Temperature is a fundamental environmental force shaping species abundance and distributions through its effects on biochemical reaction rates, metabolism, activity, and reproduction. In light of future climate shifts, mainly driven by temperature increases, how will organisms persist in warmer environments? One molecular mechanism that may play an important role in coping with heat stress is the heat shock response (HSR), which protects against molecular damage. To prevent and repair protein damage specifically, Hsps activate and become up-regulated. However, the functional diversity and relevance of heat shock proteins (Hsps) in extending upper thermal limits in taxonomic groups outside marine and model systems is poorly understood. Ants are a good system to understand the physiological mechanisms for coping with heat stress because they have successfully diversified into thermally stressful environments. To identify and characterize the functional diversity of Hsps in ants, I surveyed Hsp orthologues from published ant genomes to test for signatures of positive selection and to reconstruct their evolutionary history. Within Hymenoptera, ants utilize unique sets of Hsps for the HSR. Stabilizing selection was the prevailing force among Hsp orthologues, suggesting that protein activity is conserved. At the same time, regulatory regions (promoters) governing transcriptional up-regulation diversified: species differ in the number and location of heat shock elements (HSEs). Therefore, Hsp expression patterns may be a target for selection in warm environments. I tested whether Hsp expression corresponded with variation in upper thermal limits in forest ant species within the genus Aphaenogaster. Whole colonies were collected throughout the eastern United States and were lab acclimated. There was a positive relationship between upper thermal limits (Critical Thermal maxima, CTmax) and local temperature extremes. Upper thermal limits were also higher in ant species that lived in open habitats (shrub-oak and long-leaf pine savannah) than species occupying closed habitats (deciduous forest). Ant species with higher CTmax expressed Hsps more slowly, at higher temperatures, and at higher maximum levels than those with low CTmax. Because Hsps sense and repair molecular damage, these results suggest the proteomes of open relative to closed canopy forests are more stable. Although deciduous forest ant species may be buffered from temperature stress, it is likely that temperature interacts with other environmental stressors such as water and nutrient availability that may impact upper thermal limits. I measured the influence of dehydration and nutrition stress on upper thermal limits of forest ants from a single population. Ants that were initially starved were much less thermally tolerant than controls and ants that were initially desiccated. Because ants are likely to experience similar combination of stressors in the wild, upper thermal limits may be severely overestimated in single factor experiments. Therefore, realistic forecasting models need to consider multiple environmental stressors. Overall, adaptive tuning of Hsp expression that reflects better protection and tolerance of protein unfolding may have facilitated ant diversification into warm environments. However, additional stressors and mechanisms may constrain the evolution of upper thermal limits.

Ascaris suum were exposed to a number of stressors, including heavy metals and both high (40°C) and low (18°C) temperatures. The 70kD and 90kD heat shock proteins (HSPs) in the different A. suum tissues were analyzed by Western blot and quantitated by Macintosh Image Program.

The response deficit following exposure to inescapable shock has been termed "learned helplessness." This experiment was designed (a) to determine whether learned helplessness following an inescapable footshock induction procedure extends to 48 hours, and (b) to test the hypothesis that electroconvulsive shock (ECS) reverses learned helplessness in rats. Subjects were tested for helplessness in a bar-press shock-escape task. Results indicated that helplessness was not present 48 hours after exposure to inescapable shock. A slight indication of helplessness was observed in the first 10 trials of the 60-trial task. In addition, ECS was shown to enhance performance in the test task; however, this facilitation effect was seen only in control animals that were not previously exposed to inescapable footshock.

The thesis examines the ability of DSGE models with financial elements to explain financial asset prices. A neoclassical macroeconomic model is used, in- cluding a financial constraint in the form of a restriction on external financing. Moreover, the strictness of the restriction is affected by an external financial shock. It is shown, that the combination of the financial constraint and the fi- nancial shock contributes to understanding of the macroeconomic fluctuations, asset price dynamics and their mutual impact. The calibration for the United States demonstrates that the financial shock is an important source of the as- set price volatility. Contrary, when calibrated to the Czech data, the financial shock generates only moderate asset price volatility, as a consequence of a posi- tive correlation with the productivity shock. To address the issue, the model is further extended by a sector of financial intermediaries and a preference shock related to the risk-aversion of economic subjects, and the extension is shown to improve the result.

