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991.
992.
Jaeuk Hwang Jieun E. Kim Marc J. Kaufman Perry F. Renshaw Sujung Yoon Deborah A. Yurgelun-Todd Yera Choi Chansoo Jun In Kyoon Lyoo 《PloS one》2013,8(10)
Objective
Adolescent-onset exposure to highly addictive substances such as opiates may induce far-reaching deleterious effects on later mental and physical health. However, little is known about the neurodevelopmental basis for adolescent-onset opiate dependence. Here we examined whether having an abnormally large cavum septum pellucidum (CSP), a putative marker of limbic structural maldevelopment, is associated with opiate dependence particularly beginning in adolescence.Method
The overall length of the CSP and the prevalence of abnormal enlargement of the CSP were assessed and compared in 65 opiate-dependent subjects (41 adolescent-onset opiate users and 24 adult-onset opiate users) and 67 healthy subjects.Results
Opiate-dependent subjects showed a greater prevalence of abnormal CSP enlargement relative to healthy subjects (odds ratio [OR]=3.64, p=0.034). The overall CSP length of adolescent-onset opiate-dependent subjects was greater, as compared not only with healthy subjects (F1,104=11.03, p=0.001) but also with those who began opiate use during adulthood (F1,61=4.43, p=0.039).Conclusions
The current findings provide the first evidence that abnormal CSP enlargement, which reflects limbic system dysgenesis of neurodevelopmental origin, may be linked to later development of opiate dependence. In addition, a greater CSP length, which indicates more severe limbic abnormalities, appears to confer higher risk for earlier onset of opiate use. 相似文献993.
Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12) and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG). The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226) grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv) is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies. 相似文献
994.
Seung Mi Lee Jeong Woo Park Byoung Jae Kim Chan-Wook Park Joong Shin Park Jong Kwan Jun Bo Hyun Yoon 《PloS one》2013,8(12)
Background
The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM.Methodology/Principal Findings
The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids.Conclusions/Significance
The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM. 相似文献995.
María Díez-León Jeff Bowman Steve Bursian Hélène Filion David Galicia Jeannette Kanefsky Angelo Napolitano Rupert Palme Albrecht Schulte-Hostedde Kim Scribner Georgia Mason 《PloS one》2013,8(11)
Wild carnivores in zoos, conservation breeding centres, and farms commonly live in relatively small, unstimulating enclosures. Under these captive conditions, in a range of species including giant pandas, black-footed ferrets, and European mink, male reproductive abilities are often poor. Such problems have long been hypothesized to be caused by these animals'' housing conditions. We show for the first time that rearing under welfare-improving (i.e., highly valued and stress-reducing) environmental enrichments enhances male carnivores'' copulatory performance: in mate choice competitions, enriched male American mink (Neovison vison) mated more often than non-enriched males. We screened for several potential mediators of this effect. First was physiological stress and its impact on reproductive physiology; second, stress-mediated changes in morphology and variables related to immunocompetence that could influence male attractiveness; and third, behavioural changes likely to affect social competence, particularly autistic-like excessive routine and repetition (‘perseveration’) as is reflected in the stereotypies common in captive animals. Consistent with physiological stress, excreted steroid metabolites revealed that non-enriched males had higher cortisol levels and lower androgen levels than enriched conspecifics. Their os penises (bacula) also tended to be less developed. Consistent with reduced attractiveness, non-enriched males were lighter, with comparatively small spleens and a trend to greater fluctuating asymmetry. Consistent with impaired social competence, non-enriched males performed more stereotypic behaviour (e.g., pacing) in their home cages. Of all these effects, the only significant predictor of copulation number was stereotypy (a trend suggesting that low bodyweights may also be influential): highly stereotypic males gained the fewest copulations. The neurophysiological changes underlying stereotypy thus handicap males sexually. We hypothesise that such males are abnormally perseverative when interacting with females. Investigating similar problems in other taxa would be worthwhile, since many vertebrates, wild and domestic, live in conditions that cause stereotypic behaviour and/or impair neurological development. 相似文献
996.
Jeehee Kim Aurora Badaloni Torsten Willert Ursula Zimber-Strobl Ralf Kühn Wolfgang Wurst Matthias Kieslinger 《PloS one》2013,8(11)
Genetic redundancy poses a major problem to the analysis of gene function. RNA interference allows the down-regulation of several genes simultaneously, offering the possibility to overcome genetic redundancy, something not easily achieved with traditional genetic approaches. Previously we have used a polycistronic miR155-based framework to knockdown expression of three genes of the early B cell factor family in cultured cells. Here we develop the system further by generating transgenic mice expressing the RNAi construct in vivo in an inducible manner. Expression of the transgene from the strong CAG promoter is compatible with a normal function of the basal miRNA/RNAi machinery, and the miR155 framework readily allows inducible expression from the Rosa26 locus as shown by Gfp. However, expression of the transgene in hematopoietic cells does not lead to changes in B cell development and neuronal expression does not affect cerebellar architecture as predicted from genetic deletion studies. Protein as well as mRNA levels generated from Ebf genes in hetero- and homozygous animals are comparable to wild-type levels. A likely explanation for the discrepancy in the effectiveness of the RNAi construct between cultured cells and transgenic animals lies in the efficiency of the sequences used, possibly together with the complexity of the transgene. Since new approaches allow to overcome efficiency problems of RNAi sequences, the data lay the foundation for future work on the simultaneous knockdown of several genes in vivo. 相似文献
997.
