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61.
In protein-protein interaction (PPI) networks certain topological properties appear to be recurrent: network maps are considered scale-free. It is possible that this topology is reflected in the protein structure. In this paper, we investigate the role of protein disorder in the network topology. We find that the disorder of a protein (or of its neighbors) is independent of its number of PPIs. This result suggests that protein disorder does not play a role in the scale-free architecture of protein networks. 相似文献
62.
Laura Lunghi Maria E Ferretti Silvia Medici Carla Biondi Fortunato Vesce 《Reproductive biology and endocrinology : RB&E》2007,5(1):6-14
The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation.
Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane
ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct
trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal
exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the
invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion,
the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation
establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which
the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes
of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications
of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we
describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations
in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory
changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence
such processes may be useful in the prevention and treatment of pregnancy disorders. 相似文献
63.
64.
Morelli MP Cascone T Troiani T Tuccillo C Bianco R Normanno N Romano M Veneziani BM Fontanini G Eckhardt SG De Pacido S Tortora G Ciardiello F 《Journal of cellular physiology》2006,208(2):344-353
PURPOSE: The epidermal growth factor receptor (EGFR) autocrine pathway plays an important role in cancer cell growth. Vascular endothelial growth factor A (VEGF-A) is a key regulator of tumor-induced endothelial cell proliferation and vascular permeability. ZD6474 is an orally available, small molecule inhibitor of VEGF receptor-2 (VEGFR-2), EGFR and RET tyrosine kinase activity. We investigated the activity of ZD6474 in combination with cetuximab, an anti-EGFR blocking monoclonal antibody, to determine the anti-tumor activity of EGFR blockade through the combined use of two agents targeting the receptor at different molecular sites in cancer cells and of VEGFR-2 blockade in endothelial cells. EXPERIMENTAL DESIGN: The anti-tumor activity in vitro and in vivo of ZD6474 and/or cetuximab was tested in human cancer cell lines with a functional EGFR autocrine pathway. RESULTS: The combination of ZD6474 and cetuximab determined synergistic growth inhibition in all cancer cell lines tested as assessed by the Chou and Talalay method. In nude mice bearing established human colon carcinoma (GEO) or lung adenocarcinoma (A549) xenografts and treated with ZD6474 and/or cetuximab for 4 weeks, a reversible tumor growth inhibition was caused by each drug. In contrast, a more significant tumor growth delay resulted from the combination of the two agents with an approximately 100-110 days increase in mice median overall survival as compared to single agent treatment. CONCLUSIONS: This study provides a rationale for evaluating in a clinical setting the double blockade of EGFR in combination with inhibition of VEGFR-2 signaling as cancer therapy. 相似文献
65.
Fortunato F Deng X Gates LK McClain CJ Bimmler D Graf R Whitcomb DC 《American journal of physiology. Gastrointestinal and liver physiology》2006,290(2):G232-G241
Chronic alcohol consumption is known to increase the susceptibility to acute and chronic pancreatitis, and it is likely that a cofactor is required to initiate the progression to alcoholic pancreatitis. The severity and complications of alcoholic and nonalcoholic acute pancreatitis may be influenced by a number of cofactors, including endotoxemia. To explore the effect of a possible cofactor, we used endotoxin [lipopolysaccharide (LPS)] as a tool to induce cellular injury in the alcoholic pancreas. Single, increasing doses of endotoxin were injected in rats fed an alcohol or control diet and killed 24 h after the injection. We examined the mechanism by which LPS exacerbates pancreatic injury in alcohol-fed rats and whether the injury is associated with apoptosis or necrosis. We showed that chronic alcohol exposure alone inhibits apoptosis through the intrinsic pathway and the downstream apoptosis executor caspase-3 compared with the controls. Pancreatic necrosis and inflammation increased after LPS injection in control and alcohol-fed rats in a dose-dependent fashion but with a significantly greater response in the alcohol-fed animals. Caspase activities and TdT-mediated dUTP nick-end labeling positivity were lower in the alcoholic pancreas injected with LPS, whereas the histopathology and inflammation were more severe compared with the control-fed animals. Assessment of a putative indicator of necrosis, the ratio of ADP to ATP, indicated that alcohol exposure accelerates pancreatic necrosis in response to endotoxin. These findings suggest that the pancreas exposed to alcohol is more sensitive to LPS-induced damage because of increased sensitivity to necrotic cell death rather than apoptotic cell death. Similar to the liver, the pancreas is capable of responding to LPS with a more severe response in alcohol-fed animals, favoring pancreatic necrosis rather than apoptosis. We speculate that this mechanism may occur in acute alcoholic pancreatitis patients. 相似文献
66.
