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131.
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133.
Most sexually reproducing animal species are characterized by two morphologically and behaviorally distinct sexes. The genetic, molecular and cellular processes that produce sexual dimorphisms are phylogenetically diverse, though in most cases they are thought to occur early in development. In some species, however, sexual dimorphisms are manifested after development is complete, suggesting the intriguing hypothesis that sex, more generally, might be considered a continuous trait that is influenced by both developmental and postdevelopmental processes. Here, we explore how biological sex is defined at the genetic, neuronal and behavioral levels, its effects on neuronal development and function, and how it might lead to sexually dimorphic behavioral traits in health and disease. We also propose a unifying framework for understanding neuronal and behavioral sexual dimorphisms in the context of both developmental and postdevelopmental, physiological timescales. Together, these two temporally separate processes might drive sex‐specific neuronal functions in sexually mature adults, particularly as it pertains to behavior in health and disease. 相似文献
134.
Ayelet Zauberman Yehuda Flashner Yinon Levy Yaron Vagima Avital Tidhar Ofer Cohen Erez Bar-Haim David Gur Moshe Aftalion Gideon Halperin Avigdor Shafferman Emanuelle Mamroud 《PloS one》2013,8(12)
Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. The existence of antibiotic-resistant Y. pestis strains emphasizes the need for the development of novel countermeasures against plague. We previously reported the generation of a recombinant Y. pestis strain (Kim53ΔJ+P) that over-expresses Y. enterocolitica YopP. When this strain was administered subcutaneously to mice, it elicited a fast and effective protective immune response in models of bubonic, pneumonic and septicemic plague. In the present study, we further characterized the immune response induced by the Kim53ΔJ+P recombinant strain. Using a panel of mouse strains defective in specific immune functions, we observed the induction of a prompt protective innate immune response that was interferon-γ dependent. Moreover, inoculation of mice with Y. pestis Kim53ΔJ+P elicited a rapid protective response against secondary infection by other bacterial pathogens, including the enteropathogen Y. enterocolitica and the respiratory pathogen Francisella tularensis. Thus, the development of new therapies to enhance the innate immune response may provide an initial critical delay in disease progression following the exposure to highly virulent bacterial pathogens, extending the time window for successful treatment. 相似文献
135.
Shefer K Brown Y Gorkovoy V Nussbaum T Ulyanov NB Tzfati Y 《Molecular and cellular biology》2007,27(6):2130-2143
Telomerase copies a short template within its integral telomerase RNA onto eukaryotic chromosome ends, compensating for incomplete replication and degradation. Telomerase action extends the proliferative potential of cells, and thus it is implicated in cancer and aging. Nontemplate regions of telomerase RNA are also crucial for telomerase function. However, they are highly divergent in sequence among species, and their roles are largely unclear. Using in silico three-dimensional modeling, constrained by mutational analysis, we propose a three-dimensional model for a pseudoknot in telomerase RNA of the budding yeast Kluyveromyces lactis. Interestingly, this structure includes a U-A.U major-groove triple helix. We confirmed the triple-helix formation in vitro using oligoribonucleotides and showed that it is essential for telomerase function in vivo. While triplex-disrupting mutations abolished telomerase function, triple compensatory mutations that formed pH-dependent G-C.C(+) triples restored the pseudoknot structure in a pH-dependent manner and partly restored telomerase function in vivo. In addition, we identified a novel type of triple helix that is formed by G-C.U triples, which also partly restored the pseudoknot structure and function. We propose that this unusual structure, so far found only in telomerase RNA, provides an essential and conserved telomerase-specific function. 相似文献
136.
Orit Barneah Itzchak Brickner Matthew Hooge Virginia M. Weis Yehuda Benayahu 《Invertebrate Biology》2007,126(2):113-119
Abstract. Examination of sexual reproduction in a symbiotic acoelomorph worm, Waminoa brickneri from Eilat (Red Sea), presents the first definitive evidence for maternal transmission of dinoflagellate algal symbionts in a triploblastic organism. Sexually mature worms were removed from the stony coral Plesiastrea laxa and raised in the laboratory. Eggs were detected 18 d after the collection of the worms and hatched 4 d later. Histological sections performed on sexually mature worms showed an ovary with oocytes containing two distinct types of algal endosymbionts within their ooplasm. Transmission electron microscopy corroborated the presence of algal symbionts within the developing embryos. Our findings regarding maternal transmission of symbionts shed new light on the diversity of modes of algal symbiont acquisition known in triploblastic organisms. 相似文献
137.
