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61.
62.
Kristin L. Leimgruber Adrian F. Ward Jane Widness Michael I. Norton Kristina R. Olson Kurt Gray Laurie R. Santos 《PloS one》2014,9(1)
The breadth of human generosity is unparalleled in the natural world, and much research has explored the mechanisms underlying and motivating human prosocial behavior. Recent work has focused on the spread of prosocial behavior within groups through paying-it-forward, a case of human prosociality in which a recipient of generosity pays a good deed forward to a third individual, rather than back to the original source of generosity. While research shows that human adults do indeed pay forward generosity, little is known about the origins of this behavior. Here, we show that both capuchin monkeys (Cebus apella) and 4-year-old children pay forward positive and negative outcomes in an identical testing paradigm. These results suggest that a cognitively simple mechanism present early in phylogeny and ontogeny leads to paying forward positive, as well as negative, outcomes. 相似文献
63.
A novel approach to DNase I-sensitivity analysis was applied to examining genes of the spermatogenic pathway, reflective of
the substantial morphological and genomic changes that occur during this program of differentiation. A new real-time PCR-based
strategy that considers the nuances of response to nuclease treatment was used to assess the nuclease susceptibility through
differentiation. Data analysis was automated with the K-Lab PCR algorithm, facilitating the rapid analysis of multiple samples
while eliminating the subjectivity usually associated with Ct analyses. The utility of this assay and analytical paradigm as applied to nuclease-sensitivity mapping is presented. 相似文献
64.
Munguia-Vega A Esquer-Garrigos Y Rojas-Bracho L Vazquez-Juarez R Castro-Prieto A Flores-Ramirez S 《Molecular ecology》2007,16(19):4051-4065
Although many studies confirm long-term small isolated populations (e.g. island endemics) commonly sustain low neutral genetic variation as a result of genetic drift, it is less clear how selection on adaptive or detrimental genes interplay with random forces. We investigated sequence variation at two major histocompatibility complex (Mhc) class II loci on a porpoise endemic to the upper Gulf of California, México (Phocoena sinus, or vaquita). Its unique declining population is estimated around 500 individuals. Single-strand conformation polymorphism analysis revealed one putative functional allele fixed at the locus DQB (n = 25). At the DRB locus, we found two presumed functional alleles (n = 29), differing by a single nonsynonymous nucleotide substitution that could increase the stability at the dimer interface of alphabeta-heterodimers on heterozygous individuals. Identical trans-specific DQB1 and DRB1 alleles were identified between P. sinus and its closest relative, the Burmeister's porpoise (Phocoena spinipinnis). Comparison with studies on four island endemic mammals suggests fixation of one allele, due to genetic drift, commonly occurs at the DQA or DQB loci (effectively neutral). Similarly, deleterious alleles of small effect are also effectively neutral and can become fixed; a high frequency of anatomical malformations on vaquita gave empirical support to this prediction. In contrast, retention of low but functional polymorphism at the DRB locus was consistent with higher selection intensity. These observations indicated natural selection could maintain (and likely also purge) some crucial alleles even in the face of strong and prolonged genetic drift and inbreeding, suggesting long-term small populations should display low inbreeding depression. Low levels of Mhc variation warn about a high susceptibility to novel pathogens and diseases in vaquita. 相似文献
65.
Dellagi K Rollot O Temmam S Salez N Guernier V Pascalis H Gérardin P Fianu A Lapidus N Naty N Tortosa P Boussaïd K Jaffar-Banjee MC Filleul L Flahault A Carrat F Favier F de Lamballerie X 《PloS one》2011,6(9):e25738
Background
To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season.Methodology/Principal Findings
A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive.Conclusions
Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses. 相似文献66.
Refolding, purification, and crystallization of apical membrane antigen 1 from Plasmodium falciparum
Gupta A Bai T Murphy V Strike P Anders RF Batchelor AH 《Protein expression and purification》2005,41(1):186-198
Extracellular domains of malaria antigens almost invariably contain disulphide linkages but lack N- and O-linked glycosylation. The best practical approach to generating recombinant extracellular Plasmodium proteins is not established and the problems encountered when using a bacterial expression/refolding approach are discussed in detail. Limited proteolysis experiments were used to identify a relatively non-flexible core region of the Plasmodium falciparum protein apical membrane antigen 1 (AMA1), and refolding/purification was used to generate two fragments of AMA1. Several chromatographically distinct AMA1 variants were identified that are presumably differentially refolded proteins. One of these AMA1 preparations proved to be crystallizable and generated two crystal forms that diffracted X-rays to 2 A resolution. 相似文献
67.
