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Sample records for central stress-regulating structures

Developmental regulation of fear learning and anxiety behavior by endocannabinoids

PubMed Central

Lee, Tiffany T.-Y.; Hill, Matthew N.; Lee, Francis S.

2015-01-01

The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic endocannabinoid signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that endocannabinoid signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic endocannabinoid signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the endocannabinoid system and discuss clinical and rodent models demonstrating endocannabinoid regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the endocannabinoid system in the central nervous system, and models of pharmacological augmentation of endocannabinoid signaling during development in the context of fear learning and anxiety. PMID:26419643
An aberrant parasympathetic response: a new perspective linking chronic stress and itch.

PubMed

Kim, Hei Sung; Yosipovitch, Gil

2013-04-01

Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the 'Polyvagal Theory', certain limbic structures that serve as a 'higher brain equivalent of the parasympathetic nervous system' play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch. © 2012 John Wiley & Sons A/S.
Developmental regulation of fear learning and anxiety behavior by endocannabinoids.

PubMed

Lee, T T-Y; Hill, M N; Lee, F S

2016-01-01

The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid (eCB) system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic eCB signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that eCB signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic eCB signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the eCB system and discuss clinical and rodent models showing eCB regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the eCB system in the central nervous system, and models of pharmacological augmentation of eCB signaling during development in the context of fear learning and anxiety. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

PubMed Central

Walley, Justin W.; Rowe, Heather C.; Xiao, Yanmei; Chehab, E. Wassim; Kliebenstein, Daniel J.; Wagner, Doris; Dehesh, Katayoon

2008-01-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584
The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

PubMed

Walley, Justin W; Rowe, Heather C; Xiao, Yanmei; Chehab, E Wassim; Kliebenstein, Daniel J; Wagner, Doris; Dehesh, Katayoon

2008-12-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.
A Central Role of Abscisic Acid in Stress-Regulated Carbohydrate Metabolism

PubMed Central

Kempa, Stefan; Krasensky, Julia; Dal Santo, Silvia; Kopka, Joachim; Jonak, Claudia

2008-01-01

Background Abiotic stresses adversely affect plant growth and development. The hormone abscisic acid (ABA) plays a central role in the response and adaptation to environmental constraints. However, apart from the well established role of ABA in regulating gene expression programmes, little is known about its function in plant stress metabolism. Principal Findings Using an integrative multiparallel approach of metabolome and transcriptome analyses, we studied the dynamic response of the model glyophyte Arabidopsis thaliana to ABA and high salt conditions. Our work shows that salt stress induces complex re-adjustment of carbohydrate metabolism and that ABA triggers the initial steps of carbon mobilisation. Significance These findings open new perspectives on how high salinity and ABA impact on central carbohydrate metabolism and highlight the power of iterative combinatorial approaches of non-targeted and hypothesis-driven experiments in stress biology. PMID:19081841
Key Role of CRF in the Skin Stress Response System

PubMed Central

Zmijewski, Michal A.; Zbytek, Blazej; Tobin, Desmond J.; Theoharides, Theoharis C.; Rivier, Jean

2013-01-01

The discovery of corticotropin-releasing factor (CRF) or CRH defining the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis, along with the identification of the corresponding receptors (CRFRs 1 and 2), represents a milestone in our understanding of central mechanisms regulating body and local homeostasis. We focused on the CRF-led signaling systems in the skin and offer a model for regulation of peripheral homeostasis based on the interaction of CRF and the structurally related urocortins with corresponding receptors and the resulting direct or indirect phenotypic effects that include regulation of epidermal barrier function, skin immune, pigmentary, adnexal, and dermal functions necessary to maintain local and systemic homeostasis. The regulatory modes of action include the classical CRF-led cutaneous equivalent of the central HPA axis, the expression and function of CRF and related peptides, and the stimulation of pro-opiomelanocortin peptides or cytokines. The key regulatory role is assigned to the CRFR-1α receptor, with other isoforms having modulatory effects. CRF can be released from sensory nerves and immune cells in response to emotional and environmental stressors. The expression sequence of peptides includes urocortin/CRF→pro-opiomelanocortin→ACTH, MSH, and β-endorphin. Expression of these peptides and of CRFR-1α is environmentally regulated, and their dysfunction can lead to skin and systemic diseases. Environmentally stressed skin can activate both the central and local HPA axis through either sensory nerves or humoral factors to turn on homeostatic responses counteracting cutaneous and systemic environmental damage. CRF and CRFR-1 may constitute novel targets through the use of specific agonists or antagonists, especially for therapy of skin diseases that worsen with stress, such as atopic dermatitis and psoriasis. PMID:23939821
Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling

PubMed Central

Diaz, Maira; Sanchez-Barrena, Maria Jose; Gonzalez-Rubio, Juana Maria; Rodriguez, Lesia; Fernandez, Daniel; Antoni, Regina; Yunta, Cristina; Belda-Palazon, Borja; Gonzalez-Guzman, Miguel; Peirats-Llobet, Marta; Menendez, Margarita; Boskovic, Jasminka; Marquez, Jose A.; Rodriguez, Pedro L.; Albert, Armando

2016-01-01

Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca2+ are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca2+ signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca2+-dependent recruitment of the pyrabactin resistance 1/PYR1-like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca2+ sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca2+-dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress. PMID:26719420
Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling.

PubMed

Diaz, Maira; Sanchez-Barrena, Maria Jose; Gonzalez-Rubio, Juana Maria; Rodriguez, Lesia; Fernandez, Daniel; Antoni, Regina; Yunta, Cristina; Belda-Palazon, Borja; Gonzalez-Guzman, Miguel; Peirats-Llobet, Marta; Menendez, Margarita; Boskovic, Jasminka; Marquez, Jose A; Rodriguez, Pedro L; Albert, Armando

2016-01-19

Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca(2+) are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca(2+) signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca(2+)-dependent recruitment of the pyrabactin resistance 1/PYR1-like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca(2+) sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca(2+)-dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress.
The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Anqi; Gan, Xueqi; Chen, Ruiqi

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics inmore » oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways. - Highlights: • Demonstrated first time the link between the mPTP to mitochondrial dynamics. • The role of Cyclophilin D in the regulation of Drp1-mediated mitochondrial fission. • CsA as a potential target for governing oxidative stress related neuropathology.« less
Neuronal connectivity and interactions between the auditory and limbic systems. Effects of noise and tinnitus.

PubMed

Kraus, Kari Suzanne; Canlon, Barbara

2012-06-01

Acoustic experience such as sound, noise, or absence of sound induces structural or functional changes in the central auditory system but can also affect limbic regions such as the amygdala and hippocampus. The amygdala is particularly sensitive to sound with valence or meaning, such as vocalizations, crying or music. The amygdala plays a central role in auditory fear conditioning, regulation of the acoustic startle response and can modulate auditory cortex plasticity. A stressful acoustic stimulus, such as noise, causes amygdala-mediated release of stress hormones via the HPA-axis, which may have negative effects on health, as well as on the central nervous system. On the contrary, short-term exposure to stress hormones elicits positive effects such as hearing protection. The hippocampus can affect auditory processing by adding a temporal dimension, as well as being able to mediate novelty detection via theta wave phase-locking. Noise exposure affects hippocampal neurogenesis and LTP in a manner that affects structural plasticity, learning and memory. Tinnitus, typically induced by hearing malfunctions, is associated with emotional stress, depression and anatomical changes of the hippocampus. In turn, the limbic system may play a role in the generation as well as the suppression of tinnitus indicating that the limbic system may be essential for tinnitus treatment. A further understanding of auditory-limbic interactions will contribute to future treatment strategies of tinnitus and noise trauma. Copyright © 2012 Elsevier B.V. All rights reserved.
The Skn7 Response Regulator of Saccharomyces cerevisiae Interacts with Hsf1 In Vivo and Is Required for the Induction of Heat Shock Genes by Oxidative Stress

PubMed Central

Raitt, Desmond C.; Johnson, Anthony L.; Erkine, Alexander M.; Makino, Kozo; Morgan, Brian; Gross, David S.; Johnston, Leland H.

2000-01-01

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein–protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we demonstrate that a strain deleted for the SKN7 gene and containing a temperature-sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock genes in response specifically to oxidative stress. We further show that, like Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal growth conditions as well as during oxidative stress. PMID:10888672
Metabolic consequences of stress during childhood and adolescence.

PubMed

Pervanidou, Panagiota; Chrousos, George P

2012-05-01

Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity-related health problems. Copyright © 2012 Elsevier Inc. All rights reserved.
Effect of pertussis toxin pretreated centrally on blood glucose level induced by stress.

PubMed

Suh, Hong-Won; Sim, Yun-Beom; Park, Soo-Hyun; Sharma, Naveen; Im, Hyun-Ju; Hong, Jae-Seung

2016-09-01

In the present study, we examined the effect of pertussis toxin (PTX) administered centrally in a variety of stress-induced blood glucose level. Mice were exposed to stress after the pretreatment of PTX (0.05 or 0.1 µg) i.c.v. or i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min after stress stimulation. The blood glucose level was increased in all stress groups. The blood glucose level reached at maximum level after 30 min of stress stimulation and returned to a normal level after 2 h of stress stimulation in restraint stress, physical, and emotional stress groups. The blood glucose level induced by cold-water swimming stress was gradually increased up to 1 h and returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX, a Gi inhibitor, alone produced a hypoglycemia and almost abolished the elevation of the blood level induced by stress stimulation. The central pretreatment with PTX caused a reduction of plasma insulin level, whereas plasma corticosterone level was further up-regulated in all stress models. Our results suggest that the hyperglycemia produced by physical stress, emotional stress, restraint stress, and the cold-water swimming stress appear to be mediated by activation of centrally located PTX-sensitive G proteins. The reduction of blood glucose level by PTX appears to due to the reduction of plasma insulin level. The reduction of blood glucose level by PTX was accompanied by the reduction of plasma insulin level. Plasma corticosterone level up-regulation by PTX in stress models may be due to a blood glucose homeostatic mechanism.
Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems Relationships between Metabolites, Structural Genes, and Transcriptional Regulators in Developing Grape Berries (Vitis vinifera L.) Exposed to Water Deficit.

PubMed

Savoi, Stefania; Wong, Darren C J; Degu, Asfaw; Herrera, Jose C; Bucchetti, Barbara; Peterlunger, Enrico; Fait, Aaron; Mattivi, Fulvio; Castellarin, Simone D

2017-01-01

Grapes are one of the major fruit crops and they are cultivated in many dry environments. This study comprehensively characterizes the metabolic response of grape berries exposed to water deficit at different developmental stages. Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins, and free volatile organic compounds have been previously observed in grape berries exposed to water deficit. Integrating RNA-sequencing analysis of the transcriptome with large-scale analysis of central and specialized metabolites, we reveal that these increases occur via a coordinated regulation of key structural pathway genes. Water deficit-induced up-regulation of flavonoid genes is also coordinated with the down-regulation of many stilbene synthases and a consistent decrease in stilbenoid concentration. Water deficit activated both ABA-dependent and ABA-independent signal transduction pathways by modulating the expression of several transcription factors. Gene-gene and gene-metabolite network analyses showed that water deficit-responsive transcription factors such as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress-responsive metabolites. Enrichment of known and novel cis -regulatory elements in the promoters of several ripening-specific/water deficit-induced modules further affirms the involvement of a transcription factor cross-talk in the berry response to water deficit. Together, our integrated approaches show that water deficit-regulated gene modules are strongly linked to key fruit-quality metabolites and multiple signal transduction pathways may be critical to achieve a balance between the regulation of the stress-response and the berry ripening program. This study constitutes an invaluable resource for future discoveries and comparative studies, in grapes and other fruits, centered on reproductive tissue metabolism under abiotic stress.
The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells.

PubMed

Xiao, Anqi; Gan, Xueqi; Chen, Ruiqi; Ren, Yanming; Yu, Haiyang; You, Chao

2017-01-29

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics in oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways. Copyright © 2016 Elsevier Inc. All rights reserved.
Yeast Hog1 proteins are sequestered in stress granules during high-temperature stress.

PubMed

Shiraishi, Kosuke; Hioki, Takahiro; Habata, Akari; Yurimoto, Hiroya; Sakai, Yasuyoshi

2018-01-09

The yeast high-osmolarity glycerol (HOG) pathway plays a central role in stress responses. It is activated by various stresses, including hyperosmotic stress, oxidative stress, high-temperature stress and exposure to arsenite. Hog1, the crucial MAP kinase of the pathway, localizes to the nucleus in response to high osmotic concentrations, i.e. high osmolarity; but, otherwise, little is known about its intracellular dynamics and regulation. By using the methylotrophic yeast Candida boidinii , we found that CbHog1-Venus formed intracellular dot structures after high-temperature stress in a reversible manner. Microscopic observation revealed that CbHog1-mCherry colocalized with CbPab1-Venus, a marker protein of stress granules. Hog1 homologs in Pichia pastoris and Schizosaccharomyces pombe also exhibited similar dot formation under high-temperature stress, whereas Saccharomyces cerevisiae Hog1 (ScHog1)-GFP did not. Analysis of CbHog1-Venus in C. boidinii revealed that a β-sheet structure in the N-terminal region was necessary and sufficient for its localization to stress granules. Physiological studies revealed that sequestration of activated Hog1 proteins in stress granules was responsible for downregulation of Hog1 activity under high-temperature stress.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.
Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity.

PubMed

Kim, Jongwan; Yun, Eun-Young; Quan, Fu-Shi; Park, Seung-Won; Goo, Tae-Won

2017-01-01

The α -glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS).
Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis1

PubMed Central

Chen, Yanmei; Hoehenwarter, Wolfgang

2015-01-01

Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K+ and Na+ transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. PMID:26471895
A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary.

PubMed

Whirledge, Shannon; Cidlowski, John A

2013-12-01

In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success.

A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

PubMed Central

Whirledge, Shannon

2013-01-01

In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success. PMID:24064362
Unraveling Regulation of the Small Heat Shock Proteins by the Heat Shock Factor HvHsfB2c in Barley: Its Implications in Drought Stress Response and Seed Development

PubMed Central

Reddy, Palakolanu Sudhakar; Kavi Kishor, Polavarapu B.; Seiler, Christiane; Kuhlmann, Markus; Eschen-Lippold, Lennart; Lee, Justin; Reddy, Malireddy K.; Sreenivasulu, Nese

2014-01-01

The rapid increase in heat shock proteins upon exposure to damaging stresses and during plant development related to desiccation events reveal their dual importance in plant development and stress tolerance. Genome-wide sequence survey identified 20 non-redundant small heat shock proteins (sHsp) and 22 heat shock factor (Hsf) genes in barley. While all three major classes (A, B, C) of Hsfs are localized in nucleus, the 20 sHsp gene family members are localized in different cell organelles like cytoplasm, mitochondria, plastid and peroxisomes. Hsf and sHsp members are differentially regulated during drought and at different seed developmental stages suggesting the importance of chaperone role under drought as well as seed development. In silico cis-regulatory motif analysis of Hsf promoters showed an enrichment with abscisic acid responsive cis-elements (ABRE), implying regulatory role of ABA in mediating transcriptional response of HvsHsf genes. Gene regulatory network analysis identified HvHsfB2c as potential central regulator of the seed-specific expression of several HvsHsps including 17.5CI sHsp. These results indicate that HvHsfB2c is co-expressed in the central hub of small Hsps and therefore it may be regulating the expression of several HvsHsp subclasses HvHsp16.88-CI, HvHsp17.5-CI and HvHsp17.7-CI. The in vivo relevance of binding specificity of HvHsfB2C transcription factor to HSE-element present in the promoter of HvSHP17.5-CI under heat stress exposure is confirmed by gel shift and LUC-reporter assays. Further, we isolated 477 bp cDNA from barley encoding a 17.5 sHsp polypeptide, which was predominantly upregulated under drought stress treatments and also preferentially expressed in developing seeds. Recombinant HvsHsp17.5-CI protein was expressed in E. coli and purified to homogeneity, which displayed in vitro chaperone activity. The predicted structural model of HvsHsp-17.5-CI protein suggests that the α-crystallin domain is evolutionarily highly conserved. PMID:24594978
Unraveling regulation of the small heat shock proteins by the heat shock factor HvHsfB2c in barley: its implications in drought stress response and seed development.

PubMed

Reddy, Palakolanu Sudhakar; Kavi Kishor, Polavarapu B; Seiler, Christiane; Kuhlmann, Markus; Eschen-Lippold, Lennart; Lee, Justin; Reddy, Malireddy K; Sreenivasulu, Nese

2014-01-01

The rapid increase in heat shock proteins upon exposure to damaging stresses and during plant development related to desiccation events reveal their dual importance in plant development and stress tolerance. Genome-wide sequence survey identified 20 non-redundant small heat shock proteins (sHsp) and 22 heat shock factor (Hsf) genes in barley. While all three major classes (A, B, C) of Hsfs are localized in nucleus, the 20 sHsp gene family members are localized in different cell organelles like cytoplasm, mitochondria, plastid and peroxisomes. Hsf and sHsp members are differentially regulated during drought and at different seed developmental stages suggesting the importance of chaperone role under drought as well as seed development. In silico cis-regulatory motif analysis of Hsf promoters showed an enrichment with abscisic acid responsive cis-elements (ABRE), implying regulatory role of ABA in mediating transcriptional response of HvsHsf genes. Gene regulatory network analysis identified HvHsfB2c as potential central regulator of the seed-specific expression of several HvsHsps including 17.5CI sHsp. These results indicate that HvHsfB2c is co-expressed in the central hub of small Hsps and therefore it may be regulating the expression of several HvsHsp subclasses HvHsp16.88-CI, HvHsp17.5-CI and HvHsp17.7-CI. The in vivo relevance of binding specificity of HvHsfB2C transcription factor to HSE-element present in the promoter of HvSHP17.5-CI under heat stress exposure is confirmed by gel shift and LUC-reporter assays. Further, we isolated 477 bp cDNA from barley encoding a 17.5 sHsp polypeptide, which was predominantly upregulated under drought stress treatments and also preferentially expressed in developing seeds. Recombinant HvsHsp17.5-CI protein was expressed in E. coli and purified to homogeneity, which displayed in vitro chaperone activity. The predicted structural model of HvsHsp-17.5-CI protein suggests that the α-crystallin domain is evolutionarily highly conserved.
Effects of acute handling stress on short-term central expression of orexigenic/anorexigenic genes in zebrafish.

PubMed

Cortés, Raul; Teles, Mariana; Oliveira, Miguel; Fierro-Castro, Camino; Tort, Lluis; Cerdá-Reverter, José Miguel

2018-02-01

Physiological mechanisms driving stress response in vertebrates are evolutionarily conserved. These mechanisms involve the activation of both the hypothalamic-sympathetic-chromaffin cell (HSC) and the hypothalamic-pituitary-adrenal (HPA) axes. In fish, the reduction of food intake levels is a common feature of the behavioral response to stress but the central mechanisms coordinating the energetic response are not well understood yet. In this work, we explore the effects of acute stress on key central systems regulating food intake in fish as well as on total body cortisol and glucose levels. We show that acute stress induced a rapid increase in total body cortisol with no changes in body glucose, at the same time promoting a prompt central response by activating neuronal pathways. All three orexigenic peptides examined, i.e., neuropeptide y (npy), agouti-related protein (agrp), and ghrelin, increased their central expression level suggesting that these neuronal systems are not involved in the short-term feeding inhibitory effects of acute stress. By contrast, the anorexigenic precursors tested, i.e., cart peptides and pomc, exhibited increased expression after acute stress, suggesting their involvement in the anorexigenic effects.
The heel and toe of the cell’s foot: A multifaceted approach for understanding the structure and dynamics of focal adhesions

PubMed Central

Wolfenson, Haguy; Henis, Yoav I.; Geiger, Benjamin; Bershadsky, Alexander D.

2010-01-01

Focal adhesions (FAs) are large clusters of transmembrane receptors of the integrin family and a multitude of associated cytoplasmic “plaque” proteins, which connect the extracellular matrix-bound receptors with the actin cytoskeleton. The formation of nearly stationary focal adhesions defines a boundary between dense and highly dynamic actin network in lamellipodium and the sparser and more diverse cytoskeletal organization in the lamella proper, creating a template for the organization of entire actin network. The major “mechanical” and “sensory” functions of FAs, namely, the nucleation and regulation of the contractile, myosin-II-containing, stress fibers and the mechanosensing of external surfaces depend, to a major extent, on the dynamics of molecular components within FAs. A central element in FA regulation concerns the positive feedback loop, based on the most intriguing feature of FAs, namely, their dependence on mechanical tension developing by the growing stress fibers. FAs grow in response to such tension, and rapidly disassemble upon its relaxation. In this article we address the mechanistic relationships between the process of FA development, maturation and dissociation and the dynamic molecular events, which take place in different regions of the FA, primarily in the distal end of this structure (the “toe”) and the proximal “heel”, and discuss the central role of local mechanical forces in orchestrating the complex interplay between FAs and the actin system. PMID:19598236
MATERNAL TRAUMA AFFECTS PRENATAL MENTAL HEALTH AND INFANT STRESS REGULATION AMONG PALESTINIAN DYADS.

PubMed

Isosävi, Sanna; Diab, Safwat Y; Kangaslampi, Samuli; Qouta, Samir; Kankaanpää, Saija; Puura, Kaija; Punamäki, Raija-Leena

2017-09-01

We examined how diverse and cumulated traumatic experiences predicted maternal prenatal mental health and infant stress regulation in war conditions and whether maternal mental health mediated the association between trauma and infant stress regulation. Participants were 511 Palestinian mothers from the Gaza Strip who reported exposure to current war trauma (WT), past childhood emotional (CEA) and physical abuse, socioeconomic status (SES), prenatal mental health problems (posttraumatic stress disorder and depression symptoms), and perceived stress during their secondtrimester of pregnancy as well as infant stress regulation at 4 months. While all trauma types were associated with high levels of prenatal symptoms, CEA had the most wide-ranging effects and was uniquely associated with depression symptoms. Concerning infant stress regulation, mothers' CEA predicted negative affectivity, but only among mothers with low WT. Against hypothesis, the effects of maternal trauma on infant stress regulation were not mediated by mental health symptoms. Mothers' higher SES was associated with better infant stress regulation whereas infant prematurity and male sex predisposed for difficulties. Our findings suggest that maternal childhood abuse, especially CEA, should be a central treatment target among war-exposed families. Cumulated psychosocial stressors might increase the risk for transgenerational problems. © 2017 Michigan Association for Infant Mental Health.
Maternal stress and diet may influence affective behavior and stress-response in offspring via epigenetic regulation of central peptidergic function.

PubMed

Thorsell, Annika; Nätt, Daniel

2016-08-01

It has been shown that maternal stress and malnutrition, or experience of other adverse events, during the perinatal period may alter susceptibility in the adult offspring in a time-of-exposure dependent manner. The mechanism underlying this may be epigenetic in nature. Here, we summarize some recent findings on the effects on gene-regulation following maternal malnutrition, focusing on epigenetic regulation of peptidergic activity. Numerous neuropeptides within the central nervous system are crucial components in regulation of homeostatic energy-balance, as well as affective health (i.e. health events related to affective disorders, psychiatric disorders also referred to as mood disorders). It is becoming evident that expression, and function, of these neuropeptides can be regulated via epigenetic mechanisms during fetal development, thereby contributing to the development of the adult phenotype and, possibly, modulating disease susceptibility. Here, we focus on two such neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH), both involved in regulation of endocrine function, energy homeostasis, as well as affective health. While a number of published studies indicate the involvement of epigenetic mechanisms in CRH-dependent regulation of the offspring adult phenotype, NPY has been much less studied in this context and needs further work.
Sex and Stress Hormone Influences on the Expression and Activity of Brain-Derived Neurotrophic Factor

PubMed Central

Carbone, David L.; Handa, Robert J.

2012-01-01

The neurotrophin, brain-derived neurotrophic factor (BDNF), is recognized as a key component in the regulation of central nervous system ontogeny, homeostasis and adult neuroplasticity. The importance of BDNF in central nervous system development and function is well documented by numerous reports from animal studies linking abnormal BDNF signaling to metabolic disturbances and anxiety or depressive-like behavior. Despite the diverse roles for BDNF in nearly all aspects of central nervous system physiology, the regulation of BDNF expression, as well as our understanding of the signaling mechanisms associated with this neurotrophin, remains incomplete. However, links between sex hormones such as estradiol and testosterone, as well as endogenous and synthetic glucocorticoids, have emerged as important mediators of BDNF expression and function. Examples of such regulation include brain region-specific induction of Bdnf mRNA in response to estradiol. Additional studies have also documented regulation of the expression of the high-affinity BDNF receptor TrkB by estradiol, thus implicating sex steroids not only in the regulation of BDNF expression, but on mechanisms of signaling associated with it. In addition to gonadal steroids, further evidence also suggests functional interaction between BDNF and glucocorticoids, such as in the regulation of corticotrophin-releasing hormone and other important neuropeptides. In this review, we provide an overview of the roles played by selected sex or stress hormones in the regulation of BDNF expression and signaling in the central nervous system PMID:23211562
A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria

PubMed Central

2018-01-01

ABSTRACT The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus. We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria. PMID:29789370
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.

PubMed

Martínez-Sánchez, Noelia; Seoane-Collazo, Patricia; Contreras, Cristina; Varela, Luis; Villarroya, Joan; Rial-Pensado, Eva; Buqué, Xabier; Aurrekoetxea, Igor; Delgado, Teresa C; Vázquez-Martínez, Rafael; González-García, Ismael; Roa, Juan; Whittle, Andrew J; Gomez-Santos, Beatriz; Velagapudi, Vidya; Tung, Y C Loraine; Morgan, Donald A; Voshol, Peter J; Martínez de Morentin, Pablo B; López-González, Tania; Liñares-Pose, Laura; Gonzalez, Francisco; Chatterjee, Krishna; Sobrino, Tomás; Medina-Gómez, Gema; Davis, Roger J; Casals, Núria; Orešič, Matej; Coll, Anthony P; Vidal-Puig, Antonio; Mittag, Jens; Tena-Sempere, Manuel; Malagón, María M; Diéguez, Carlos; Martínez-Chantar, María Luz; Aspichueta, Patricia; Rahmouni, Kamal; Nogueiras, Rubén; Sabio, Guadalupe; Villarroya, Francesc; López, Miguel

2017-07-05

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

PubMed

Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

2014-01-01

The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.
Desiccation and osmotic stress increase the abundance of mRNA of the tonoplast aquaporin BobTIP26-1 in cauliflower cells.

PubMed

Barrieu, F; Marty-Mazars, D; Thomas, D; Chaumont, F; Charbonnier, M; Marty, F

1999-07-01

Changes in vacuolar structure and the expression at the RNA level of a tonoplast aquaporin (BobTIP26-1) were examined in cauliflower (Brassicaoleracea L. var. botrytis) under water-stress conditions. Gradual drying out of slices of cauliflower floret tissue caused its collapse, with a shrinkage in tissue and cell volumes and an apparent vesiculation of the central vacuole, whereas osmotic stress resulted in plasmolysis with a collapse of the cytoplasm and the central vacuole within. Osmotic stress caused a rapid and substantial increase in BobTIP26 mRNA in slices of floret tissue. Exposure of tissue slices to a regime of desiccation showed a slower but equally large rise in BobTIP26 mRNA followed by a rapid decline upon rehydration. In situ hybridization showed that BobTIP26-2 mRNA is expressed most highly in meristematic and expanding cells of the cauliflower florets and that desiccation strongly increased the expression in those cells and in differentiated cells near the xylem vessels. These data indicate that under water-deficit conditions, expression of the tonoplast aquaporin gene in cauliflower is subject to a precise regulation that can be correlated with important cytological changes in the cells.
The moderator role of emotion regulation ability in the link between stress and well-being

PubMed Central

Extremera, Natalio; Rey, Lourdes

2015-01-01

This article examined the moderating role of a central core dimension of emotional intelligence—emotion-regulation ability—in the relationship between perceived stress and indicators of well-being (depression and subjective happiness) in a sample from a community adult population. The relationships for males and females on these dimensions were also compared. Results revealed that emotion-regulation abilities moderated both the association between perceived stress and depression/happiness for the total sample. However, a gender-specific analysis showed that the moderation effect was only significant for males. In short, when males reported a high level of perceived stress, those with high scores in regulating emotions reported higher scores in subjective happiness and lower depression symptoms than those with low regulating emotions. However, no interaction effect of regulating emotions and stress for predicting subjective happiness and depression was found for females. In developing stress management programmes for reducing depression and increasing well-being, these findings suggest that training in emotional regulation may be more beneficial for males than females. Our findings are discussed in terms of the need for future research to understand the different gender associations and to consider these differences in further intervention programmes. PMID:26579017
Rates and predictors of mental stress in Rwanda: investigating the impact of gender, persecution, readiness to reconcile and religiosity via a structural equation model.

PubMed

Heim, Lale; Schaal, Susanne

2014-01-01

As a consequence of the 1994 Rwandan genocide, prevalences of mental disorders are elevated in Rwanda. More knowledge about determinants of mental stress can help to improve mental health services and treatment in the east-central African country. The present study aimed to investigate actual rates of mental stress (posttraumatic stress disorder, syndromal depression and syndromal anxiety) in Rwanda and to examine if gender, persecution during the genocide, readiness to reconcile as well as importance given to religiosity and quality of religiosity are predictors of mental stress. The study comprised a community sample of N = 200 Rwandans from Rwanda's capital Kigali, who experienced the Rwandan genocide. By conducting structured interviews, ten local Master level psychologists examined types of potentially lifetime traumatic events, symptoms of posttraumatic stress disorder (PTSD), depression and anxiety, readiness to reconcile and religiosity. Applying non-recursive structural equation modeling (SEM), the associations between gender, persecution, readiness to reconcile, religiosity and mental stress were investigated. Respondents had experienced an average number of 11.38 types of potentially lifetime traumatic events. Of the total sample, 11% met diagnostic criteria for PTSD, 19% presented with syndromal depression and 23% with syndromal anxiety. Female sex, persecution and readiness to reconcile were significant predictors of mental stress. Twofold association was found between centrality of religion (which captures the importance given to religiosity) and mental stress, showing, that higher mental stress provokes a higher centrality and that higher centrality reduces mental stress. The variables positive and negative religious functioning (which determine the quality of religiosity) respectively had an indirect negative and positive effect on mental stress. Study results provide evidence that rates of mental stress are still elevated in Rwanda and that female sex, persecution, readiness to reconcile, centrality and religious functioning are predictors of mental stress. Seventeen years after the genocide, there remains a large gap between the need for and provision of mental health services in Rwanda. Results underline the importance of improving the respective infrastructure, with a focus on the requirements of women and persons, who were persecuted during the genocide. They further highlight that the consideration of readiness to reconcile, centrality and religious functioning in therapeutic interventions can aid mental health in Rwanda.
Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.

PubMed

Tsai, Jordan C; Miller-Vedam, Lakshmi E; Anand, Aditya A; Jaishankar, Priyadarshini; Nguyen, Henry C; Renslo, Adam R; Frost, Adam; Walter, Peter

2018-03-30

Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Neuroendocrine mechanisms for immune system regulation during stress in fish.

PubMed

Nardocci, Gino; Navarro, Cristina; Cortés, Paula P; Imarai, Mónica; Montoya, Margarita; Valenzuela, Beatriz; Jara, Pablo; Acuña-Castillo, Claudio; Fernández, Ricardo

2014-10-01

In the last years, the aquaculture crops have experienced an explosive and intensive growth, because of the high demand for protein. This growth has increased fish susceptibility to diseases and subsequent death. The constant biotic and abiotic changes experienced by fish species in culture are challenges that induce physiological, endocrine and immunological responses. These changes mitigate stress effects at the cellular level to maintain homeostasis. The effects of stress on the immune system have been studied for many years. While acute stress can have beneficial effects, chronic stress inhibits the immune response in mammals and teleost fish. In response to stress, a signaling cascade is triggered by the activation of neural circuits in the central nervous system because the hypothalamus is the central modulator of stress. This leads to the production of catecholamines, corticosteroid-releasing hormone, adrenocorticotropic hormone and glucocorticoids, which are the essential neuroendocrine mediators for this activation. Because stress situations are energetically demanding, the neuroendocrine signals are involved in metabolic support and will suppress the "less important" immune function. Understanding the cellular mechanisms of the neuroendocrine regulation of immunity in fish will allow the development of new pharmaceutical strategies and therapeutics for the prevention and treatment of diseases triggered by stress at all stages of fish cultures for commercial production. Copyright © 2014 Elsevier Ltd. All rights reserved.
The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core

PubMed Central

Rajasekar, Karthik V.; Zdanowski, Konrad; Yan, Jun; Hopper, Jonathan T. S.; Francis, Marie-Louise R.; Seepersad, Colin; Sharp, Connor; Pecqueur, Ludovic; Werner, Jörn M.; Robinson, Carol V.; Mohammed, Shabaz; Potts, Jennifer R.; Kleanthous, Colin

2016-01-01

Redox-regulated effector systems that counteract oxidative stress are essential for all forms of life. Here we uncover a new paradigm for sensing oxidative stress centred on the hydrophobic core of a sensor protein. RsrA is an archetypal zinc-binding anti-sigma factor that responds to disulfide stress in the cytoplasm of Actinobacteria. We show that RsrA utilizes its hydrophobic core to bind the sigma factor σR preventing its association with RNA polymerase, and that zinc plays a central role in maintaining this high-affinity complex. Oxidation of RsrA is limited by the rate of zinc release, which weakens the RsrA–σR complex by accelerating its dissociation. The subsequent trigger disulfide, formed between specific combinations of RsrA's three zinc-binding cysteines, precipitates structural collapse to a compact state where all σR-binding residues are sequestered back into its hydrophobic core, releasing σR to activate transcription of anti-oxidant genes. PMID:27432510
The ambient stress field in the continental margin around the Korean Peninsula and Japanese islands

NASA Astrophysics Data System (ADS)

Lee, J.; Hong, T. K.; Chang, C.

