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排序方式: 共有185条查询结果,搜索用时 15 毫秒
31.
The basement membrane microenvironment directs the normalization and survival of bioengineered human skin equivalents. 总被引:1,自引:0,他引:1
Nadav Segal Frank Andriani Lawrence Pfeiffer Padmaja Kamath Ning Lin Kapettu Satyamurthy Christophe Egles Jonathan A Garlick 《Matrix biology》2008,27(3):163-170
Epithelial-mesenchymal interactions promote the morphogenesis and homeostasis of human skin. However, the role of the basement membrane (BM) during this process is not well-understood. To directly study how BM proteins influence epidermal differentiation, survival and growth, we developed novel 3D human skin equivalents (HSEs). These tissues were generated by growing keratinocytes at an air-liquid interface on polycarbonate membranes coated with individual matrix proteins (Type I Collagen, Type IV Collagen or fibronectin) that were placed on contracted Type I Collagen gels populated with dermal fibroblasts. We found that only keratinocytes grown on membranes coated with the BM protein Type IV Collagen showed optimal tissue architecture that was similar to control tissues grown on de-epidermalized dermis (AlloDerm) that contained intact BM. In contrast, tissues grown on proteins not found in BM, such as fibronectin and Type I Collagen, demonstrated aberrant tissue architecture that was linked to a significant elevation in apoptosis and lower levels of proliferation of basal keratinocytes. While all tissues demonstrated a normalized, linear pattern of deposition of laminin 5, tissues grown on Type IV Collagen showed elevated expression of alpha6 integrin, Type IV Collagen and Type VII Collagen, suggesting induction of BM organization. Keratinocyte differentiation (Keratin 1 and filaggrin) was not dependent on the presence of BM proteins. Thus, Type IV Collagen acts as a critical microenvironmental factor in the BM that is needed to sustain keratinocyte growth and survival and to optimize epithelial architecture. 相似文献
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Peter Tsvetkov Nadav Myers Raz Eliav Yaarit Adamovich Tzachi Hagai Julia Adler Ami Navon Yosef Shaul 《The Journal of biological chemistry》2014,289(16):11272-11281
The 26S proteasome is the end point of the ubiquitin- and ATP-dependent degradation pathway. The 26S proteasome complex (26S PC) integrity and function has been shown to be highly dependent on ATP and its homolog nucleotides. We report here that the redox molecule NADH binds the 26S PC and is sufficient in maintaining 26S PC integrity even in the absence of ATP. Five of the 19S proteasome complex subunits contain a putative NADH binding motif (GxGxxG) including the AAA-ATPase subunit, Psmc1 (Rpt2). We demonstrate that recombinant Psmc1 binds NADH via the GxGxxG motif. Introducing the ΔGxGxxG Psmc1 mutant into cells results in reduced NADH-stabilized 26S proteasomes and decreased viability following redox stress induced by the mitochondrial inhibitor rotenone. The newly identified NADH binding of 26S proteasomes advances our understanding of the molecular mechanisms of protein degradation and highlights a new link between protein homeostasis and the cellular metabolic/redox state. 相似文献
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Survival patterns in a population of western gulls (Larus occidentalis)of known age of first breeding, a, indicate a cost of reproductionrelated to the age of initial breeding. Among both sexes, birdsthat commenced breeding at the earliest ages (3 years in malesand 4 years in females) had higher annual mortality than thosethat deferred breeding one or more years. In addition, females(but not males) evidenced a cumulative cost of reproduction:holding age constant, females with more annual breeding attemptsdemonstrated poorer survival. These patterns of -specific survivalwere statistically significant after controlling for interannualvariation in food availability and are not explained simplyby variation in the intrinsic quality of individuals. To assessthe effects of these sex-specific costs on fitness, we combinedthe observed survival patterns with data on prebreeding survivorshipand -specific reproductive success to estimate rates of populationgrowth and lifetime reproductive success for different agesat first reproduction. Males showed a clearly defined fitnessoptimum at = 4 years, which coincided with the modal for malesin the population. Females showed no clear optimum, except thatbreeding at age 4 was suboptimal, hence females benefited fromdeferring breeding to ages 5-7 years. Observed age of firstbreeding also showed no clear mode for females, with slightpeaks at ages 5 and 7. As a result, in both sexes, the fitnesssurface for corresponded well with observed frequencies of. We suggest that stabilizing selection has acted to shape thephenotypic distribution of in males but, due to trade-offsbetween survival and early reproduction, stabilizing selectionis weak or absent in females 相似文献
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Facilitated variation: how evolution learns from past environments to generalize to new environments 下载免费PDF全文
