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Emilia Krypotou Vasiliki Kosti Sotiris Amillis Vassilios Myrianthopoulos Emmanuel Mikros George Diallinas 《The Journal of biological chemistry》2012,287(44):36792-36803
The recent elucidation of crystal structures of a bacterial member of the NCS1 family, the Mhp1 benzyl-hydantoin permease from Microbacterium liquefaciens, allowed us to construct and validate a three-dimensional model of the Aspergillus nidulans purine-cytosine/H+ FcyB symporter. The model consists of 12 transmembrane α-helical, segments (TMSs) and cytoplasmic N- and C-tails. A distinct core of 10 TMSs is made of two intertwined inverted repeats (TMS1–5 and TMS6–10) that are followed by two additional TMSs. TMS1, TMS3, TMS6, and TMS8 form an open cavity that is predicted to host the substrate binding site. Based on primary sequence alignment, three-dimensional topology, and substrate docking, we identified five residues as potentially essential for substrate binding in FcyB; Ser-85 (TMS1), Trp-159, Asn-163 (TMS3), Trp-259 (TMS6), and Asn-354 (TMS8). To validate the role of these and other putatively critical residues, we performed a systematic functional analysis of relevant mutants. We show that the proposed substrate binding residues, plus Asn-350, Asn-351, and Pro-353 are irreplaceable for FcyB function. Among these residues, Ser-85, Asn-163, Asn-350, Asn-351, and Asn-354 are critical for determining the substrate binding affinity and/or the specificity of FcyB. Our results suggest that Ser-85, Asn-163, and Asn-354 directly interact with substrates, Trp-159 and Trp-259 stabilize binding through π-π stacking interactions, and Pro-353 affects the local architecture of substrate binding site, whereas Asn-350 and Asn-351 probably affect substrate binding indirectly. Our work is the first systematic approach to address structure-function-specificity relationships in a eukaryotic member of NCS1 family by combining genetic and computational approaches. 相似文献
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Katherine Reding Vasiliki Michopoulos Kim Wallen Mar Sanchez Mark E. Wilson Donna Toufexis 《Hormones and behavior》2012
Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions. 相似文献
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Kostas Kampourakis Eirini Palaiokrassa Maria Papadopoulou Vasiliki Pavlidi Myrto Argyropoulou 《Evolution》2012,5(2):279-291
Research has shown that children usually provide teleological explanations for the features of organisms and artifacts, from
a very early age (3–4 years old). However, there is no consensus on whether teleological explanations are given in the same
manner for non-living natural objects as well. The present study aimed to document the teleological explanations of 5- to
8-year-old children for particular features (color and shape) of organisms, artifacts and non-living natural objects. In addition,
it was examined if there was any correlation between these explanations and children’s explanations for the usefulness of
those features. Our results indicate a developmental shift in children’s teleological explanations, from a non-selective teleology
in pre-school to a selective one in the second grade. In the latter case, children provided teleological explanations mostly
for the shape of the feet of organisms and for the shape of artifacts, whereas pre-school children provided teleological explanations
for non-living natural objects as well, both for the color and for the shape in all cases. Our results are not conclusive
and further research is required, including a larger spectrum of students, since teleology is one of the most important conceptual
obstacles in understanding evolution that persists even into adulthood. We conclude by proposing a particular research program
for this purpose. 相似文献
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Bessa V Loukides S Hillas G Delimpoura V Simoes D Kontogianni K Papiris S Kostikas K Alchanatis M Bakakos P 《Cytokine》2012,58(3):455-460
Pathological features of chronic obstructive pulmonary disease (COPD) include lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of angiopoietins in sputum supernatants of patients with COPD and investigated their possible association with mediators and cells involved in the inflammatory and remodeling process. Fifty-nine patients with COPD, 25 healthy smokers and 20 healthy non-smokers were studied. All subjects underwent lung function tests, sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-2 levels were significantly higher in patients with COPD compared to healthy smokers and healthy non-smokers [median, interquartile ranges pg/ml, 267 (147-367) vs. 112 (67-171) and 98 (95-107), respectively; p<0.001]. Regression analysis showed a significant association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in COPD, the strongest being with VEGF. Our results indicate that induced sputum Ang-2 levels are higher in COPD compared to healthy smokers and healthy non-smokers. Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a possible role for Ang-2 in the pathogenesis of the disease. 相似文献
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Marta Coll Chiara Piroddi Camille Albouy Frida Ben Rais Lasram William W. L. Cheung Villy Christensen Vasiliki S. Karpouzi François Guilhaumon David Mouillot Michelle Paleczny Maria Lourdes Palomares Jeroen Steenbeek Pablo Trujillo Reg Watson Daniel Pauly 《Global Ecology and Biogeography》2012,21(4):465-480
Aim A large body of knowledge exists on individual anthropogenic threats that have an impact on marine biodiversity in the Mediterranean Sea, although we know little about how these threats accumulate and interact to affect marine species and ecosystems. In this context, we aimed to identify the main areas where the interaction between marine biodiversity and threats is more pronounced and to assess their spatial overlap with current marine protected areas in the Mediterranean. Location Mediterranean Sea. Methods We first identified areas of high biodiversity of marine mammals, marine turtles, seabirds, fishes and commercial or well‐documented invertebrates. We mapped potential areas of high threat where multiple threats are occurring simultaneously. Finally we quantified the areas of conservation concern for biodiversity by looking at the spatial overlap between high biodiversity and high cumulative threats, and we assessed the overlap with protected areas. Results Our results show that areas with high marine biodiversity in the Mediterranean Sea are mainly located along the central and north shores, with lower values in the south‐eastern regions. Areas of potential high cumulative threats are widespread in both the western and eastern basins, with fewer areas located in the south‐eastern region. The interaction between areas of high biodiversity and threats for invertebrates, fishes and large animals in general (including large fishes, marine mammals, marine turtles and seabirds) is concentrated in the coastal areas of Spain, Gulf of Lions, north‐eastern Ligurian Sea, Adriatic Sea, Aegean Sea, south‐eastern Turkey and regions surrounding the Nile Delta and north‐west African coasts. Areas of concern are larger for marine mammal and seabird species. Main conclusions These areas may represent good candidates for further research, management and protection activities, since there is only a maximum 2% overlap between existing marine protected areas (which cover 5% of the Mediterranean Sea) and our predicted areas of conservation concern for biodiversity. 相似文献
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Michele Hepponstall Vera Ignjatovic Steve Binos Chantal Attard Vasiliki Karlaftis Yves d’Udekem Paul Monagle Igor E. Konstantinov 《PloS one》2015,10(3)