2016-12-01

The ambient stress field is mainly influenced by regional tectonics. The stress field composition is crucial information for seismic hazard assessment. The Korean Peninsula, Japanese Islands and East Sea comprise the eastern margin of the Eurasian plate. The regions are surrounded by the Okhotsk, Pacific, and Philippine Sea plates. We investigate the regional stress field around the Korean Peninsula and Japanese islands using the focal mechanism solutions of regional earthquakes. Complex lateral and vertical variations of regional crustal stress fields are observed around a continental margin. The dominant compression directions are ENE-WSW around the Korean Peninsula and eastern China, E-W in the central East Sea and northern and southern Japan, NW-SE in the central Japan, and N-S around the northern Nankai trough. The horizontal compression directions are observed to be different by fault type, suggesting structure-dependent stress field distortion. The regional stress field change by depth and location, suggesting that the compression and tension stress may alternate in local region. The stress field and structures affect mutually, causing stress field distortion and reactivation of paleo-structures. These observation may be useful for understanding of local stress-field perturbation for seismic hazard mitigation of the region.
Dissecting the roles of ROCK isoforms in stress-induced cell detachment.

PubMed

Shi, Jianjian; Surma, Michelle; Zhang, Lumin; Wei, Lei

2013-05-15

The homologous Rho kinases, ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant. Using mouse embryonic fibroblasts (MEFs) derived from ROCK1(-/-) and ROCK2(-/-) mice, we have recently reported that they play different roles in regulating doxorubicin-induced stress fiber disassembly and cell detachment: ROCK1 is involved in destabilizing the actin cytoskeleton and cell detachment, whereas ROCK2 is required for stabilizing the actin cytoskeleton and cell adhesion. Here, we present additional insights into the roles of ROCK1 and ROCK2 in regulating stress-induced impairment of cell-matrix and cell-cell adhesion. In response to doxorubicin, ROCK1(-/-) MEFs showed significant preservation of both focal adhesions and adherens junctions, while ROCK2(-/-) MEFs exhibited impaired focal adhesions but preserved adherens junctions compared with the wild-type MEFs. Additionally, inhibition of focal adhesion or adherens junction formations by chemical inhibitors abolished the anti-detachment effects of ROCK1 deletion. Finally, ROCK1(-/-) MEFs, but not ROCK2(-/-) MEFs, also exhibited preserved central stress fibers and reduced cell detachment in response to serum starvation. These results add new insights into a novel mechanism underlying the anti-detachment effects of ROCK1 deletion mediated by reduced peripheral actomyosin contraction and increased actin stabilization to promote cell-cell and cell-matrix adhesion. Our studies further support the differential roles of ROCK isoforms in regulating stress-induced loss of central stress fibers and focal adhesions as well as cell detachment.
A mechanism for sickness sleep: lessons from invertebrates.

PubMed

Davis, Kristen C; Raizen, David M

2017-08-15

During health, animal sleep is regulated by an internal clock and by the duration of prior wakefulness. During sickness, sleep is regulated by cytokines released from either peripheral cells or from cells within the nervous system. These cytokines regulate central nervous system neurons to induce sleep. Recent research in the invertebrates Caenorhabditis elegans and Drosophila melanogaster has led to new insights into the mechanism of sleep during sickness. Sickness is triggered by exposure to environments such as infection, heat, or ultraviolet light irradiation, all of which cause cellular stress. Epidermal growth factor is released from stressed cells and signals to activate central neuroendocrine cell(s). These neuron(s) release neuropeptides including those containing an amidated arginine(R)-phenylalanine(F) motif at their C-termini (RFamide peptides). Importantly, mechanisms regulating sickness sleep are partially distinct from those regulating healthy sleep. We will here review key findings that have elucidated the central neuroendocrine mechanism of sleep during sickness. Adaptive mechanisms employed in the control of sickness sleep may play a role in correcting cellular homeostasis after various insults. We speculate that these mechanisms may play a maladaptive role in human pathological conditions such as in the fatigue and anorexia associated with autoimmune diseases, with major depression, and with unexplained chronic fatigue. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Roles of STATs signaling in cardiovascular diseases.

PubMed

Kishore, Raj; Verma, Suresh K

2012-04-01

In cardiac and many other systems, chronic stress activates avfamily of structurally and functionally conserved receptors and their downstream signaling molecules that entail tyrosine, serine or threonine phosphorylation to transfer the messages to the genetic machinery. However, the activation of the Janus kinases (JAKs) and their downstream signal transducer and activator of transcription (STATs) proteins is both characteristic of and unique to cytokine and growth factor signaling which plays a central role in heart physiology. Dysregulation of JAK-STAT signaling is associated with various cardiovascular diseases. The molecular signaling and specificity of the JAK-STAT pathway are modulated at many levels by distinct regulatory proteins. Here, we review recent studies on the regulation of the STAT signaling pathway that will enhance our ability to design rational therapeutic strategies for stress-induced heart failure.
Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

PubMed

Agostini, A; Ballotta, D; Righi, S; Moretti, M; Bertani, A; Scarcelli, A; Sartini, A; Ercolani, M; Nichelli, P; Campieri, M; Benuzzi, F

2017-10-01

In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity. © 2017 John Wiley & Sons Ltd.
A Network Biology Approach to Decipher Stress Response in Bacteria Using Escherichia coli As a Model.

PubMed

Nagar, Shashwat Deepali; Aggarwal, Bhavye; Joon, Shikha; Bhatnagar, Rakesh; Bhatnagar, Sonika

2016-05-01

The development of drug-resistant pathogenic bacteria poses challenges to global health for their treatment and control. In this context, stress response enables bacterial populations to survive extreme perturbations in the environment but remains poorly understood. Specific modules are activated for unique stressors with few recognized global regulators. The phenomenon of cross-stress protection strongly suggests the presence of central proteins that control the diverse stress responses. In this work, Escherichia coli was used to model the bacterial stress response. A Protein-Protein Interaction Network was generated by integrating differentially expressed genes in eight stress conditions of pH, temperature, and antibiotics with relevant gene ontology terms. Topological analysis identified 24 central proteins. The well-documented role of 16 central proteins in stress indicates central control of the response, while the remaining eight proteins may have a novel role in stress response. Cluster analysis of the generated network implicated RNA binding, flagellar assembly, ABC transporters, and DNA repair as important processes during response to stress. Pathway analysis showed crosstalk of Two Component Systems with metabolic processes, oxidative phosphorylation, and ABC transporters. The results were further validated by analysis of an independent cross-stress protection dataset. This study also reports on the ways in which bacterial stress response can progress to biofilm formation. In conclusion, we suggest that drug targets or pathways disrupting bacterial stress responses can potentially be exploited to combat antibiotic tolerance and multidrug resistance in the future.
Grassland species differentially regulate proline concentrations under future climate conditions: an integrated biochemical and modelling approach.

PubMed

AbdElgawad, Hamada; De Vos, Dirk; Zinta, Gaurav; Domagalska, Malgorzata A; Beemster, Gerrit T S; Asard, Han

2015-10-01

Proline (Pro) is a versatile metabolite playing a role in the protection of plants against environmental stresses. To gain a deeper understanding of the regulation of Pro metabolism under predicted future climate conditions, including drought stress, elevated temperature and CO2 , we combined measurements in contrasting grassland species (two grasses and two legumes) at multiple organisational levels, that is, metabolite concentrations, enzyme activities and gene expression. Drought stress (D) activates Pro biosynthesis and represses its catabolism, and elevated temperature (DT) further elevated its content. Elevated CO2 attenuated the DT effect on Pro accumulation. Computational pathway control analysis allowed a mechanistic understanding of the regulatory changes in Pro metabolism. This analysis indicates that the experimentally observed coregulation of multiple enzymes is more effective in modulating Pro concentrations than regulation of a single step. Pyrroline-5-carboxylate synthetase (P5CS) and pyrroline-5-carboxylate reductase (P5CR) play a central role in grasses (Lolium perenne, Poa pratensis), and arginase (ARG), ornithine aminotransferase (OAT) and P5CR play a central role in legumes (Medicago lupulina, Lotus corniculatus). Different strategies in the regulation of Pro concentrations under stress conditions were observed. In grasses the glutamate pathway is activated predominantly, and in the legumes the ornithine pathway, possibly related to differences in N-nutritional status. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Stress- and Rho-activated ZO-1–associated nucleic acid binding protein binding to p21 mRNA mediates stabilization, translation, and cell survival

PubMed Central

Nie, Mei; Balda, Maria S.; Matter, Karl

2012-01-01

A central component of the cellular stress response is p21WAF1/CIP1, which regulates cell proliferation, survival, and differentiation. Inflammation and cell stress often up-regulate p21 posttranscriptionally by regulatory mechanisms that are poorly understood. ZO-1–associated nucleic acid binding protein (ZONAB)/DbpA is a Y-box transcription factor that is regulated by components of intercellular junctions that are affected by cytokines and tissue damage. We therefore asked whether ZONAB activation is part of the cellular stress response. Here, we demonstrate that ZONAB promotes cell survival in response to proinflammatory, hyperosmotic, and cytotoxic stress and that stress-induced ZONAB activation involves the Rho regulator GEF-H1. Unexpectedly, stress-induced ZONAB activation does not stimulate ZONAB’s activity as a transcription factor but leads to the posttranscriptional up-regulation of p21 protein and mRNA. Up-regulation is mediated by ZONAB binding to specific sites in the 3′-untranslated region of the p21 mRNA, resulting in mRNA stabilization and enhanced translation. Binding of ZONAB to mRNA is activated by GEF-H1 via Rho stimulation and also mediates Ras-induced p21 expression. We thus identify a unique type of stress and Rho signaling activated pathway that drives mRNA stabilization and translation and links the cellular stress response to p21 expression and cell survival. PMID:22711822
Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax

PubMed Central

2010-01-01

Background Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. Results We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. Conclusion The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man. PMID:20074340
Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax.

PubMed

Tognoli, Chiara; Rossi, Federica; Di Cola, Francesco; Baj, Gabriele; Tongiorgi, Enrico; Terova, Genciana; Saroglia, Marco; Bernardini, Giovanni; Gornati, Rosalba

2010-01-14

Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.
An mRNA-Derived Noncoding RNA Targets and Regulates the Ribosome

PubMed Central

Pircher, Andreas; Bakowska-Zywicka, Kamilla; Schneider, Lukas; Zywicki, Marek; Polacek, Norbert

2014-01-01

Summary The structural and functional repertoire of small non-protein-coding RNAs (ncRNAs) is central for establishing gene regulation networks in cells and organisms. Here, we show that an mRNA-derived 18-nucleotide-long ncRNA is capable of downregulating translation in Saccharomyces cerevisiae by targeting the ribosome. This 18-mer ncRNA binds to polysomes upon salt stress and is crucial for efficient growth under hyperosmotic conditions. Although the 18-mer RNA originates from the TRM10 locus, which encodes a tRNA methyltransferase, genetic analyses revealed the 18-mer RNA nucleotide sequence, rather than the mRNA-encoded enzyme, as the translation regulator. Our data reveal the ribosome as a target for a small regulatory ncRNA and demonstrate the existence of a yet unkown mechanism of translation regulation. Ribosome-targeted small ncRNAs are found in all domains of life and represent a prevalent but so far largely unexplored class of regulatory molecules. PMID:24685157
Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

PubMed

Varodayan, F P; Khom, S; Patel, R R; Steinman, M Q; Hedges, D M; Oleata, C S; Homanics, G E; Roberto, M; Bajo, M

2018-01-04

Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress. © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.
Farm Crisis Response: Extension and Research Activities in the North Central Region.

ERIC Educational Resources Information Center

Lasley, Paul, Comp.; And Others

The 12 states comprising the North Central Region have been affected in similar ways by the farm crisis of the 1980s. Statewide surveys show sizeable proportions of farm operations that are experiencing moderately high levels of financial stress. The problems caused by chronic stress on family structure and functioning, the loss of mainstreet…
The neurobiology of emotion regulation in posttraumatic stress disorder: Amygdala downregulation via real-time fMRI neurofeedback.

PubMed

Nicholson, Andrew A; Rabellino, Daniela; Densmore, Maria; Frewen, Paul A; Paret, Christian; Kluetsch, Rosemarie; Schmahl, Christian; Théberge, Jean; Neufeld, Richard W J; McKinnon, Margaret C; Reiss, Jim; Jetly, Rakesh; Lanius, Ruth A

2017-01-01

Amygdala dysregulation has been shown to be central to the pathophysiology of posttraumatic stress disorder (PTSD) representing a critical treatment target. Here, amygdala downregulation was targeted using real-time fMRI neurofeedback (rt-fMRI-nf) in patients with PTSD, allowing us to examine further the regulation of emotional states during symptom provocation. Patients (n = 10) completed three sessions of rt-fMRI-nf with the instruction to downregulate activation in the amygdala, while viewing personalized trauma words. Amygdala downregulation was assessed by contrasting (a) regulate trials, with (b) viewing trauma words and not attempting to regulate. Training was followed by one transfer run not involving neurofeedback. Generalized psychophysiological interaction (gPPI) and dynamic causal modeling (DCM) analyses were also computed to explore task-based functional connectivity and causal structure, respectively. It was found that PTSD patients were able to successfully downregulate both right and left amygdala activation, showing sustained effects within the transfer run. Increased activation in the dorsolateral and ventrolateral prefrontal cortex (PFC), regions related to emotion regulation, was observed during regulate as compared with view conditions. Importantly, activation in the PFC, rostral anterior cingulate cortex, and the insula, were negatively correlated to PTSD dissociative symptoms in the transfer run. Increased functional connectivity between the amygdala- and both the dorsolateral and dorsomedial PFC was found during regulate, as compared with view conditions during neurofeedback training. Finally, our DCM analysis exploring directional structure suggested that amygdala downregulation involves both top-down and bottom-up information flow with regard to observed PFC-amygdala connectivity. This is the first demonstration of successful downregulation of the amygdala using rt-fMRI-nf in PTSD, which was critically sustained in a subsequent transfer run without neurofeedback, and corresponded to increased connectivity with prefrontal regions involved in emotion regulation during the intervention. Hum Brain Mapp 38:541-560, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Sex-Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin-1a Receptors.

PubMed

Grundwald, N J; Benítez, D P; Brunton, P J

2016-04-01

Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin-1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up-regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS-induced sex-dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans. © 2015 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.
Self-Compassion, Emotion Regulation and Stress among Australian Psychologists: Testing an Emotion Regulation Model of Self-Compassion Using Structural Equation Modeling

PubMed Central

Finlay-Jones, Amy L.; Rees, Clare S.; Kane, Robert T.

2015-01-01

Psychologists tend to report high levels of occupational stress, with serious implications for themselves, their clients, and the discipline as a whole. Recent research suggests that self-compassion is a promising construct for psychologists in terms of its ability to promote psychological wellbeing and resilience to stress; however, the potential benefits of self-compassion are yet to be thoroughly explored amongst this occupational group. Additionally, while a growing body of research supports self-compassion as a key predictor of psychopathology, understanding of the processes by which self-compassion exerts effects on mental health outcomes is limited. Structural equation modelling (SEM) was used to test an emotion regulation model of self-compassion and stress among psychologists, including postgraduate trainees undertaking clinical work (n = 198). Self-compassion significantly negatively predicted emotion regulation difficulties and stress symptoms. Support was also found for our preliminary explanatory model of self-compassion, which demonstrates the mediating role of emotion regulation difficulties in the self-compassion-stress relationship. The final self-compassion model accounted for 26.2% of variance in stress symptoms. Implications of the findings and limitations of the study are discussed. PMID:26207900
Mitochondrial dysfunction as a central actor in intellectual disability-related diseases: an overview of Down syndrome, autism, Fragile X and Rett syndrome.

PubMed

Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Henrion-Caude, Alexandra; Vacca, Rosa Anna

2014-10-01

Clinical manifestations typical of mitochondrial diseases are often present in various genetic syndromes associated with intellectual disability, a condition leading to deficit in cognitive functions and adaptive behaviors. Until now, the causative mechanism leading to intellectual disability is unknown and the progression of the condition is poorly understood. We first report latest advances on genetic and environmental regulation of mitochondrial function and its role in brain development. Starting from the structure, function and regulation of the oxidative phosphorylation apparatus, we review how mitochondrial biogenesis and dynamics play a central role in neurogenesis and neuroplasticity. We then discuss how dysfunctional mitochondria and alterations in reactive oxygen species homeostasis are potentially involved in the pathogenesis of various neurodevelopmental syndromes with a special focus on Down, Rett, Fragile X syndromes and autism spectrum disorders. Finally, we review and suggest novel therapeutic approaches aimed at improving intellectual disability by activating mitochondrial function and reducing oxidative stress to amiliorate the quality of life in the subjects affected. Copyright © 2014 Elsevier Ltd. All rights reserved.
The role of predictability and structure in word stress processing: an ERP study on Cairene Arabic and a cross-linguistic comparison

PubMed Central

Domahs, Ulrike; Knaus, Johannes A.; El Shanawany, Heba; Wiese, Richard

2014-01-01

This article presents neurolinguistic data on word stress perception in Cairene Arabic, in comparison to previous results on German and Turkish. The main goal is to investigate how central properties of stress systems such as predictability of stress and metrical structure are reflected in the prosodic processing of words. Cairene Arabic is a language with a regular foot-based word stress system, leading to highly predictable placement of word stress. An ERP study on Cairene Arabic is reported, in which a stress violation paradigm is used to investigate the factors predictability of stress and foot structure. The results of the experiment show that for Cairene Arabic the internal structure of prosodic words in terms of feet determines prosodic processing. This structure effect is complemented by a frequency effect for stress patterns. PMID:25374546
Mechanisms of stress in the brain.

PubMed

McEwen, Bruce S; Bowles, Nicole P; Gray, Jason D; Hill, Matthew N; Hunter, Richard G; Karatsoreos, Ilia N; Nasca, Carla

2015-10-01

The brain is the central organ involved in perceiving and adapting to social and physical stressors via multiple interacting mediators, from the cell surface to the cytoskeleton to epigenetic regulation and nongenomic mechanisms. A key result of stress is structural remodeling of neural architecture, which may be a sign of successful adaptation, whereas persistence of these changes when stress ends indicates failed resilience. Excitatory amino acids and glucocorticoids have key roles in these processes, along with a growing list of extra- and intracellular mediators that includes endocannabinoids and brain-derived neurotrophic factor (BDNF). The result is a continually changing pattern of gene expression mediated by epigenetic mechanisms involving histone modifications and CpG methylation and hydroxymethylation as well as by the activity of retrotransposons that may alter genomic stability. Elucidation of the underlying mechanisms of plasticity and vulnerability of the brain provides a basis for understanding the efficacy of interventions for anxiety and depressive disorders as well as age-related cognitive decline.
Mindfulness for Adolescents: A Promising Approach to Supporting Emotion Regulation and Preventing Risky Behavior

ERIC Educational Resources Information Center

Broderick, Patricia C.; Jennings, Patricia A.

2012-01-01

This article reviews the contextual and neuropsychological challenges of the adolescent period with particular attention to the role that universal prevention can play in moderating the harmful effects of stress. The centrality of emotion regulation skills to long-term health and wellness suggests their importance in prevention and intervention…
Tectonic controlled submarine slidings and dewatering structures

NASA Astrophysics Data System (ADS)

Yamamoto, Y.; Hirono, T.; Takahashi, M.

2003-04-01

Geologic structures associated with mass movements processes such as slumping, sliding, and creeping can be the key to understanding the tectonic or geologic constraints in the time they were formed. Because they are sensitively reflected by the paleo-topography which must be associated with active tectonics. It must be very useful if the direction of paleo-slope instability is known easily in a wide area. We paid attentions to convolute lamination and flame structure which might be associated with dewatering and loading, respectively. Some recent researches report the possibility that well regulated flame structures might be formed in relation to paleo-slope instability. However, there is an alternative idea that they were reflection of heterogeneous loading associated with ripple marks on the sandy layers. This controversy has not been settled. Accordingly, to evaluate the reliability of the relationship between formation of such structures with well regulated arrays and paleo-slope instability, the Pliocene Chikura Group in the southern part of the Boso Peninsula, central Japan, was studied. The Chikura Group overlying the Miura Group, Miocene accretionary prism, is composed of trench-fill sediments in the lowermost and of trench-slope basin sediments in the upper. The Chikura Group was deposited on an east-west extended sedimentary basin during east-west trending folds and faults development. These indicate the direction of paleo-slope in the Chikura Group due north or south. Flame structures and convolute laminations were recognized over 60 sites in the Chikura Group. They have well-regulated planar arrays which extend almost east west, perpendicular to the direction of paleo-slope instability. Some examples of such structures and slump deposit were observed in the same outcrop. Vergence of these slump deposits were toward north or south, and ridges of flame structures and convolute laminations extend east-west. Experimental study of direct imaging of dewatering under shear stress regime by using X-ray CT and X-ray microscope shows similar arrays of dewatering paths. Water escapes through the foliation which might be a tension fracture caused by direct shear strain. The foliation has vertical trends to the applied shear stress and has high angle dippings with approximately 65 to 75 degrees to the direct shear plane. These field-based study and experiment indicate that well regulated flame structures and convolute laminations were formed by dewatering or mud liquidization by which water escapes through the tension fractures associated with shear stress corresponding to the paleo-slope instability. These structures are very important because we can identify easily the paleo-slope directions, direction of synsedimentary shear and also macro-scopic geologic constraints on tectonics around a study area.
Stress integration after acute and chronic predator stress: differential activation of central stress circuitry and sensitization of the hypothalamo-pituitary-adrenocortical axis.

PubMed

Figueiredo, Helmer F; Bodie, Bryan L; Tauchi, Miyuki; Dolgas, C Mark; Herman, James P

2003-12-01

Predator exposure is a naturalistic stressor of high ethological relevance. In the current study, our group examined central and peripheral integration of stress responses in rats after acute or repeated exposure to a natural predator (cat). Acute cat exposure rapidly induced hypothalamo-pituitary-adrenocortical (HPA) axis activation and paraventricular nucleus (PVN) CRH mRNA production. Repeated daily cat exposure (7 and 14 d) also up-regulated PVN mRNA CRH expression, but did not result in frank adrenocortical hyperactivity. Unlike other chronic homotypic stress regimens, repeated cat exposure facilitated corticosterone secretion after the 6th or 13th day of exposure. Notably, ACTH secretion and central amygdaloid nucleus CRH mRNA expression were enhanced in animals that were preexposed to the holding chamber relative to chamber-naive rats, suggesting that contextual cues can sensitize subsequent responses to a fearful stimulus. Analysis of c-fos activation was then used to identify brain circuits activated by acute predator stress. Cat exposure elicited a pattern of central c-fos activation that differed substantially from that after either restraint or hypoxia. Predator-specific c-fos mRNA induction was observed in several brain regions comprising the hypothetical brain defense circuit (bed nucleus of the stria terminalis, medial region of the ventromedial nucleus, and dorsal premammillary nucleus). Surprisingly, acute cat exposure did not induce c-fos expression in the PVN. In summary, the data indicate that 1) predation stress invokes a unique stress circuitry that promotes homotypic sensitization of the HPA axis, and 2) familiarization of animals to testing environments can prime central stress pathways to respond robustly to novel threats.
Central roles of iron in the regulation of oxidative stress in the yeast Saccharomyces cerevisiae.

PubMed

Matsuo, Ryo; Mizobuchi, Shogo; Nakashima, Maya; Miki, Kensuke; Ayusawa, Dai; Fujii, Michihiko

2017-10-01

Oxygen is essential for aerobic organisms but causes cytotoxicity probably through the generation of reactive oxygen species (ROS). In this study, we screened for the genes that regulate oxidative stress in the yeast Saccharomyces cerevisiae, and found that expression of CTH2/TIS11 caused an increased resistance to ROS. CTH2 is up-regulated upon iron starvation and functions to remodel metabolism to adapt to iron starvation. We showed here that increased resistance to ROS by CTH2 would likely be caused by the decreased ROS production due to the decreased activity of mitochondrial respiration, which observation is consistent with the fact that CTH2 down-regulates the mitochondrial respiratory proteins. We also found that expression of CTH1, a paralog of CTH2, also caused an increased resistance to ROS. This finding supported the above view, because mitochondrial respiratory proteins are the common targets of CTH1 and CTH2. We further showed that supplementation of iron in medium augmented the growth of S. cerevisiae under oxidative stress, and expression of CTH2 and supplementation of iron collectively enhanced its growth under oxidative stress. Since CTH2 is regulated by iron, these findings suggested that iron played crucial roles in the regulation of oxidative stress in S. cerevisiae.

Structured Cable for High-Current Coils of Tokamaks

NASA Astrophysics Data System (ADS)

Benson, Christopher; McIntyre, Peter; Sattarov, Akhdiyor; Mann, Thomas

2011-10-01

The 45 kA superconducting cable for the ITER central solenoid coil has yielded questionable results in two recent tests. In both cases the cable Tc increased after cycling only a fraction of the design life, indicating degradation due to fatigue and fracture among the superconducting strands. The Accelerator Research Lab at Texas A&M University is developing a design for a Nb3Sn structured cable suitable for such tokamak coils. The superconductor is configured in 6 sub-cables, and each subcable is supported within a channel of a central support structure within a high-strength armor sheath. The structured cable addresses two issues that are thought to compromise opposition at high current. The strands are supported without cross-overs (which produce stress concentration); and armor sheath and core structure bypass stress through the coil and among subcables so that the stress within each subcable is only what is produced directly upon it. Details of the design and plans for development will be presented.
The mammalian circadian clock and its entrainment by stress and exercise.

PubMed

Tahara, Yu; Aoyama, Shinya; Shibata, Shigenobu

2017-01-01

The mammalian circadian clock regulates day-night fluctuations in various physiological processes. The circadian clock consists of the central clock in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks in peripheral tissues. External environmental cues, including light/dark cycles, food intake, stress, and exercise, provide important information for adjusting clock phases. This review focuses on stress and exercise as potent entrainment signals for both central and peripheral clocks, especially in regard to the timing of stimuli, types of stressors/exercises, and differences in the responses of rodents and humans. We suggest that the common signaling pathways of clock entrainment by stress and exercise involve sympathetic nervous activation and glucocorticoid release. Furthermore, we demonstrate that physiological responses to stress and exercise depend on time of day. Therefore, using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective for preventing obesity, diabetes, and cardiovascular disease.
Palmitate-induced ER stress and subsequent C 1 HOP activation attenuates leptin and IGF1expression in the brain

USDA-ARS?s Scientific Manuscript database

Background: The peptide hormones insulin-like growth factor-1 (IGF1) and leptin mediate a myriad of biological effects both in the peripheral and central nervous systems. The transcription of these two hormones is regulated by the transcription factor C/EBPa, which in turn is negatively regulated by...
Pirin-like proteins are regulated by oxidative stress and iron in bacteroides fragilis and involved in the modulation of central energy metabolism and metronidazole susceptibility

USDA-ARS?s Scientific Manuscript database

Bacteroides fragilis is the most frequent anaerobe isolated from human infections. Clinical isolates of B. fragilis are among the highest aerotolerant anaerobic bacteria. The oxidative stress response (OSR) in B. fragilis induces an array of genes enabling them to survive prolonged oxygen exposure i...
The Effects of Occupational Stress, Work-Centrality, Self-Efficacy, and Job Satisfaction on Intent to Quit Among Long-Term Care Workers in Korea.

PubMed

Park, Jeongkyu; Yoon, Seokwon; Moon, Sung Seek; Lee, Kyoung Hag; Park, Jueun

2017-01-01

A large and growing population of elderly Koreans with chronic conditions necessitates an increase in long-term care. This study is aimed at investigating the effects of occupational stress, work-centrality, self-efficacy, and job satisfaction on intent to leave among long-term care workers in Korea. We tested the hypothesized structural equation model predicting the intention to quit among long-term care workers in Korea. Survey data were collected from 532 long-term care workers in Seoul, Korea. Results showed that occupational stress was positively associated with intention to leave the job. The study also identified several possible mediators (self-efficacy, work-centrality, job satisfaction) in the relationship between stress and intent to quit. Evidence-based stress management interventions are suggested to help the workers better cope with stressors. Mentoring programs should also be considered for new workers.
Stress pulls us apart: anxiety leads to differences in competitive confidence under stress.

PubMed

Goette, Lorenz; Bendahan, Samuel; Thoresen, John; Hollis, Fiona; Sandi, Carmen

2015-04-01

Social competition is a fundamental mechanism of evolution and plays a central role in structuring individual interactions and communities. Little is known about the factors that affect individuals' competitive success, particularly in humans. Key factors might include stress, a major evolutionary pressure that can affect the establishment of social hierarchies in animals, and individuals' trait anxiety, which largely determines susceptibility to stress and constitutes an important determinant of differences in competitive outcomes. Using an economic-choice experiment to assess competitive self-confidence in 229 human subjects we found that, whereas competitive self-confidence is unaffected by an individual's anxiety level in control conditions, exposure to the Trier social stress test for groups drives the behavior of individuals apart: low-anxiety individuals become overconfident, and high-anxiety individuals become underconfident. Cortisol responses to stress were found to relate to self-confidence, with the direction of the effects depending on trait anxiety. Our findings identify stress as a major regulator of individuals' competitiveness, affecting self-confidence in opposite directions in high and low anxious individuals. Therefore, our findings imply that stress may provide a new channel for generating social and economic inequality and, thus, not only be a consequence, but also a cause of inequality through its impact on competitive self-confidence and decision making in financially-relevant situations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Central gene expression changes associated with enhanced neuroendocrine and autonomic response habituation to repeated noise stress after voluntary wheel running in rats

PubMed Central

Sasse, Sarah K.; Nyhuis, Tara J.; Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge

2013-01-01

Accumulating evidence indicates that regular physical exercise benefits health in part by counteracting some of the negative physiological impacts of stress. While some studies identified reductions in some measures of acute stress responses with prior exercise, limited data were available concerning effects on cardiovascular function, and reported effects on hypothalamic-pituitary-adrenocortical (HPA) axis responses were largely inconsistent. Given that exposure to repeated or prolonged stress is strongly implicated in the precipitation and exacerbation of illness, we proposed the novel hypothesis that physical exercise might facilitate adaptation to repeated stress, and subsequently demonstrated significant enhancement of both HPA axis (glucocorticoid) and cardiovascular (tachycardia) response habituation to repeated noise stress in rats with long-term access to running wheels compared to sedentary controls. Stress habituation has been attributed to modifications of brain circuits, but the specific sites of adaptation and the molecular changes driving its expression remain unclear. Here, in situ hybridization histochemistry was used to examine regulation of select stress-associated signaling systems in brain regions representing likely candidates to underlie exercise-enhanced stress habituation. Analyzed brains were collected from active (6 weeks of wheel running) and sedentary rats following control, acute, or repeated noise exposures that induced a significantly faster rate of glucocorticoid response habituation in active animals but preserved acute noise responsiveness. Nearly identical experimental manipulations also induce a faster rate of cardiovascular response habituation in exercised, repeatedly stressed rats. The observed regulation of the corticotropin-releasing factor and brain-derived neurotrophic factor systems across several brain regions suggests widespread effects of voluntary exercise on central functions and related adaptations to stress across multiple response modalities. PMID:24324441
Global analysis of gene expression in maize leaves treated with low temperature. II. Combined effect of severe cold (8 °C) and circadian rhythm.

PubMed

Jończyk, M; Sobkowiak, A; Trzcinska-Danielewicz, J; Skoneczny, M; Solecka, D; Fronk, J; Sowiński, P

2017-10-01

In maize seedlings, severe cold results in dysregulation of circadian pattern of gene expression causing profound modulation of transcription of genes related to photosynthesis and other key biological processes. Plants live highly cyclic life and their response to environmental stresses must allow for underlying biological rhythms. To study the interplay of a stress and a rhythmic cue we investigated transcriptomic response of maize seedlings to low temperature in the context of diurnal gene expression. Severe cold stress had pronounced effect on the circadian rhythm of a substantial proportion of genes. Their response was strikingly dual, comprising either flattening (partial or complete) of the diel amplitude or delay of expression maximum/minimum by several hours. Genes encoding central oscillator components behaved in the same dual manner, unlike their Arabidopsis counterparts reported earlier to cease cycling altogether upon cold treatment. Also numerous genes lacking circadian rhythm responded to the cold by undergoing up- or down-regulation. Notably, the transcriptome changes preceded major physiological manifestations of cold stress. In silico analysis of metabolic processes likely affected by observed gene expression changes indicated major down-regulation of photosynthesis, profound and multifarious modulation of plant hormone levels, and of chromatin structure, transcription, and translation. A role of trehalose and stachyose in cold stress signaling was also suggested. Meta-analysis of published transcriptomic data allowed discrimination between general stress response of maize and that unique to severe cold. Several cis- and trans-factors likely involved in the latter were predicted, albeit none of them seemed to have a major role. These results underscore a key role of modulation of diel gene expression in maize response to severe cold and the unique character of the cold-response of the maize circadian clock.
A Populus TIR1 gene family survey reveals differential expression patterns and responses to 1-naphthaleneacetic acid and stress treatments

PubMed Central

Shu, Wenbo; Liu, Yingli; Guo, Yinghua; Zhou, Houjun; Zhang, Jin; Zhao, Shutang; Lu, Mengzhu

2015-01-01

The plant hormone auxin is a central regulator of plant growth. TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALING F-BOX (TIR1/AFB) is a component of the E3 ubiquitin ligase complex SCFTIR1/AFB and acts as an auxin co-receptor for nuclear auxin signaling. The SCFTIR1/AFB-proteasome machinery plays a central regulatory role in development-related gene transcription. Populus trichocarpa, as a model tree, has a unique fast-growth trait to which auxin signaling may contribute. However, no systematic analyses of the genome organization, gene structure, and expression of TIR1-like genes have been undertaken in this woody model plant. In this study, we identified a total of eight TIR1 genes in the Populus genome that are phylogenetically clustered into four subgroups, PtrFBL1/PtrFBL2, PtrFBL3/PtrFBL4, PtrFBL5/PtrFBL6, and PtrFBL7/PtrFBL8, representing four paralogous pairs. In addition, the gene structure and motif composition were relatively conserved in each paralogous pair and all of the PtrFBL members were localized in the nucleus. Different sets of PtrFBLs were strongly expressed in the leaves, stems, roots, cambial zones, and immature xylem of Populus. Interestingly, PtrFBL1 and 7 were expressed mainly in vascular and cambial tissues, respectively, indicating their potential but different roles in wood formation. Furthermore, Populus FBLs responded differentially upon exposure to various stresses. Finally, over-expression studies indicated a role of FBL1 in poplar stem growth and response to drought stress. Collectively, these observations lay the foundation for further investigations into the potential roles of PtrFBL genes in tree growth and development. PMID:26442033
Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF) in mouse ovaries: relationship to oocytes developmental potential.