Madsen PP Kibaek M Roca X Sachidanandam R Krainer AR Christensen E Steiner RD Gibson KM Corydon TJ Knudsen I Wanders RJ Ruiter JP Gregersen N Andresen BS 《Human genetics》2006,118(6):680-690
Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of l-isoleucine catabolism. Little is known about the clinical presentation associated with this enzyme defect, as it has been
reported in only a limited number of patients. Because the presence of C5-carnitine in blood may indicate SBCADD, the disorder
may be detected by MS/MS-based routine newborn screening. It is, therefore, important to gain more knowledge about the clinical
presentation and the mutational spectrum of SBCADD. In the present study, we have studied two unrelated families with SBCADD,
both with seizures and psychomotor delay as the main clinical features. One family illustrates the fact that affected individuals
may also remain asymptomatic. In addition, the normal level of newborn blood spot C5-acylcarnitine in one patient underscores
the fact that newborn screening by MS/MS currently lacks sensitivity in detecting SBCADD. Until now, seven mutations in the SBCAD gene have been reported, but only three have been tested experimentally. Here, we identify and characterize an IVS3+3A>G
mutation (c.303+3A>G) in the SBCAD gene, and provide evidence that this mutation is disease-causing in both families. Using a minigene approach, we show that
the IVS3+3A>G mutation causes exon 3 skipping, despite the fact that it does not appear to disrupt the consensus sequence
of the 5′ splice site. Based on these results and numerous literature examples, we suggest that this type of mutation (IVS+3A>G)
induces missplicing only when in the context of non-consensus (weak) 5′ splice sites. Statistical analysis of the sequences
shows that the wild-type versions of 5′ splice sites in which +3A>G mutations cause exon skipping and disease are weaker on
average than a random set of 5′ splice sites. This finding is relevant to the interpretation of the functional consequences
of this type of mutation in other disease genes. 相似文献
68.
69.
Lila M. Landowski Macarena Pavez Lachlan S. Brown Robert Gasperini Bruce V. Taylor Adrian K. West Lisa Foa 《The Journal of biological chemistry》2016,291(3):1092-1102
The low-density lipoprotein receptor-related protein receptors 1 and 2 (LRP1 and LRP2) are emerging as important cell signaling mediators in modulating neuronal growth and repair. We examined whether LRP1 and LRP2 are able to mediate a specific aspect of neuronal growth: axon guidance. We sought to identify LRP1 and LRP2 ligands that could induce axonal chemoattraction, which might have therapeutic potential. Using embryonic sensory neurons (rat dorsal root ganglia) in a growth cone turning assay, we tested a range of LRP1 and LRP2 ligands for the ability to guide growth cone navigation. Three ligands were chemorepulsive: α-2-macroglobulin, tissue plasminogen activator, and metallothionein III. Conversely, only one LRP ligand, metallothionein II, was found to be chemoattractive. Chemoattraction toward a gradient of metallothionein II was calcium-dependent, required the expression of both LRP1 and LRP2, and likely involves further co-receptors such as the tropomyosin-related kinase A (TrkA) receptor. The potential for LRP-mediated chemoattraction to mediate axonal regeneration was examined in vivo in a model of chemical denervation in adult rats. In these in vivo studies, metallothionein II was shown to enhance epidermal nerve fiber regeneration so that it was complete within 7 days compared with 14 days in saline-treated animals. Our data demonstrate that both LRP1 and LRP2 are necessary for metallothionein II-mediated chemotactic signal transduction and that they may form part of a signaling complex. Furthermore, the data suggest that LRP-mediated chemoattraction represents a novel, non-classical signaling system that has therapeutic potential as a disease-modifying agent for the injured peripheral nervous system. 相似文献
70.