In another study, hyperthermic treatment was applied to study whether HSP27 expression would be induced in un-injured RGCs, and whether this treatment performed after axotomy would have effects on HSP27 expression, RGC survival and/or regeneration into PN graft. Brief duration of heat shock that elevate the body temperature to 42°C did not up-regulate HSP27 in normal retina. About 8-10% increase in RGC survival in the hyperthermia group was observed compared to those received a 37°C treatment at one week post-axotomy and it depended on the number of post-injury heat treatments applied. At the same time, the number of HSP27-RGCs was also doubled, although the same increase occurred was irrespective of the number of hyperthermic treatments. Multiple heat shock application also significantly enhanced RGC regeneration into PN graft through increased the number of HSP27 regenerating RGCs. These results suggest that post-injury hyperthermic treatment enhance HSP27 induction in RGCs and lead to their successful regeneration into the PNG, whereas further studies are necessary to determine whether the protective effect on survival by heat shock is due to the increase in a subset of HSP27-RGCs. (Abstract shortened by UMI.) / In the second study, different neurotrophic factors were injected into the vitreous to enhance RGC survival and/or regeneration. Brain-derived neurotrophic factor (BDNF) significantly reduced RGC death transiently at 14 days after ON cut, but the expression of HSP27 was reduced compared to bovine serum albumin-injected controls. In peripheral nerve (PN)-grafted retina, BDNF suppressed RGC regeneration via reducing the number of HSP27-RGCs regenerating into the PN graft. In ciliary neurotrophic factor (CNTF)-injected group, although there was only a 10% increase in RGC survival, a 5-fold drastic increase in the number of RGCs which expressed HSP27 was observed, and some of these were found to undergo intra-retinal sprouting similar to VPN-transplanted retina. Combined treatment of intra-vitreal CNTF injection with PNG resulted in a 5 fold-increase in the number of regenerating RGCs as well as increasing the proportion of cells which expressed HSP27 from about 60% to about 80%. The data indicates that HSP27 participates in axonal regrowth especially under synergistic interaction of CNTF and PNG. Intra-vitreal injection of hepatocyte growth factor (HGF) significantly sustained RGC survival compared to BDNF at 28 days after axotomy, but the HSP27 expression in RGCs did not change correspondingly. In the PN-ON grafted retina, HGF promoted more RGCs regenerate without altering the number of HSP27-RGCs regrowing into the PNG. Such results indicate that some trophic factors can specifically enhance or suppress RGC regeneration by modulating HSP27 expression, while other trophic factors promote regeneration which is independent to HSP27. Therefore, it suggests that RGCs may regenerate through at least two different mechanisms. / In this study, the detailed in vivo expression of HSP27 in retinal ganglion cells (RGCs) of golden hamster following axotomy and regeneration stimulated by peripheral nerve grafting and neurotrophic factors have been examined. / In whole-mount normal retinas, HSP27 was constitutively expressed in astrocytes and blood vessels, but not in RGCs. Three days after optic nerve (ON) transection, a small subset of surviving RGC began to express HSP27, the number of which peaked at 7 days and dropped to a minimal level at two weeks post-axotomy. When axotomy was done more proximally to their cell bodies, RGCs survival was significantly decreased but HSP27 expression did not change. This suggests the HSP27 expression does not correlate with cell survival after axonal injury. When a viable peripheral nerve (VPN) was transplanted intravitreally into the eye after ON cut, it induced intra-retinal sprouting of RGCs. Although it did not promote RGC survival, VPN prolonged HSP27 expression up to 56 days after surgery and significantly increased the number of HSP27-RGCs. This protein was localized in the cell body, and especially, in dendritic sprouts and growth cones, indicating that it was transported to active growing sites where it may have a functional role associated with regenerative sprouting. / Wong, Wai Kai. / Adviser: Eric Cho. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3270. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 159-198). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