PubMed

Wu, Li-Min; Hu, Mei-Hong; Tong, Xian-Hong; Han, Hui; Shen, Ni; Jin, Ren-Tao; Wang, Wei; Zhou, Gui-Xiang; He, Guo-Ping; Liu, Yu-Sheng

2012-01-01

Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA) axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.
Chronic Unpredictable Stress Decreases Expression of Brain-Derived Neurotrophic Factor (BDNF) in Mouse Ovaries: Relationship to Oocytes Developmental Potential

PubMed Central

Tong, Xian-Hong; Han, Hui; Shen, Ni; Jin, Ren-Tao; Wang, Wei; Zhou, Gui-Xiang; He, Guo-Ping; Liu, Yu-Sheng

2012-01-01

Background Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. Methods Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA) axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. Results Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn’t affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. Conclusion BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress. PMID:23284991
Glutathione Efflux and Cell Death

PubMed Central

2012-01-01

Abstract Significance: Glutathione (GSH) depletion is a central signaling event that regulates the activation of cell death pathways. GSH depletion is often taken as a marker of oxidative stress and thus, as a consequence of its antioxidant properties scavenging reactive species of both oxygen and nitrogen (ROS/RNS). Recent Advances: There is increasing evidence demonstrating that GSH loss is an active phenomenon regulating the redox signaling events modulating cell death activation and progression. Critical Issues: In this work, we review the role of GSH depletion by its efflux, as an important event regulating alterations in the cellular redox balance during cell death independent from oxidative stress and ROS/RNS formation. We discuss the mechanisms involved in GSH efflux during cell death progression and the redox signaling events by which GSH depletion regulates the activation of the cell death machinery. Future Directions: The evidence summarized here clearly places GSH transport as a central mechanism mediating redox signaling during cell death progression. Future studies should be directed toward identifying the molecular identity of GSH transporters mediating GSH extrusion during cell death, and addressing the lack of sensitive approaches to quantify GSH efflux. Antioxid. Redox Signal. 17, 1694–1713. PMID:22656858
Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor.

PubMed

Benekareddy, Madhurima; Nair, Amrita R; Dias, Brian G; Suri, Deepika; Autry, Anita E; Monteggia, Lisa M; Vaidya, Vidita A

2013-03-01

Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytoskeletal-associated protein (Arc), is important for both activity and experience dependent plasticity. We sought to examine whether trophic factor signalling through brain-derived neurotrophic factor (BDNF) contributes to the neocortical regulation of Arc mRNA in response to distinct stimuli such as immobilization stress and the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Acute exposure to either immobilization stress or DOI induced Arc mRNA levels within the neocortex. BDNF infusion into the neocortex led to a robust up-regulation of local Arc transcript expression. Further, baseline Arc mRNA expression in the neocortex was significantly decreased in inducible BDNF knockout mice with an adult-onset, forebrain specific BDNF loss. The induction of Arc mRNA levels in response to both acute immobilization stress or a single administration of DOI was significantly attenuated in the inducible BDNF knockout mice. Taken together, our results implicate trophic factor signalling through BDNF in the regulation of cortical Arc mRNA expression, both under baseline conditions and following stress and hallucinogen exposure. These findings suggest the possibility that the regulation of Arc expression via BDNF provides a molecular substrate for the structural and synaptic plasticity observed following stimuli such as stress and hallucinogens.
The molecular mechanisms of plant plasma membrane intrinsic proteins trafficking and stress response.

PubMed

Wang, Xing; Zhang, Ji-long; Feng, Xiu-xiu; Li, Hong-jie; Zhang, Gen-fa

2017-04-20

Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on the plasma membrane. PIPs transfer water, CO 2 and small uncharged solutes through the plasma membrane. PIPs have high selectivity to substrates, suggestive of a central role in maintaining cellular water balance. The expression, activity and localization of PIPs are regulated at the transcriptional and post-translational levels, and also affected by environmental factors. Numerous studies indicate that the expression patterns and localizations of PIPs can change in response to abiotic stresses. In this review, we summarize the mechanisms of PIP trafficking, transcriptional and post-translational regulations, and abiotic stress responses. Moreover, we also discuss the current research trends and future directions on PIPs.
Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle.

PubMed

Valenti, Vitor E; de Abreu, Luiz Carlos; Sato, Monica A; Ferreira, Celso; Adami, Fernando; Fonseca, Fernando L A; Xavier, Valdelias; Godoy, Moacir; Monteiro, Carlos B; Vanderlei, Luiz Carlos M; Saldiva, Paulo H N

2012-03-30

Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 μL) injection into the 4th V. Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity.
Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

PubMed Central

2012-01-01

Background Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). Methods We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 μL) injection into the 4th V. Results Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. Conclusion We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity. PMID:22463380
Heterotrimeric G-Protein γ Subunit CsGG3.2 Positively Regulates the Expression of CBF Genes and Chilling Tolerance in Cucumber

PubMed Central

Bai, Longqiang; Liu, Yumei; Mu, Ying; Anwar, Ali; He, Chaoxing; Yan, Yan; Li, Yansu; Yu, Xianchang

2018-01-01

Heterotrimeric guanine nucleotide-binding proteins (G proteins) composed of alpha (Gα), beta (Gβ), and gamma (Gγ) subunits are central signal transducers mediating the cellular response to multiple stimuli, such as cold, in eukaryotes. Plant Gγ subunits, divided into A, B, and C three structurally distinct types, provide proper cellular localization and functional specificity to the heterotrimer complex. Here, we demonstrate that a type C Gγ subunit CsGG3.2 is involved in the regulation of the CBF regulon and plant tolerance to cold stresses in cucumber (Cucumis sativus L.). We showed that CsGG3.2 transcript abundance was positively induced by cold treatments. Transgenic cucumber plants (T1) constitutively over-expressing CsGG3.2 exhibits tolerance to chilling conditions and increased expression of CBF genes and their regulon. Antioxidative enzymes, i.e., superoxide dismutase, catalase, peroxidase, and glutathione reductase activities increased in cold-stressed transgenic plants. The reactive oxygen species, oxygen free radical and H2O2, production, as well as membrane lipid peroxidation (MDA) production decreased in transgenic plants, suggesting a better antioxidant system to cope the oxidative-damages caused by cold stress. These findings provide evidence for a critical role of CsGG3.2 in mediating cold signal transduction in plant cells. PMID:29719547
Three-dimensional confocal morphometry – a new approach for studying dynamic changes in cell morphology in brain slices

PubMed Central

Chvátal, Alexandr; Anděrová, Miroslava; Kirchhoff, Frank

2007-01-01

Pathological states in the central nervous system lead to dramatic changes in the activity of neuroactive substances in the extracellular space, to changes in ionic homeostasis and often to cell swelling. To quantify changes in cell morphology over a certain period of time, we employed a new technique, three-dimensional confocal morphometry. In our experiments, performed on enhanced green fluorescent protein/glial fibrillary acidic protein astrocytes in brain slices in situ and thus preserving the extracellular microenvironment, confocal morphometry revealed that the application of hypotonic solution evoked two types of volume change. In one population of astrocytes, hypotonic stress evoked small cell volume changes followed by a regulatory volume decrease, while in the second population volume changes were significantly larger without subsequent volume regulation. Three-dimensional cell reconstruction revealed that even though the total astrocyte volume increased during hypotonic stress, the morphological changes in various cell compartments and processes were more complex than have been previously shown, including swelling, shrinking and structural rearrangement. Our data show that astrocytes in brain slices in situ during hypotonic stress display complex behaviour. One population of astrocytes is highly capable of cell volume regulation, while the second population is characterized by prominent cell swelling, accompanied by plastic changes in morphology. It is possible to speculate that these two astrocyte populations play different roles during physiological and pathological states. PMID:17488344
Neurochemical background and approaches in the understanding of motion sickness

NASA Technical Reports Server (NTRS)

Kohl, R. L.

1982-01-01

The problems and nature of space motion sickness were defined. The neurochemical and neurophysiological bases of vestibular system function and of the expression of motion sickness wre reviewed. Emphasis was given to the elucidation of the neuropharmacological mechanisms underlying the effects of scopolamine and amphetamine on motion sickness. Characterization of the ascending reticular activating system and the limbic system provided clues to the etiology of the side effects of scopolamine. The interrelationship between central cholinergic pathways and the peripheral (autonomic) expression of motion sickness was described. A correlation between the stress of excessive motion and a variety of hormonal responses to that stress was also detailed. The cholinergic system is involved in the efferent modulation of the vestibular hair cells, as an afferent modulator of the vestibular nuclei, in the activation of cortical and limbic structures, in the expression of motion sickness symptoms and most likely underscores a number of the hormonal changes that occur in stressful motion environments. The role of lecithin in the regulation of the levels of neurotransmitters was characterized as a possible means by which cholinergic neurochemistry can be modulated.
Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses

PubMed Central

Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

2016-01-01

γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage. PMID:27021285

Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

PubMed

Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

2016-03-29

γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.
Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796
Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.
Epigenetic Mechanisms in Learned Fear: Implications for PTSD

PubMed Central

Zovkic, Iva B; Sweatt, J David

2013-01-01

One of the most exciting discoveries in the learning and memory field in the past two decades is the observation that active regulation of gene expression is necessary for experience to trigger lasting functional and behavioral change, in a wide variety of species, including humans. Thus, as opposed to the traditional view of ‘nature' (genes) being separate from ‘nurture' (environment and experience), it is now clear that experience actively drives alterations in central nervous system (CNS) gene expression in an ongoing fashion, and that the resulting transcriptional changes are necessary for experience to trigger altered long-term behavior. In parallel over the past decade, epigenetic mechanisms, including regulation of chromatin structure and DNA methylation, have been shown to be potent regulators of gene transcription in the CNS. In this review, we describe data supporting the hypothesis that epigenetic molecular mechanisms, especially DNA methylation and demethylation, drive long-term behavioral change through active regulation of gene transcription in the CNS. Specifically, we propose that epigenetic molecular mechanisms underlie the formation and stabilization of context- and cue-triggered fear conditioning based in the hippocampus and amygdala, a conclusion reached in a wide variety of studies using laboratory animals. Given the relevance of cued and contextual fear conditioning to post-traumatic stress, by extension we propose that these mechanisms may contribute to post-traumatic stress disorder (PTSD) in humans. Moreover, we speculate that epigenetically based pharmacotherapy may provide a new avenue of drug treatment for PTSD-related cognitive and behavioral function. PMID:22692566
The Pseudoenzyme PDX1.2 Boosts Vitamin B6 Biosynthesis under Heat and Oxidative Stress in Arabidopsis*

PubMed Central

Moccand, Cyril; Boycheva, Svetlana; Surriabre, Pedro; Tambasco-Studart, Marina; Raschke, Maja; Kaufmann, Markus; Fitzpatrick, Teresa B.

2014-01-01

Vitamin B6 is an indispensable compound for survival, well known as a cofactor for numerous central metabolic enzymes and more recently for playing a role in several stress responses, particularly in association with oxidative stress. Regulatory aspects for the use of the vitamin in these roles are not known. Here we show that certain plants carry a pseudoenzyme (PDX1.2), which is involved in regulating vitamin B6 biosynthesis de novo under stress conditions. Specifically, we demonstrate that Arabidopsis PDX1.2 enhances the activity of its catalytic paralogs by forming a heterododecameric complex. PDX1.2 is strongly induced by heat as well as singlet oxygen stress, concomitant with an enhancement of vitamin B6 production. Analysis of pdx1.2 knockdown lines demonstrates that boosting vitamin B6 content is dependent on PDX1.2, revealing that this pseudoenzyme acts as a positive regulator of vitamin B6 biosynthesis during such stress conditions in plants. PMID:24505140
Endocannabinoid Signaling, Glucocorticoid-Mediated Negative Feedback and Regulation of the HPA Axis

PubMed Central

Hill, M. N.; Tasker, J. G.

2012-01-01

The hypothalamic-pituitary-adrenal (HPA) axis regulates the outflow of glucocorticoid hormones under basal conditions and in response to stress. Within the last decade, a large body of evidence has mounted indicating that the endocannabinoid system is involved in the central regulation of the stress response; however, the specific role endocannabinoid signalling plays in phases of HPA axis regulation, or the neural sites of action mediating this regulation, was not mapped out until recently. This review aims to collapse the current state of knowledge regarding the role of the endocannabinoid system in the regulation of the HPA axis to put together a working model of how and where endocannabinoids act within the brain to regulate outflow of the HPA axis. Specifically, we discuss the role of the endocannabinoid system in the regulation of the HPA axis under basal conditions, activation in response to acute stress and glucocorticoid-mediated negative feedback. Interestingly, there appears to be some anatomical specificity to the role of the endocannabinoid system in each phase of HPA axis regulation, as well as distinct roles of both anandamide and 2-arachidonoylglycerol in these phases. Ultimately, the current level of information indicates that endocannabinoid signalling acts to suppress HPA axis activity through concerted actions within the prefrontal cortex, amygdala and hypothalamus. PMID:22214537
Photosynthetic light reactions--an adjustable hub in basic production and plant immunity signaling.

PubMed

Kangasjärvi, Saijaliisa; Tikkanen, Mikko; Durian, Guido; Aro, Eva-Mari

2014-08-01

Photosynthetic efficiency is a key trait that influences the sustainable utilization of plants for energy and nutrition. By now, extensive research on photosynthetic processes has underscored important structural and functional relationships among photosynthetic thylakoid membrane protein complexes, and their roles in determining the productivity and stress resistance of plants. Photosystem II photoinhibition-repair cycle, for example, has arisen vital in protecting also Photosystem I against light-induced damage. Availability of highly sophisticated genetic, biochemical and biophysical tools has greatly expanded the catalog of components that carry out photoprotective functions in plants. On thylakoid membranes, these components encompass a network of overlapping systems that allow delicate regulation of linear and cyclic electron transfer pathways, balancing of excitation energy distribution between the two photosystems and dissipation of excess light energy in the antenna system as heat. An increasing number of reports indicate that the above mentioned mechanisms also mediate important functions in the regulation of biotic stress responses in plants. Particularly the handling of excitation energy in the light harvesting II antenna complexes appears central to plant immunity signaling. Comprehensive understanding of the underlying mechanisms and regulatory cross-talk, however, still remain elusive. This review highlights the current understanding of components that regulate the function of photosynthetic light reactions and directly or indirectly also modulate disease resistance in higher plants. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

PubMed Central

Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

2006-01-01

The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377
Probing the Effects of Stress Mediators on the Human Hair Follicle

PubMed Central

Peters, Eva M.J.; Liotiri, Sofia; Bodó, Enikő; Hagen, Evelin; Bíró, Tamás; Arck, Petra C.; Paus, Ralf

2007-01-01

Stress alters murine hair growth, depending on substance P-mediated neurogenic inflammation and nerve growth factor (NGF), a key modulator of hair growth termination (catagen induction). Whether this is of any relevance in human hair follicles (HFs) is completely unclear. Therefore, we have investigated the effects of substance P, the central cutaneous prototypic stress-associated neuropeptide, on normal, growing human scalp HFs in organ culture. We show that these prominently expressed substance P receptor (NK1) at the gene and protein level. Organ-cultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath, indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growth-promoting NGF receptor (TrkA), whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR). In addition, MHC class I and β2-microglobulin immunoreactivity were up-regulated and detected ectopically, indicating collapse of the HF immune privilege. In conclusion, we present a simplistic, but instructive, organ culture assay to demonstrate sensitivity of the human HF to key skin stress mediators. The data obtained therewith allow one to sketch the first evidence-based biological explanation for how stress may trigger or aggravate telogen effluvium and alopecia areata. PMID:18055548
An Integrative Review on Role and Mechanisms of Ghrelin in Stress, Anxiety and Depression.

PubMed

Bali, Anjana; Jaggi, Amteshwar Singh

2016-01-01

Ghrelin is orexigenic hormone primarily synthesized by endocrine X/A-like cells of gastric oxyntic mucosa to stimulate appetite and food intake along with regulation of growth hormone and insulin secretion; glucose and lipid metabolism; gastrointestinal motility; blood pressure, heart rate and neurogenesis. Furthermore, peripherally (after crossing the blood brain barrier) as well as centrally synthesized ghrelin (in the hypothalamus) regulates diverse functions of central nervous system including stress-associated behavioral functions. Exposure to stress alters the ghrelin levels and alteration in ghrelin levels significantly affects neuro-endocrinological parameters; metabolism-related physiology, behavior and mood. Studies have shown both anxiolytic and anxiogenic role of ghrelin suggesting its dual role in modulating anxiety-related behavior. However, it is proposed that increase in ghrelin levels during stress condition is an endogenous stress coping behavior and increased ghrelin levels may be required to prevent excessive anxiety. In preclinical and clinical studies, an elevation in ghrelin levels during depression has been correlated with their antidepressant activities. Ghrelin-induced modulation of stress and associated conditions has been linked to alteration in hypothalamic-pituitary-adrenal (HPA) axis; autonomic nervous system (mainly sympathetic nervous system and serotonergic neurotransmission. A reciprocal relationship has been reported between corticotropin-releasing hormone (CRH) and ghrelin as ghrelin increases the release of CRH, ACTH and corticosteroids; while CRH decreases the expression of ghrelin. Similarly, ghrelin increases the serotonin turnover and in turn, serotonin controls ghrelin signaling to modulate anxiety-related behavior. The present review discusses the dual role of ghrelin in stress and related behavioral disorders along with possible mechanisms.
Caenorhabditis elegans OSR-1 regulates behavioral and physiological responses to hyperosmotic environments.

PubMed Central

Solomon, Aharon; Bandhakavi, Sricharan; Jabbar, Sean; Shah, Rena; Beitel, Greg J; Morimoto, Richard I

2004-01-01

The molecular mechanisms that enable multicellular organisms to sense and modulate their responses to hyperosmotic environments are poorly understood. Here, we employ Caenorhabditis elegans to characterize the response of a multicellular organism to osmotic stress and establish a genetic screen to isolate mutants that are osmotic stress resistant (OSR). In this study, we describe the cloning of a novel gene, osr-1, and demonstrate that it regulates osmosensation, adaptation, and survival in hyperosmotic environments. Whereas wild-type animals exposed to hyperosmotic conditions rapidly lose body volume, motility, and viability, osr-1(rm1) mutant animals maintain normal body volume, motility, and viability even upon chronic exposures to high osmolarity environments. In addition, osr-1(rm1) animals are specifically resistant to osmotic stress and are distinct from previously characterized osmotic avoidance defective (OSM) and general stress resistance age-1(hx546) mutants. OSR-1 is expressed in the hypodermis and intestine, and expression of OSR-1 in hypodermal cells rescues the osr-1(rm1) phenotypes. Genetic epistasis analysis indicates that OSR-1 regulates survival under osmotic stress via CaMKII and a conserved p38 MAP kinase signaling cascade and regulates osmotic avoidance and resistance to acute dehydration likely by distinct mechanisms. We suggest that OSR-1 plays a central role in integrating stress detection and adaptation responses by invoking multiple signaling pathways to promote survival under hyperosmotic environments. PMID:15166144
Key functional role of the optical properties of coral skeletons in coral ecology and evolution.

PubMed

Enríquez, Susana; Méndez, Eugenio R; Hoegh-Guldberg, Ove; Iglesias-Prieto, Roberto

2017-04-26

Multiple scattering of light on coral skeleton enhances light absorption efficiency of coral symbionts and plays a key role in the regulation of their internal diffuse light field. To understand the dependence of this enhancement on skeleton meso- and macrostructure, we analysed the scattering abilities of naked coral skeletons for 74 Indo-Pacific species. Sensitive morphotypes to thermal and light stress, flat-extraplanate and branching corals, showed the most efficient structures, while massive-robust species were less efficient. The lowest light-enhancing scattering abilities were found for the most primitive colonial growth form: phaceloid. Accordingly, the development of highly efficient light-collecting structures versus the selection of less efficient but more robust holobionts to cope with light stress may constitute a trade-off in the evolution of modern symbiotic scleractinian corals, characterizing two successful adaptive solutions. The coincidence of the most important structural modifications with epitheca decline supports the importance of the enhancement of light transmission across coral skeleton in modern scleractinian diversification, and the central role of these symbioses in the design and optimization of coral skeleton. Furthermore, the same ability that lies at the heart of the success of symbiotic corals as coral-reef-builders can also explain the 'Achilles's heel' of these symbioses in a warming ocean. © 2017 The Author(s).
The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity.

PubMed

Raivio, Tracy L; Leblanc, Shannon K D; Price, Nancy L

2013-06-01

The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.
Network approach to the symptom-level association between alcohol use disorder and posttraumatic stress disorder.

PubMed

Afzali, Mohammad H; Sunderland, Matthew; Batterham, Philip J; Carragher, Natacha; Calear, Alison; Slade, Tim

2017-03-01

The high prevalence of alcohol use disorder among individuals with a history of trauma and posttraumatic stress disorder is well documented. The current study applied network analysis to map the structure of symptom associations between these disorders. Data come from a community sample of 449 Australian adults with a history of trauma and alcohol consumption during the last 12 months. Data analysis consisted of the construction of the comorbidity network of PTSD/AUD symptoms, identification of the bridging symptoms, computation of the centrality measures, and evaluation of the robustness of the results. Results highlighted two main symptom clusters, corresponding to two disorders, and that only nine edges connected the two clusters. Bridging symptoms connecting the two clusters were: alcohol use in dangerous situations, physical or mental health problems as a result of alcohol use, loss of interest or reduced social activities, and reckless/self-destructive behaviour. Identification of both central symptoms, because of their key role in the constellation and strong associations with majority of symptoms, and bridge symptoms, because of their mediating role between two disorders, has some implications in terms of self-medication and risk-taking/self-regulation theories of comorbidity and provides a number of clinical implications, which warrants further exploration within clinical samples.
Coming of leaf age: control of growth by hydraulics and metabolics during leaf ontogeny.

PubMed

Pantin, Florent; Simonneau, Thierry; Muller, Bertrand

2012-10-01

Leaf growth is the central process facilitating energy capture and plant performance. This is also one of the most sensitive processes to a wide range of abiotic stresses. Because hydraulics and metabolics are two major determinants of expansive growth (volumetric increase) and structural growth (dry matter increase), we review the interaction nodes between water and carbon. We detail the crosstalks between water and carbon transports, including the dual role of stomata and aquaporins in regulating water and carbon fluxes, the coupling between phloem and xylem, the interactions between leaf water relations and photosynthetic capacity, the links between Lockhart's hydromechanical model and carbon metabolism, and the central regulatory role of abscisic acid. Then, we argue that during leaf ontogeny, these interactions change dramatically because of uncoupled modifications between several anatomical and physiological features of the leaf. We conclude that the control of leaf growth switches from a metabolic to a hydromechanical limitation during the course of leaf ontogeny. Finally, we illustrate how taking leaf ontogeny into account provides insights into the mechanisms underlying leaf growth responses to abiotic stresses that affect water and carbon relations, such as elevated CO2, low light, high temperature and drought. © 2012 INRA. New Phytologist © 2012 New Phytologist Trust.
Structural Insights into Central Hypertension Regulation by Human Aminopeptidase A*

PubMed Central

Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

2013-01-01

Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3′ subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors. PMID:23888046
Structural insights into central hypertension regulation by human aminopeptidase A.

PubMed

Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

2013-08-30

Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors.
Seeking Success amid Today's Chaotic Demands.

ERIC Educational Resources Information Center

Dillon, Michael R.

1992-01-01

This paper reacts to previous symposium papers (EC 604 155-161) concerning regulations and quality assurance in Intermediate Care Facilities for the Mentally Retarded (ICF/MR) and stresses the central mission of helping people and the need to achieve quality and not just compliance. (DB)
BDNF function as a potential mediator of bipolar disorder and post-traumatic stress disorder comorbidity

PubMed Central

Rakofsky, JJ; Ressler, KJ; Dunlop, BW

2013-01-01

Bipolar disorder (BD) and post-traumatic stress disorder (PTSD) frequently co-occur among psychiatric patients, leading to increased morbidity and mortality. Brain-derived neurotrophic factor (BDNF) function is associated with core characteristics of both BD and PTSD. We propose a neurobiological model that underscores the role of reduced BDNF function resulting from several contributing sources, including the met variant of the BDNF val66met (rs6265) single-nucleotide polymorphism, trauma-induced epigenetic regulation and current stress, as a contributor to the onset of both illnesses within the same person. Further studies are needed to evaluate the genetic association between the val66met allele and the BD-PTSD population, along with central/peripheral BDNF levels and epigenetic patterns of BDNF gene regulation within these patients. PMID:21931317
Concerted Flexibility of Chromatin Structure, Methylome, and Histone Modifications along with Plant Stress Responses

PubMed Central

Santos, Ana Paula; Ferreira, Liliana J.; Oliveira, M. Margarida

2017-01-01

The spatial organization of chromosome structure within the interphase nucleus, as well as the patterns of methylome and histone modifications, represent intersecting layers that influence genome accessibility and function. This review is focused on the plastic nature of chromatin structure and epigenetic marks in association to stress situations. The use of chemical compounds (epigenetic drugs) or T-DNA-mediated mutagenesis affecting epigenetic regulators (epi-mutants) are discussed as being important tools for studying the impact of deregulated epigenetic backgrounds on gene function and phenotype. The inheritability of epigenetic marks and chromatin configurations along successive generations are interpreted as a way for plants to “communicate” past experiences of stress sensing. A mechanistic understanding of chromatin and epigenetics plasticity in plant response to stress, including tissue- and genotype-specific epigenetic patterns, may help to reveal the epigenetics contributions for genome and phenotype regulation. PMID:28275209

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

PubMed

Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

2015-11-01

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.
The PP2C Alphabet is a negative regulator of stress-activated protein kinase signaling in Drosophila.

PubMed

Baril, Caroline; Sahmi, Malha; Ashton-Beaucage, Dariel; Stronach, Beth; Therrien, Marc

2009-02-01

The Jun N-terminal kinase and p38 pathways, also known as stress-activated protein kinase (SAPK) pathways, are signaling conduits reiteratively used throughout the development and adult life of metazoans where they play central roles in the control of apoptosis, immune function, and environmental stress responses. We recently identified a Drosophila Ser/Thr phosphatase of the PP2C family, named Alphabet (Alph), which acts as a negative regulator of the Ras/ERK pathway. Here we show that Alph also plays an inhibitory role with respect to Drosophila SAPK signaling during development as well as under stress conditions such as oxidative or genotoxic stresses. Epistasis experiments suggest that Alph acts at a step upstream of the MAPKKs Hep and Lic. Consistent with this interpretation, biochemical experiments identify the upstream MAPKKKs Slpr, Tak1, and Wnd as putative substrates. Together with previous findings, this work identifies Alph as a general attenuator of MAPK signaling in Drosophila.
[The action of bemitil on the self-regulation systems during short-term immobilization].

PubMed

Kirichek, L T; Bobkov, Iu G

1991-01-01

In the immobilized rats bemithyl (50 mg/kg in a single dose) was shown to normalize the state of the musculomotor and cardiovascular systems exerting the positive influence on the key links of the process of autoregulation in the form of the sedative (the central nervous system), stress-protective (hormonal regulation) and antihypoxic (metabolism) effects that characterizes it as the drug with the distinct antistress activity.
Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia.

PubMed

Chiappelli, Joshua; Rowland, Laura M; Notarangelo, Francesca M; Wijtenburg, S Andrea; Thomas, Marian A R; Pocivavsek, Ana; Jones, Aaron; Wisner, Krista; Kochunov, Peter; Schwarcz, Robert; Hong, L Elliot

2018-04-18

Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia. In 56 patients with schizophrenia and 58 healthy controls, our results confirm that levels of KYNA in saliva increase following psychological stress. The magnitude of the effect correlated negatively with proton magnetic resonance spectroscopy (MRS) glutamate + glutamine (r = -.31, p = .017) and glutamate (r = -0.27, p = .047) levels in the ACC in patients but not in the controls (all p ≥ .45). Although, a causal relationship cannot be ascertained in this cross-sectional study, these findings suggest a potentially meaningful link between central glutamate levels and kynurenine pathway response to stress in individuals with schizophrenia.
Dysregulation of Ion Homeostasis by Antifungal Agents

PubMed Central

Zhang, Yongqiang; Muend, Sabina; Rao, Rajini

2012-01-01

Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca2+ burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides. PMID:22493595
Dysregulation of ion homeostasis by antifungal agents.

PubMed

Zhang, Yongqiang; Muend, Sabina; Rao, Rajini

2012-01-01

Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca(2+) burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca(2+) stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.
Neuropeptide Y and sleep.

PubMed

Dyzma, Michal; Boudjeltia, Karim Z; Faraut, Brice; Kerkhofs, Myriam

2010-06-01

Neuropeptide Y (NPY), a 36-amino-acid peptide from the pancreatic polypeptide family, is one of the more abundant peptides in the central nervous system. It acts as a neurohormone and as a neuromodulator. NPY is widely distributed in the brain, particularly the hypothalamus, the amygdala, the locus coeruleus and the cerebral cortex. At least six NPY receptors subtypes have been identified. NPY is involved in the regulation of several physiological functions such as food intake, hormonal release, circadian rhythms, cardiovascular disease, thermoregulation, stress response, anxiety and sleep. Sleep promoting effects of NPY as well as wakefulness effects of NPY were found in animals, depending on the site of injection as well as on the functional state of the structure. In humans, NPY was found to have hypnotic properties, possibly acting as a physiological antagonist of corticotropin-releasing hormone (CRH). In conclusion, NPY participates in sleep regulation in humans, particularly in the timing of sleep onset and may as such play a role in the integration of sleep regulation, food intake and metabolism. Copyright 2009 Elsevier Ltd. All rights reserved.
Regulation of photochemical energy transfer accompanied by structural changes in thylakoid membranes of heat-stressed wheat.

PubMed

Marutani, Yoko; Yamauchi, Yasuo; Miyoshi, Akihito; Inoue, Kanako; Ikeda, Ken-ichi; Mizutani, Masaharu; Sugimoto, Yukihiro

2014-12-11

Photosystems of higher plants alleviate heat-induced damage in the presence of light under moderate stressed conditions; however, in the absence of light (i.e., in the dark), the same plants are damaged more easily. (Yamauchi and Kimura, 2011) We demonstrate that regulating photochemical energy transfer in heat-treated wheat at 40 °C with light contributed to heat tolerance of the photosystem. Chlorophyll fluorescence analysis using heat-stressed wheat seedlings in light showed increased non-photochemical quenching (NPQ) of chlorophyll fluorescence, which was due to thermal dissipation that was increased by state 1 to state 2 transition. Transmission electron microscopy revealed structural changes in thylakoid membranes, including unstacking of grana regions under heat stress in light. It was accompanied by the phosphorylation of thylakoid proteins such as D1 and D2 proteins and the light harvesting complex II proteins Lhcb1 and Lhcb2. These results suggest that heat stress at 40 °C in light induces state 1 to state 2 transition for the preferential excitation of photosystem I (PSI) by phosphorylating thylakoid proteins more strongly. Structural changes of thylakoid membrane also assist the remodeling of photosystems and regulation of energy distribution by transition toward state 2 probably contributes to plastoquione oxidation; thus, light-driven electrons flowing through PSI play a protective role against PSII damage under heat stress.
A Central Role for Thiols in Plant Tolerance to Abiotic Stress

PubMed Central

Zagorchev, Lyuben; Seal, Charlotte E.; Kranner, Ilse; Odjakova, Mariela

2013-01-01

Abiotic stress poses major problems to agriculture and increasing efforts are being made to understand plant stress response and tolerance mechanisms and to develop new tools that underpin successful agriculture. However, the molecular mechanisms of plant stress tolerance are not fully understood, and the data available is incomplete and sometimes contradictory. Here, we review the significance of protein and non-protein thiol compounds in relation to plant tolerance of abiotic stress. First, the roles of the amino acids cysteine and methionine, are discussed, followed by an extensive discussion of the low-molecular-weight tripeptide, thiol glutathione, which plays a central part in plant stress response and oxidative signalling and of glutathione-related enzymes, including those involved in the biosynthesis of non-protein thiol compounds. Special attention is given to the glutathione redox state, to phytochelatins and to the role of glutathione in the regulation of the cell cycle. The protein thiol section focuses on glutaredoxins and thioredoxins, proteins with oxidoreductase activity, which are involved in protein glutathionylation. The review concludes with a brief overview of and future perspectives for the involvement of plant thiols in abiotic stress tolerance. PMID:23549272
Central circuitries for body temperature regulation and fever.

PubMed

Nakamura, Kazuhiro

2011-11-01

Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonshivering thermogenesis in brown adipose tissue, shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation, heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend thermal homeostasis from environmental thermal challenges, feedforward thermosensory information on environmental temperature sensed by skin thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus to the preoptic area (POA). The POA also receives feedback signals from local thermosensitive neurons, as well as pyrogenic signals of prostaglandin E(2) produced in response to infection. These afferent signals are integrated and affect the activity of GABAergic inhibitory projection neurons descending from the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic and somatic premotor neurons in the rMR, which then drive spinal motor output mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction. Warming signals enhance the descending inhibition from the POA to inhibit the motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis. This central thermoregulatory mechanism also functions for metabolic regulation and stress-induced hyperthermia.
Impacts of precipitation variability on plant species and community water stress in a temperate deciduous forest in the central US

DOE PAGES

Gu, Lianhong; Pallardy, Stephen G.; Hosman, Kevin P.; ...