Mahiuddin Ahmed Ming Cheng Qi Zhao Yehuda Goldgur Sarah M. Cheal Hong-Fen Guo Steven M. Larson Nai-Kong V. Cheung 《The Journal of biological chemistry》2015,290(50):30018-30029
B7-H3 (CD276) is both an inhibitory ligand for natural killer cells and T cells and a tumor antigen that is widely expressed among human solid tumors. Anti-B7-H3 mouse monoclonal antibody 8H9 has been successfully used for radioimmunotherapy for patients with B7-H3(+) tumors. We present the humanization, affinity maturation, and epitope mapping of 8H9 based on structure determination, modeling, and yeast display methods. The crystal structure of ch8H9 Fab fragment was solved to 2.5-Å resolution and used as a template for humanization. By displaying the humanized 8H9 single chain Fv (scFv) on the surface of yeast, the affinity was matured by sequential random mutagenesis and fluorescence-activated cell sorting. Six mutations (three in the complementarity-determining region and three in the framework regions) were identified and incorporated into an affinity-matured humanized 8H9 construct (hu8H9-6m) and an affinity-matured chimeric 8H9 construct (ch8H9-6m). The hu8H9-6m scFv had a 160-fold improvement in affinity (0.9 nm
KD) compared with parental hu8H9 scFv (144 nm
KD). The IgG formats of ch8H9-6m and hu8H9-6m (nanomolar to subnanomolar KD) had 2–9-fold enhancements in affinity compared with their parental forms, potent in vitro antibody-dependent cell-mediated cytotoxicity (0.1–0.3 μg/ml EC50), and high tumor uptake in mouse xenografts. Based on in silico docking studies and experimental validation, the molecular epitope of 8H9 was determined to be dependent on the FG loop of B7-H3, a region critical to its function in immunologic blockade and unique among anti-B7-H3 antibodies published to date. 相似文献
138.
Yarden Golan Bluma Berman Yehuda G. Assaraf 《The Journal of biological chemistry》2015,290(14):9050-9063
Zinc plays a crucial role in numerous key physiological functions. Zinc transporters (ZnTs) mediate zinc efflux and compartmentalization in intracellular organelles; thus, ZnTs play a central role in zinc homeostasis. We have recently shown the in situ dimerization and function of multiple normal and mutant ZnTs using bimolecular fluorescence complementation (BiFC). Prompted by these findings, we here uncovered the heterodimerization, altered subcellular localization, and function of multiple ZnTs in live cells using this sensitive BiFC technique. We show that ZnT1, -2, -3, and -4 form stable heterodimers at distinct intracellular compartments, some of which are completely different from their homodimer localization. Specifically, unlike the plasma membrane (PM) localization of ZnT1 homodimers, ZnT1-ZnT3 heterodimers localized at intracellular vesicles. Furthermore, upon heterodimerization with ZnT1, the zinc transporters ZnT2 and ZnT4 surprisingly localized at the PM, as opposed to their vesicular homodimer localization. We further demonstrate the deleterious effect that the G87R-ZnT2 mutation, associated with transient neonatal zinc deficiency, has on ZnT1, ZnT3, and ZnT4 upon heterodimerization. The functionality of the various ZnTs was assessed by the dual BiFC-Zinquin assay. We also undertook a novel transfection competition assay with ZnT cDNAs to confirm that the driving force for heterodimer formation is the core structure of ZnTs and not the BiFC tags. These findings uncover a novel network of homo- and heterodimers of ZnTs with distinct subcellular localizations and function, hence highlighting their possible role in zinc homeostasis under physiological and pathological conditions. 相似文献
139.
Eric R. Braverman David Han Marlene Oscar-Berman Tatiana Karikh Courtney Truesdell Kristina Dushaj Florian Kreuk Mona Li Danielle Stratton Kenneth Blum 《PloS one》2014,9(9)
Various studies have demonstrated that increased leptin levels and obesity are inversely related to cognitive decline in menopausal women. It is hypothesized that adiposity is inversely correlated with cognitive decline, as women with increased weight are less vulnerable to diminishing cognition. However, it is increasingly observed that menopausal women, even with increased adiposity, experience significant cognitive decline. Positron emission tomography (PET) has been used to analyze cognitive function and processing in menopausal women. Evoked potentials (P300) and neurophysiologic tests have validated brain metabolism in cognitively impaired patients. Post-hoc analyses of 796 female patients entering PATH Medical Clinic, between January 4, 2009 and February 24, 2013, were performed as part of the “Menopause Analytical Hormonal Correlate Outcome Study” (MAHCOS). Patient age range was 39–76 years (46.7±0.2). P300 latency and amplitude correlated with a number of hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, estrone, estriol, DHEA, pregnenolone, progesterone, free and total testosterone, thyroid stimulating hormone (TSH), Vitamins D 1.25 and D 25OH, leptin, and insulin-like growth factor-binding protein 3 (IGF-BP3). Corrected statistics did not reveal significant associations with P300 latency or amplitude for these hormones except for leptin plasma levels. However, factor analysis showed that FSH and LH clustered together with Vitamin D1.25 and Vitamin D25OH, P300 latency (not amplitude), and log leptin were found to be associated in the same cluster. Utilizing regression analysis, once age adjusted, leptin was the only significant predictor for latency or speed (p = 0.03) with an effect size of 0.23. Higher plasma leptin levels were associated with abnormal P300 speed (OR = 0.98). Our findings show a significant relationship of higher plasma leptin levels, potentially due to leptin resistance, and prolonged P300 latency. This suggests leptin resistance may delay electrophysiological processing of memory and attention, which appears to be the first of such an association. 相似文献
140.
Jascha Vervoort Anna Baraniak Muriel Gazin Julia Sabirova Christine Lammens Meital Kazma Anna Grabowska Rados?aw Izdebski Yehuda Carmeli Samir Kumar-Singh Marek Gniadkowski Herman Goossens Surbhi Malhotra-Kumar 《PloS one》2012,7(9)