One of the striking features of evolution is the appearance of novel structures in organisms. Recently, Kirschner and Gerhart have integrated discoveries in evolution, genetics, and developmental biology to form a theory of facilitated variation (FV). The key observation is that organisms are designed such that random genetic changes are channeled in phenotypic directions that are potentially useful. An open question is how FV spontaneously emerges during evolution. Here, we address this by means of computer simulations of two well-studied model systems, logic circuits and RNA secondary structure. We find that evolution of FV is enhanced in environments that change from time to time in a systematic way: the varying environments are made of the same set of subgoals but in different combinations. We find that organisms that evolve under such varying goals not only remember their history but also generalize to future environments, exhibiting high adaptability to novel goals. Rapid adaptation is seen to goals composed of the same subgoals in novel combinations, and to goals where one of the subgoals was never seen in the history of the organism. The mechanisms for such enhanced generation of novelty (generalization) are analyzed, as is the way that organisms store information in their genomes about their past environments. Elements of facilitated variation theory, such as weak regulatory linkage, modularity, and reduced pleiotropy of mutations, evolve spontaneously under these conditions. Thus, environments that change in a systematic, modular fashion seem to promote facilitated variation and allow evolution to generalize to novel conditions. 相似文献
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What is the underlying mechanism behind the fat-tailed statistics observed for species abundance distributions? The two main hypotheses in the field are the adaptive (niche) theories, where species abundance reflects its fitness, and the neutral theory that assumes demographic stochasticity as the main factor determining community structure. Both explanations suggest quite similar species-abundance distributions, but very different histories: niche scenarios assume that a species population in the past was similar to the observed one, while neutral scenarios are characterized by strongly fluctuating populations. Since the genetic variations within a population depend on its abundance in the past, we present here a way to discriminate between the theories using the genetic diversity of noncoding DNA. A statistical test, based on the Fu-Li method, has been developed and enables such a differentiation. We have analyzed the results gathered from individual-based simulation of both types of histories and obtained clear distinction between the Fu-Li statistics of the neutral scenario and that of the niche scenario. Our results suggest that data for 10–50 species, with approximately 30 sequenced individuals for each species, may allow one to distinguish between these two theories. 相似文献
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Ravid Doron Dafna Lotan Ziv Versano Layla Benatav Motty Franko Shir Armoza Nadav Kately Moshe Rehavi 《PloS one》2014,9(4)
Anxiety disorders are a major public health concern worldwide. Studies indicate that repeated exposure to adverse experiences early in life can lead to anxiety disorders in adulthood. Current treatments for anxiety disorders are characterized by a low success rate and are associated with a wide variety of side effects. The aim of the present study was to evaluate the anxiolytic effects of a novel herbal treatment, in comparison to treatment with the selective serotonin reuptake inhibitor escitalopram. We recently demonstrated the anxiolytic effects of these treatments in BALB mice previously exposed to one week of stress. In the present study, ICR mice were exposed to post natal maternal separation and to 4 weeks of unpredictable chronic mild stress in adolescence, and treated during or following exposure to stress with the novel herbal treatment or with escitalopram. Anxiety-like behavior was evaluated in the elevated plus maze. Blood corticosterone levels were evaluated using radioimmunoassay. Brain derived neurotrophic factor levels in the hippocampus were evaluated using enzyme-linked immunosorbent assay. We found that (1) exposure to stress in childhood and adolescence increased anxiety-like behavior in adulthood; (2) the herbal treatment reduced anxiety-like behavior, both when treated during or following exposure to stress; (3) blood corticosterone levels were reduced following treatment with the herbal treatment or escitalopram, when treated during or following exposure to stress; (4) brain derived neurotrophic factor levels in the hippocampus of mice treated with the herbal treatment or escitalopram were increased, when treated either during or following exposure to stress. This study expands our previous findings and further points to the proposed herbal compound''s potential to be highly efficacious in treating anxiety disorders in humans. 相似文献