Bateman’s experimental study of Drosophila melanogaster produced conclusions that are now part of the bedrock premises of modern sexual selection. Today it is the most cited experimental study in sexual selection, and famous as the first experimental demonstration of sex differences in the relationship between number of mates and relative reproductive success. We repeated the experimental methodology of the original to evaluate its reliability. The results indicate that Bateman’s methodology of visible mutations to assign parentage and reproductive success to subject adults is significantly biased. When combined in offspring, the mutations decrease offspring survival, so that counts of mate number and reproductive success are mismeasured. Bateman’s method overestimates the number of subjects with no mates and underestimates the number with one or more mates for both sexes. Here we discuss why Bateman’s paper is important and present additional analyses of data from our monogamy trials. Monogamy trials can inform inferences about the force of sexual selection in populations because in monogamy trials male–male competition and female choice are absent. Monogamy trials also would have provided Bateman with an a priori test of the fit of his data to Mendel’s laws, an unstated, but vital assumption of his methodology for assigning parentage from which he inferred the number of mates per individual subject and their reproductive success. Even under enforced monogamous mating, offspring frequencies of double mutant, single mutant and no mutant offspring were significantly different from Mendelian expectations proving that Bateman’s method was inappropriate for answering the questions he posed. Double mutant offspring (those with a mutation from each parent) suffered significant inviability as did single mutant offspring whenever they inherited their mother’s marker but the wild-type allele at their father’s marker locus. These inviability effects produced two important inaccuracies in Bateman’s results and conclusions. (1) Some matings that actually occurred were invisible and (2) reproductive success of some mothers was under-estimated. Both observations show that Bateman’s conclusions about sex differences in number of mates and reproductive success were unwarranted, based on biased observations. We speculate about why Bateman’s classic study remained without replication for so long, and we discuss why repetition almost 60 years after the original is still timely, necessary and critical to the scientific enterprise. We highlight overlooked alternative hypotheses to urge that modern tests of Bateman’s conclusions go beyond confirmatory studies to test alternative hypotheses to explain the relationship between mate number and reproductive success. 相似文献
998.
Efficient cell migration is central to the normal development of tissues and organs and is involved in a wide range of human diseases, including cancer metastasis, immune responses, and cardiovascular disorders. Mesenchymal migration is modulated by focal-adhesion proteins, which organize into large integrin-rich protein complexes at the basal surface of adherent cells. Whether the extent of clustering of focal-adhesion proteins is actually required for effective migration is unclear. We recently demonstrated that the depletion of major focal-adhesion proteins, as well as modulation of matrix compliance, actin assembly, mitochondrial activity, and DNA recombination, all converged into highly predictable, inter-related, biphasic changes in focal adhesion size and cell migration. Herein, we further discuss the role of focal adhesions in controlling cell spreading and test their potential role in cell migration. 相似文献
999.
Congenital heart disease (CHD) is the most frequent noninfectious cause of death at birth. The incidence of CHD ranges from 4 to 50/1,000 births (Disease and injury regional estimates, World Health Organization, 2004). Surgeries that often compromise the quality of life are required to correct heart defects, reminding us of the importance of finding the causes of CHD. Mutant mouse models and live imaging technology have become essential tools to study the etiology of this disease. Although advanced methods allow live imaging of abnormal hearts in embryos, the physiological and hemodynamic states of the latter are often compromised due to surgical and/or lengthy procedures. Noninvasive ultrasound imaging, however, can be used without surgically exposing the embryos, thereby maintaining their physiology. Herein, we use simple M-mode ultrasound to assess heart rates of embryos at E18.5 in utero. The detection of abnormal heart rates is indeed a good indicator of dysfunction of the heart and thus constitutes a first step in the identification of developmental defects that may lead to heart failure. 相似文献
1000.
Sohela Shah Yonghwan Kim Irina Ostrovnaya Rajmohan Murali Kasmintan A. Schrader Francis P. Lach Kara Sarrel Rohini Rau-Murthy Nichole Hansen Liyng Zhang Tomas Kirchhoff Zsofia Stadler Mark Robson Joseph Vijai Kenneth Offit Agata Smogorzewska 《PloS one》2013,8(6)