2015-12-11

Variations in precipitation regimes can shift ecosystem structure and function by altering frequency, severity and timing of plant water stress. There is a need for predictively understanding impacts of precipitation regimes on plant water stress in relation to species water use strategies. Here we first formulated two complementary, physiologically-linked measures of precipitation variability (PV) - Precipitation Variability Index (PVI) and Average Recurrence Interval of Effective Precipitation (ARIEP). We then used nine-year continuous measurements of Predawn Leaf Water Potential Integral (PLWPI) in a central US forest to relate PVI and ARIEP to actual plant water availability and comparative water stress responsesmore » of six species with different capacities to regulate their internal water status. We found that PVI and ARIEP explained nearly all inter-annual variations in PLWPI for all species as well as for the community scaled from species measurements. The six species investigated showed differential sensitivities to variations in precipitation regimes. Their sensitivities were reflected more in the responses to PVI and ARIEP than to the mean precipitation rate. Further, they exhibited tradeoffs between responses to low and high PV. Finally, PVI and ARIEP were closely correlated with temporal integrals of positive temperature anomalies and vapor pressure deficit. We suggest that the comparative responses of plant species to PV are part of species-specific water use strategies in a plant community facing the uncertainty of fluctuating precipitation regimes. In conclusion, PVI and ARIEP should be adopted as key indices to quantify physiological drought and the ecological impacts of precipitation regimes in a changing climate.« less
Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

PubMed

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-05-01

Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.
Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks

PubMed Central

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-01-01

Abstract Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic–pituitary–adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases. PMID:29713692
[The Effects of Neurofeedback Training on Physical, Psychoemotional Stress Response and Self-Regulation for Late Adolescence: A Non-Randomized Trial].

PubMed

Choi, Moon Ji; Park, Wan Ju

2018-04-01

The aim of this study was to analyze the effects of neurofeedback training for reducing stress and enhancing self-regulation in late adolescence to identify the possibility of use for nursing intervention. A nonequivalent control group pre-post quasi-experimental design was used. Participants were 78 late adolescents assigned to the experimental group (n=39) that received the neurofeedback training and the control group (n=39). Data were collected on heart rate variability (HRV) and skin conductance level (SCL) to assess stress-biomarker response. The questionnaire contained 164 items from: Positive and Negative Affect Schedule (PANAS), Symptom Checklist-90-Revised (SCL-90-R) and Self-regulatory Ability scale. The neurofeedback training was based on the general adaptation syndrome and body-mind medicine. The intervention was conducted in a total of 10 sessions for 30 minutes per session with high-beta, theta and sensory motor rhythm training on scalp at central zero. There were significant difference in standard deviation of normal to normal interval (p=.036) in HRV and SCL (p=.029) of stress-biomarker response between the two groups. Negative affect (p=.036) in PANAS and obsessive compulsive (p=.023) and depression (p<.001) in SCL-90-R were statistically significant. Self-regulation mode (p=.004) in self-regulation ability scale showed a significant difference between the two groups. The results indicated that the neurofeedback training is effective in stress-biomarkers, psychoemotional stress response and self-regulation. Therefore, neurofeedback training using neuroscientific approach based on brain-mind-body model can be used as an effective nursing intervention for late adolescents in clinics and communities for effective stress responses. © 2018 Korean Society of Nursing Science.
Stress, epigenetics, and alcoholism.

PubMed

Moonat, Sachin; Pandey, Subhash C

2012-01-01

Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker's dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity-for example, by modifying the structure of the DNA-protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism.
Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior.

PubMed

Zhao, Liping; Kim, Ki Woo; Ikeda, Yayoi; Anderson, Kimberly K; Beck, Laurel; Chase, Stephanie; Tobet, Stuart A; Parker, Keith L

2008-06-01

Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.
Thermoregulation in multiple sclerosis.

PubMed

Davis, Scott L; Wilson, Thad E; White, Andrea T; Frohman, Elliot M

2010-11-01

Multiple sclerosis (MS) is a progressive neurological disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60-80% of MS patients experience temporary worsening of clinical signs and neurological symptoms with heat exposure. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. This review focuses on five main themes regarding the current understanding of thermoregulatory dysfunction in MS: 1) heat sensitivity; 2) central regulation of body temperature; 3) thermoregulatory effector responses; 4) heat-induced fatigue; and 5) countermeasures to improve or maintain function during thermal stress. Heat sensitivity in MS is related to the detrimental effects of increased temperature on action potential propagation in demyelinated axons, resulting in conduction slowing and/or block, which can be quantitatively characterized using precise measurements of ocular movements. MS lesions can also occur in areas of the brain responsible for the control and regulation of body temperature and thermoregulatory effector responses, resulting in impaired neural control of sudomotor pathways or neural-induced changes in eccrine sweat glands, as evidenced by observations of reduced sweating responses in MS patients. Fatigue during thermal stress is common in MS and results in decreased motor function and increased symptomatology likely due to impairments in central conduction. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacological) for the MS patient to preserve function and decrease symptom worsening during heat stress.
Place, social exchange and health: proposed sociological framework.

PubMed

Siegrist, J

2000-11-01

A sociological framework is proposed to better understand how spatial characteristics translate into people's physical and psychosocial conditions that are relevant to their health. In particular, high susceptibility to poor health among specific adult population groups is analyzed in terms of exclusion from or inadequate participation in a society's structure of opportunities. Acquisition of, and agency through, core social roles, such as the work role, the family and marital role, and civic roles, are essential prerequisites for successful personal self-regulation in adult life, strengthening a sense of self-esteem, self-efficacy, and belonging (self-integration). It is argued that exclusion from, or loss of core social roles, threats to their continuity and confinement to non-reciprocal exchange impair personal self-regulation and trigger a state of 'social reward deficiency'. This state, in turn, elicits prolonged stressful experience, and it may reinforce a person's craving for stress-relieving, potentially addictive health-damaging behavior. This framework is applied to the explanation of the life expectancy gap between Western and Central/Eastern European countries. Although most of the epidemiological evidence reviewed in support of this approach originates from investigations that were conducted in western countries several results reported in the collection of articles published in this Special Issue of Social Science and Medicine are in line with the proposed framework.
Sex-specific association between functional neuropeptide S receptor gene (NPSR1) variants and cortisol and central stress responses.

PubMed

Streit, Fabian; Akdeniz, Ceren; Haddad, Leila; Kumsta, Robert; Entringer, Sonja; Frank, Josef; Yim, Ilona S; Zänkert, Sandra; Witt, Stephanie H; Kirsch, Peter; Rietschel, Marcella; Wüst, Stefan

2017-02-01

The brain neuropeptide S (NPS) system has recently generated substantial interest and may be of major relevance for central stress regulation. The NPS receptor (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated. In humans, associations between NPSR1 variants and anxiety and panic disorder, as well as amygdala responsiveness to fear- relevant faces and prefrontal cortex activity in a fear conditioning paradigm have been reported. Moreover, a NPSR1 sequence variant was found to be associated with cortisol stress responses in males. Here, we performed a haplotype-based analysis covering three functional NPSR1 single nucleotide polymorphisms in the promoter (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects who were exposed to the Trier Social Stress Test (TSST). A significant sex-specific association with salivary cortisol responses to acute psychosocial stress was detected for the common TTC haplotype 2 (frequency of about 20%). In an additional study using an imaging genetics approach, 65 healthy subjects were exposed to a stress paradigm for scanner environments (“ScanSTRESS”). We found a significant and, again, sex-specific interaction between rs324981 (whose minor T-allele is harbored by haplotype 2) and the neural stress response in a cluster close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the TSST sample, NPSR1 variation was associated with salivary cortisol responses (on a trend level) in a sex-specific way. In summary, our preliminary findings in two independent cohorts exposed to different stress paradigms suggest that the NPS system significantly influences acute stress responses and that sequence variation in NPSR1 may contribute to sex differences in stress regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.
Variation in Ecophysiological Traits and Drought Tolerance of Beech (Fagus sylvatica L.) Seedlings from Different Populations

PubMed Central

Cocozza, Claudia; de Miguel, Marina; Pšidová, Eva; Ditmarová, L'ubica; Marino, Stefano; Maiuro, Lucia; Alvino, Arturo; Czajkowski, Tomasz; Bolte, Andreas; Tognetti, Roberto

2016-01-01

Frequency and intensity of heat waves and drought events are expected to increase in Europe due to climate change. European beech (Fagus sylvatica L.) is one of the most important native tree species in Europe. Beech populations originating throughout its native range were selected for common-garden experiments with the aim to determine whether there are functional variations in drought stress responses among different populations. One-year old seedlings from four to seven beech populations were grown and drought-treated in a greenhouse, replicating the experiment at two contrasting sites, in Italy (Mediterranean mountains) and Germany (Central Europe). Experimental findings indicated that: (1) drought (water stress) mainly affected gas exchange describing a critical threshold of drought response between 30 and 26% SWA for photosynthetic rate and Ci/Ca, respectively; (2) the Ci to Ca ratio increased substantially with severe water stress suggesting a stable instantaneous water use efficiency and an efficient regulation capacity of water balance achieved by a tight stomatal control; (3) there was a different response to water stress among the considered beech populations, differently combining traits, although there was not a well-defined variability in drought tolerance. A combined analysis of functional and structural traits for detecting stress signals in beech seedlings is suggested to assess plant performance under limiting moisture conditions and, consequently, to estimate evolutionary potential of beech under a changing environmental scenario. PMID:27446118

Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety- and depressive- like behaviors.

PubMed

Ramirez, Karol; Sheridan, John F

2016-10-01

In order to relieve anxiety and depression accompanying stress, physicians resort to tricyclic antidepressants, such as imipramine. We had previously shown that imipramine reversed stress-induced social avoidance behavior, and down-regulated microglial activation 24days after stress cessation. To further characterize the effects of imipramine on stress induced neuroimmune dysregulation and associated changes in behavior, the aims of this study were to determine if imipramine 1) ameliorated stress-induced inflammation in the periphery and central nervous system, and 2) prevented stress related anxiety- and depressive-like behaviors. C57BL/6 mice were treated with imipramine (15mg/kg) in their drinking water, and exposed to repeated social defeat (RSD). Imipramine attenuated stress-induced corticosterone and IL-6 responses in plasma. Imipramine decreased the percentage of monocytes and granulocytes in the bone marrow and circulation. However, imipramine did not prevent splenomegaly, stress-related increased percentage of granulocytes in this organ, and the production of pro-inflammatory cytokines in the spleen, following RSD. Moreover, imipramine abrogated the accumulation of macrophages in the brain in mice exposed to RSD. Imipramine blocked neuroinflammatory signaling and prevented stress-related anxiety- and depressive-like behaviors. These data support the notion that pharmacomodulation of the monoaminergic system, besides exerting anxiolytic and antidepressant effects, may have therapeutic effects as a neuroimmunomodulator during stress. Copyright © 2016 Elsevier Inc. All rights reserved.
Renal sympathetic nerve, blood flow, and epithelial transport responses to thermal stress.

PubMed

Wilson, Thad E

2017-05-01

Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo, this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress. Copyright © 2016 Elsevier B.V. All rights reserved.
Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety- and depressive- like behaviors

PubMed Central

Ramirez, Karol; Sheridan, John F.

2016-01-01

In order to relieve anxiety and depression accompanying stress, physicians resort to tricyclic antidepressants, such as imipramine. We had previously shown that imipramine reversed stress-induced social avoidance behavior, and down-regulated microglial activation 24 days after stress cessation. To further characterize the effects of imipramine on stress induced neuroimmune dysregulation and associated changes in behavior, the aims of this study were to determine if imipramine 1) ameliorated stress-induced inflammation in the periphery and central nervous system, and 2) prevented stress related anxiety- and depressive-like behaviors. C57BL/6 mice were treated with imipramine (15mg/kg) in their drinking water, and exposed to repeated social defeat (RSD). Imipramine attenuated stress-induced corticosterone and IL-6 responses in plasma. Imipramine decreased the percentage of monocytes and granulocytes in the bone marrow and circulation. However, imipramine did not prevent splenomegaly, stress-related increased percentage of granulocytes in this organ, and the production of pro-inflammatory cytokines in the spleen, following RSD. Moreover, imipramine abrogated the accumulation of macrophages in the brain in mice exposed to RSD. Imipramine blocked neuroinflammatory signaling and prevented stress-related anxiety- and depressive-like behaviors. These data support the notion that pharmacomodulation of the monoaminergic system, besides exerting anxiolytic and antidepressant effects, may have therapeutic effects as a neuroimmunomodulator during stress. PMID:27223094
Hydrogen peroxide priming modulates abiotic oxidative stress tolerance: insights from ROS detoxification and scavenging

PubMed Central

Hossain, Mohammad A.; Bhattacharjee, Soumen; Armin, Saed-Moucheshi; Qian, Pingping; Xin, Wang; Li, Hong-Yu; Burritt, David J.; Fujita, Masayuki; Tran, Lam-Son P.

2015-01-01

Plants are constantly challenged by various abiotic stresses that negatively affect growth and productivity worldwide. During the course of their evolution, plants have developed sophisticated mechanisms to recognize external signals allowing them to respond appropriately to environmental conditions, although the degree of adjustability or tolerance to specific stresses differs from species to species. Overproduction of reactive oxygen species (ROS; hydrogen peroxide, H2O2; superoxide, O2⋅-; hydroxyl radical, OH⋅ and singlet oxygen, 1O2) is enhanced under abiotic and/or biotic stresses, which can cause oxidative damage to plant macromolecules and cell structures, leading to inhibition of plant growth and development, or to death. Among the various ROS, freely diffusible and relatively long-lived H2O2 acts as a central player in stress signal transduction pathways. These pathways can then activate multiple acclamatory responses that reinforce resistance to various abiotic and biotic stressors. To utilize H2O2 as a signaling molecule, non-toxic levels must be maintained in a delicate balancing act between H2O2 production and scavenging. Several recent studies have demonstrated that the H2O2-priming can enhance abiotic stress tolerance by modulating ROS detoxification and by regulating multiple stress-responsive pathways and gene expression. Despite the importance of the H2O2-priming, little is known about how this process improves the tolerance of plants to stress. Understanding the mechanisms of H2O2-priming-induced abiotic stress tolerance will be valuable for identifying biotechnological strategies to improve abiotic stress tolerance in crop plants. This review is an overview of our current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants, with special reference to antioxidant metabolism. PMID:26136756
The Influence of Work-Related Chronic Stress on the Regulation of Emotion and on Functional Connectivity in the Brain

PubMed Central

Golkar, Armita; Johansson, Emilia; Kasahara, Maki; Osika, Walter; Perski, Aleksander; Savic, Ivanka

2014-01-01

Despite mounting reports about the negative effects of chronic occupational stress on cognitive and emotional functions, the underlying mechanisms are unknown. Recent findings from structural MRI raise the question whether this condition could be associated with a functional uncoupling of the limbic networks and an impaired modulation of emotional stress. To address this, 40 subjects suffering from burnout symptoms attributed to chronic occupational stress and 70 controls were investigated using resting state functional MRI. The participants' ability to up- regulate, down-regulate, and maintain emotion was evaluated by recording their acoustic startle response while viewing neutral and negatively loaded images. Functional connectivity was calculated from amygdala seed regions, using explorative linear correlation analysis. Stressed subjects were less capable of down-regulating negative emotion, but had normal acoustic startle responses when asked to up-regulate or maintain emotion and when no regulation was required. The functional connectivity between the amygdala and the anterior cingulate cortex correlated with the ability to down-regulate negative emotion. This connectivity was significantly weaker in the burnout group, as was the amygdala connectivity with the dorsolateral prefrontal cortex and the motor cortex, whereas connectivity from the amygdala to the cerebellum and the insular cortex were stronger. In subjects suffering from chronic occupational stress, the functional couplings within the emotion- and stress-processing limbic networks seem to be altered, and associated with a reduced ability to down-regulate the response to emotional stress, providing a biological substrate for a further facilitation of the stress condition. PMID:25184294
Emotional Stress as a Risk for Hypertension in Sub-Saharan Africans: Are We Ignoring the Odds?

PubMed

Malan, Leoné; Malan, Nico T

2017-01-01

Globally most interventions focus on improving lifestyle habits and treatment regimens to combat hypertension as a non-communicable disease (NCD). However, despite these interventions and improved medical treatments, blood pressure (BP) values are still on the rise and poorly controlled in sub-Saharan Africa (SSA). Other factors contributing to hypertension prevalence, such as chronic emotional stress, might provide some insight for future health policy approaches.Currently, Hypertension Society guidelines do not mention emotional stress as a probable cause for hypertension. Recently the 2014 World Global Health reports, suggested that African governments should consider using World Health Organization hypertension data as a proxy indicator for social well-being. However, the possibility that a stressful life and taxing environmental factors might disturb central neural control of BP regulation has largely been ignored in SSA.Linking emotional stress to vascular dysregulation is therefore one way to investigate increased cardiometabolic challenges, neurotransmitter depletion and disturbed hemodynamics. Disruption of stress response pathways and subsequent changes in lifestyle habits as ways of coping with a stressful life, and as probable cause for hypertension prevalence in SSA, may be included in future preventive measures. We will provide an overview on emotional stress and central neural control of BP and will include also implications thereof for clinical practice in SSA cohorts.
Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension.

PubMed

Ihalainen, Teemu O; Aires, Lina; Herzog, Florian A; Schwartlander, Ruth; Moeller, Jens; Vogel, Viola

2015-12-01

Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Ig-epitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help decipher how the physical properties of cellular microenvironments regulate nuclear events.
Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension

NASA Astrophysics Data System (ADS)

Ihalainen, Teemu O.; Aires, Lina; Herzog, Florian A.; Schwartlander, Ruth; Moeller, Jens; Vogel, Viola

2015-12-01

Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Ig-epitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help decipher how the physical properties of cellular microenvironments regulate nuclear events.
Lithospheric Structure and Isostasy of Central Andes: Implication for plate Coupling

NASA Astrophysics Data System (ADS)

Mahatsente, R.; Rutledge, S.

2017-12-01

A significant section of the Peru-Chile convergent zone is building up stresses. The interseismic coupling in northern and southern Peru is significantly high indicating, elastic energy accumulation since the 1746 and 1868 earthquakes of magnitude 8.6 and 8.8 , respectively. Similar seismic patterns have also been observed in Central Chile. The plate interface beneath Central Chile is highly coupled, and the narrow zones of low coupling separate seismic gaps. The reasons for the seismic gaps and plate coupling are yet unknown, but the configuration of the slab is thought to be the main factor. Here, we assessed the locking mechanism and isostatic state of the Central Andes based on gravity models of the crust and upper mantle structure. The density models are based on satellite gravity data and are constrained by velocity models and earthquake hypocenters. The gravity models indicate a high-density batholithic structure in the fore-arc, overlying the subducting Nazca plate. This high-density body pushes downward on the slab, causing the slab to lock with the overlying continental plate. The increased compressive stress closer to the trench, due to the increased contact area between the subducting and overriding plates, may have increased the plate coupling in the Central Andes. Thus, trench parallel crustal thickness and density variations along the Central Andes and buoyancy force on the subducting Nazca plate may control plate coupling and asperity generation. The western part of the Central Andes may be undercompensated. There is a residual topography of 800 m in the western part of the Central Andes that cannot be explained by the observed crustal thicknesses. Thus, part of the observed topography in the western part of the Central Andes may be dynamically supported by mantle wedge flow below the overriding plate.
Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

ERIC Educational Resources Information Center

Gee, Dylan G.

2016-01-01

Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…
Understanding the Structure of Children's Emotion-Regulation Strategies

ERIC Educational Resources Information Center

Callear, Angela; Harvey, Shane Trevor; Bimler, David

2017-01-01

Emotion regulation is a central feature in human emotional development. However, measures based on children's observable emotion regulation behaviors are largely absent. An inventory of children's emotion regulation strategies was developed from current measures and four focus group discussions with experts in child behavior and emotion. From…
Family Financial Stress and Adolescent Sexual Risk-Taking: The Role of Self-Regulation.

PubMed

Crandall, AliceAnn; Magnusson, Brianna M; Novilla, M Lelinneth B; Novilla, Lynneth Kirsten B; Dyer, W Justin

2017-01-01

The ability to control one's emotions, thoughts, and behaviors is known as self-regulation. Family stress and low adolescent self-regulation have been linked with increased engagement in risky sexual behaviors, which peak in late adolescence and early adulthood. The purpose of this study was to assess whether adolescent self-regulation, measured by parent and adolescent self-report and respiratory sinus arrhythmia, mediates or moderates the relationship between family financial stress and risky sexual behaviors. We assessed these relationships in a 4-year longitudinal sample of 450 adolescents (52 % female; 70 % white) and their parents using structural equation modeling. Results indicated that high family financial stress predicts engagement in risky sexual behaviors as mediated, but not moderated, by adolescent self-regulation. The results suggest that adolescent self-regulatory capacities are a mechanism through which proximal external forces influence adolescent risk-taking. Promoting adolescent self-regulation, especially in the face of external stressors, may be an important method to reduce risk-taking behaviors as adolescents transition to adulthood.
Altered Regulation of Gene and Protein Expression of Hypothalamic-Pituitary-Adrenal Axis Components in an Immature Rat Model of Chronic Stress

PubMed Central

Avishai-Eliner, S.; Gilles, E. E.; Eghbal-Ahmadi, M.; Bar-El, Y.; Baram, T. Z.

2011-01-01

Chronic stress early in postnatal life influences hormonal and behavioural responses to stress persistently, but the mechanisms and molecular cascades that are involved in this process have not been clarified. To approach these issues, a chronic stress paradigm for the neonatal rat, using limited bedding material to alter the cage environment, was devised. In 9-day-old rats subjected to this chronic stress for 1 week, significant and striking changes in the expression and release patterns of key molecules that govern the neuroendocrine stress responses were observed. The presence of sustained stress was evident from enhanced activation of peripheral elements of the neuroendocrine stress response, i.e. increased basal plasma corticosterone concentrations, high adrenal weight and decreased body weight. Central regulatory elements of the neuroendocrine stress response were perturbed, including reduced expression of hypothalamic corticotropin-releasing hormone that, surprisingly, was accompanied by reduced glucocorticoid receptor expression. Thus, the effects of chronic sustained stress in the neonatal rat on the hypothalamic-pituitary-adrenal axis included substantial changes in the expression and activity of major regulators of this axis. Importantly, the changes induced by this chronic stress differed substantially from those related to acute or recurrent stress, providing a novel model for studying the long-term effects of chronic, early life stress on neuroendocrine functions throughout life. PMID:11578530
Role of various hormones in photosynthetic responses of green plants under environmental stresses.

PubMed

Poonam; Bhardwaj, Renu; Kaur, Ravdeep; Bali, Shagun; Kaur, Parminder; Sirhindi, Geetika; Thukral, Ashwani K; Ohri, Puja; Vig, Adarsh P

2015-01-01

Environmental stress includes adverse factors like water deficit, high salinity, enhanced temperature and heavy metals etc. These stresses alter the normal growth and metabolic processes of plants including photosynthesis. Major photosynthetic responses under various stresses include inhibition of photosystems (I and II), changes in thylakoid complexes, decreased photosynthetic activity and modifications in structure and functions of chloroplasts etc. Various defense mechanisms are triggered inside the plants in response to these stresses that are regulated by plant hormones or plant growth regulators. These phytohormones include abscisic acid, auxins, cytokinins, ethylene, brassinosteroids, jasmonates and salicylic acid etc. The present review focuses on stress protective effects of plants hormones on the photosynthetic responses.
Late-Variscan Tectonic Inheritance and Salt Tectonics Interplay in the Central Lusitanian Basin

NASA Astrophysics Data System (ADS)

Nogueira, Carlos R.; Marques, Fernando O.

2017-04-01

Tectonic inheritance and salt structures can play an important role in the tectono-sedimentary evolution of basins. The Alpine regional stress field in west Iberia had a horizontal maximum compressive stress striking approximately NNW-SSE, related to the Late Miocene inversion event. However, this stress field cannot produce a great deal of the observed and mapped structures in the Lusitanian Basin. Moreover, many observed structures show a trend similar to well-known basement fault systems. The Central Lusitanian basin shows an interesting tectonic structure, the Montejunto structure, generally assigned to this inversion event. Therefore, special attention was paid to: (1) basement control of important observed structures; and (2) diapir tectonics (vertical maximum compressive stress), which can be responsible for significant vertical movements. Based on fieldwork, tectonic analysis and interpretation of geological maps (Portuguese Geological Survey, 1:50000 scale) and geophysical data, our work shows: (1) the Montejunto structure is a composite structure comprising an antiform with a curved hinge and middle Jurassic core, and bounding main faults; (2) the antiform can be divided into three main segments: (i) a northern segment with NNE-SSW trend showing W-dipping bedding bounded at the eastern border by a NNE-SSW striking fault, (ii) a curved central segment, showing the highest topography, with a middle Jurassic core and radial dipping bedding, (iii) a western segment with ENE-WSW trend comprising an antiform with a steeper northern limb and periclinal termination towards WSW, bounded to the south by ENE-WSW reverse faulting, (3) both fold and fault trends at the northern and western segments are parallel to well-known basement faults related to late-Variscan strike-slip systems with NNE-SSW and ENE-WSW trends; (4) given the orientation of Alpine maximum compressive stress, the northern segment border fault should be mostly sinistral strike-slip and the western segment border fault should be a pure thrust; (5) uplift along the northern and central segments may point out to the presence of a salt diapir at depth, aiding vertical movement and local uplift of the structure; (6) geometry of seismic units of the neighboring basins is consistent with halokinesis related to the antiform growth during the Jurassic; (7) sedimentary filling of the neighbouring basins shows relationship to antiform development and growth into a structural high before the Late Miocene Alpine event. These data suggest that: (1) pre-existing basement faults and their reactivation played important role on the development of Montejunto complex tectonic structure; (2) important vertical movements occurred as the result of regional and local (diapir) tectonics; (3) subsidence in neighbouring basins may have promoted maturation, and possible targets with strong potential for hydrocarbon trapping and accumulation may have also developed; (4) diapir tectonics initiated before the Cretaceous; (5) given the topography, and the geometry and inferred kinematics of all segments, it seems that the Montejunto structure formed in a restraining bend controlled by inherited late-Variscan basement faults.
Structural covariance network centrality in maltreated youth with posttraumatic stress disorder

PubMed Central

Sun, Delin; Peverill, Matthew R.; Swanson, Chelsea S.; McLaughlin, Katie A.; Morey, Rajendra A.

2018-01-01

Childhood maltreatment is associated with posttraumatic stress disorder (PTSD) and elevated rates of adolescent and adult psychopathology including major depression, bipolar disorder, substance use disorders, and other medical comorbidities. Gray matter volume changes have been found in maltreated youth with (versus without) PTSD. However, little is known about the alterations of brain structural covariance network topology derived from cortical thickness in maltreated youth with PTSD. High-resolution T1-weighted magnetic resonance imaging scans were from demographically matched maltreated youth with PTSD (N = 24), without PTSD (N =64), and non-maltreated healthy controls (n = 67). Cortical thickness data from 148 cortical regions was entered into interregional partial correlation analyses across participants. The supra-threshold correlations constituted connections in a structural brain network derived from four types of centrality measures (degree, betweenness, closeness, and eigenvector) estimated network topology and the importance of nodes. Between-group differences were determined by permutation testing. Maltreated youth with PTSD exhibited larger centrality in left anterior cingulate cortex than the other two groups, suggesting cortical network topology specific to maltreated youth with PTSD. Moreover, maltreated youth with versus without PTSD showed smaller centrality in right orbitofrontal cortex, suggesting that this may represent a vulnerability factor to PTSD following maltreatment. Longitudinal follow-up of the present results will help characterize the role that altered centrality plays in vulnerability and resilience to PTSD following childhood maltreatment. PMID:29294430
Hormone balance and abiotic stress tolerance in crop plants.

PubMed

Peleg, Zvi; Blumwald, Eduardo

2011-06-01

Plant hormones play central roles in the ability of plants to adapt to changing environments, by mediating growth, development, nutrient allocation, and source/sink transitions. Although ABA is the most studied stress-responsive hormone, the role of cytokinins, brassinosteroids, and auxins during environmental stress is emerging. Recent evidence indicated that plant hormones are involved in multiple processes. Cross-talk between the different plant hormones results in synergetic or antagonic interactions that play crucial roles in response of plants to abiotic stress. The characterization of the molecular mechanisms regulating hormone synthesis, signaling, and action are facilitating the modification of hormone biosynthetic pathways for the generation of transgenic crop plants with enhanced abiotic stress tolerance. Copyright © 2011 Elsevier Ltd. All rights reserved.
New translational perspectives for blood-based biomarkers of PTSD: From glucocorticoid to immune mediators of stress susceptibility

PubMed Central

Daskalakis, Nikolaos P.; Cohen, Hagit; Nievergelt, Caroline M.; Baker, Dewleen G.; Buxbaum, Joseph D.; Russo, Scott J.; Yehuda, Rachel

2016-01-01

Although biological systems have evolved to promote stress-resilience, there is variation in stress-responses. Understanding the biological basis of such individual differences has implications for understanding Posttraumatic Stress Disorder (PTSD) etiology, which is a maladaptive response to trauma occurring only in a subset of vulnerable individuals. PTSD involves failure to reinstate physiological homeostasis after traumatic events and is due to either intrinsic or trauma-related alterations in physiological systems across the body. Master homeostatic regulators that circulate and operate throughout the organism, such as stress hormones (e.g., glucocorticoids) and immune mediators (e.g., cytokines), are at the crossroads of peripheral and central susceptibility pathways and represent promising functional biomarkers of stress-response and target for novel therapeutics. PMID:27481726
Antidepressants recruit new neurons to improve stress response regulation

PubMed Central

Surget, A; Tanti, A; Leonardo, E D; Laugeray, A; Rainer, Q; Touma, C; Palme, R; Griebel, G; Ibarguen-Vargas, Y; Hen, R; Belzung, C

2011-01-01

Recent research suggests an involvement of hippocampal neurogenesis in behavioral effects of antidepressants. However, the precise mechanisms through which newborn granule neurons might influence the antidepressant response remain elusive. Here, we demonstrate that unpredictable chronic mild stress in mice not only reduces hippocampal neurogenesis, but also dampens the relationship between hippocampus and the main stress hormone system, the hypothalamo-pituitary-adrenal (HPA) axis. Moreover, this relationship is restored by treatment with the antidepressant fluoxetine, in a neurogenesis-dependent manner. Specifically, chronic stress severely impairs HPA axis activity, the ability of hippocampus to modulate downstream brain areas involved in the stress response, the sensitivity of the hippocampal granule cell network to novelty/glucocorticoid effects and the hippocampus-dependent negative feedback of the HPA axis. Remarkably, we revealed that, although ablation of hippocampal neurogenesis alone does not impair HPA axis activity, the ability of fluoxetine to restore hippocampal regulation of the HPA axis under chronic stress conditions, occurs only in the presence of an intact neurogenic niche. These findings provide a mechanistic framework for understanding how adult-generated new neurons influence the response to antidepressants. We suggest that newly generated neurons may facilitate stress integration and that, during chronic stress or depression, enhancing neurogenesis enables a dysfunctional hippocampus to restore the central control on stress response systems, then allowing recovery. PMID:21537331
Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

PubMed

Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

2016-05-01

Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and promote growth.

PubMed

Su, Kuo-Hui; Cao, Junyue; Tang, Zijian; Dai, Siyuan; He, Yishu; Sampson, Stephen Byers; Benjamin, Ivor J; Dai, Chengkai

2016-05-01

To cope with proteotoxic stress, cells attenuate protein synthesis. However, the precise mechanisms underlying this fundamental adaptation remain poorly defined. Here we report that mTORC1 acts as an immediate cellular sensor of proteotoxic stress. Surprisingly, the multifaceted stress-responsive kinase JNK constitutively associates with mTORC1 under normal growth conditions. On activation by proteotoxic stress, JNK phosphorylates both RAPTOR at S863 and mTOR at S567, causing partial disintegration of mTORC1 and subsequent translation inhibition. Importantly, HSF1, the central player in the proteotoxic stress response (PSR), preserves mTORC1 integrity and function by inactivating JNK, independently of its canonical transcriptional action. Thereby, HSF1 translationally augments the PSR. Beyond promoting stress resistance, this intricate HSF1-JNK-mTORC1 interplay, strikingly, regulates cell, organ and body sizes. Thus, these results illuminate a unifying mechanism that controls stress adaptation and growth.
A structural model of anti-anti-[sigma] inhibition by a two-component receiver domain: the PhyR stress response regulator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrou, Julien; Foreman, Robert; Fiebig, Aretha

2012-05-09

PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Directmore » intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.« less
A structural model of anti-anti-[sigma];#963; inhibition by a two-component receiver domain: the PhyR stress response regulator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrou, Julien; Foreman, Robert; Fiebig, Aretha

2012-03-30

PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Directmore » intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.« less
Anuran amphibians as comparative models for understanding extreme dehydration tolerance: a negative feedback lymphatic mechanism for blood volume regulation.

PubMed

Hillman, Stanley S

2018-06-06

Anurans are the most terrestrial order of amphibians. Couple the high driving forces for evaporative loss in terrestrial environments and their low resistance to evaporation, dehydration is an inevitable stress on their water balance. Anurans have the greatest tolerances for dehydration of any vertebrate group, some species can tolerate evaporative losses up to 45% of their standard body mass. Anurans have remarkable capacities to regulate blood volume with hemorrhage and dehydration compared to mammals. Stabilization of blood volume is central to extending dehydration tolerance, since it avoids both the hypovolemic and hyperviscosity stresses on cardiac output and its consequential effects on aerobic capacity. Anurans, in contrast to mammals, seem incapable of generating a sufficient pressure difference, either oncotically or via interstitial compliance, to move fluid from the interstitium into the capillaries. Couple this inability to generate a sufficient pressure difference for transvascular uptake to a circulatory system with high filtration coefficients and a high rate of plasma turnover is the consequence. The novel lymphatic system of anurans is critical to a remarkable capacity for blood volume regulation. This review summarizes what is known about the anatomical and physiological specializations which are involved in explaining differential blood volume regulation and dehydration tolerance involving a true centrally mediated negative feedback of lymphatic function involving baroreceptors as sensors and lymph hearts, AVT, pulmonary ventilation and specialized skeletal muscles as effectors.
Reactivity of seismicity rate to static Coulomb stress changes of two consecutive large earthquakes in the central Philippines

NASA Astrophysics Data System (ADS)

Dianala, J. D. B.; Aurelio, M.; Rimando, J. M.; Taguibao, K.