Ethnic differences in key candidate genes for spontaneous preterm birth: TNF-alpha and its receptors
Menon R Velez DR Thorsen P Vogel I Jacobsson B Williams SM Fortunato SJ 《Human heredity》2006,62(2):107-118
OBJECTIVES: Spontaneous preterm birth (PTB) has a significant ethnic disparity with people of African descent having an almost 2-fold higher incidence than those of European descent in the United States. This disparity may be caused by differences in the distribution of genetic risk factors. The objective of this study is to examine genetic differences between African-Americans and European Americans for single nucleotide polymorphisms (SNPs) in candidate genes for PTB. METHODS: We examined patterns of variation in 19 SNPs in 3 candidate genes for preterm birth: TNF-alpha, TNF-receptor 1 and TNF-receptor 2. Allele, genotype and haplotype frequencies were compared between African-Americans (AA) and European-Americans (EA) in cases and controls separately. Both maternal and fetal genotypes were studied, as it is unclear whether one or both of these are important in the etiology of PTB. RESULTS: The vast majority of the SNPs differed significantly between ethnic groups, although there are only a few suggestive results comparing cases and controls within an ethnic group. For TNF-alpha, four of six SNPs; for TNF-R1, 5/6; and for TNF-R2, 6/7 showed significant differences between ethnic groups in either allele and/or genotype frequency. CONCLUSIONS: Our data demonstrate highly significant genetic differences between ethnic groups in genes that may play a role in the risk of PTB. 相似文献
67.
Angelo Fortunato 《Journal of Insect Behavior》2009,22(1):49-53
Male ornaments are predicted to be a signal of the genetic quality of a male but often the relationship between ornaments
and the physiological performances of males is unclear. Males of Metichnogaster cillipennis, a hover-wasp, during their courtship flights send luminous signals to females by using two abdominal reflectors. Malpighian
tubules, an essential organ in the physiology of insects, participate in the building of the larger of these reflectors but
at a physiological cost. By evaluating the capacity of light reflection from males during their courtship, females can assess
directly the physiological quality of males. 相似文献
68.
Fortunato L Jordan F 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1559):3913-3922
Accurate reconstruction of prehistoric social organization is important if we are to put together satisfactory multidisciplinary scenarios about, for example, the dispersal of human groups. Such considerations apply in the case of Indo-European and Austronesian, two large-scale language families that are thought to represent Neolithic expansions. Ancestral kinship patterns have mostly been inferred through reconstruction of kin terminologies in ancestral proto-languages using the linguistic comparative method, and through geographical or distributional arguments based on the comparative patterns of kin terms and ethnographic kinship 'facts'. While these approaches are detailed and valuable, the processes through which conclusions have been drawn from the data fail to provide explicit criteria for systematic testing of alternative hypotheses. Here, we use language trees derived using phylogenetic tree-building techniques on Indo-European and Austronesian vocabulary data. With these trees, ethnographic data and Bayesian phylogenetic comparative methods, we statistically reconstruct past marital residence and infer rates of cultural change between different residence forms, showing Proto-Indo-European to be virilocal and Proto-Malayo-Polynesian uxorilocal. The instability of uxorilocality and the rare loss of virilocality once gained emerge as common features of both families. 相似文献
69.
Background
Community structure is one of the key properties of complex networks and plays a crucial role in their topology and function. While an impressive amount of work has been done on the issue of community detection, very little attention has been so far devoted to the investigation of communities in real networks.Methodology/Principal Findings
We present a systematic empirical analysis of the statistical properties of communities in large information, communication, technological, biological, and social networks. We find that the mesoscopic organization of networks of the same category is remarkably similar. This is reflected in several characteristics of community structure, which can be used as “fingerprints” of specific network categories. While community size distributions are always broad, certain categories of networks consist mainly of tree-like communities, while others have denser modules. Average path lengths within communities initially grow logarithmically with community size, but the growth saturates or slows down for communities larger than a characteristic size. This behaviour is related to the presence of hubs within communities, whose roles differ across categories. Also the community embeddedness of nodes, measured in terms of the fraction of links within their communities, has a characteristic distribution for each category.Conclusions/Significance
Our findings, verified by the use of two fundamentally different community detection methods, allow for a classification of real networks and pave the way to a realistic modelling of networks'' evolution. 相似文献70.