糖調節蛋白78 (Glucose-regulated protein 78),也稱之Bip,是70kDa熱休克蛋白家族成员之一。已有的研究表明，Bip 是一個具有多功能的蛋白，參與眾多的生物調控過程，包括蛋白折疊，調節鈣平衡，以及作為內質網緊張（ER stress) 的感應器。有研究表明，Bip可以在細胞膜上定位，作為Nodal信號通路的一個輔助受體發揮作用。大量的研究表明，Bip在疾病和代謝方面也發揮重要作用。它參與胰島素的生物合成，並可以提高長期高血糖下β細胞的功能。同時具有抗細胞凋亡的作用。然而Bip在胚胎髮育中的生物功能卻知之甚少。 / 高等脊椎動物腎臟發育中經歷形成3種腎臟形式：前腎，中腎和後腎。腎單位是這3種形式的基本結構和功能單位。在兩棲類，前腎在胚胎時期發揮作用，在胚胎的兩側各只有一個腎單位。這使得爪蟾成為前腎研究的一個非常好的模型。 / 在此項研究中，我們採用非洲爪蛙作為動物模型來研究Bip在胚胎髮育過程中，尤其是在前腎發育中的生物功能。Bip是一個母性因子，在尾芽期，Bip 表達在粘液腺，前腎，肝以及耳囊。 Bip在前腎清晰明確的表達，表明Bip可能在前腎的發育中發揮作用。我們利用BipMO來進行敲低功能實驗，免疫印記顯示BipMO能阻斷帶Flag標記Bip的翻譯。通過原位雜交技術檢測前腎的不同標記基因的表達發現，敲低Bip抑制前腎的形成，表明Bip的正常表達是前腎發育所必須的。 / 為了研究Bip調節前腎的發育的分子機制， 我們使用Affmetrix基因芯片分析在Bip敲低情況下的不同時期胚胎中基因的表達譜，發現在Bip敲低表達的胚胎中，視黃酸信號通路的一些重要的組分的表達受到抑制。爪蛙胚胎原腸胚的動物帽細胞具有多能性， 使用激活素和視黃酸一同處理動物帽細胞可以誘導其分化成為原腎組織。在此體外分化體系中敲低Bip表達，前腎標記基因表達降低，顯示在這一體外系統中前腎的分化受到抑制。該實驗結果與體內實驗結果一致。在體外培養的HEK293T細胞中敲低Bip，抑制視黃酸處理後視黃酸信號通路螢光素報告的活性。 lhx1是前腎發育早期表達標記之一，對於前腎原基的初始化具有重要的作用，同是它也是視黃酸信號通路的靶基因。共同註射BipMO和lhx1表明，前腎的異常可以明顯降低，顯示lhx1可以部份拯救由於Bip缺失所造成的腎臟發育缺陷。該實驗表明Bip通過調節視黃酸信號通路，來調控lhx1的表達前腎的形成。我們進一不發現，敲低Bip後，前腎異常形成的區域內，細胞凋亡增加，增殖減少。該結果在細胞水平上解釋了Bip敲低表達時前腎形成異常的一個原因。 / 综述所述，Bip正確表達对胚胎前肾的发育極為重要。它胚胎发育过程中通过視黃酸信号通路調控lhx1的表達，從而对前肾的形成发挥重要作用。 / Glucose-regulated protein 78 (Grp78), also known as Bip, belongs to heat shock protein 70kDa family. It has been implicated in various biological processes including protein folding, regulation of calcium homeostasis, and serving as a sensor of ER (Endoplasmic Reticulum) stress. Moreover, it can localize in cell membrane, acting as co-receptor of nodal signaling. It is essential for insulin biosynthesis. In addition, Bip plays important roles in a number of diseases. For example, BIP can improve β-cell function in the prolonged hyperglycemia. Knockdown of BIP in β-cell can induce apoptosis. However, little is known about its function during embryonic development. / In high vertebrate, three sets of nephric forms develop successively during embryonic kidney development. They are pronephros, mesonephros, and metanephros. Nephron is the basic structural and functional unit of all these three forms. In amphibian, the pronephros performs function at the embryonic stages, which has only one nephron on either side of the body. It makes Xenopus a very good model for pronephros study. / In this study, we took advantage of Xenopus leavis as an animal model to investigate Bip function during embryonic development, especially its role in pronephros development. We first examined the expression of Bip in developing embryos. Whole mount in situ hybridization showed that Bip was expressed in the cement gland, pronephros, liver and ear vesicle during tailbud stages. It was expressed in the pronephros strongly and clearly which suggested that Bip might play roles in pronephros development. We performed loss-of-function experiment by using morpholino oligonucleotide (MO) knock down translation of endogenous Bip expression. Depletion of Bip impaired formation of pronephros revealed by reduction expression of different pronephros maker genes. The pluripotent animal caps can differentiate into pronephros tissue when treated with activin and all-trans retinoic acid (atRA) in vitro kidney induction assay. In line with our in vivo observation, knockdown of Bip inhibited pronephros differentiation that can normally achieved by combined effects of activin and atRA in animal cap assay. / In order to investigate the molecular mechanisms as how Bip regulated pronephros development, we performed Affymetrix DNA microarray assay to generate gene expression profile in Bip morphants. We found that some components of RA signaling were inhibited when Bip was knockdown. Moreover, knockdown of Bip caused reduction of RA target genes expression after treatment with RA. Consistent with above observations, luciferase activities of RA signaling reporter was reduced in HEK293T cells when BIP expression was depleted by RNAi. lhx1 is one of RA target genes and has been implicated playing essential roles in pronephros development. The inhibition of pronephros formation induced by Bip depletion can be partially rescued by co-overpression, suggesting 1) lhx1 is downstream of Bip in the regulatory network of pronephros formation; and 2) Bip regulates pronephros formation through RA signaling via lhx1. We also found increased apoptosis and decreased cell proliferation at pronephros-forming region in Bip morphants. That could explain the reason of pronephros malformation when Bip is downregulated. / Taken together, Bip is essential for pronephros development. It functions through RA signaling during the complex developmental processes. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Shi, Weili. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 125-143). / Abstracts also in Chinese.