2015-12-01

In a region with little understanding in terms of active faults and seismicity, two large-magnitude reverse-fault related earthquakes occurred within 100km of each other in separate islands of the Central Philippines—the Mw=6.7 February 2012 Negros earthquake and the Mw=7.2 October 2013 Bohol earthquake. Based on source faults that were defined using onshore, offshore seismic reflection, and seismicity data, stress transfer models for both earthquakes were calculated using the software Coulomb. Coulomb stress triggering between the two main shocks is unlikely as the stress change caused by Negros earthquake on the Bohol fault was -0.03 bars. Correlating the stress changes on optimally-oriented reverse faults with seismicity rate changes shows that areas that decreased both in static stress and seismicity rate after the first earthquake were then areas with increased static stress and increased seismicity rate caused by the second earthquake. These areas with now increased stress, especially those with seismicity showing reactivity to static stress changes caused by the two earthquakes, indicate the presence of active structures in the island of Cebu. Comparing the history of instrumentally recorded seismicity and the recent large earthquakes of Negros and Bohol, these structures in Cebu have the potential to generate large earthquakes. Given that the Philippines' second largest metropolitan area (Metro Cebu) is in close proximity, detailed analysis of the earthquake potential and seismic hazards in these areas should be undertaken.
Glucose Starvation Alters Heat Shock Response, Leading to Death of Wild Type Cells and Survival of MAP Kinase Signaling Mutant

PubMed Central

Higgins, LeeAnn; Markowski, Todd; Brambl, Robert

2016-01-01

A moderate heat shock induces Neurospora crassa to synthesize large quantities of heat shock proteins that are protective against higher, otherwise lethal temperatures. However, wild type cells do not survive when carbohydrate deprivation is added to heat shock. In contrast, a mutant strain defective in a stress-activated protein kinase does survive the combined stresses. In order to understand the basis for this difference in survival, we have determined the relative levels of detected proteins in the mutant and wild type strain during dual stress, and we have identified gene transcripts in both strains whose quantities change in response to heat shock or dual stress. These data and supportive experimental evidence point to reasons for survival of the mutant strain. By using alternative respiratory mechanisms, these cells experience less of the oxidative stress that proves damaging to wild type cells. Of central importance, mutant cells recycle limited resources during dual stress by undergoing autophagy, a process that we find utilized by both wild type and mutant cells during heat shock. Evidence points to inappropriate activation of TORC1, the central metabolic regulator, in wild type cells during dual stress, based upon behavior of an additional signaling mutant and inhibitor studies. PMID:27870869
Stress, Epigenetics, and Alcoholism

PubMed Central

Moonat, Sachin; Pandey, Subhash C.

2012-01-01

Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker’s dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity—for example, by modifying the structure of the DNA–protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism. PMID:23584115
DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz, A.; Valdez, V; Rudino-Pinera, E

Neurospora crassa has two large-subunit catalases, CAT-1 and CAT-3. CAT-1 is associated with non-growing cells and accumulates particularly in asexual spores; CAT-3 is associated with growing cells and is induced under different stress conditions. It is our interest to elucidate the structure-function relationships in large-subunit catalases. Here we have determined the CAT-3 crystal structure and compared it with the previously determined CAT-1 structure. Similar to CAT-1, CAT-3 hydrogen peroxide (H{sub 2}O{sub 2}) saturation kinetics exhibited two components, consistent with the existence of two active sites: one saturated in the millimolar range and the other in the molar range. In themore » CAT-1 structure, we found three interesting features related to its unusual kinetics: (a) a constriction in the channel that conveys H{sub 2}O{sub 2} to the active site; (b) a covalent bond between the tyrosine, which forms the fifth coordination bound to the iron of the heme, and a vicinal cysteine; (c) oxidation of the pyrrole ring III to form a cis-hydroxyl group in C5 and a cis-{gamma}-spirolactone in C6. The site of heme oxidation marks the starts of the central channel that communicates to the central cavity and the shortest way products can exit the active site. CAT-3 has a similar constriction in its major channel, which could function as a gating system regulated by the H{sub 2}O{sub 2} concentration before the gate. CAT-3 functional tyrosine is not covalently bonded, but has instead the electron relay mechanism described for the human catalase to divert electrons from it. Pyrrole ring III in CAT-3 is not oxidized as it is in other large-subunit catalases whose structure has been determined. Different in CAT-3 from these enzymes is an occupied central cavity. Results presented here indicate that CAT-3 and CAT-1 enzymes represent a functional group of catalases with distinctive structural characteristics that determine similar kinetics.« less
Adaptation of maize source leaf metabolism to stress related disturbances in carbon, nitrogen and phosphorus balance

PubMed Central

2013-01-01

Background Abiotic stress causes disturbances in the cellular homeostasis. Re-adjustment of balance in carbon, nitrogen and phosphorus metabolism therefore plays a central role in stress adaptation. However, it is currently unknown which parts of the primary cell metabolism follow common patterns under different stress conditions and which represent specific responses. Results To address these questions, changes in transcriptome, metabolome and ionome were analyzed in maize source leaves from plants suffering low temperature, low nitrogen (N) and low phosphorus (P) stress. The selection of maize as study object provided data directly from an important crop species and the so far underexplored C4 metabolism. Growth retardation was comparable under all tested stress conditions. The only primary metabolic pathway responding similar to all stresses was nitrate assimilation, which was down-regulated. The largest group of commonly regulated transcripts followed the expression pattern: down under low temperature and low N, but up under low P. Several members of this transcript cluster could be connected to P metabolism and correlated negatively to different phosphate concentration in the leaf tissue. Accumulation of starch under low temperature and low N stress, but decrease in starch levels under low P conditions indicated that only low P treated leaves suffered carbon starvation. Conclusions Maize employs very different strategies to manage N and P metabolism under stress. While nitrate assimilation was regulated depending on demand by growth processes, phosphate concentrations changed depending on availability, thus building up reserves under excess conditions. Carbon and energy metabolism of the C4 maize leaves were particularly sensitive to P starvation. PMID:23822863
Adaptation of maize source leaf metabolism to stress related disturbances in carbon, nitrogen and phosphorus balance.

PubMed

Schlüter, Urte; Colmsee, Christian; Scholz, Uwe; Bräutigam, Andrea; Weber, Andreas P M; Zellerhoff, Nina; Bucher, Marcel; Fahnenstich, Holger; Sonnewald, Uwe

2013-07-03

Abiotic stress causes disturbances in the cellular homeostasis. Re-adjustment of balance in carbon, nitrogen and phosphorus metabolism therefore plays a central role in stress adaptation. However, it is currently unknown which parts of the primary cell metabolism follow common patterns under different stress conditions and which represent specific responses. To address these questions, changes in transcriptome, metabolome and ionome were analyzed in maize source leaves from plants suffering low temperature, low nitrogen (N) and low phosphorus (P) stress. The selection of maize as study object provided data directly from an important crop species and the so far underexplored C4 metabolism. Growth retardation was comparable under all tested stress conditions. The only primary metabolic pathway responding similar to all stresses was nitrate assimilation, which was down-regulated. The largest group of commonly regulated transcripts followed the expression pattern: down under low temperature and low N, but up under low P. Several members of this transcript cluster could be connected to P metabolism and correlated negatively to different phosphate concentration in the leaf tissue. Accumulation of starch under low temperature and low N stress, but decrease in starch levels under low P conditions indicated that only low P treated leaves suffered carbon starvation. Maize employs very different strategies to manage N and P metabolism under stress. While nitrate assimilation was regulated depending on demand by growth processes, phosphate concentrations changed depending on availability, thus building up reserves under excess conditions. Carbon and energy metabolism of the C4 maize leaves were particularly sensitive to P starvation.
Oxidative stress-mediated HMGB1 biology

PubMed Central

Yu, Yan; Tang, Daolin; Kang, Rui

2015-01-01

High mobility group box 1 (HMGB1) is a widely-expressed and highly-abundant protein that acts as an extracellular signal upon active secretion by immune cells or passive release by dead, dying, and injured cells. Both intracellular and extracellular HMGB1 play pivotal roles in regulation of the cellular response to stress. Targeting the translocation, release, and activity of HMGB1 can limit inflammation and reduce tissue damage during infection and sterile inflammation. Although the mechanisms contributing to HMGB1 biology are still under investigation, it appears that oxidative stress is a central regulator of HMGB1's translocation, release, and activity in inflammation and cell death (e.g., necrosis, apoptosis, autophagic cell death, pyroptosis, and NETosis). Thus, targeting HMGB1 with antioxidant compounds may be an attractive therapeutic strategy for inflammation-associated diseases such as sepsis, ischemia and reperfusion injury, arthritis, diabetes, and cancer. PMID:25904867
Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress.

PubMed

Wek, Ronald C

2018-02-12

A central mechanism regulating translation initiation in response to environmental stress involves phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Phosphorylation of eIF2α causes inhibition of global translation, which conserves energy and facilitates reprogramming of gene expression and signaling pathways that help to restore protein homeostasis. Coincident with repression of protein synthesis, many gene transcripts involved in the stress response are not affected or are even preferentially translated in response to increased eIF2α phosphorylation by mechanisms involving upstream open reading frames (uORFs). This review highlights the mechanisms regulating eIF2α kinases, the role that uORFs play in translational control, and the impact that alteration of eIF2α phosphorylation by gene mutations or small molecule inhibitors can have on health and disease. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.
Apolipoprotein A-IV constrains HPA and behavioral stress responsivity in a strain-dependent manner.

PubMed

Packard, Amy E B; Zhang, Jintao; Myers, Brent; Ko, Chih-Wei; Wang, Fei; Tso, Patrick; Ulrich-Lai, Yvonne M

2017-12-01

There is a critical gap in our knowledge of the mechanisms that govern interactions between daily life experiences (e.g., stress) and metabolic diseases, despite evidence that stress can have profound effects on cardiometabolic health. Apolipoprotein A-IV (apoA-IV) is a protein found in chylomicrons (lipoprotein particles that transport lipids throughout the body) where it participates in lipid handling and the regulation of peripheral metabolism. Moreover, apoA-IV is expressed in brain regions that regulate energy balance including the arcuate nucleus. Given that both peripheral and central metabolic processes are important modulators of hypothalamic-pituitary-adrenocortical (HPA) axis activity, the present work tests the hypothesis that apoA-IV activity affects stress responses. As emerging data suggests that apoA-IV actions can vary with background strain, we also explore the strain-dependence of apoA-IV stress regulation. These studies assess HPA axis, metabolic (hyperglycemia), and anxiety-related behavioral responses to psychogenic stress in control (wildtype) and apoA-IV-deficient (KO) mice on either the C57Bl/6J (C57) or 129×1/SvJ (129) background strain. The results indicate that apoA-IV KO increases post-stress corticosterone and anxiety-related behavior specifically in the 129 strain, and increases stress-induced hyperglycemia exclusively in the C57 strain. These data support the hypothesis that apoA-IV is a novel factor that limits stress reactivity in a manner that depends on genetic background. An improved understanding of the complex relationship among lipid homeostasis, stress sensitivity, and genetics is needed to optimize the development of personalized treatments for stress- and metabolism-related diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.
Effects of genotype and dietary fish oil replacement with vegetable oil on the intestinal transcriptome and proteome of Atlantic salmon (Salmo salar)

PubMed Central

2012-01-01

Background Expansion of aquaculture requires alternative feeds and breeding strategies to reduce dependency on fish oil (FO) and better utilization of dietary vegetable oil (VO). Despite the central role of intestine in maintaining body homeostasis and health, its molecular response to replacement of dietary FO by VO has been little investigated. This study employed transcriptomic and proteomic analyses to study effects of dietary VO in two family groups of Atlantic salmon selected for flesh lipid content, 'Lean' or 'Fat'. Results Metabolism, particularly of lipid and energy, was the functional category most affected by diet. Important effects were also measured in ribosomal proteins and signalling. The long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis pathway, assessed by fatty acid composition and gene expression, was influenced by genotype. Intestinal tissue contents of docosahexaenoic acid were equivalent in Lean salmon fed either a FO or VO diet and expression of LC-PUFA biosynthesis genes was up-regulated in VO-fed fish in Fat salmon. Dietary VO increased lipogenesis in Lean fish, assessed by expression of FAS, while no effect was observed on β-oxidation although transcripts of the mitochondrial respiratory chain were down-regulated, suggesting less active energetic metabolism in fish fed VO. In contrast, dietary VO up-regulated genes and proteins involved in detoxification, antioxidant defence and apoptosis, which could be associated with higher levels of polycyclic aromatic hydrocarbons in this diet. Regarding genotype, the following pathways were identified as being differentially affected: proteasomal proteolysis, response to oxidative and cellular stress (xenobiotic and oxidant metabolism and heat shock proteins), apoptosis and structural proteins particularly associated with tissue contractile properties. Genotype effects were accentuated by dietary VO. Conclusions Intestinal metabolism was affected by diet and genotype. Lean fish may have higher responsiveness to low dietary n-3 LC-PUFA, up-regulating the biosynthetic pathway when fed dietary VO. As global aquaculture searches for alternative oils for feeds, this study alerts to the potential of VO introducing contaminants and demonstrates the detoxifying role of intestine. Finally, data indicate genotype-specific responses in the intestinal transcriptome and proteome to dietary VO, including possibly structural properties of the intestinal layer and defence against cellular stress, with Lean fish being more susceptible to diet-induced oxidative stress. PMID:22943471
In pursuit of resilience: stress, epigenetics, and brain plasticity.

PubMed

McEwen, Bruce S

2016-06-01

The brain is the central organ for adaptation to experiences, including stressors, which are capable of changing brain architecture as well as altering systemic function through neuroendocrine, autonomic, immune, and metabolic systems. Because the brain is the master regulator of these systems, as well as of behavior, alterations in brain function by chronic stress can have direct and indirect effects on cumulative allostatic overload, which refers to the cost of adaptation. There is much new knowledge on the neural control of systemic physiology and the feedback actions of physiologic mediators on brain regions regulating higher cognitive function, emotional regulation, and self-regulation. The healthy brain has a considerable capacity for resilience, based upon its ability to respond to interventions designed to open "windows of plasticity" and redirect its function toward better health. As a result, plasticity-facilitating treatments should be given within the framework of a positive behavioral intervention; negative experiences during this window may even make matters worse. Indeed, there are no magic bullets and drugs cannot substitute for targeted interventions that help an individual become resilient, of which mindfulness-based stress reduction and meditation are emerging as useful tools. © 2016 New York Academy of Sciences.
Emotion regulation in mothers and young children faced with trauma.

PubMed

Pat-Horenczyk, Ruth; Cohen, S; Ziv, Y; Achituv, M; Asulin-Peretz, L; Blanchard, T R; Schiff, M; Brom, D

2015-01-01

The present study investigated maternal emotion regulation as mediating the association between maternal posttraumatic stress symptoms and children's emotional dysregulation in a community sample of 431 Israeli mothers and children exposed to trauma. Little is known about the specific pathways through which maternal posttraumatic symptoms and deficits in emotion regulation contribute to emotional dysregulation. Inspired by the intergenerational process of relational posttraumatic stress disorder (PTSD), in which posttraumatic distress is transmitted from mothers to children, we suggest an analogous concept of relational emotion regulation, by which maternal emotion regulation problems may contribute to child emotion regulation deficits. Child emotion regulation problems were measured using the Child Behavior Checklist-Dysregulation Profile (CBCL-DP; T.M. Achenbach & I. Rescorla, 2000), which is comprised of three subscales of the CBCL: Attention, Aggression, and Anxiety/Depression. Maternal PTSD symptoms were assessed by the Posttraumatic Diagnostic Scale (E.B. Foa, L. Cashman, L. Jaycox, & K. Perry, 1997) and maternal emotion regulation by the Difficulties in Emotion Regulation Scale (K.L. Gratz & L. Roemer, 2004). Results showed that the child's emotion regulation problems were associated with both maternal posttraumatic symptoms and maternal emotion dysregulation. Further, maternal emotion regulation mediated the association between maternal posttraumatic symptoms and the child's regulation deficits. These findings highlight the central role of mothers' emotion regulation skills in the aftermath of trauma as it relates to children's emotion regulation skills. The degree of mothers' regulatory skills in the context of posttraumatic stress symptoms reflects a key process through which the intergenerational transmission of trauma may occur. Study results have critical implications for planning and developing clinical interventions geared toward the treatment of families in the aftermath of trauma and, in particular, the enhancement of mothers' emotion regulation skills after trauma. © 2015 Michigan Association for Infant Mental Health.
Visceral obesity and psychosocial stress: a generalised control theory model

NASA Astrophysics Data System (ADS)

Wallace, Rodrick

2016-07-01

The linking of control theory and information theory via the Data Rate Theorem and its generalisations allows for construction of necessary conditions statistical models of body mass regulation in the context of interaction with a complex dynamic environment. By focusing on the stress-related induction of central obesity via failure of HPA axis regulation, we explore implications for strategies of prevention and treatment. It rapidly becomes evident that individual-centred biomedical reductionism is an inadequate paradigm. Without mitigation of HPA axis or related dysfunctions arising from social pathologies of power imbalance, economic insecurity, and so on, it is unlikely that permanent changes in visceral obesity for individuals can be maintained without constant therapeutic effort, an expensive - and likely unsustainable - public policy.
Redox-dependent transcriptional regulation.

PubMed

Liu, Hongjun; Colavitti, Renata; Rovira, Ilsa I; Finkel, Toren

2005-11-11

Reactive oxygen species contribute to the pathogenesis of a number of disparate disorders including tissue inflammation, heart failure, hypertension, and atherosclerosis. In response to oxidative stress, cells activate expression of a number of genes, including those required for the detoxification of reactive molecules as well as for the repair and maintenance of cellular homeostasis. In many cases, these induced genes are regulated by transcription factors whose structure, subcellular localization, or affinity for DNA is directly or indirectly regulated by the level of oxidative stress. This review summarizes the recent progress on how cellular redox status can regulate transcription-factor activity and the implications of this regulation for cardiovascular disease.
DNA damage-induced nuclear translocation of Apaf-1 is mediated by nucleoporin Nup107

PubMed Central

Jagot-Lacoussiere, Léonard; Faye, Audrey; Bruzzoni-Giovanelli, Heriberto; Villoutreix, Bruno O; Rain, Jean-Christophe; Poyet, Jean-Luc

2015-01-01

Beside its central role in the mitochondria-dependent cell death pathway, the apoptotic protease activating factor 1 (Apaf-1) is involved in the DNA damage response through cell-cycle arrest induced by genotoxic stress. This non-apoptotic function requires a nuclear translocation of Apaf-1 during the G1-to-S transition. However, the mechanisms that trigger the nuclear accumulation of Apaf-1 upon DNA damage remain to be investigated. Here we show that the main 4 isoforms of Apaf-1 can undergo nuclear translocation and restore Apaf-1 deficient MEFs cell cycle arrest in the S phase following genotoxic stress through activation of Chk-1. Interestingly, DNA damage-dependent nuclear accumulation of Apaf-1 occurs independently of p53 and the retinoblastoma (pRb) pathway. We demonstrated that Apaf-1 associates with the nucleoporin Nup107 and this association is necessary for Apaf-1 nuclear import. The CED-4 domain of Apaf-1 directly binds to the central domain of Nup107 in an ATR-regulated, phosphorylation-dependent manner. Interestingly, expression of the Apaf-1-interacting domain of Nup107 interfered with Apaf-1 nuclear translocation upon genotoxic stress, resulting in a marked reduction of Chk-1 activation and cell cycle arrest. Thus, our results confirm the crucial role of Apaf-1 nuclear relocalization in mediating cell-cycle arrest induced by genotoxic stress and implicate Nup107 as a critical regulator of the DNA damage-induced intra-S phase checkpoint response. PMID:25695197
Social Buffering of Stress in Development: A Career Perspective

PubMed Central

Gunnar, Megan R.

2016-01-01

This review provides a broad overview of my research group's work on social buffering in human development in the context of the field. Much of the focus is on social buffering of the hypothalamic-pituitary-adrenocortical (HPA) system, one of the two major arms of the mammalian stress system. This focus reflects the centrality of the HPA system in research on social buffering in the fields of developmental psychobiology and developmental science. However, buffering of the cardiovascular and autonomic nervous system is also discussed. The central developmental question in this area derives from attachment theory which argues that the infant's experience of stress and arousal regulation in the context of her early attachment relationships is not an immature form of social buffering experienced in adulthood, but rather the foundation out of which individual differences in the capacity to gain stress relief from social partners emerge. The emergence of social buffering in infancy, changes in social buffering throughout childhood and adolescence, the influence of early experience on later individual differences in social buffering, and critical gaps in our knowledge are described. PMID:28544861

Wavelet-analysis of gastric microcirculation in rats with ulcer bleedings

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Semyachkina-Glushkovskaya, O. V.; Pavlova, O. N.; Bibikova, O. A.; Kurths, J.

2013-10-01

Nitric oxide (NO) plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhagic stress. Because the impaired gastric mucosal blood flow is the major cause of gastroduodenal lesions including ulcer bleeding (UB), we study in this work the NO-ergic mechanism responsible for regulation of this blood flow. Our study is performed in rats with a model of stress-induced UB using laser Doppler flowmetry (LDF) that characterizes the rate of blood flow by measuring a Doppler shift of the laser beam scattered by the moving red blood cells. Numerical analysis of LDF-data is based on the discrete wavelet-transform (DWT) using Daubechies wavelets aiming to quantify influences of NO on the gastric microcirculation. We show that the stress-induced UB is associated with an increased level of NO in the gastric tissue and a stronger vascular sensitivity to pharmacological modulation of NO-production by L-NAME. We demonstrate that wavelet-based analyses of NO-dependent regulation of gastric microcirculation can provide an effective endoscopic diagnostics of a risk of UB.
Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism.

PubMed

Kashyap, Des R; Kuzma, Marcin; Kowalczyk, Dominik A; Gupta, Dipika; Dziarski, Roman

2017-09-01

Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill both Gram-positive and Gram-negative bacteria through simultaneous induction of oxidative, thiol and metal stress responses in bacteria. However, metabolic pathways through which PGRPs induce these bactericidal stress responses are unknown. We screened Keio collection of Escherichia coli deletion mutants and revealed that deleting genes for respiratory chain flavoproteins or for tricarboxylic acid (TCA) cycle resulted in increased resistance of E. coli to PGRP killing. PGRP-induced killing depended on the production of hydrogen peroxide, which required increased supply of NADH for respiratory chain oxidoreductases from central carbon catabolism (glycolysis and TCA cycle), and was controlled by cAMP-Crp. Bactericidal PGRP induced a rapid decrease in respiration, which suggested that the main source of increased production of hydrogen peroxide was a block in respiratory chain and diversion of electrons from NADH oxidoreductases to oxygen. CpxRA two-component system was a negative regulator of PGRP-induced oxidative stress. By contrast, PGRP-induced thiol stress (depletion of thiols) and metal stress (increase in intracellular free Zn 2+ through influx of extracellular Zn 2+ ) were mostly independent of oxidative stress. Thus, manipulating pathways that induce oxidative, thiol and metal stress in bacteria could be a useful strategy to design new approaches to antibacterial therapy. © 2017 John Wiley & Sons Ltd.
Identifying Configurations of Perceived Teacher Autonomy Support and Structure: Associations with Self-Regulated Learning, Motivation and Problem Behavior

ERIC Educational Resources Information Center

Vansteenkiste, Maarten; Sierens, Eline; Goossens, Luc; Soenens, Bart; Dochy, Filip; Mouratidis, Athanasios; Aelterman, Nathalie; Haerens, Leen; Beyers, Wim

2012-01-01

Grounded in self-determination theory, the aim of this study was (a) to examine naturally occurring configurations of perceived teacher autonomy support and clear expectations (i.e., a central aspect of teacher structure), and (b) to investigate associations with academic motivation, self-regulated learning, and problem behavior. Based on…
Cell Death, Neuronal Plasticity and Functional Loading in the Development of the Central Nervous System

NASA Technical Reports Server (NTRS)

Keefe, J. R.

1985-01-01

Research on the precise timing and regulation of neuron production and maturation in the vestibular and visual systems of Wistar rats and several inbred strains of mice (C57B16 and Pallid mutant) concentrated upon establishing a timing baseline for mitotic development of the neurons of the vestibular nuclei and the peripheral vestibular sensory structures (maculae, cristae). This involved studies of the timing and site of neuronal cell birth and preliminary studies of neuronal cell death in both central and peripheral elements of the mammalian vestibular system. Studies on neuronal generation and maturation in the retina were recently added to provide a mechanism for more properly defining the in utero' developmental age of the individual fetal subject and to closely monitor potential transplacental effects of environmentally stressed maternal systems. Information is given on current efforts concentrating upon the (1) perinatal period of development (E18 thru P14) and (2) the role of cell death in response to variation in the functional loading of the vestibular and proprioreceptive systems in developing mammalian organisms.
Growing Out of Stress: The Role of Cell- and Organ-Scale Growth Control in Plant Water-Stress Responses[OPEN

PubMed Central

Robbins, Neil E.

2016-01-01

Water is the most limiting resource on land for plant growth, and its uptake by plants is affected by many abiotic stresses, such as salinity, cold, heat, and drought. While much research has focused on exploring the molecular mechanisms underlying the cellular signaling events governing water-stress responses, it is also important to consider the role organismal structure plays as a context for such responses. The regulation of growth in plants occurs at two spatial scales: the cell and the organ. In this review, we focus on how the regulation of growth at these different spatial scales enables plants to acclimate to water-deficit stress. The cell wall is discussed with respect to how the physical properties of this structure affect water loss and how regulatory mechanisms that affect wall extensibility maintain growth under water deficit. At a higher spatial scale, the architecture of the root system represents a highly dynamic physical network that facilitates access of the plant to a heterogeneous distribution of water in soil. We discuss the role differential growth plays in shaping the structure of this system and the physiological implications of such changes. PMID:27503468
Acidified nitrite inhibits proliferation of Listeria monocytogenes - Transcriptional analysis of a preservation method.

PubMed

Müller-Herbst, Stefanie; Wüstner, Stefanie; Kabisch, Jan; Pichner, Rohtraud; Scherer, Siegfried

2016-06-02

Sodium nitrite (NaNO2) is added as a preservative during raw meat processing such as raw sausage production to inhibit growth of pathogenic bacteria. In the present study it was shown in challenge assays that the addition of sodium nitrite indeed inhibited growth and survival of Listeria monocytogenes in short-ripened spreadable raw sausages. Furthermore, in vitro growth analyses were performed, which took into account combinations of various parameters of the raw sausage ripening process like temperature, oxygen availability, pH, NaCl concentration, and absence or presence of NaNO2. Data based on 300 growth conditions revealed that the inhibitory effect of nitrite was most prominent in combination with acidification, a combination that is also achieved during short-ripened spreadable raw sausage production. At pH6.0 and below, L. monocytogenes was unable to replicate in the presence of 200mg/l NaNO2. During the adaptation of L. monocytogenes to acidified nitrite stress (pH6.0, 200mg/l NaNO2) in comparison to acid exposure only (pH6.0, 0mg/l NaNO2), a massive transcriptional adaptation was observed using microarray analyses. In total, 202 genes were up-regulated and 204 genes were down-regulated. In accordance with growth inhibition, a down-regulation of genes encoding for proteins which are involved in central cellular processes, like cell wall/membrane/envelope biogenesis, translation and ribosomal structure and biogenesis, transcription, and replication, recombination and repair, was observed. Among the up-regulated genes the most prominent group belonged to poorly characterized genes. A considerable fraction of the up-regulated genes has been shown previously to be up-regulated intracellularly in macrophages, after exposure to acid shock or to be part of the SigB regulon. These data indicate that the adaptation to acidified nitrite partly overlaps with the adaptation to stress conditions being present during host colonization. Copyright © 2016 Elsevier B.V. All rights reserved.
Chemical synthesis and orexigenic activity of rat/mouse relaxin-3.

PubMed

Hossain, Mohammed Akhter; Smith, Craig M; Ryan, Philip J; Büchler, Elena; Bathgate, Ross A D; Gundlach, Andrew L; Wade, John D

2013-06-01

The insulin-like peptide, relaxin-3 was first identified just a decade ago via a genomic database search and is now recognized to be a key neuropeptide with several roles including the regulation of arousal, stress responses and neuroendocrine homeostasis. It also has significant potential as a drug to treat stress and obesity. Its actions are mediated via its cognate G protein-coupled receptor, RXFP3, which is found in abundant numbers in the brain. However, much remains to be determined with respect to the mechanism of neurological action of this peptide. Consequently, the chemical synthesis of the rat and mouse (which share identical primary structures) two-chain, three disulfide peptide was undertaken and the resulting peptide subjected to detailed in vitro and in vivo assay. Use of efficient solid-phase synthesis methods provided the two regioselectively S-protected A- and B-chains which were readily combined via sequential disulfide bond formation. The synthetic rat/mouse relaxin-3 was obtained in high purity and good overall yield. It demonstrated potent orexigenic activity in rats in that central intracerebroventricular infusion led to significantly increased food intake and water drinking.
Transcriptome Profiling of Shewanella oneidensis Gene Expression following Exposure to Acidic and Alkaline pH†

PubMed Central

Leaphart, Adam B.; Thompson, Dorothea K.; Huang, Katherine; Alm, Eric; Wan, Xiu-Feng; Arkin, Adam; Brown, Steven D.; Wu, Liyou; Yan, Tingfen; Liu, Xueduan; Wickham, Gene S.; Zhou, Jizhong

2006-01-01

The molecular response of Shewanella oneidensis MR-1 to variations in extracellular pH was investigated based on genomewide gene expression profiling. Microarray analysis revealed that cells elicited both general and specific transcriptome responses when challenged with environmental acid (pH 4) or base (pH 10) conditions over a 60-min period. Global responses included the differential expression of genes functionally linked to amino acid metabolism, transcriptional regulation and signal transduction, transport, cell membrane structure, and oxidative stress protection. Response to acid stress included the elevated expression of genes encoding glycogen biosynthetic enzymes, phosphate transporters, and the RNA polymerase sigma-38 factor (rpoS), whereas the molecular response to alkaline pH was characterized by upregulation of nhaA and nhaR, which are predicted to encode an Na+/H+ antiporter and transcriptional activator, respectively, as well as sulfate transport and sulfur metabolism genes. Collectively, these results suggest that S. oneidensis modulates multiple transporters, cell envelope components, and pathways of amino acid consumption and central intermediary metabolism as part of its transcriptome response to changing external pH conditions. PMID:16452448
Nursing work stress: the impacts of social network structure and organizational citizenship behavior.

PubMed

Tsang, Seng-Su; Chen, Tzu-Yin; Wang, Shih-Fong; Tai, Hsin-Ling

2012-03-01

The nursing workplace imposes significantly more stress on its employees than other workplace settings. Organizational resources, both physical and psychological, have been recognized in prior studies as important alleviators of nursing workplace stress. Whereas physical resources are less difficult to manipulate because of their tangibility, psychological resources, particularly psychological support from colleagues, are typically not deployed to greatest effect. This article investigated the alleviation of nursing work stress using resources already extant in coworker social networks. Researchers conducted a survey in a dialysis department at a medical center located in Taipei City, Taiwan. This survey measured nurse work stress, satisfaction, organizational citizenship behavior (OCB) and social network structures. Researchers employed UCINET to analyze the network structure data, which were in dyadic matrix format to estimate nurse network centralities and used partial least squares analysis to estimate research construct path coefficients and test extrapolated hypotheses. The level of OCB induced by nurse social ties was satisfactory and did not only directly increased work satisfaction but also alleviated work stress, which indirectly boosted work satisfaction. Findings suggest that managers may be able to use social network analysis to identify persons appropriate to conduct the distribution of organizational resources. Choosing those with multiple social connections can help distribute resources effectively and induce higher OCB levels within the organization. In addition, staff with strong friendship network connections may provide appropriate psychological resources (support) to coworkers. If those with high friendship network centrality receive proper counseling training, they should be in a good position to provide assistance when needed.
Subcellular and supracellular mechanical stress prescribes cytoskeleton behavior in Arabidopsis cotyledon pavement cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sampathkumar, Arun; Krupinski, Pawel; Wightman, Raymond

Although it is a central question in biology, how cell shape controls intracellular dynamics largely remains an open question. Here, we show that the shape of Arabidopsis pavement cells creates a stress pattern that controls microtubule orientation, which then guides cell wall reinforcement. Live-imaging, combined with modeling of cell mechanics, shows that microtubules align along the maximal tensile stress direction within the cells, and atomic force microscopy demonstrates that this leads to reinforcement of the cell wall parallel to the microtubules. This feedback loop is regulated: cell-shape derived stresses could be overridden by imposed tissue level stresses, showing how competitionmore » between subcellular and supracellular cues control microtubule behavior. Furthermore, at the microtubule level, we identified an amplification mechanism in which mechanical stress promotes the microtubule response to stress by increasing severing activity. These multiscale feedbacks likely contribute to the robustness of microtubule behavior in plant epidermis.« less
Subcellular and supracellular mechanical stress prescribes cytoskeleton behavior in Arabidopsis cotyledon pavement cells

DOE PAGES

Sampathkumar, Arun; Krupinski, Pawel; Wightman, Raymond; ...

2014-04-16

Although it is a central question in biology, how cell shape controls intracellular dynamics largely remains an open question. Here, we show that the shape of Arabidopsis pavement cells creates a stress pattern that controls microtubule orientation, which then guides cell wall reinforcement. Live-imaging, combined with modeling of cell mechanics, shows that microtubules align along the maximal tensile stress direction within the cells, and atomic force microscopy demonstrates that this leads to reinforcement of the cell wall parallel to the microtubules. This feedback loop is regulated: cell-shape derived stresses could be overridden by imposed tissue level stresses, showing how competitionmore » between subcellular and supracellular cues control microtubule behavior. Furthermore, at the microtubule level, we identified an amplification mechanism in which mechanical stress promotes the microtubule response to stress by increasing severing activity. These multiscale feedbacks likely contribute to the robustness of microtubule behavior in plant epidermis.« less
Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.)

PubMed Central

2011-01-01

Background Global transcriptional analysis of loblolly pine (Pinus taeda L.) is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine. Results Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes). Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01). Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs) including those with significant homology (E-values ≤ 2 × 10-30) to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function. Conclusion PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in roots. Many of the genes identified are known to be up-regulated in response to osmotic stress in pine and other plant species and encode proteins involved in both signal transduction and stress tolerance. Gene expression levels returned to control values within a 48-hour recovery period in all but 76 transcripts. Correlation network analysis indicates a scale-free network topology for the pine root transcriptome and identifies central nodes that may serve as drivers of drought-responsive transcriptome dynamics in the roots of loblolly pine. PMID:21609476
The expression of interleukin-6 and its receptor in various brain regions and their roles in exploratory behavior and stress responses.

