 A or K7 B gene cluster with specific primers could be used for detection and quantification of L. gasseri K7 in human faecal samples without prior cultivation. The results of this study also present new insights into the prevalence of bacteriocin-encoding genes in gastrointestinal tract. 相似文献
87.
Corey R. Johnson Suresh Kumar Gorla Mandapati Kavitha Minjia Zhang Xiaoping Liu Boris Striepen Jan R. Mead Gregory D. Cuny Lizbeth Hedstrom 《Bioorganic & medicinal chemistry letters》2013,23(4):1004-1007
Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5′-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure–activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented. 相似文献
88.
Guobin Cai Lisheng Deng Jian Xue Silvia N.J. Moreno Boris Striepen Yongcheng Song 《Bioorganic & medicinal chemistry letters》2013,23(7):2158-2161
The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, is an important human pathogen. 1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is essential to the organism and therefore a target for developing anti-toxoplasmosis drugs. In order to find potent inhibitors, we expressed and purified recombinant T. gondii DXR (TgDXR). Biochemical properties of this enzyme were characterized and an enzyme activity/inhibition assay was developed. A collection of 11 compounds with a broad structural diversity were tested against TgDXR and several potent inhibitors were identified with Ki values as low as 48 nM. Analysis of the results as well as those of Escherichia coli and Plasmodium falciparum DXR enzymes revealed a different structure–activity relationship profile for the inhibition of TgDXR. 相似文献
89.
We studied 1140 bp cytochrome b sequences of social voles from three localities in Lebanon. The results were compared with published sequences representing seven species of social voles. New sequences from Lebanon clustered with reference samples of two species: M. guentheri and M. irani. While M. guentheri was already reported for Lebanon, M. irani is a new addition to the fauna of Lebanon, and the third known record for the species. Animals were collected in two localities above Tripolis at 855 m and 1430 m a.s.l., respectively. 相似文献
90.
Malte Lenders Thomas Duning Michael Schelleckes Boris Schmitz Sonja Stander Arndt Rolfs Stefan-Martin Brand Eva Brand 《PloS one》2013,8(2)
White matter lesions (WML) are clinically relevant since they are associated with strokes, cognitive decline, depression, or epilepsy, but the underlying etiology in young adults without classical risk factors still remains elusive. Our aim was to elucidate the possible clinical diagnosis and mechanisms leading to WML in patients carrying the D313Y mutation in the α-galactosidase A (GLA) gene, a mutation that was formerly described as nonpathogenic. Pathogenic GLA mutations cause Fabry disease, a vascular endothelial glycosphingolipid storage disease typically presenting with a symptom complex of renal, cardiac, and cerebrovascular manifestations. We performed in-depths clinical, biochemical and genetic examinations as well as advanced magnetic resonance imaging analyses in a pedigree with the genetically determined GLA mutation D313Y. We detected exclusive neurologic manifestations of the central nervous system of the “pseudo”-deficient D313Y mutation leading to manifest WML in 7 affected adult family members. Furthermore, two family members that do not carry the mutation showed no WML. The D313Y mutation resulted in a normal GLA enzyme activity in leukocytes and severely decreased activities in plasma. In conclusion, our results provide evidence that GLA D313Y is potentially involved in neural damage with significant WML, demonstrating the necessity of evaluating patients carrying D313Y more thoroughly. D313Y might broaden the spectrum of hereditary small artery diseases of the brain, which preferably occur in young adults without classical risk factors. In view of the existing causal therapy regime, D313Y should be more specifically taken into account in these patients. 相似文献