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International Journal of Primatology - The selection of sleeping sites and sleeping trees in nonhuman primates is related to social and ecological factors. We investigate the role of body...  相似文献   
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Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.  相似文献   
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Mechanism of activation of bovine factor XI by factor XII and factor XIIa   总被引:2,自引:0,他引:2  
K Kurachi  K Fujikawa  E W Davie 《Biochemistry》1980,19(7):1330-1338
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Early humans were obligately social, living in nested kin groups or close associations of related individuals. Theoretical and empirical research has demonstrated that group life is characterized by both costs (e.g. increased likelihood of disease transmission) and benefits (e.g. enhanced predator defense). This paper addresses the evolution of exploitation in humans (e.g. slavery, infanticide) as a response to within‐group competition for limiting resources (e.g. food, mates), a potential cost of living in groups. Exploitation is defined as one individual's use of another for selfish ends, in particular, the acquisition and/or use of another's resources for the optimization of inclusive fitness. It is argued that exploitation is most likely to occur in relationships characterized by asymmetries such as dependence, intimacy, and/or differential access to resources. A simple mathematical treatment assesses exploitation as a facultative response to local competition among relatives, providing insights into the conditions favorable and adverse to exploitation of conspecifics. Possible applications of the formulations are discussed, including the conditions under which intraspecific exploitation may be beneficial to both actor and recipient(s). Constraints on the evolution of exploitation in humans are identified, and suggestions are made for testing hypotheses related to the differential costs and benefits of exploitation to conspecifics. Future studies may promote the mitigation of exploitation's deleterious effects in Homo sapiens, a body of research which may apply, as well, to other social mammals.  相似文献   
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Using monoclonal anti-idiotopes with previously defined specificities for the variable (V) domain of HGAC 39, a monoclonal antibody against streptococcal group A carbohydrate (GAC), we have studied the effect of anti-idiotope on an anticarbohydrate immune response. Anti-IdI-3a and anti-IdI-3b are anti-idiotopes which recognize binding site-associated determinants, whereas anti-IdX recognizes a framework-associated determinant on the HGAC 39 V kappa domain. Each of three anti-idiotopes elicited a specific idiotope response, as measured by inhibition radioimmunoassay, in A/J and C57BL/6J mice. A single immunization with conjugated anti-IdI-3a elicited an idiotope(+), GAC-binding(+) response in C57BL/6J and (BALB/c X CBA/N)F1 male mice, but not in A/J or (CBA/N X BALB/c)F1 male, X-linked immunodeficient mice. When C57BL/6J mice immunized initially with anti-idiotope were further treated with group A vaccine, those receiving anti-IdX had the greatest increase in anti-GAC activity. Stimulation of an anticarbohydrate response with anti-idiotope may therefore be enhanced by selecting anti-idiotopes against both binding site- and framework-associated determinants.  相似文献   
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Propeptide of human protein C is necessary for gamma-carboxylation   总被引:7,自引:0,他引:7  
Protein C is one of a family of vitamin K dependent proteins, including blood coagulation factors and bone proteins, that contains gamma-carboxyglutamic acid. Sequence analysis of the cDNAs for these proteins has revealed the presence of a prepro leader sequence that contains a pre sequence or hydrophobic signal sequence and a propeptide containing a number of highly conserved amino acids. The pre region is removed from the growing polypeptide chain by signal peptidase, while the pro region is subsequently removed from the protein prior to secretion. In the present study, deletion mutants have been constructed in the propeptide region of the cDNA for human protein C, and the cDNAs were then expressed in mammalian cell culture. These deletions included the removal of 4, 9, 12, 15, 16, or 17 amino acids comprising the carboxyl end of the leader sequence of 42 amino acids. The mutant proteins were then examined by Western blotting, barium citrate adsorption and precipitation, amino acid sequence analysis, and biological activity and compared with the native protein present in normal plasma. These experiments have shown that protein C is readily synthesized in mammalian cell cultures, processed, and secreted as a two-chain molecule with biological activity. Furthermore, the pre portion or signal sequence in human protein C is 18 amino acids in length, and the pro portion of the leader sequence is 24 amino acids in length. Also, during biosynthesis and secretion, the amino-terminal region of the propeptide (residues from about -12 through -17) is important for gamma-carboxylation of protein C, while the present data and those of others indicate that the carboxyl-terminal portion of the propeptide (residues -1 through -4) is important for the removal of the pro leader sequence by proteolytic processing.  相似文献   
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