PubMed

Aniszewska, A; Chłodzińska, N; Bartkowska, K; Winnicka, M M; Turlejski, K; Djavadian, R L

2015-07-15

We examined the involvement of interleukin-6 (IL-6) and its receptor IL-6Rα on behavior and stress responses in mice. In the open field, both wild-type (WT) and IL-6 deficient mice displayed similar levels of locomotor activity; however, IL-6 deficient mice spent more time in the central part of the arena compared to control WT mice. After behavioral testing, mice were subjected to stress and then sacrificed. The levels of IL-6 and its receptor in their brains were determined. Immunohistochemical labeling of brain sections for IL-6 showed a high level of expression in the subventricular zone of the lateral ventricles and in the border zone of the third and fourth ventricles. Interestingly, 95% of the IL-6-expressing cells had an astrocytic phenotype, and the remaining 5% were microglial cells. A low level of IL-6 expression was observed in the olfactory bulb, hypothalamus, hippocampus, cerebral cortex, cerebellum, midbrain and several brainstem structures. The vast majority of IL-6-expressing cells in these structures had a neuronal phenotype. Stress increased the number of IL-6-immunoreactive astrocytes and microglial cells. The levels of the IL-6Rα receptor were increased in the hypothalamus of stressed mice. Therefore, in this study, we describe for the first time the distribution of IL-6 in various types of brain cells and in previously unreported regions, such as the subventricular zone of the lateral ventricle. Moreover, we provide data on regional distribution and expression within specific cell phenotypes. This highly differential expression of IL-6 indicates its specific roles in the regulation of neuronal and astrocytic functions, in addition to the roles of IL-6 and its receptor IL-6Rα in stress responses. Copyright © 2015 Elsevier B.V. All rights reserved.
Transcriptome signatures of class I and III stress response deregulation in Lactobacillus plantarum reveal pleiotropic adaptation

PubMed Central

2013-01-01

Background To cope with environmental challenges bacteria possess sophisticated defense mechanisms that involve stress-induced adaptive responses. The canonical stress regulators CtsR and HrcA play a central role in the adaptations to a plethora of stresses in a variety of organisms. Here, we determined the CtsR and HrcA regulons of the lactic acid bacterium Lactobacillus plantarum WCFS1 grown under reference (28°C) and elevated (40°C) temperatures, using ctsR, hrcA, and ctsR-hrcA deletion mutants. Results While the maximum specific growth rates of the mutants and the parental strain were similar at both temperatures (0.33 ± 0.02 h-1 and 0.34 ± 0.03 h-1, respectively), DNA microarray analyses revealed that the CtsR or HrcA deficient strains displayed altered transcription patterns of genes encoding functions involved in transport and binding of sugars and other compounds, primary metabolism, transcription regulation, capsular polysaccharide biosynthesis, as well as fatty acid metabolism. These transcriptional signatures enabled the refinement of the gene repertoire that is directly or indirectly controlled by CtsR and HrcA of L. plantarum. Deletion of both regulators, elicited transcriptional changes of a large variety of additional genes in a temperature-dependent manner, including genes encoding functions involved in cell-envelope remodeling. Moreover, phenotypic assays revealed that both transcription regulators contribute to regulation of resistance to hydrogen peroxide stress. The integration of these results allowed the reconstruction of CtsR and HrcA regulatory networks in L. plantarum, highlighting the significant intertwinement of class I and III stress regulons. Conclusions Taken together, our results enabled the refinement of the CtsR and HrcA regulatory networks in L. plantarum, illustrating the complex nature of adaptive stress responses in this bacterium. PMID:24238744
Structural covariance network centrality in maltreated youth with posttraumatic stress disorder.

PubMed

Sun, Delin; Peverill, Matthew R; Swanson, Chelsea S; McLaughlin, Katie A; Morey, Rajendra A

2018-03-01

Childhood maltreatment is associated with posttraumatic stress disorder (PTSD) and elevated rates of adolescent and adult psychopathology including major depression, bipolar disorder, substance use disorders, and other medical comorbidities. Gray matter volume changes have been found in maltreated youth with (versus without) PTSD. However, little is known about the alterations of brain structural covariance network topology derived from cortical thickness in maltreated youth with PTSD. High-resolution T1-weighted magnetic resonance imaging scans were from demographically matched maltreated youth with PTSD (N = 24), without PTSD (N = 64), and non-maltreated healthy controls (n = 67). Cortical thickness data from 148 cortical regions was entered into interregional partial correlation analyses across participants. The supra-threshold correlations constituted connections in a structural brain network derived from four types of centrality measures (degree, betweenness, closeness, and eigenvector) estimated network topology and the importance of nodes. Between-group differences were determined by permutation testing. Maltreated youth with PTSD exhibited larger centrality in left anterior cingulate cortex than the other two groups, suggesting cortical network topology specific to maltreated youth with PTSD. Moreover, maltreated youth with versus without PTSD showed smaller centrality in right orbitofrontal cortex, suggesting that this may represent a vulnerability factor to PTSD following maltreatment. Longitudinal follow-up of the present results will help characterize the role that altered centrality plays in vulnerability and resilience to PTSD following childhood maltreatment. Copyright © 2017. Published by Elsevier Ltd.
Heat regulation: homeostasis of central temperature in man.

PubMed

Benzinger, T H

1969-10-01

Focus is on the concept of the quantitative thermostat or setpoint as it evolved experimentally, not theoretically, from measurements of central temperature at the tympanic membrane and from measurements of physiological responses by human gradient layer calorimetry and continuous analysis of oxygen consumption. Heat-flow responses as they relate to stimuli by which they are evoked -- peripheral or central temperatures at thermoreceptive sites -- and discussed, and individual systems of reflex action are described. These systems are then correlated with what is known of their tangible components -- sensory receptors, effector organs, nervous centers, and afferent or efferent nervous pathways -- classically derived from anatomical studies, lesion experiments, recording of action currents, or electrical or thermal stimulation of pertinent structures. Such as correlation is a crucial test, and when the results are consistent, they provide independent, mutual confirmation via the 2 approaches. Doubts are then removed that lesions or interferences, which are unavoidable with most neurophysiological methods, may have produced artifacts. Conversely, calorimetry allows one to observe and analyze thermoregulation in process in a human subject without disturbing normal structures or functions other than by the stresses to which the body is made to respond. Prior to a description of experimental findings, the essential methods are reviewed. With the methods of gradient layer calorimetry, tympanic (eardrum) thermonetry, and indirect calorimetry, thermoregulatory responses -- by chemical overproduction of metabolic heat -- were observed in transient states as a result of a stimulus of cold impinging on peripheral neurons or warm-inhibition removed from central structures. With tympanic thermometry permitting for the 1st time om humans the continuous recording of central thermal stimulation, and with gradient calorimetry permitting the continuous recording (with insignificant inertial distortion) of the sweating responses in precisely controlled environments of a large variety and under conditions where complete evaporation of sweat is ensured by strong but smooth air convection, a new study of physical thermoregulation was initiated in 1958. The experimental results did not support the expection that sweating would follow the average temperature of the skin in the classical tradition, with skin warm-receptors as the hypothetical origin of exciting warm-impulses and cenral temperature as a participant prescribing the action of the "thermoregulator" in some as yet undetermined, additive, manner. Vasomotor mechanisms to human thermoregulation can be assessed in quantitative manner only by whole-body calorimetry. Mechanisms of thermal homeostasis also considered include hormonal regulation, transmitter substances, conscious sensation of warmth and coordinations of behavioral and autonomic mechanisms, setpoint and its variations, and fever.
32 CFR 1901.41 - Establishment of appeals structure.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Section 1901.41 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE... Director of Central Intelligence to facilitate the processing of administrative appeals under the Freedom... Director for Administration, the Deputy Director for Intelligence, the Deputy Director for Operations, the...
32 CFR 1901.41 - Establishment of appeals structure.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Section 1901.41 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE... Director of Central Intelligence to facilitate the processing of administrative appeals under the Freedom... Director for Administration, the Deputy Director for Intelligence, the Deputy Director for Operations, the...
[Neural activity related to emotional and empathic deficits in subjects with post-traumatic stress disorder who survived the L'Aquila (Central Italy) 2009 earthquake].

PubMed

Mazza, Monica; Pino, Maria Chiara; Tempesta, Daniela; Catalucci, Alessia; Masciocchi, Carlo; Ferrara, Michele

2016-01-01

Post-Traumatic Stress Disorder (PTSD) is a chronic anxiety disorder. The continued efforts to control the distressing memories by traumatized individuals, together with the reduction of responsiveness to the outside world, are called Emotional Numbing (EN). The EN is one of the central symptoms in PTSD and it plays an integral role not only in the development and maintenance of post-traumatic symptomatology, but also in the disability of emotional regulation. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. Patients with PTSD exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional and empathic dysfunction. We showed that PTSD patients, all survivors of the L'Aquila 2009 earthquake, have a higher sensitivity to negative emotion and lower empathy levels. These emotional and empathic deficits are accompanied by neural brain functional correlates. Indeed PTSD subjects exhibit functional abnormalities in brain regions that are involved in stress regulation and emotional responses. The reduced activation of the frontal areas and a stronger activation of the limbic areas when responding to emotional stimuli could lead the subjects to enact coping strategies aimed at protecting themselves from the re-experience of pain related to traumatic events. This would result in a dysfunctional hyperactivation of subcortical areas, which may cause emotional distress and, consequently, impaired social relationships often reported by PTSD patients.
Regulation of the reserve carbohydrate metabolism by alkaline pH and calcium in Neurospora crassa reveals a possible cross-regulation of both signaling pathways.

PubMed

Virgilio, Stela; Cupertino, Fernanda Barbosa; Ambrosio, Daniela Luz; Bertolini, Maria Célia

2017-06-09

Glycogen and trehalose are storage carbohydrates and their levels in microorganisms vary according to environmental conditions. In Neurospora crassa, alkaline pH stress highly influences glycogen levels, and in Saccharomyces cerevisiae, the response to pH stress also involves the calcineurin signaling pathway mediated by the Crz1 transcription factor. Recently, in yeast, pH stress response genes were identified as targets of Crz1 including genes involved in glycogen and trehalose metabolism. In this work, we present evidence that in N. crassa the glycogen and trehalose metabolism is modulated by alkaline pH and calcium stresses. We demonstrated that the pH signaling pathway in N. crassa controls the accumulation of the reserve carbohydrates glycogen and trehalose via the PAC-3 transcription factor, which is the central regulator of the signaling pathway. The protein binds to the promoters of most of the genes encoding enzymes of glycogen and trehalose metabolism and regulates their expression. We also demonstrated that the reserve carbohydrate levels and gene expression are both modulated under calcium stress and that the response to calcium stress may involve the concerted action of PAC-3. Calcium activates growth of the Δpac-3 strain and influences its glycogen and trehalose accumulation. In addition, calcium stress differently regulates glycogen and trehalose metabolism in the mutant strain compared to the wild-type strain. While glycogen levels are decreased in both strains, the trehalose levels are significantly increased in the wild-type strain and not affected by calcium in the mutant strain when compared to mycelium not exposed to calcium. We previously reported the role of PAC-3 as a transcription factor involved in glycogen metabolism regulation by controlling the expression of the gsn gene, which encodes an enzyme of glycogen synthesis. In this work, we extended the investigation by studying in greater detail the effects of pH on the metabolism of the reserve carbohydrate glycogen and trehalose. We also demonstrated that calcium stress affects the reserve carbohydrate levels and the response to calcium stress may require PAC-3. Considering that the reserve carbohydrate metabolism may be subjected to different signaling pathways control, our data contribute to the understanding of the N. crassa responses under pH and calcium stresses.

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

PubMed Central

van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

2017-01-01

Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA-axis hyper-reactivity in adulthood, as also found in major depression. This hyper-activity is related to increased corticotrophin-releasing hormone signaling and impaired glucocorticoid receptor-mediated negative feedback. In contrast, initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder, and future studies should investigate its neural/neuroendocrine foundation in further detail. Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory. PMID:28469557
Temperature and Carbon Assimilation Regulate the Chlorosome Biogenesis in Green Sulfur Bacteria

PubMed Central

Tang, Joseph Kuo-Hsiang; Saikin, Semion K.; Pingali, Sai Venkatesh; Enriquez, Miriam M.; Huh, Joonsuk; Frank, Harry A.; Urban, Volker S.; Aspuru-Guzik, Alán

2013-01-01

Green photosynthetic bacteria adjust the structure and functionality of the chlorosome—the light-absorbing antenna complex—in response to environmental stress factors. The chlorosome is a natural self-assembled aggregate of bacteriochlorophyll (BChl) molecules. In this study, we report the regulation of the biogenesis of the Chlorobaculum tepidum chlorosome by carbon assimilation in conjunction with temperature changes. Our studies indicate that the carbon source and thermal stress culture of C. tepidum grows slower and incorporates fewer BChl c in the chlorosome. Compared with the chlorosome from other cultural conditions we investigated, the chlorosome from the carbon source and thermal stress culture displays (a) smaller cross-sectional radius and overall size, (b) simplified BChl c homologs with smaller side chains, (c) blue-shifted Qy absorption maxima, and (d) a sigmoid-shaped circular dichroism spectra. Using a theoretical model, we analyze how the observed spectral modifications can be associated with structural changes of BChl aggregates inside the chlorosome. Our report suggests a mechanism of metabolic regulation for chlorosome biogenesis. PMID:24047985
Neural models on temperature regulation for cold-stressed animals

NASA Technical Reports Server (NTRS)

Horowitz, J. M.

1975-01-01

The present review evaluates several assumptions common to a variety of current models for thermoregulation in cold-stressed animals. Three areas covered by the models are discussed: signals to and from the central nervous system (CNS), portions of the CNS involved, and the arrangement of neurons within networks. Assumptions in each of these categories are considered. The evaluation of the models is based on the experimental foundations of the assumptions. Regions of the nervous system concerned here include the hypothalamus, the skin, the spinal cord, the hippocampus, and the septal area of the brain.
High and Dry? Stomatal Regulation and the Water Use Efficiency of Vegetation

NASA Astrophysics Data System (ADS)

Seibt, U.; Maseyk, K. S.; Sun, W.; Lett, C.; Pivovaroff, A. L.

2016-12-01

The water use efficiency (WUE, ratio of carbon assimilated to water transpired) of vegetation plays an important role in determining the exchange of water between ecosystems and the atmosphere and thus affects the global water cycle. It also shapes the water-energy balance of ecosystems as a decrease in water fluxes may lead to an increase in surface temperature. A large number of studies have reported systematic changes in WUE from the stand to landscape scale, however, there is no general agreement on the sign and magnitude of the observed trends. The divergent responses reflect that the WUE of vegetation is shaped by a complex interplay of factors acting on a wide range of temporal scales: On diurnal to seasonal time scales, if evaporative demand is altered by atmospheric moisture or temperature, plants respond by adjusting stomatal conductance with associated changes in both transpiration and photosynthetic carbon uptake. On seasonal to interannual time scales, leaf size, structure and activity may adapt to water stress. This can alter boundary layer and mesophyll conductances, radiation profiles, and the surface energy balance. On longer time scales, the carbon-water balance of ecosystems is additionally affected by the ongoing global rise in CO2 and temperatures. Stomatal regulation is a central factor across all scales. We present new results on leaf and stand scale WUE from a range of ecosystems (arctic, boreal, semi-arid, tropical), and discuss the role of stomatal regulation on diurnal and seasonal changes in WUE in response to water stress and on potential long-term trends in WUE in response to climate change.
Abiotic stress responses in plants: roles of calmodulin-regulated proteins.

PubMed

Virdi, Amardeep S; Singh, Supreet; Singh, Prabhjeet

2015-01-01

Intracellular changes in calcium ions (Ca(2+)) in response to different biotic and abiotic stimuli are detected by various sensor proteins in the plant cell. Calmodulin (CaM) is one of the most extensively studied Ca(2+)-sensing proteins and has been shown to be involved in transduction of Ca(2+) signals. After interacting with Ca(2+), CaM undergoes conformational change and influences the activities of a diverse range of CaM-binding proteins. A number of CaM-binding proteins have also been implicated in stress responses in plants, highlighting the central role played by CaM in adaptation to adverse environmental conditions. Stress adaptation in plants is a highly complex and multigenic response. Identification and characterization of CaM-modulated proteins in relation to different abiotic stresses could, therefore, prove to be essential for a deeper understanding of the molecular mechanisms involved in abiotic stress tolerance in plants. Various studies have revealed involvement of CaM in regulation of metal ions uptake, generation of reactive oxygen species and modulation of transcription factors such as CAMTA3, GTL1, and WRKY39. Activities of several kinases and phosphatases have also been shown to be modulated by CaM, thus providing further versatility to stress-associated signal transduction pathways. The results obtained from contemporary studies are consistent with the proposed role of CaM as an integrator of different stress signaling pathways, which allows plants to maintain homeostasis between different cellular processes. In this review, we have attempted to present the current state of understanding of the role of CaM in modulating different stress-regulated proteins and its implications in augmenting abiotic stress tolerance in plants.
Abiotic stress responses in plants: roles of calmodulin-regulated proteins

PubMed Central

Virdi, Amardeep S.; Singh, Supreet; Singh, Prabhjeet

2015-01-01

Intracellular changes in calcium ions (Ca2+) in response to different biotic and abiotic stimuli are detected by various sensor proteins in the plant cell. Calmodulin (CaM) is one of the most extensively studied Ca2+-sensing proteins and has been shown to be involved in transduction of Ca2+ signals. After interacting with Ca2+, CaM undergoes conformational change and influences the activities of a diverse range of CaM-binding proteins. A number of CaM-binding proteins have also been implicated in stress responses in plants, highlighting the central role played by CaM in adaptation to adverse environmental conditions. Stress adaptation in plants is a highly complex and multigenic response. Identification and characterization of CaM-modulated proteins in relation to different abiotic stresses could, therefore, prove to be essential for a deeper understanding of the molecular mechanisms involved in abiotic stress tolerance in plants. Various studies have revealed involvement of CaM in regulation of metal ions uptake, generation of reactive oxygen species and modulation of transcription factors such as CAMTA3, GTL1, and WRKY39. Activities of several kinases and phosphatases have also been shown to be modulated by CaM, thus providing further versatility to stress-associated signal transduction pathways. The results obtained from contemporary studies are consistent with the proposed role of CaM as an integrator of different stress signaling pathways, which allows plants to maintain homeostasis between different cellular processes. In this review, we have attempted to present the current state of understanding of the role of CaM in modulating different stress-regulated proteins and its implications in augmenting abiotic stress tolerance in plants. PMID:26528296
Mitochondria in the middle: exercise preconditioning protection of striated muscle

PubMed Central

Rodriguez, Dinah A.; Hord, Jeffrey M.

2016-01-01

Abstract Cellular and physiological adaptations to an atmosphere which became enriched in molecular oxygen spurred the development of a layered system of stress protection, including antioxidant and stress response proteins. At physiological levels reactive oxygen and nitrogen species regulate cell signalling as well as intracellular and intercellular communication. Exercise and physical activity confer a variety of stressors on skeletal muscle and the cardiovascular system: mechanical, metabolic, oxidative. Transient increases of stressors during acute bouts of exercise or exercise training stimulate enhancement of cellular stress protection against future insults of oxidative, metabolic and mechanical stressors that could induce injury or disease. This phenomenon has been termed both hormesis and exercise preconditioning (EPC). EPC stimulates transcription factors such as Nrf‐1 and heat shock factor‐1 and up‐regulates gene expression of a cadre of cytosolic (e.g. glutathione peroxidase and heat shock proteins) and mitochondrial adaptive or stress proteins (e.g. manganese superoxide dismutase, mitochondrial KATP channels and peroxisome proliferator activated receptor γ coactivator‐1 (PGC‐1)). Stress response and antioxidant enzyme inducibility with exercise lead to protection against striated muscle damage, oxidative stress and injury. EPC may indeed provide significant clinical protection against ischaemia–reperfusion injury, Type II diabetes and ageing. New molecular mechanisms of protection, such as δ‐opioid receptor regulation and mitophagy, reinforce the notion that mitochondrial adaptations (e.g. heat shock proteins, antioxidant enzymes and sirtuin‐1/PGC‐1 signalling) are central to the protective effects of exercise preconditioning. PMID:27060608
The paraventricular thalamus controls a central amygdala fear circuit.

PubMed

Penzo, Mario A; Robert, Vincent; Tucciarone, Jason; De Bundel, Dimitri; Wang, Minghui; Van Aelst, Linda; Darvas, Martin; Parada, Luis F; Palmiter, Richard D; He, Miao; Huang, Z Josh; Li, Bo

2015-03-26

Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psychological stressors. However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression. Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM(+)) CeL neurons, which has previously been shown to store fear memory. Consistently, we found that PVT neurons preferentially innervate SOM(+) neurons in the CeL, and stimulation of PVT afferents facilitated SOM(+) neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression. Notably, PVT modulation of SOM(+) CeL neurons was mediated by activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either Bdnf in the PVT or Trkb in SOM(+) CeL neurons impaired fear conditioning, while infusion of BDNF into the CeL enhanced fear learning and elicited unconditioned fear responses. Our results demonstrate that the PVT-CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.
Neotectonic Deformation in Central Eurasia: A Geodynamic Model Approach

NASA Astrophysics Data System (ADS)

Tunini, Lavinia; Jiménez-Munt, Ivone; Fernandez, Manel; Vergés, Jaume; Bird, Peter

2017-11-01

Central Eurasia hosts wide orogenic belts of collision between India and Arabia with Eurasia, with diffuse or localized deformation occurring up to hundreds of kilometers from the primary plate boundaries. Although numerous studies have investigated the neotectonic deformation in central Eurasia, most of them have focused on limited segments of the orogenic systems. Here we explore the neotectonic deformation of all of central Eurasia, including both collision zones and the links between them. We use a thin-spherical sheet approach in which lithosphere strength is calculated from lithosphere structure and its thermal regime. We investigate the contributions of variations in lithospheric structure, rheology, boundary conditions, and fault friction coefficients on the predicted velocity and stress fields. Results (deformation pattern, surface velocities, tectonic stresses, and slip rates on faults) are constrained by independent observations of tectonic regime, GPS, and stress data. Our model predictions reproduce the counterclockwise rotation of Arabia and Iran, the westward escape of Anatolia, and the eastward extrusion of the northern Tibetan Plateau. To simulate the observed extensional faults in the Tibetan Plateau, a weaker lithosphere is required, provided by a change in the rheological parameters. The southward movement of the SE Tibetan Plateau can be explained by the combined effects of the Sumatra trench retreat, a thinner lithospheric mantle, and strik-slip faults in the region. This study offers a comprehensive model for regions with little or no data coverage, like the Arabia-India intercollision zone, where the surface velocity is northward showing no deflection related to Arabia and India indentations.
Human Cardiovascular Responses to Passive Heat Stress

PubMed Central

Crandall, Craig G.; Wilson, Thad E.

2016-01-01

Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur. PMID:25589263
Flow-Mediated Endothelial Mechanotransduction

PubMed Central

Davies, Peter F.

2011-01-01

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed. PMID:7624393
Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.

PubMed

Deville, Célia; Carroni, Marta; Franke, Kamila B; Topf, Maya; Bukau, Bernd; Mogk, Axel; Saibil, Helen R

2017-08-01

Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'- O -(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.
Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

PubMed Central

Jiang, De-guo; Jin, Shi-li; Li, Gong-ying; Li, Qing-qing; Li, Zhi-ruo; Ma, Hong-xia; Zhuo, Chuan-jun; Jiang, Rong-huan; Ye, Min-jie

2016-01-01

Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress. PMID:27857753
Approaches Mediating Oxytocin Regulation of the Immune System.

PubMed

Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

2016-01-01

The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.
The ETHYLENE RESPONSE FACTORs ERF6 and ERF11 Antagonistically Regulate Mannitol-Induced Growth Inhibition in Arabidopsis1[OPEN

PubMed Central

Dubois, Marieke; Van den Broeck, Lisa; Claeys, Hannes; Van Vlierberghe, Kaatje; Matsui, Minami; Inzé, Dirk

2015-01-01

Leaf growth is a tightly regulated and complex process, which responds in a dynamic manner to changing environmental conditions, but the mechanisms that reduce growth under adverse conditions are rather poorly understood. We previously identified a growth inhibitory pathway regulating leaf growth upon exposure to a low concentration of mannitol and characterized the ETHYLENE RESPONSE FACTOR (ERF)/APETALA2 transcription factor ERF6 as a central activator of both leaf growth inhibition and induction of stress tolerance genes. Here, we describe the role of the transcriptional repressor ERF11 in relation to the ERF6-mediated stress response in Arabidopsis (Arabidopsis thaliana). Using inducible overexpression lines, we show that ERF6 induces the expression of ERF11. ERF11 in turn molecularly counteracts the action of ERF6 and represses at least some of the ERF6-induced genes by directly competing for the target gene promoters. As a phenotypical consequence of the ERF6-ERF11 antagonism, the extreme dwarfism caused by ERF6 overexpression is suppressed by overexpression of ERF11. Together, our data demonstrate that dynamic mechanisms exist to fine-tune the stress response and that ERF11 counteracts ERF6 to maintain a balance between plant growth and stress defense. PMID:25995327
Corticotropin-Releasing Hormone Drives Anandamide Hydrolysis in the Amygdala to Promote Anxiety

PubMed Central

Gray, J. Megan; Vecchiarelli, Haley A.; Morena, Maria; Lee, Tiffany T.Y.; Hermanson, Daniel J.; Kim, Alexander B.; McLaughlin, Ryan J.; Hassan, Kowther I.; Kühne, Claudia; Wotjak, Carsten T.; Deussing, Jan M.; Patel, Sachin

2015-01-01

Corticotropin-releasing hormone (CRH) is a central integrator in the brain of endocrine and behavioral stress responses, whereas activation of the endocannabinoid CB1 receptor suppresses these responses. Although these systems regulate overlapping functions, few studies have investigated whether these systems interact. Here we demonstrate a novel mechanism of CRH-induced anxiety that relies on modulation of endocannabinoids. Specifically, we found that CRH, through activation of the CRH receptor type 1 (CRHR1), evokes a rapid induction of the enzyme fatty acid amide hydrolase (FAAH), which causes a reduction in the endocannabinoid anandamide (AEA), within the amygdala. Similarly, the ability of acute stress to modulate amygdala FAAH and AEA in both rats and mice is also mediated through CRHR1 activation. This interaction occurs specifically in amygdala pyramidal neurons and represents a novel mechanism of endocannabinoid–CRH interactions in regulating amygdala output. Functionally, we found that CRH signaling in the amygdala promotes an anxious phenotype that is prevented by FAAH inhibition. Together, this work suggests that rapid reductions in amygdala AEA signaling following stress may prime the amygdala and facilitate the generation of downstream stress-linked behaviors. Given that endocannabinoid signaling is thought to exert “tonic” regulation on stress and anxiety responses, these data suggest that CRH signaling coordinates a disruption of tonic AEA activity to promote a state of anxiety, which in turn may represent an endogenous mechanism by which stress enhances anxiety. These data suggest that FAAH inhibitors may represent a novel class of anxiolytics that specifically target stress-induced anxiety. PMID:25740517
p53 -Dependent and -Independent Nucleolar Stress Responses

PubMed Central

Olausson, Karl Holmberg; Nistér, Monica; Lindström, Mikael S.

2012-01-01

The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. Ribosomal proteins, including RPL11 and RPL5, become increasingly bound to the p53 regulatory protein MDM2 following nucleolar stress. Ribosomal protein binding to MDM2 blocks its E3 ligase function leading to stabilization and activation of p53. In this review we focus on a number of novel regulators of the RPL5/RPL11-MDM2-p53 complex including PICT1 (GLTSCR2), MYBBP1A, PML and NEDD8. p53-independent pathways mediating the nucleolar stress response are also emerging and in particular the negative control that RPL11 exerts on Myc oncoprotein is of importance, given the role of Myc as a master regulator of ribosome biogenesis. We also briefly discuss the potential of chemotherapeutic drugs that specifically target RNA polymerase I to induce nucleolar stress. PMID:24710530
Structurally Controlled Geothermal Systems in the Central Cascades Arc-Backarc Regime, Oregon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wannamaker, Philip E.

The goal of this project has been to analyze available magnetotelluric (MT) geophysical surveys, structural geology based on mapping and LiDAR, and fluid geochemical data, to identify high-temperature fluid upwellings, critically stressed rock volumes, and other evidence of structurally-controlled geothermal resources. Data were to be integrated to create conceptual models of volcanic-hosted geothermal resources along the Central Cascades arc segment, especially in the vicinity of Mt. Jefferson to Three Sisters. LiDAR data sets available at Oregon State University (OSU) allowed detailed structural geology modeling through forest canopy. Copious spring and well fluid chemistries, including isotopes, were modeled using Geo-T andmore » TOUGHREACT software.« less
The VPAC1 receptor: structure and function of a class B GPCR prototype

PubMed Central

Couvineau, A.; Ceraudo, E.; Tan, Y.-V.; Nicole, P.; Laburthe, M.

2012-01-01

The class B G protein-coupled receptors (GPCRs) represents a small sub-family encompassing 15 members, and are very promising targets for the development of drugs to treat many diseases such as chronic inflammation, neurodegeneration, diabetes, stress, and osteoporosis. The VPAC1 receptor which is an archetype of the class B GPCRs binds Vasoactive Intestinal Peptide (VIP), a neuropeptide widely distributed in central and peripheral nervous system modulating many physiological processes including regulation of exocrine secretions, hormone release, foetal development, immune response … VIP appears to exert beneficial effect in neurodegenerative and inflammatory diseases. This article reviews the current knowledge regarding the structure and molecular pharmacology of VPAC1 receptors. Over the past decade, structure–function relationship studies have demonstrated that the N-terminal ectodomain (N-ted) of VPAC1 plays a pivotal role in VIP recognition. The use of different approaches such as directed mutagenesis, photoaffinity labeling, Nuclear Magnetic Resonance (NMR), molecular modeling, and molecular dynamic simulation has led to demonstrate that: (1) the central and C-terminal part of the VIP molecule interacts with the N-ted of VPAC1 receptor which is itself structured as a « Sushi » domain; (2) the N-terminal end of the VIP molecule interacts with the first transmembrane domain of the receptor where three residues (K143, T144, and T147) play an important role in VPAC1 interaction with the first histidine residue of VIP. PMID:23162538
Stress-Induced Accumulation of DcAOX1 and DcAOX2a Transcripts Coincides with Critical Time Point for Structural Biomass Prediction in Carrot Primary Cultures (Daucus carota L.)

PubMed Central

Campos, M. Doroteia; Nogales, Amaia; Cardoso, Hélia G.; Kumar, Sarma R.; Nobre, Tânia; Sathishkumar, Ramalingam; Arnholdt-Schmitt, Birgit

2016-01-01

Stress-adaptive cell plasticity in target tissues and cells for plant biomass growth is important for yield stability. In vitro systems with reproducible cell plasticity can help to identify relevant metabolic and molecular events during early cell reprogramming. In carrot, regulation of the central root meristem is a critical target for yield-determining secondary growth. Calorespirometry, a tool previously identified as promising for predictive growth phenotyping has been applied to measure the respiration rate in carrot meristem. In a carrot primary culture system (PCS), this tool allowed identifying an early peak related with structural biomass formation during lag phase of growth, around the 4th day of culture. In the present study, we report a dynamic and correlated expression of carrot AOX genes (DcAOX1 and DcAOX2a) during PCS lag phase and during exponential growth. Both genes showed an increase in transcript levels until 36 h after explant inoculation, and a subsequent down-regulation, before the initiation of exponential growth. In PCS growing at two different temperatures (21°C and 28°C), DcAOX1 was also found to be more expressed in the highest temperature. DcAOX genes’ were further explored in a plant pot experiment in response to chilling, which confirmed the early AOX transcript increase prior to the induction of a specific anti-freezing gene. Our findings point to DcAOX1 and DcAOX2a as being reasonable candidates for functional marker development related to early cell reprogramming. While the genomic sequence of DcAOX2a was previously described, we characterize here the complete genomic sequence of DcAOX1. PMID:26858746

An epigenetic intervention interacts with genetic strain differences to modulate the stress-induced reduction of flurazepam's antiseizure efficacy in the mouse.

PubMed

Deutsch, Stephen I; Mastropaolo, John; Burket, Jessica A; Rosse, Richard B

2009-06-01

Stress induces changes in the endogenous tone of both GABA and NMDA receptor-mediated neurotransmission in the intact mouse. Because changes are observed 24 h after stress, epigenetically-regulated alterations in gene expression may mediate these effects. In earlier work, sodium butyrate, a centrally-active histone deacetylase inhibitor that promotes gene expression, was shown to modulate the stress-induced reduction of the ability of MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, to antagonize electrically-precipitated seizures. In the current study, we extended this work to look at sodium butyrate's modulatory effect on stress-induced changes in the antiseizure efficacy of flurazepam, a benzodiazepine receptor agonist, in two strains of mice. Epigenetic mechanisms, genetic strain differences and a standard stress interacted to alter flurazepam's antiseizure efficacy. These data support examination and development of epigenetic treatment strategies.
Role of relaxin-3/RXFP3 system in stress-induced binge-like eating in female rats.