Une réponse rapide et adaptée est nécessaire à la survie des cellules soumises à un stress. La réponse cellulaire au stress (HSR pour Heat-Shock response) médié par le facteur de transcription HSF1 est induite par les contextes environnementaux (chaleur, hypoxie, …) et les processus biologiques normaux et pathologiques (vieillissement, inflammation, …) associés à une accumulation de protéines endommagées (Morimoto, 1998). Ces protéines endommagées forment des agrégats toxiques aux conséquences létales pour les cellules.Conservé chez tous les eucaryotes, HSF1 orchestre les actions nécessaires à la survie et à la croissance des cellules malgré le stress. Ses cibles les mieux connues sont les gènes codants pour les Heat Shock Protein (HSP) qui font office de chaperon moléculaire. Une caractéristique de la HSR chez l’Homme est l’accumulation massive du facteur HSF1 en foyers nucléaires nommés Nuclear Stress Bodies (nSBs). Curieusement, ces foyers ciblent l’hétérochromatine péricentrique composée de séquences répétées en tandem de type Satellite III (SATIII), particulièrement au niveau du locus 9q12. HSF1 induit une forte transcription en ARN SATIII Sens (Jolly et al., 2004). Le rôle des nSBs est une des problématiques majeures de notre équipe cependant jusqu’à présent aucune fonction n’a été confirmée pour ces structures.Les nSBs, spécifiques aux cellules humaines, n’ont été décrits que dans des cellules en culture. Mon projet de thèse a consisté dans un premier temps à montrer la présence des nSBs in vivo chez l’Homme. Cette étude, réalisée sur du tissu testiculaire nous a également permis d’identifier une nouvelle cible SATIII majeure pour HSF1, la région Yq12. Dans les testicules, les nSBs sont associés à des processus méiotiques et post-méiotiques, suggérant un rôle dans le remodelage de l’hétérochromatine. Dans un deuxième temps, nous avons cherché à mieux comprendre le rôle des nSBs lors de la HSR. Nous avons pu montrer que l’étape de transcription des SATIII induit une déstabilisation de l’hétérochromatine péricentrique caractérisée par une dissociation des facteurs HP1 (Heterochromatin Protein 1) alpha et beta et une perte de la marque répressive H3K9me3. Au cours de la période de récupération qui accompagne la reformation de l’hétérochromatine, une transcription séquentielle d’ARN SATIII Sens puis Anti-sens précède la restructuration des loci 9q12. Nous avons également pu montrer que la transcription des SATIII est associée à un blocage de la mitose. Nous montrons que dans les cellules stressées, une altération de ce point de contrôle par un Knock down des ARN sat III par des approches LNA conduisent à une l’instabilité génomique des cellules tumorales avec apparition de cellules polynucléées. / A rapid and well-adapted response is required for cell survival upon stress. The cellular stress response (HSR) is mediated by the transcription factor Heat Shock Factor 1 (HSF1) (Morimoto, 1998). It is activated by environmental stress (heat, hypoxia, ...) and by a series of patho-physiological contexts (aging, inflammation, ...) involving protein damages.The best-characterized targets of HSF1 are genes encoding for Heat Shock Protein (HSP) acting as molecular chaperone. A specific feature of the HSR in human cells is the presence of HSF1 nuclear foci named Nuclear Stress Bodies (NSBs). Surprisingly, nSBs target pericentric heterochromatin consisting in tandem repeats of type III Satellite (SATIII) sequences, primarily at the 9q12 locus. HSF1 triggers a strong transcriptional activation of this locus (Jolly et al., 2004). The role of nSBS is a major issue since no function related to these structures has been reported so far.So far, nSBs have been only identified in cells in culture. My thesis project has been to further explore whether these structures also existed in normal tissues. Indeed, we have been able to identify the presence of nSBs in testis where they were found to be associated to meiotic and post-meiotic stages, suggesting a role related to heterochromatin remodeling. Moreover, we have identified the Yq12 locus as a new target of nSBs in these tissues. Secondly, we have brought new evidence that sat III sequences triggers a transient dissociation of HP1 (heterochromatin Protein 1) α and β as well as a loss of the repressive epigenetic H3K9me3 histone mark at pericentric heterochromatin. Interestingly we have also found that, following stress, a sequential accumulation of SATIII RNA in a Sense and Antisense orientation occurs, suggesting that this specific pattern of expression plays an important role in heterochromatin reformation. Finally, we have found that the accumulation of SATIII RNA is associated with a slowdown of mitosis. Indeed we have found that in stressed cells, accumulation of sat III impcats the progression of mitosis and that a knock down of sat III RNA using LNA approaches releases this blockade, leading to genomic instability of tumor cells and to the appearance of poly nucleated cells.