PubMed

Calvez, Juliane; de Ávila, Camila; Matte, Louis-Olivier; Guèvremont, Geneviève; Gundlach, Andrew L; Timofeeva, Elena

2016-03-01

Binge eating is frequently stimulated by stress. The neuropeptide relaxin-3 (RLN3) and its native receptor RXFP3 are implicated in stress and appetitive behaviors. We investigated the dynamics of the central RLN3/RXFP3 system in a newly established model of stress-induced binge eating. Female Sprague-Dawley rats were subjected to unpredictable intermittent 1-h access to 10% sucrose. When sucrose intake stabilized, rats were assessed for consistency of higher or lower sucrose intake in response to three unpredictable episodes of foot-shock stress; and assigned as binge-like eating prone (BEP) or binge-like eating resistant (BER). BEP rats displayed elevated consumption of sucrose under non-stressful conditions (30% > BER) and an additional marked increase in sucrose intake (60% > BER) in response to stress. Conversely, sucrose intake in BER rats was unaltered by stress. Chow intake was similar in both phenotypes on 'non-stress' days, but was significantly reduced by stress in BER, but not BEP, rats. After stress, BEP, but not BER, rats displayed a significant increase in RLN3 mRNA levels in the nucleus incertus. In addition, in response to stress, BEP, but not BER, rats had increased RXFP3 mRNA levels in the paraventricular and supraoptic nuclei of the hypothalamus. Intracerebroventricular administration of a selective RXFP3 antagonist, R3(B1-22)R, blocked the stress-induced increase in sucrose intake in BEP rats and had no effect on sucrose intake in BER rats. These results provide important evidence for a role of the central RLN3/RXFP3 system in the regulation of stress-induced binge eating in rats, and have therapeutic implications for eating disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.
The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence bacterial responses to oxidative and aerobic stresses.

PubMed

Gundogdu, Ozan; da Silva, Daiani T; Mohammad, Banaz; Elmi, Abdi; Mills, Dominic C; Wren, Brendan W; Dorrell, Nick

2015-01-01

The ability of the human intestinal pathogen Campylobacter jejuni to respond to oxidative stress is central to bacterial survival both in vivo during infection and in the environment. Re-annotation of the C. jejuni NCTC11168 genome revealed the presence of two MarR-type transcriptional regulators Cj1546 and Cj1556, originally annotated as hypothetical proteins, which we have designated RrpA and RrpB (regulator of response to peroxide) respectively. Previously we demonstrated a role for RrpB in both oxidative and aerobic (O2) stress and that RrpB was a DNA binding protein with auto-regulatory activity, typical of MarR-type transcriptional regulators. In this study, we show that RrpA is also a DNA binding protein and that a rrpA mutant in strain 11168H exhibits increased sensitivity to hydrogen peroxide oxidative stress. Mutation of either rrpA or rrpB reduces catalase (KatA) expression. However, a rrpAB double mutant exhibits higher levels of resistance to hydrogen peroxide oxidative stress, with levels of KatA expression similar to the wild-type strain. Mutation of either rrpA or rrpB also results in a reduction in the level of katA expression, but this reduction was not observed in the rrpAB double mutant. Neither the rrpA nor rrpB mutant exhibits any significant difference in sensitivity to either cumene hydroperoxide or menadione oxidative stresses, but both mutants exhibit a reduced ability to survive aerobic (O2) stress, enhanced biofilm formation and reduced virulence in the Galleria mellonella infection model. The rrpAB double mutant exhibits wild-type levels of biofilm formation and wild-type levels of virulence in the G mellonella infection model. Together these data indicate a role for both RrpA and RrpB in the C. jejuni peroxide oxidative and aerobic (O2) stress responses, enhancing bacterial survival in vivo and in the environment.
Homogalacturonan-modifying enzymes: structure, expression, and roles in plants

PubMed Central

Sénéchal, Fabien; Wattier, Christopher; Rustérucci, Christine; Pelloux, Jérôme

2014-01-01

Understanding the changes affecting the plant cell wall is a key element in addressing its functional role in plant growth and in the response to stress. Pectins, which are the main constituents of the primary cell wall in dicot species, play a central role in the control of cellular adhesion and thereby of the rheological properties of the wall. This is likely to be a major determinant of plant growth. How the discrete changes in pectin structure are mediated is thus a key issue in our understanding of plant development and plant responses to changes in the environment. In particular, understanding the remodelling of homogalacturonan (HG), the most abundant pectic polymer, by specific enzymes is a current challenge in addressing its fundamental role. HG, a polymer that can be methylesterified or acetylated, can be modified by HGMEs (HG-modifying enzymes) which all belong to large multigenic families in all species sequenced to date. In particular, both the degrees of substitution (methylesterification and/or acetylation) and polymerization can be controlled by specific enzymes such as pectin methylesterases (PMEs), pectin acetylesterases (PAEs), polygalacturonases (PGs), or pectate lyases-like (PLLs). Major advances in the biochemical and functional characterization of these enzymes have been made over the last 10 years. This review aims to provide a comprehensive, up to date summary of the recent data concerning the structure, regulation, and function of these fascinating enzymes in plant development and in response to biotic stresses. PMID:25056773
Oxidation of Са2+-Binding Domain of NADPH Oxidase 5 (NOX5): Toward Understanding the Mechanism of Inactivation of NOX5 by ROS.

PubMed

Petrushanko, Irina Yu; Lobachev, Vladimir M; Kononikhin, Alexey S; Makarov, Alexander A; Devred, Francois; Kovacic, Hervé; Kubatiev, Aslan A; Tsvetkov, Philipp O

2016-01-01

NOX5 protein, one of the most active generators of reactive oxygen species (ROS), plays an important role in many processes, including regulation of cell growth, death and differentiation. Because of its central role in ROS generation, it needs to be tightly regulated to guarantee cellular homeostasis. Contrary to other members of NADPH-oxidases family, NOX5 has its own regulatory calcium-binding domain and thus could be activated directly by calcium ions. While several mechanisms of activation have been described, very little is known about the mechanisms that could prevent the overproduction of ROS by NOX5. In the present study using calorimetric methods and circular dichroism we found that oxidation of cysteine and methionine residues of NOX5 decreases binding of Ca2+ ions and perturbs both secondary and tertiary structure of protein. Our data strongly suggest that oxidation of calcium-binding domain of NOX5 could be implicated in its inactivation, serving as a possible defense mechanism against oxidative stress.
[Analysis of fragments of intergenome spacers of human body observed in chromosomes containing no nuclear organization].

PubMed

Kupriyanova, N S; Nechvolodov, K K; Korsunenko, A V

2014-01-01

Tandem repetitions of rDNA provide so-called nuclear organizations (NOR). On the other hand, rDNA-structures are observed in some NOR chromosomes. It was demonstrated that, in addition to ribosome biogenesis, nucleoli provided a number of functions: cell cycle regulation, stress-induced response, transcription regulation, which often induced cell cascades. The mechanisms of the induction of rDNA segments in NOR chromosomes are obscure and require further research. About 1/3 repetitions are associated with nucleoli and SINE/Alu repetitions, homogeneous repetition, and tandem repetition. Perhaps, relative position of nucleoli and chromosomes may facilitate/prevent interaction of chromosomes with rDNA clusters. The variability of two larger repetitions in the central part of rMGS, LR1, and LR2 similar by -90% and separated by several hundred pairs of bases from each other was studied in our previous works. This work was devoted to the search for the LR1-LR2 segments in other chromosomes, characterization of their terminal tips at rupture points and genome areas of incorporation of the LR1-LR2 segments.
Neuromedin U: physiology, pharmacology and therapeutic potential.

PubMed

Budhiraja, S; Chugh, A

2009-04-01

Neuromedin U (NmU), a multifunctional neuropeptide, belongs to a family of neuropeptides, the neuromedins. It is ubiquitously distributed with highest levels found in the gastrointestinal tract and pituitary. The conservation of structural elements of NmU across species, the widespread distribution of NmU and its receptors throughout the body point to a fundamental role in key physiological processes. Two G protein coupled receptors for NmU have been cloned NmU R1 and NmU R2. NmU R1 is expressed pre-dominantly in the periphery especially the gastrointestinal tract whereas NmU R2 is expressed pre-dominantly in the central nervous system. Current evidence suggests a role of NmU in pain, in regulation of feeding and energy homeostasis, stress, cancer, immune mediated inflammatory diseases like asthma, inflammatory diseases, maintaining the biological clock, in the regulation of smooth muscle contraction in the gastrointestinal and genitourinary tract, and in the control of blood flow and blood pressure. With the development of drugs selectively acting on receptors and knockout animal models, exact pathophysiological roles of NmU will become clearer.
Role of substance P in the cardiovascular system.

PubMed

Mistrova, Eliska; Kruzliak, Peter; Chottova Dvorakova, Magdalena

2016-08-01

This article provides an overview of the structure and function of substance P signalling system and its involvement in the cardiovascular regulation. Substance P is an undecapeptide originating from TAC1 gen and belonging to the tachykinin family. The biological actions of substance P are mainly mediated through neurokinin receptor 1 since substance P is the ligand with the highest affinity to neurokinin receptor 1. Substance P is widely distributed within the central and peripheral nervous systems as well as in the cardiovascular system. Substance P is involved in the regulation of heart frequency, blood pressure and in the stretching of vessels. Substance P plays an important role in ischemia and reperfusion and cardiovascular response to stress. Additionally, it has been also implicated in angiogenesis, pain transmission and inflammation. The substance P/neurokinin receptor 1 receptor system is involved in the molecular bases of many human pathological processes. Antagonists of neurokinin receptor 1 receptor could provide clinical solutions for a variety of diseases. Neurokinin receptor 1 antagonists are already used in the prevention of chemotherapy induced nausea and vomiting. Copyright © 2015 Elsevier Ltd. All rights reserved.
The Novel Poly(A) Polymerase Star-PAP is a Signal-Regulated Switch at the 3′-end of mRNAs

PubMed Central

Li, Weimin; Laishram, Rakesh S.; Anderson, Richard A.

2013-01-01

The mRNA 3′-untranslated region (3′-UTR) modulates message stability, transport, intracellular location and translation. We have discovered a novel nuclear poly(A) polymerase termed Star-PAP (nuclear speckle targeted PIPKIα regulated-poly(A) polymerase) that couples with the transcriptional machinery and is regulated by the phosphoinositide lipid messenger phosphatidylinositol-4,5-bisphosphate (PI4,5P2), the central lipid in phosphoinositide signaling. PI4,5P2 is generated primarily by type I phosphatidylinositol phosphate kinases (PIPKI). Phosphoinositides are present in the nucleus including at nuclear speckles compartments separate from known membrane structures. PIPKs regulate cellular functions by interacting with PI4,5P2 effectors where PIPKs generate PI4,5P2 that then modulates the activity of the associated effectors. Nuclear PIPKIα interacts with and regulates Star-PAP, and PI4,5P2 specifically activates Star-PAP in a gene- and signaling-dependent manner. Importantly, other select signaling molecules integrated into the Star-PAP complex seem to regulate Star-PAP activities and processivities toward RNA substrates, and unique sequence elements around the Star-PAP binding sites within the 3′-UTR of target genes contribute to Star-PAP specificity for processing. Therefore, Star-PAP and its regulatory molecules form a signaling nexus at the 3′-end of target mRNAs to control the expression of select group of genes including the ones involved in stress responses. PMID:23306079
Molecular Mechanotransduction: how forces trigger cytoskeletal dynamics

NASA Astrophysics Data System (ADS)

Ehrlicher, Allen

2012-02-01

Mechanical stresses elicit cellular reactions mediated by chemical signals. Defective responses to forces underlie human medical disorders, such as cardiac failure and pulmonary injury. Despite detailed knowledge of the cytoskeleton's structure, the specific molecular switches that convert mechanical stimuli into chemical signals have remained elusive. Here we identify the actin-binding protein, filamin A (FLNa) as a central mechanotransduction element of the cytoskeleton by using Fluorescence Loss After photoConversion (FLAC), a novel high-speed alternative to FRAP. We reconstituted a minimal system consisting of actin filaments, FLNa and two FLNa-binding partners: the cytoplasmic tail of ß-integrin, and FilGAP. Integrins form an essential mechanical linkage between extracellular and intracellular environments, with ß integrin tails connecting to the actin cytoskeleton by binding directly to filamin. FilGAP is a FLNa-binding GTPase-activating protein specific for Rac, which in vivo regulates cell spreading and bleb formation. We demonstrate that both externally-imposed bulk shear and myosin II driven forces differentially regulate the binding of integrin and FilGAP to FLNa. Consistent with structural predictions, strain increases ß-integrin binding to FLNa, whereas it causes FilGAP to dissociate from FLNa, providing a direct and specific molecular basis for cellular mechanotransduction. These results identify the first molecular mechanotransduction element within the actin cytoskeleton, revealing that mechanical strain of key proteins regulates the binding of signaling molecules. Moreover, GAP activity has been shown to switch cell movement from mesenchymal to amoeboid motility, suggesting that mechanical forces directly impact the invasiveness of cancer.
Nogo-A couples with Apg-1 through interaction and co-ordinate expression under hypoxic and oxidative stress.

PubMed

Kern, Florian; Stanika, Ruslan I; Sarg, Bettina; Offterdinger, Martin; Hess, Daniel; Obermair, Gerald J; Lindner, Herbert; Bandtlow, Christine E; Hengst, Ludger; Schweigreiter, Rüdiger

2013-10-15

Nogo-A is the largest isoform of the Nogo/RTN4 (reticulon 4) proteins and has been characterized as a major myelin-associated inhibitor of regenerative nerve growth in the adult CNS (central nervous system). Apart from the myelin sheath, Nogo-A is expressed at high levels in principal neurons of the CNS. The specificity of Nogo-A resides in its central domain, NiG. We identified Apg-1, a member of the stress-induced Hsp110 (heat-shock protein of 110 kDa) family, as a novel interactor of NiG/Nogo-A. The interaction is selective because Apg-1 interacts with Nogo-A/RTN4-A, but not with RTN1-A, the closest paralogue of Nogo-A. Conversely, Nogo-A binds to Apg-1, but not to Apg-2 or Hsp105, two other members of the Hsp110 family. We characterized the Nogo-A-Apg-1 interaction by affinity precipitation, co-immunoprecipitation and proximity ligation assay, using primary hippocampal neurons derived from Nogo-deficient mice. Under conditions of hypoxic and oxidative stress we found that Nogo-A and Apg-1 were tightly co-regulated in hippocampal neurons. Although both proteins were up-regulated under hypoxic conditions, their expression levels were reduced upon the addition of hydrogen peroxide. Taken together, we suggest that Nogo-A is closely involved in the neuronal response to hypoxic and oxidative stress, an observation that may be of relevance not only in stroke-induced ischaemia, but also in neuroblastoma formation.
Nogo-A couples with Apg-1 through interaction and co-ordinate expression under hypoxic and oxidative stress

PubMed Central

Kern, Florian; Stanika, Ruslan I.; Sarg, Bettina; Offterdinger, Martin; Hess, Daniel; Obermair, Gerald J.; Lindner, Herbert; Bandtlow, Christine E.; Hengst, Ludger; Schweigreiter, Rüdiger

2013-01-01

Nogo-A is the largest isoform of the Nogo/RTN4 (reticulon 4) proteins and has been characterized as a major myelin-associated inhibitor of regenerative nerve growth in the adult CNS (central nervous system). Apart from the myelin sheath, Nogo-A is expressed at high levels in principal neurons of the CNS. The specificity of Nogo-A resides in its central domain, NiG. We identified Apg-1, a member of the stress-induced Hsp110 (heat-shock protein of 110 kDa) family, as a novel interactor of NiG/Nogo-A. The interaction is selective because Apg-1 interacts with Nogo-A/RTN4-A, but not with RTN1-A, the closest paralogue of Nogo-A. Conversely, Nogo-A binds to Apg-1, but not to Apg-2 or Hsp105, two other members of the Hsp110 family. We characterized the Nogo-A–Apg-1 interaction by affinity precipitation, co-immunoprecipitation and proximity ligation assay, using primary hippocampal neurons derived from Nogo-deficient mice. Under conditions of hypoxic and oxidative stress we found that Nogo-A and Apg-1 were tightly co-regulated in hippocampal neurons. Although both proteins were up-regulated under hypoxic conditions, their expression levels were reduced upon the addition of hydrogen peroxide. Taken together, we suggest that Nogo-A is closely involved in the neuronal response to hypoxic and oxidative stress, an observation that may be of relevance not only in stroke-induced ischaemia, but also in neuroblastoma formation. PMID:23909438
Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents.

PubMed

Huang, Hui-Jie; Zhu, Xiao-Cang; Han, Qiu-Qin; Wang, Ya-Lin; Yue, Na; Wang, Jing; Yu, Rui; Li, Bing; Wu, Gen-Cheng; Liu, Qiong; Yu, Jin

2017-05-30

As a regulator of food intake, ghrelin also plays a key role in mood disorders. Previous studies reported that acute ghrelin administration defends against depressive symptoms of chronic stress. However, the effects of long-term ghrelin on rodents under chronic stress hasn't been revealed. In this study, we found chronic peripheral administration of ghrelin (5nmol/kg/day for 2 weeks, i.p.) could alleviate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress (CUMS). The depression-like behaviors were assessed by the forced swimming test (FST), and anxiety-like behaviors were assessed by the open field test (OFT) and the elevated plus maze test (EPM). Meanwhile, we observed that peripheral acylated ghrelin, together with gastral and hippocampal ghrelin prepropeptide mRNA level, were significantly up-regulated in CUMS mice. Besides, the increased protein level of growth hormone secretagogue receptor (GHSR) in hippocampus were also detected. These results suggested that the endogenous ghrelin/GHSR pathway activated by CUMS plays a role in homeostasis. Further results showed that central treatment of ghrelin (10μg/rat/day for 2 weeks, i.c.v.) or GHRP-6 (the agonist of GHSR, 10μg/rat/day for 2 weeks, i.c.v.) significantly alleviated the depression-like behaviors induced by CUMS in FST and sucrose preference test (SPT). Based on these results, we concluded that central GHSR is involved in the antidepressant-like effect of exogenous ghrelin treatment, and ghrelin/GHSR may have the inherent neuromodulatory properties against depressive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.
ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress.

PubMed

Bai, Yin-Yin; Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Kang, Zhi-Long; Zhou, Li; Liu, Dennis; Zeng, Yue-Qing; Wang, Ting-Hua; Tian, Chang-Fu; Liao, Hong; Bobrovskaya, Larisa; Zhou, Xin-Fu

2016-11-01

Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75 NTR /sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific anti-proBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders.
Role of Temperature Stress on Chloroplast Biogenesis and Protein Import in Pea1[OA

PubMed Central

Dutta, Siddhartha; Mohanty, Sasmita; Tripathy, Baishnab C.

2009-01-01

Modulation of photosynthesis and chloroplast biogenesis, by low and high temperatures, was studied in 12-d-old pea (Pisum sativum) plants grown at 25°C and subsequently exposed to 7°C or 40°C up to 48 h. The decline in variable chlorophyll a fluorescence/maximum chlorophyll a fluorescence and estimated electron transport rate in temperature-stressed plants was substantially restored when they were transferred to room temperature. The ATP-driven import of precursor of small subunit of Rubisco (pRSS) into plastids was down-regulated by 67% and 49% in heat-stressed and chill-stressed plants, respectively. Reduction in binding of the pRSS to the chloroplast envelope membranes in heat-stressed plants could be due to the down-regulation of Toc159 gene/protein expression. In addition to impaired binding, reduced protein import into chloroplast in heat-stressed plants was likely due to decreased gene/protein expression of certain components of the TOC complex (Toc75), the TIC complex (Tic20, Tic32, Tic55, and Tic62), stromal Hsp93, and stromal processing peptidase. In chill-stressed plants, the gene/protein expression of most of the components of protein import apparatus other than Tic110 and Tic40 were not affected, suggesting the central role of Tic110 and Tic40 in inhibition of protein import at low temperature. Heating of intact chloroplasts at 35°C for 10 min inhibited protein import, implying a low thermal stability of the protein import apparatus. Results demonstrate that in addition to decreased gene and protein expression, down-regulation of photosynthesis in temperature-stressed plants is caused by reduced posttranslational import of plastidic proteins required for the replacement of impaired proteins coded by nuclear genome. PMID:19403728
The Structure of Arabidopsis thaliana OST1 Provides Insights into the Kinase Regulation Mechanism in Response to Osmotic Stress

PubMed Central

Yunta, Cristina; Martínez-Ripoll, Martín; Zhu, Jian-Kang; Albert, Armando

2013-01-01

SnRK [SNF1 (sucrose non-fermenting-1)-related protein kinase] 2.6 [open stomata 1 (OST1)] is well characterized at molecular and physiological levels to control stomata closure in response to water-deficit stress. OST1 is a member of a family of 10 protein kinases from Arabidopsis thaliana (SnRK2) that integrates abscisic acid (ABA)-dependent and ABA-independent signals to coordinate the cell response to osmotic stress. A subgroup of protein phosphatases type 2C binds OST1 and keeps the kinase dephosphorylated and inactive. Activation of OST1 relies on the ABA-dependent inhibition of the protein phosphatases type 2C and the subsequent self-phosphorylation of the kinase. The OST1 ABA-independent activation depends on a short sequence motif that is conserved among all the members of the SnRK2 family. However, little is known about the molecular mechanism underlying this regulation. The crystallographic structure of OST1 shows that ABA-independent regulation motif stabilizes the conformation of the kinase catalytically essential α C helix, and it provides the basis of the ABA-independent regulation mechanism for the SnRK2 family of protein kinases. PMID:21983340
Prospects of engineering thermotolerance in crops through modulation of heat stress transcription factor and heat shock protein networks.

PubMed

Fragkostefanakis, Sotirios; Röth, Sascha; Schleiff, Enrico; Scharf, Klaus-Dieter

2015-09-01

Cell survival under high temperature conditions involves the activation of heat stress response (HSR), which in principle is highly conserved among different organisms, but shows remarkable complexity and unique features in plant systems. The transcriptional reprogramming at higher temperatures is controlled by the activity of the heat stress transcription factors (Hsfs). Hsfs allow the transcriptional activation of HSR genes, among which heat shock proteins (Hsps) are best characterized. Hsps belong to multigene families encoding for molecular chaperones involved in various processes including maintenance of protein homeostasis as a requisite for optimal development and survival under stress conditions. Hsfs form complex networks to activate downstream responses, but are concomitantly subjected to cell-type-dependent feedback regulation through factor-specific physical and functional interactions with chaperones belonging to Hsp90, Hsp70 and small Hsp families. There is increasing evidence that the originally assumed specialized function of Hsf/chaperone networks in the HSR turns out to be a complex central stress response system that is involved in the regulation of a broad variety of other stress responses and may also have substantial impact on various developmental processes. Understanding in detail the function of such regulatory networks is prerequisite for sustained improvement of thermotolerance in important agricultural crops. © 2014 John Wiley & Sons Ltd.
24 CFR 3280.303 - General requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Section 3280.303 Housing and Urban Development Regulations Relating to Housing and Urban Development... quality of work of the various trades. (c) Structural analysis. The strength and rigidity of the component... tests specified in paragraph (g) of this section. (f) Allowable design stress. The design stresses of...
24 CFR 3280.303 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Section 3280.303 Housing and Urban Development Regulations Relating to Housing and Urban Development... quality of work of the various trades. (c) Structural analysis. The strength and rigidity of the component... tests specified in paragraph (g) of this section. (f) Allowable design stress. The design stresses of...
24 CFR 3280.303 - General requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Section 3280.303 Housing and Urban Development Regulations Relating to Housing and Urban Development... quality of work of the various trades. (c) Structural analysis. The strength and rigidity of the component... tests specified in paragraph (g) of this section. (f) Allowable design stress. The design stresses of...

24 CFR 3280.303 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 3280.303 Housing and Urban Development Regulations Relating to Housing and Urban Development... quality of work of the various trades. (c) Structural analysis. The strength and rigidity of the component... tests specified in paragraph (g) of this section. (f) Allowable design stress. The design stresses of...
24 CFR 3280.303 - General requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Section 3280.303 Housing and Urban Development Regulations Relating to Housing and Urban Development... quality of work of the various trades. (c) Structural analysis. The strength and rigidity of the component... tests specified in paragraph (g) of this section. (f) Allowable design stress. The design stresses of...
Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.

PubMed

Jayakumar, Siddharth; Hasan, Gaiti

2018-01-01

All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.
[Low obstruction tract by system Reemex].

PubMed

Bujons Tur, A; Errando Smet, C; Prados Saavedra, M; Báez, C; Arañó Bertrán, P; Gutiérrez Ruiz, C; Villavicencio Mavrich, H

2007-01-01

The Remeex system it's a sling with regulable tension created for the surgical correction of the female urinary incontinente. The system contains a varitensor central part of the protesis that regulates the tension of the uretra. The screwdriver that acts against the varitensor to the modify the tension under the uretra in the postop inmediately or time after also. We present a clinic case of a patient with diagnostic of urinary stress incontinence and the surgical treatment with advantages against others kind of systems used for incontinence treatment at this time.
Hypothalamic involvement in stress-induced hypocalcemia in rats.

PubMed

Aou, S; Ma, J; Hori, T

1993-08-20

Although hormonal regulation of blood calcium homeostasis has been intensively investigated in the peripheral organs, the involvement of the central nervous system in calcium regulation is still poorly understood. In the present study, we found that (1) bilateral lesions of the ventromedial nucleus of the hypothalamus (VMH), but not those of the paraventricular hypothalamic nucleus or the lateral hypothalamic area, eliminated immobilization (IMB)-induced hypocalcemia, and (2) electrical stimulation of the VMH decreased the blood calcium level. The results suggest that the VMH has a hypocalcemic function and plays a role in IMB-induced hypocalcemia.
Redox Regulation of Plant Development

PubMed Central

Considine, Michael J.

2014-01-01

Abstract Significance: We provide a conceptual framework for the interactions between the cellular redox signaling hub and the phytohormone signaling network that controls plant growth and development to maximize plant productivity under stress-free situations, while limiting growth and altering development on exposure to stress. Recent Advances: Enhanced cellular oxidation plays a key role in the regulation of plant growth and stress responses. Oxidative signals or cycles of oxidation and reduction are crucial for the alleviation of dormancy and quiescence, activating the cell cycle and triggering genetic and epigenetic control that underpin growth and differentiation responses to changing environmental conditions. Critical Issues: The redox signaling hub interfaces directly with the phytohormone network in the synergistic control of growth and its modulation in response to environmental stress, but a few components have been identified. Accumulating evidence points to a complex interplay of phytohormone and redox controls that operate at multiple levels. For simplicity, we focus here on redox-dependent processes that control root growth and development and bud burst. Future Directions: The multiple roles of reactive oxygen species in the control of plant growth and development have been identified, but increasing emphasis should now be placed on the functions of redox-regulated proteins, along with the central roles of reductants such as NAD(P)H, thioredoxins, glutathione, glutaredoxins, peroxiredoxins, ascorbate, and reduced ferredoxin in the regulation of the genetic and epigenetic factors that modulate the growth and vigor of crop plants, particularly within an agricultural context. Antioxid. Redox Signal. 21, 1305–1326. PMID:24180689
Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

PubMed Central

McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Meyer, Joel N.; Domann, Frederick E.; Van Houten, Bennett; Mostoslavsky, Raul; Bultman, Scott J.; Baccarelli, Andrea A.; Begley, Thomas J.; Sobol, Robert W.; Hirschey, Matthew D.; Ideker, Trey; Santos, Janine H.; Copeland, William C.; Tice, Raymond R.; Balshaw, David M.; Tyson, Frederick L.

2014-01-01

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors. Citation: Shaughnessy DT, McAllister K, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli AA, Begley TJ, Sobol RW, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL. 2014. Mitochondria, energetics, epigenetics, and cellular responses to stress. Environ Health Perspect 122:1271–1278; http://dx.doi.org/10.1289/ehp.1408418 PMID:25127496
Effect of Water Stress on Cotton Leaves 1

PubMed Central

Berlin, Jerry; Quisenberry, J. E.; Bailey, Franklin; Woodworth, Margaret; McMichael, B. L.

1982-01-01

Palisade cells from fully expanded leaves from irrigated and nonirrigated, field grown cotton (Gossypium hirsutum L. cv. Paymaster 266) were subjected to a microscopic examination to evaluate the effect of water stress on subcellular structures. The water potential difference between the two treatments was 13 bars at the time of sampling. The dimensions of the palisade cells and their density per unit leaf area were determined by light microscopy. Palisade cells from stressed plants had the same diameter, but were taller than their counterparts in irrigated plants. The density of the palisade cells was the same in both treatments as was the fractional volume of the intercellular space. It was concluded that the reduced leaf area observed in the stressed plants resulted primarily from a mitotic sensitivity to water stress. Further, expansion of palisade cells was not inhibited by the stress imposed in this study. Morphometric analysis of electron micrographs was used to evaluate the subcellular structure of palisade cells from nonstressed and stressed plants. The fractional volumes of cell walls, total cytoplasm, chloroplasts, starch granules, intrachloroplast bodies, mitochondria, peroxisomes, and central vacuoles were determined. The surface densities of grana and stroma lamellae, outer chloroplast membranes, mitochondrial cristae, endoplasmic reticulum and Golgi cisternae were also measured. The number of chloroplasts, mitochondria, and peroxisomes were determined. These data were expressed as actual volumes, areas, and numbers per palisade cell for each treatment. Palisade cells from stressed plants had thinner cell walls, larger central vacuoles and approximately the same amount of cytoplasm compared to cells from nonstressed plants. Within the cytoplasm, stressed plants had more but smaller chloroplasts with increased grana and stroma lamellae surfaces, larger mithchondria with reduced cristae surfaces, smaller peroxisomes and reduced membrane surfaces of endoplasmic reticulum and Golgi cisternae. Images Fig. 1 PMID:16662453
Effect of water stress on cotton leaves : I. An electron microscopic stereological study of the palisade cells.

PubMed

Berlin, J; Quisenberry, J E; Bailey, F; Woodworth, M; McMichael, B L

1982-07-01

Palisade cells from fully expanded leaves from irrigated and nonirrigated, field grown cotton (Gossypium hirsutum L. cv. Paymaster 266) were subjected to a microscopic examination to evaluate the effect of water stress on subcellular structures. The water potential difference between the two treatments was 13 bars at the time of sampling. The dimensions of the palisade cells and their density per unit leaf area were determined by light microscopy. Palisade cells from stressed plants had the same diameter, but were taller than their counterparts in irrigated plants. The density of the palisade cells was the same in both treatments as was the fractional volume of the intercellular space. It was concluded that the reduced leaf area observed in the stressed plants resulted primarily from a mitotic sensitivity to water stress. Further, expansion of palisade cells was not inhibited by the stress imposed in this study.Morphometric analysis of electron micrographs was used to evaluate the subcellular structure of palisade cells from nonstressed and stressed plants. The fractional volumes of cell walls, total cytoplasm, chloroplasts, starch granules, intrachloroplast bodies, mitochondria, peroxisomes, and central vacuoles were determined. The surface densities of grana and stroma lamellae, outer chloroplast membranes, mitochondrial cristae, endoplasmic reticulum and Golgi cisternae were also measured. The number of chloroplasts, mitochondria, and peroxisomes were determined. These data were expressed as actual volumes, areas, and numbers per palisade cell for each treatment. Palisade cells from stressed plants had thinner cell walls, larger central vacuoles and approximately the same amount of cytoplasm compared to cells from nonstressed plants. Within the cytoplasm, stressed plants had more but smaller chloroplasts with increased grana and stroma lamellae surfaces, larger mithchondria with reduced cristae surfaces, smaller peroxisomes and reduced membrane surfaces of endoplasmic reticulum and Golgi cisternae.
Child cortisol moderates the association between family routines and emotion regulation in low-income children

PubMed Central

Miller, Alison L.; Song, Ju-Hyun; Sturza, Julie; Lumeng, Julie C.; Rosenblum, Katherine; Kaciroti, Niko; Vazquez, Delia M.

2018-01-01

Biological and social influences both shape emotion regulation. In 380 low-income children, we tested whether biological stress profile (cortisol) moderated the association among positive and negative home environment factors (routines; chaos) and emotion regulation (negative lability; positive regulation). Children (M age = 50.6, SD = 6.4 months) provided saliva samples to assess diurnal cortisol parameters across 3 days. Parents reported on home environment and child emotion regulation. Structural equation modeling was used to test whether cortisol parameters moderated associations between home environment and child emotion regulation. Results showed that home chaos was negatively associated with emotion regulation outcomes; cortisol did not moderate the association. Child cortisol level moderated the routines-emotion regulation association such that lack of routine was most strongly associated with poor emotion regulation among children with lower cortisol output. Findings suggest that underlying child stress biology may shape response to environmental influences. PMID:27594200
RAS in the central nervous system: Potential role in neuropsychiatric disorders.

PubMed

Rocha, Natalia Pessoa; Simões e Silva, Ana Cristina; Prestes, Thiago Ruiz Rodrigues; Feracin, Victor; Machado, Caroline Amaral; Ferreira, Rodrigo Novaes; Teixeira, Antonio Lucio; de Miranda, Aline Silva

2018-02-25

The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders of the modulation of RAS. We carried out an extensive literature search in PubMed central. Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and haemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
The varieties of immunological experience: of pathogens, stress, and dendritic cells.

PubMed

Pulendran, Bali

2015-01-01

In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity. Here, I discuss these exciting advances in the context of a historic perspective on the discovery of DCs and their role in immune regulation. I conclude with a discussion of emerging areas in DC biology in the systems immunology era and suggest that the impact of DCs on immunity can be usefully contextualized in a hierarchy-of-organization model in which DCs, their receptors and signaling networks, cell-cell interactions, tissue microenvironment, and the host macroenvironment represent different levels of the hierarchy. Immunity or tolerance can then be represented as a complex function of each of these hierarchies.
Symptoms of posttraumatic stress disorder in a clinical sample of refugees: a network analysis

PubMed Central

Spiller, Tobias R.; Schick, Matthis; Schnyder, Ulrich; Bryant, Richard A.; Nickerson, Angela; Morina, Naser

2017-01-01

ABSTRACT Background: Network analysis is an emerging methodology for investigating psychopathological symptoms. Given the unprecedented number of refugees and the increased prevalence of mental disorders such as posttraumatic stress disorder (PTSD) in this population, new methodologies that help us better to understand psychopathology in refugees are crucial. Objective: The objective of this study was to explore the network structure and centrality indices of DSM-5 PTSD symptoms in a cross-sectional clinical sample of 151 severely traumatized refugees with and without a formal PTSD diagnosis. Method: The R-packages qgraph and bootnet were used to estimate the structure of a PTSD symptom network and its centrality indices. In addition, robustness and significance analyses for the edges weights and the order of centrality were performed. Results: Three pairs of symptoms showed significantly stronger connections than at least half of the other connections: hypervigilance and exaggerated startle response, intrusion and difficulties falling asleep, and irritability or outbursts of anger and self-destructive or reckless behaviour. Emotional cue reactivity had the highest centrality and trauma-related amnesia the lowest. Conclusion: Although only 51.0% of participants fulfilled criteria for a probable PTSD diagnosis, emotional cue reactivity showed the highest centrality, emphasizing the importance of emotional trauma reminders in severely traumatized refugees attending an outpatient clinic. However, due to the small sample size, the results should be interpreted with care. PMID:29038688
Post-traumatic stress avoidance is attenuated by corticosterone and associated with brain levels of steroid receptor co-activator-1 in rats.