Florida's undergraduate organization of higher education is a 2 + 2 system in which students are encouraged to complete freshmen and sophomore years at a community college and then transfer to a state university. Florida statutes provide for a highly articulated educational system to facilitate seamless transition from one public institution to another. The researcher investigated the transfer function's effectiveness among community college students subsequent to enrollment at a large, urban, doctoral/research extensive university in Florida using a course-based model of transfer success. The research explored whether differences existed in academic performance in targeted upper-division undergraduate courses between native and Florida Community College System (FCCS) transfer students who completed prerequisite courses prior to transferring to the university. Four upper-division courses were chosen specifically because many transfer students complete prerequisite coursework at a community college prior to matriculating at the university. A total of 764 native students and 1,053 FCCS transfer students were enrolled in at least one course of interest in fall 2002. Preliminary investigation of selected demographic characteristics identified statistically significant differences between these two groups. Native students were younger and more racially/ethnically diverse; more native students were enrolled full time (for 12 or more credits) than transfer students. Although first-term transfer students experienced transfer shock, university native students who were enrolled in three courses also experienced declines in fall 2002 GPA when compared to their previous GPA at the university. Statistically significant mean grade differences occurred between transfer and native students in three courses; transfers outperformed native students in two courses. Additional comparisons of fall 2002 term GPA between native and transfer students yielded no significant differences. Findings lend support to the effectiveness of Florida's community colleges in preparing students for upper-division undergraduate coursework, but that transition for some is not seamless, suggesting need for collaboration among universities and community colleges.

No description available.

The focus of this work is on the modeling and simulation of shock wave propagation in reactive metal powder mixtures. Reactive metal systems are non-explosive, solid-state materials that release chemical energy when subjected to sufficiently strong stimuli. Shock loading experiments have demonstrated that ultra-fast chemical reactions can be achieved in certain micron-sized metal powder mixtures. However, the mechanisms of rapid mixing that drive these chemical reactions are currently unclear. The goal of this research is to gain an understanding of the shock-induced deformation that enables these ultra-fast reactions. The problem is approached using direct numerical simulation. In this work, a finite element (FE) model is developed to simulate shock wave propagation in discrete particle mixtures. This provides explicit particle-level resolution of the thermal and mechanical fields that develop in the shock wave. The Ni/Al powder system has been selected for study. To facilitate mesoscale FE simulation, a new dislocation-based constitutive model has been developed to address the viscoplastic deformation of fcc metals at very high strain rates. Six distinct initial configurations of the Ni/Al powder system have been simulated to quantify the effects of powder configuration (e.g., particle size, phase morphology, and constituent volume fractions) on deformation in the shock wave. Results relevant to the degree of shock-induced mixing in the Ni/Al powders are presented, including specific analysis of the thermodynamic state and microstructure of the Ni/Al interfaces that develop during wave propagation. Finally, it is shown that velocity fluctuations at the Ni/Al interfaces (which arise due to material heterogeneity) may serve to fragment the particles down to the nanoscale, and thus provide an explanation of ultra-fast chemical reactions in these material systems.