PubMed

Whitaker, Annie M; Farooq, Muhammad A; Edwards, Scott; Gilpin, Nicholas W

2016-01-01

Individuals with post-traumatic stress disorder (PTSD) avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal (HPA) axis activation at the time of stress. Our rodent model of stress mimics the avoidance symptom cluster of PTSD. Rats are classified as "Avoiders" or "Non-Avoiders" post-stress based on the avoidance of a predator-odor paired context. Previously, we found Avoiders exhibit an attenuated HPA stress response to predator odor. We hypothesized that corticosterone administration before stress would reduce the magnitude and incidence of stress-paired context avoidance. Furthermore, we also predicted that Avoiders would exhibit altered expression of glucocorticoid receptor (GR) signaling machinery elements, including steroid receptor co-activator (SRC)-1. Male Wistar rats (n = 16) were pretreated with corticosterone (25 mg/kg) or saline and exposed to predator-odor stress paired with a context and tested for avoidance 24 h later. A second group of corticosterone-naïve rats (n = 24) were stressed (or not), indexed for avoidance 24 h later, and killed 48 h post-odor exposure to measure phosphorylated GR, FKBP51 and SRC-1 levels in the paraventricular nucleus (PVN), central amygdala (CeA) and ventral hippocampus (VH), all brain sites that highly express GRs and regulate HPA function. Corticosterone pretreatment reduced the magnitude and incidence of avoidance. In Avoiders, predator-odor exposure led to lower SRC-1 expression in the PVN and CeA, and higher SRC-1 expression in the VH. SRC-1 expression in PVN, CeA and VH was predicted by prior avoidance behavior. Hence, a blunted HPA stress response may contribute to stress-induced neuroadaptations in central SRC-1 levels and behavioral dysfunction in Avoider rats.
Oxidative Stress Induces Disruption of the Axon Initial Segment

PubMed Central

Clark, Kareem C.; Sword, Brooke A.; Dupree, Jeffrey L.

2017-01-01

The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear. Here, we demonstrate that oxidative stress, as induced through treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator, drives a reversible loss of AIS protein clustering in primary cortical neurons in vitro. Pharmacological inhibition of both voltage-dependent and intracellular calcium (Ca2+) channels suggests that this mechanism of AIS disruption involves Ca2+ entry specifically through L-type voltage-dependent Ca2+ channels and its release from IP3-gated intracellular stores. Furthermore, ROS/RNS-induced AIS disruption is dependent upon activation of calpain, a Ca2+-activated protease previously shown to drive AIS modulation. Overall, we demonstrate for the first time that oxidative stress, as induced through exogenously applied ROS/RNS, is capable of driving structural alterations in the AIS complex. PMID:29228786
WRKY transcription factors in plant responses to stresses.

PubMed

Jiang, Jingjing; Ma, Shenghui; Ye, Nenghui; Jiang, Ming; Cao, Jiashu; Zhang, Jianhua

2017-02-01

The WRKY gene family is among the largest families of transcription factors (TFs) in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress. Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mechanisms. However, very little summarization has been done to review their research progress. Not just important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senescence, development, and secondary metabolites synthesis. WRKY proteins can bind to W-box (TGACC (A/T)) in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses. © 2016 Institute of Botany, Chinese Academy of Sciences.
Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465
Mutual antagonism of target of rapamycin and calcineurin signaling.

PubMed

Mulet, Jose M; Martin, Dietmar E; Loewith, Robbie; Hall, Michael N

2006-11-03

Growth and stress are generally incompatible states. Stressed cells adapt to an insult by restraining growth, and conversely, growing cells keep stress responses at bay. This is evident in many physiological settings, including for example, the effect of stress on the immune or nervous system, but the underlying signaling mechanisms mediating such mutual antagonism are poorly understood. In eukaryotes, a central activator of cell growth is the protein kinase target of rapamycin (TOR) and its namesake signaling network. Calcineurin is a conserved, Ca(2+)/calmodulin-dependent protein phosphatase and target of the immunosuppressant FK506 (tacrolimus) that is activated in yeast during stress to promote cell survival. Here we show yeast mutants defective for TOR complex 2 (TORC2) or the essential homologous TORC2 effectors, SLM1 and SLM2, exhibited constitutive activation of calcineurin-dependent transcription and actin depolarization. Conversely, cells defective in calcineurin exhibited SLM1 hyperphosphorylation and enhanced interaction between TORC2 and SLM1. Furthermore, a mutant SLM1 protein (SLM1(DeltaC14)) lacking a sequence related to the consensus calcineurin docking site (PxIxIT) was insensitive to calcineurin, and SLM1(Delta)(C14) slm2 mutant cells were hypersensitive to oxidative stress. Thus, TORC2-SLM signaling negatively regulates calcineurin, and calcineurin negatively regulates TORC2-SLM. These findings provide a molecular basis for the mutual antagonism of growth and stress.
Adaptogens stimulate neuropeptide y and hsp72 expression and release in neuroglia cells.

PubMed

Panossian, Alexander; Wikman, Georg; Kaur, Punit; Asea, Alexzander

2012-01-01

The beneficial stress-protective effect of adaptogens is related to the regulation of homeostasis via mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of the stress response, such as molecular chaperones, stress-activated c-Jun N-terminal protein kinase, forkhead box O transcription factor, cortisol, and nitric oxide (NO). However, it still remains unclear what the primary upstream targets are in response to stimulation by adaptogens. The present study addresses this gap in our knowledge and suggests that an important target for adaptogen mediated stress-protective effector functions is the stress hormone neuropeptide Y (NPY). We demonstrated that ADAPT-232, a fixed combination of adaptogens Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract SHR-5, and its active constituent salidroside, stimulated the expression of NPY and 72 kDa heat shock protein (Hsp72) in isolated human neuroglia cells. The central role of NPY was validated in experiments in which pre-treatment of human neuroglia cells with NPY-siRNA and HSF1-siRNA resulted in the significant suppression of ADAPT-232-induced NPY and Hsp72 release. Taken together our studies suggest that the stimulation and release of the stress hormones, NPY and Hsp72, into systemic circulation is an innate defense response against mild stressors (ADAPT-232), which increase tolerance and adaptation to stress.
Redox Regulation and the Autistic Spectrum: Role of Tryptophan Catabolites, Immuno-inflammation, Autoimmunity and the Amygdala

PubMed Central

Anderson, George; Maes, Michael

2014-01-01

The autistic spectrum disorders (ASD) form a set of multi-faceted disorders with significant genetic, epigenetic and environmental determinants. Oxidative and nitrosative stress (O&NS), immuno-inflammatory pathways, mitochondrial dysfunction and dysregulation of the tryptophan catabolite (TRYCATs) pathway play significant interactive roles in driving the early developmental etiology and course of ASD. O&NS interactions with immuno-inflammatory pathways mediate their effects centrally via the regulation of astrocyte and microglia responses, including regional variations in TRYCATs produced. Here we review the nature of these interactions and propose an early developmental model whereby different ASD genetic susceptibilities interact with environmental and epigenetic processes, resulting in glia biasing the patterning of central interarea interactions. A role for decreased local melatonin and N-acetylserotonin production by immune and glia cells may be a significant treatment target. PMID:24669209

Alkaline stress and iron deficiency regulate iron uptake and riboflavin synthesis gene expression differently in root and leaf tissue: implications for iron deficiency chlorosis

PubMed Central

Hsieh, En-Jung; Waters, Brian M.

2016-01-01

Iron (Fe) is an essential mineral that has low solubility in alkaline soils, where its deficiency results in chlorosis. Whether low Fe supply and alkaline pH stress are equivalent is unclear, as they have not been treated as separate variables in molecular physiological studies. Additionally, molecular responses to these stresses have not been studied in leaf and root tissues simultaneously. We tested how plants with the Strategy I Fe uptake system respond to Fe deficiency at mildly acidic and alkaline pH by measuring root ferric chelate reductase (FCR) activity and expression of selected Fe uptake genes and riboflavin synthesis genes. Alkaline pH increased cucumber (Cucumis sativus L.) root FCR activity at full Fe supply, but alkaline stress abolished FCR response to low Fe supply. Alkaline pH or low Fe supply resulted in increased expression of Fe uptake genes, but riboflavin synthesis genes responded to Fe deficiency but not alkalinity. Iron deficiency increased expression of some common genes in roots and leaves, but alkaline stress blocked up-regulation of these genes in Fe-deficient leaves. In roots of the melon (Cucumis melo L.) fefe mutant, in which Fe uptake responses are blocked upstream of Fe uptake genes, alkaline stress or Fe deficiency up-regulation of certain Fe uptake and riboflavin synthesis genes was inhibited, indicating a central role for the FeFe protein. These results suggest a model implicating shoot-to-root signaling of Fe status to induce Fe uptake gene expression in roots. PMID:27605716
Temperature and carbon assimilation regulate the chlorosome biogenesis in green sulfur bacteria.

PubMed

Tang, Joseph Kuo-Hsiang; Saikin, Semion K; Pingali, Sai Venkatesh; Enriquez, Miriam M; Huh, Joonsuk; Frank, Harry A; Urban, Volker S; Aspuru-Guzik, Alán

2013-09-17

Green photosynthetic bacteria adjust the structure and functionality of the chlorosome-the light-absorbing antenna complex-in response to environmental stress factors. The chlorosome is a natural self-assembled aggregate of bacteriochlorophyll (BChl) molecules. In this study, we report the regulation of the biogenesis of the Chlorobaculum tepidum chlorosome by carbon assimilation in conjunction with temperature changes. Our studies indicate that the carbon source and thermal stress culture of C. tepidum grows slower and incorporates fewer BChl c in the chlorosome. Compared with the chlorosome from other cultural conditions we investigated, the chlorosome from the carbon source and thermal stress culture displays (a) smaller cross-sectional radius and overall size, (b) simplified BChl c homologs with smaller side chains, (c) blue-shifted Qy absorption maxima, and (d) a sigmoid-shaped circular dichroism spectra. Using a theoretical model, we analyze how the observed spectral modifications can be associated with structural changes of BChl aggregates inside the chlorosome. Our report suggests a mechanism of metabolic regulation for chlorosome biogenesis. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Catecholaminergic systems in stress: structural and molecular genetic approaches.

PubMed

Kvetnansky, Richard; Sabban, Esther L; Palkovits, Miklos

2009-04-01

Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct stressful stimuli.
Regulation of the mammalian heat shock factor 1.

PubMed

Dayalan Naidu, Sharadha; Dinkova-Kostova, Albena T

2017-06-01

Living organisms are endowed with the capability to tackle various forms of cellular stress due to the presence of molecular chaperone machinery complexes that are ubiquitous throughout the cell. During conditions of proteotoxic stress, the transcription factor heat shock factor 1 (HSF1) mediates the elevation of heat shock proteins, which are crucial components of the chaperone complex machinery and function to ameliorate protein misfolding and aggregation and restore protein homeostasis. In addition, HSF1 orchestrates a versatile transcriptional programme that includes genes involved in repair and clearance of damaged macromolecules and maintenance of cell structure and metabolism, and provides protection against a broad range of cellular stress mediators, beyond heat shock. Here, we discuss the structure and function of the mammalian HSF1 and its regulation by post-translational modifications (phosphorylation, sumoylation and acetylation), proteasomal degradation, and small-molecule activators and inhibitors. © 2017 Federation of European Biochemical Societies.
The Eukaryote-Like Serine/Threonine Kinase STK Regulates the Growth and Metabolism of Zoonotic Streptococcus suis

PubMed Central

Zhang, Chunyan; Sun, Wen; Tan, Meifang; Dong, Mengmeng; Liu, Wanquan; Gao, Ting; Li, Lu; Xu, Zhuofei; Zhou, Rui

2017-01-01

Like eukaryotes, bacteria express one or more serine/threonine kinases (STKs) that initiate diverse signaling networks. The STK from Streptococcus suis is encoded by a single-copy stk gene, which is crucial in stress response and virulence. To further understand the regulatory mechanism of STK in S. suis, a stk deletion strain (Δstk) and its complementary strain (CΔstk) were constructed to systematically decode STK characteristics by applying whole transcriptome RNA sequencing (RNA-Seq) and phosphoproteomic analysis. Numerous genes were differentially expressed in Δstk compared with the wild-type parental strain SC-19, including 320 up-regulated and 219 down-regulated genes. Particularly, 32 virulence-associated genes (VAGs) were significantly down-regulated in Δstk. Seven metabolic pathways relevant to bacterial central metabolism and translation are significantly repressed in Δstk. Phosphoproteomic analysis further identified 12 phosphoproteins that exhibit differential phosphorylation in Δstk. These proteins are associated with cell growth and division, glycolysis, and translation. Consistently, phenotypic assays confirmed that the Δstk strain displayed deficient growth and attenuated pathogenicity. Thus, STK is a central regulator that plays an important role in cell growth and division, as well as S. suis metabolism. PMID:28326294
DOE Office of Scientific and Technical Information (OSTI.GOV)

Henning, C.

This report contains papers on the following topics: conceptual design; radiation damage of ITER magnet systems; insulation system of the magnets; critical current density and strain sensitivity; toroidal field coil structural analysis; stress analysis for the ITER central solenoid; and volt-second capabilities and PF magnet configurations.
Structures of the Porphyromonas gingivalis OxyR regulatory domain explain differences in expression of the OxyR regulon in Escherichia coli and P. gingivalis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Svintradze, David V.; Virginia Commonwealth University, Richmond, VA 23219-1540; Peterson, Darrell L.

Differences in OxyR regulated expression of oxidative stress genes between Escherichia coli and Porphyromonas gingivalis are explained by very minor differences in structure and amino-acid sequence of the respective oxidized and reduced OxyR regulatory domains. These differences affect OxyR quaternary structures and are predicted from model building of full length OxyR–DNA complexes to confer distinct modes of DNA binding on this transcriptional regulator. OxyR transcriptionally regulates Escherichia coli oxidative stress response genes through a reversibly reducible cysteine disulfide biosensor of cellular redox status. Structural changes induced by redox changes in these cysteines are conformationally transmitted to the dimer subunit interfaces,more » which alters dimer and tetramer interactions with DNA. In contrast to E. coli OxyR regulatory-domain structures, crystal structures of Porphyromonas gingivalis OxyR regulatory domains show minimal differences in dimer configuration on changes in cysteine disulfide redox status. This locked configuration of the P. gingivalis OxyR regulatory-domain dimer closely resembles the oxidized (activating) form of the E. coli OxyR regulatory-domain dimer. It correlates with the observed constitutive activation of some oxidative stress genes in P. gingivalis and is attributable to a single amino-acid insertion in P. gingivalis OxyR relative to E. coli OxyR. Modelling of full-length P. gingivalis, E. coli and Neisseria meningitidis OxyR–DNA complexes predicts different modes of DNA binding for the reduced and oxidized forms of each.« less
Subcellular and supracellular mechanical stress prescribes cytoskeleton behavior in Arabidopsis cotyledon pavement cells

PubMed Central

Sampathkumar, Arun; Krupinski, Pawel; Wightman, Raymond; Milani, Pascale; Berquand, Alexandre; Boudaoud, Arezki; Hamant, Olivier; Jönsson, Henrik; Meyerowitz, Elliot M

2014-01-01

Although it is a central question in biology, how cell shape controls intracellular dynamics largely remains an open question. Here, we show that the shape of Arabidopsis pavement cells creates a stress pattern that controls microtubule orientation, which then guides cell wall reinforcement. Live-imaging, combined with modeling of cell mechanics, shows that microtubules align along the maximal tensile stress direction within the cells, and atomic force microscopy demonstrates that this leads to reinforcement of the cell wall parallel to the microtubules. This feedback loop is regulated: cell-shape derived stresses could be overridden by imposed tissue level stresses, showing how competition between subcellular and supracellular cues control microtubule behavior. Furthermore, at the microtubule level, we identified an amplification mechanism in which mechanical stress promotes the microtubule response to stress by increasing severing activity. These multiscale feedbacks likely contribute to the robustness of microtubule behavior in plant epidermis. DOI: http://dx.doi.org/10.7554/eLife.01967.001 PMID:24740969
Early Life Stress Effects on Glucocorticoid—BDNF Interplay in the Hippocampus

PubMed Central

Daskalakis, Nikolaos P.; De Kloet, Edo Ronald; Yehuda, Rachel; Malaspina, Dolores; Kranz, Thorsten M.

2015-01-01

Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and GC-signaling pathways co-exist throughout the central nervous system (CNS), particularly in the hippocampus, which has high expression levels of glucocorticoid-receptors (GR) and mineralocorticoid-receptors (MR) as well as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders. PMID:26635521
Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder.

PubMed

Lin, Chen-Cheng; Tung, Che-Se; Lin, Pin-Hsuan; Huang, Chuen-Lin; Liu, Yia-Ping

2016-09-01

Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.
30 CFR 250.609 - Well-workover structures on fixed platforms.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false Well-workover structures on fixed platforms. 250.609 Section 250.609 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND..., and previous stresses to the platform. ...
Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins

PubMed Central

Kang, Hyeog; Oka, Shinichi; Lee, Duck-Yeon; Park, Junhong; Aponte, Angel M.; Jung, Young-Sang; Bitterman, Jacob; Zhai, Peiyong; He, Yi; Kooshapur, Hamed; Ghirlando, Rodolfo; Tjandra, Nico; Lee, Sean B.; Kim, Myung K.; Sadoshima, Junichi; Chung, Jay H.

2017-01-01

Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD's ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD+, causes a conformational shift to a less compact structure. Mutations that prevent ATP binding increase Sirt1's ability to promote stress resistance and inhibit adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight into how extreme energy deprivation can impact Sirt1 activity and underscore the complex nature of Sirt1 structure and regulation. PMID:28504272
MicroRNA-125b is a novel negative regulator of p53.

PubMed

Le, Minh T N; Teh, Cathleen; Shyh-Chang, Ng; Xie, Huangming; Zhou, Beiyan; Korzh, Vladimir; Lodish, Harvey F; Lim, Bing

2009-04-01

The p53 transcription factor is a key tumor suppressor and a central regulator of the stress response. To ensure a robust and precise response to cellular signals, p53 gene expression must be tightly regulated from the transcriptional to the post-translational levels. Computational predictions suggest that several microRNAs are involved in the post-transcriptional regulation of p53. Here we demonstrate that miR-125b, a brain-enriched microRNA, is a bona fide negative regulator of p53 in both zebrafish and humans. miR-125b-mediated down-regulation of p53 is strictly dependent on the binding of miR-125b to a microRNA response element in the 3' untranslated region of p53 mRNA. Overexpression of miR-125b represses the endogenous level of p53 protein and suppresses apoptosis in human neuroblastoma cells and human lung fibroblast cells. In contrast, knockdown of miR-125b elevates the level of p53 protein and induces apoptosis in human lung fibroblasts and in the zebrafish brain. This phenotype can be rescued significantly by either an ablation of endogenous p53 function or ectopic expression of miR-125b in zebrafish. Interestingly, miR-125b is down-regulated when zebrafish embryos are treated with gamma-irradiation or camptothecin, corresponding to the rapid increase in p53 protein in response to DNA damage. Ectopic expression of miR-125b suppresses the increase of p53 and stress-induced apoptosis. Together, our study demonstrates that miR-125b is an important negative regulator of p53 and p53-induced apoptosis during development and during the stress response.
MicroRNA-125b is a novel negative regulator of p53

PubMed Central

Le, Minh T.N.; Teh, Cathleen; Shyh-Chang, Ng; Xie, Huangming; Zhou, Beiyan; Korzh, Vladimir; Lodish, Harvey F.; Lim, Bing

2009-01-01

The p53 transcription factor is a key tumor suppressor and a central regulator of the stress response. To ensure a robust and precise response to cellular signals, p53 gene expression must be tightly regulated from the transcriptional to the post-translational levels. Computational predictions suggest that several microRNAs are involved in the post-transcriptional regulation of p53. Here we demonstrate that miR-125b, a brain-enriched microRNA, is a bona fide negative regulator of p53 in both zebrafish and humans. miR-125b-mediated down-regulation of p53 is strictly dependent on the binding of miR-125b to a microRNA response element in the 3′ untranslated region of p53 mRNA. Overexpression of miR-125b represses the endogenous level of p53 protein and suppresses apoptosis in human neuroblastoma cells and human lung fibroblast cells. In contrast, knockdown of miR-125b elevates the level of p53 protein and induces apoptosis in human lung fibroblasts and in the zebrafish brain. This phenotype can be rescued significantly by either an ablation of endogenous p53 function or ectopic expression of miR-125b in zebrafish. Interestingly, miR-125b is down-regulated when zebrafish embryos are treated with γ-irradiation or camptothecin, corresponding to the rapid increase in p53 protein in response to DNA damage. Ectopic expression of miR-125b suppresses the increase of p53 and stress-induced apoptosis. Together, our study demonstrates that miR-125b is an important negative regulator of p53 and p53-induced apoptosis during development and during the stress response. PMID:19293287
Structural fabrics, mineralization and Lamaride kinematics of the Idaho Springs-Ralston shear zone, Colorado mineral belt and central Front Range uplift

USGS Publications Warehouse

Caine, Jonathan S.; Nelson, E.P.; Beach, S.T.; Layer, P.W.

2006-01-01

The Idaho Springs and Central City mining districts form the central portion of a structurally controlled hydrothermal precious- and base-metal vein system in the Front Range of the northeast-trending Colorado Mineral Belt. Three new 40Ar/39Ar plateau ages on hydrothermal sericite indicate the veins formed during the Laramide orogeny between 65.4??1.5 - 61.9??1.3 Ma. We compile structural geologic data from surface geological maps, subsurface mine maps, and theses for analysis using modern graphical methods and integration into models of formation of economic mineral deposits. Structural data sets, produced in the 1950s and 1960s by the U.S. Geological Survey, are compiled for fabric elements, including metamorphic foliations, fold axial trends, major brittle fault zones, quartz and precious- and base-metal veins and fault veins, Tertiary dikes, and joints. These fabric elements are plotted on equal-area projections and analyzed for mean fabric orientations. Strike-slip fault-vein sets are mostly parallel or sub-parallel, and not conjugate as interpreted by previous work; late-stage, normal-slip fault veins possibly show a pattern indicative of triaxial strain. Fault-slip kinematic analysis was used to model the trend of the Laramide maximum horizontal stress axis, or compression direction, and to determine compatibility of opening and shear motions within a single stress field. The combined-model maximum compression direction for all strike slip fault veins is ???068??, which is consistent with published Laramide compression directions of ???064?? (mean of 23 regional models) and ???072?? for the Front Range uplift. The orientations of fabric elements were analyzed for mechanical and kinematic compatibility with opening, and thus permeability enhancement, in the modeled regional east-northeast, Laramide compression direction. The fabric orientation analysis and paleostress modeling show that structural permeability during mineralization was enhanced along pre-existing metamorphic foliations and fold axial planes. Large orientation dispersion in most fabric elements likely caused myriad potential pathways for permeability. The dominant orientations of opening and shear mode structures are consistent with a sub-parallel network of structures that formed in the Laramide east-northeast compression direction. The results presented demonstrate the importance of using mechanical and kinematic theory integrated with contemporary ideas of permeability structure to better understand the coupled nature of fluid flow, mineral deposition, stress, and strain. Further, the results demonstrate that there is significant internal strain within this basement-cored uplift that was localized by optimally oriented pre-existing structures in a regional stress field.
[Hygiene requirements for the level of intellectual intensivity loads in foreign language learning].

PubMed

Ivashchenko, S N

2013-01-01

The material of this article provides information about the basics of hygiene conditions and nature of intellectual loads of students of secondary schools in the perception of information in a foreign language. Are the most favorable conditions for the successful training of perception and assimilation of information supplied in the course of the learning process in one foreign language or some more different ones? It was found that the process of perception and assimilation of educational information in foreign languages is associated with some degree of mental and emotional stress of students. At the same time, the effectiveness of the learning process depends on the degree of stress. Certain parameters of the psychological and emotional stress students usually have a stimulating effect on their central nervous system. Another level, the psychological and emotional stress of students on the contrary, causes a braking effect of functional activity of the relevant structures of the central nervous system of students and reduces the effectiveness of training.
Differential abundance of muscle proteome in cultured channel catfish (Ictalurus punctatus) subjected to ante-mortem stressors and its impact on fillet quality.

PubMed

Ciaramella, Michael A; Nair, Mahesh N; Suman, Surendranath P; Allen, Peter J; Schilling, M Wes

2016-12-01

The effects of environmental and handling stress during catfish (Ictalurus punctatus) aquaculture were evaluated to identify the biochemical alterations they induce in the muscle proteome and their impacts on fillet quality. Temperature (25°C and 33°C) and oxygen (~2.5mg/L [L] and >5mg/L [H]) were manipulated followed by sequential socking (S) and transport (T) stress to evaluate changes in quality when fish were subjected to handling (25-H-ST; temperature-oxygen-handling), oxygen stress (25-L-ST), temperature stress (33-H-ST) and severe stress (33-L-ST). Instrumental color and texture of fillets were evaluated, and muscle proteome profile was analyzed. Fillet redness, yellowness and chroma decreased, and hue angle increased in all treatments except temperature stress (33-H-ST). Alterations in texture compared to controls were observed when oxygen levels were held high. In general, changes in the abundance of structural proteins and those involved in protein regulation and energy metabolism were identified. Rearing under hypoxic conditions demonstrated a shift in metabolism to ketogenic pathways and a suppression of the stress-induced changes as the severity of the stress increased. Increased proteolytic activity observed through the down-regulation of various structural proteins could be responsible for the alterations in color and texture. Published by Elsevier Inc.
Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress

PubMed Central

Licznerski, Pawel; Duric, Vanja; Banasr, Mounira; Alavian, Kambiz N.; Ota, Kristie T.; Kang, Hyo Jung; Jonas, Elizabeth A.; Ursano, Robert; Krystal, John H.; Duman, Ronald S.

2015-01-01

Exposure to extreme stress can trigger the development of major depressive disorder (MDD) as well as post-traumatic stress disorder (PTSD). The molecular mechanisms underlying the structural and functional alterations within corticolimbic brain regions, including the prefrontal cortex (PFC) and amygdala of individuals subjected to traumatic stress, remain unknown. In this study, we show that serum and glucocorticoid regulated kinase 1 (SGK1) expression is down-regulated in the postmortem PFC of PTSD subjects. Furthermore, we demonstrate that inhibition of SGK1 in the rat medial PFC results in helplessness- and anhedonic-like behaviors in rodent models. These behavioral changes are accompanied by abnormal dendritic spine morphology and synaptic dysfunction. Together, the results are consistent with the possibility that altered SGK1 signaling contributes to the behavioral and morphological phenotypes associated with traumatic stress pathophysiology. PMID:26506154
A multi-process model of self-regulation: influences of mindfulness, integrative self-knowledge and self-control in Iran.

PubMed

Ghorbani, Nima; Watson, P J; Farhadi, Mehran; Chen, Zhuo

2014-04-01

Self-regulation presumably rests upon multiple processes that include an awareness of ongoing self-experience, enduring self-knowledge and self-control. The present investigation tested this multi-process model using the Five-Facet Mindfulness Questionnaire (FFMQ) and the Integrative Self-Knowledge and Brief Self-Control Scales. Using a sample of 1162 Iranian university students, we confirmed the five-factor structure of the FFMQ in Iran and documented its factorial invariance across males and females. Self-regulatory variables correlated negatively with Perceived Stress, Depression, and Anxiety and positively with Self-Esteem and Satisfaction with Life. Partial mediation effects confirmed that self-regulatory measures ameliorated the disturbing effects of Perceived Stress. Integrative Self-Knowledge and Self-Control interacted to partially mediate the association of Perceived Stress with lower levels of Satisfaction with Life. Integrative Self-Knowledge, alone or in interaction with Self-Control, was the only self-regulation variable to display the expected mediation of Perceived Stress associations with all other measures. Self-Control failed to be implicated in self-regulation only in the mediation of Anxiety. These data confirmed the need to further examine this multi-process model of self-regulation. © 2014 International Union of Psychological Science.
Conserved ABC Transport System Regulated by the General Stress Response Pathways of Alpha- and Gammaproteobacteria.

PubMed

Herrou, Julien; Willett, Jonathan W; Czyż, Daniel M; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean

2017-03-01

Brucella abortus σ E1 is an EcfG family sigma factor that regulates the transcription of dozens of genes in response to diverse stress conditions and is required for maintenance of chronic infection in a mouse model. A putative ATP-binding cassette transporter operon, bab1_0223-bab1_0226 , is among the most highly activated gene sets in the σ E1 regulon. The proteins encoded by the operon resemble quaternary ammonium-compatible solute importers but are most similar in sequence to the broadly conserved YehZYXW system, which remains largely uncharacterized. Transcription of yehZYXW is activated by the general stress sigma factor σ S in Enterobacteriaceae , which suggests a functional role for this transport system in bacterial stress response across the classes Alphaproteobacteria and Gammaproteobacteria We present evidence that B. abortus YehZYXW does not function as an importer of known compatible solutes under physiological conditions and does not contribute to the virulence defect of a σ E1 -null strain. The sole in vitro phenotype associated with genetic disruption of this putative transport system is reduced growth in the presence of high Li + ion concentrations. A crystal structure of B. abortus YehZ revealed a class II periplasmic binding protein fold with significant structural homology to Archaeoglobus fulgidus ProX, which binds glycine betaine. However, the structure of the YehZ ligand-binding pocket is incompatible with high-affinity binding to glycine betaine. This is consistent with weak measured binding of YehZ to glycine betaine and related compatible solutes. We conclude that YehZYXW is a conserved, stress-regulated transport system that is phylogenetically and functionally distinct from quaternary ammonium-compatible solute importers. IMPORTANCE Brucella abortus σ E1 regulates transcription in response to stressors encountered in its mammalian host and is necessary for maintenance of chronic infection in a mouse model. The functions of the majority of genes regulated by σ E1 remain undefined. We present a functional/structural analysis of a conserved putative membrane transport system (YehZYXW) whose expression is strongly activated by σ E1 Though annotated as a quaternary ammonium osmolyte uptake system, experimental physiological studies and measured ligand-binding properties of the periplasmic binding protein (PBP), YehZ, are inconsistent with this function. A crystal structure of B. abortus YehZ provides molecular insight into differences between bona fide quaternary ammonium osmolyte importers and YehZ-related proteins, which form a distinct phylogenetic and functional group of PBPs. Copyright © 2017 American Society for Microbiology.

Conserved ABC Transport System Regulated by the General Stress Response Pathways of Alpha- and Gammaproteobacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrou, Julien; Willett, Jonathan W.; Czyż, Daniel M.

ABSTRACT Brucella abortusσ E1is an EcfG family sigma factor that regulates the transcription of dozens of genes in response to diverse stress conditions and is required for maintenance of chronic infection in a mouse model. A putative ATP-binding cassette transporter operon,bab1_0223-bab1_0226, is among the most highly activated gene sets in the σ E1regulon. The proteins encoded by the operon resemble quaternary ammonium-compatible solute importers but are most similar in sequence to the broadly conserved YehZYXW system, which remains largely uncharacterized. Transcription ofyehZYXWis activated by the general stress sigma factor σ SinEnterobacteriaceae, which suggests a functional role for this transport systemmore » in bacterial stress response across the classesAlphaproteobacteriaandGammaproteobacteria. We present evidence thatB. abortusYehZYXW does not function as an importer of known compatible solutes under physiological conditions and does not contribute to the virulence defect of a σ E1-null strain. The solein vitrophenotype associated with genetic disruption of this putative transport system is reduced growth in the presence of high Li +ion concentrations. A crystal structure ofB. abortusYehZ revealed a class II periplasmic binding protein fold with significant structural homology toArchaeoglobus fulgidusProX, which binds glycine betaine. However, the structure of the YehZ ligand-binding pocket is incompatible with high-affinity binding to glycine betaine. This is consistent with weak measured binding of YehZ to glycine betaine and related compatible solutes. We conclude that YehZYXW is a conserved, stress-regulated transport system that is phylogenetically and functionally distinct from quaternary ammonium-compatible solute importers. IMPORTANCEBrucella abortusσ E1regulates transcription in response to stressors encountered in its mammalian host and is necessary for maintenance of chronic infection in a mouse model. The functions of the majority of genes regulated by σ E1remain undefined. We present a functional/structural analysis of a conserved putative membrane transport system (YehZYXW) whose expression is strongly activated by σ E1. Though annotated as a quaternary ammonium osmolyte uptake system, experimental physiological studies and measured ligand-binding properties of the periplasmic binding protein (PBP), YehZ, are inconsistent with this function. A crystal structure ofB. abortusYehZ provides molecular insight into differences between bona fide quaternary ammonium osmolyte importers and YehZ-related proteins, which form a distinct phylogenetic and functional group of PBPs.« less
Abscisic Acid Flux Alterations Result in Differential Abscisic Acid Signaling Responses and Impact Assimilation Efficiency in Barley under Terminal Drought Stress1[C][W][OPEN

PubMed Central

Seiler, Christiane; Harshavardhan, Vokkaliga T.; Reddy, Palakolanu S.; Hensel, Götz; Kumlehn, Jochen; Eschen-Lippold, Lennart; Rajesh, Kalladan; Korzun, Viktor; Wobus, Ulrich; Lee, Justin; Selvaraj, Gopalan; Sreenivasulu, Nese

2014-01-01

Abscisic acid (ABA) is a central player in plant responses to drought stress. How variable levels of ABA under short-term versus long-term drought stress impact assimilation and growth in crops is unclear. We addressed this through comparative analysis, using two elite breeding lines of barley (Hordeum vulgare) that show senescence or stay-green phenotype under terminal drought stress and by making use of transgenic barley lines that express Arabidopsis (Arabidopsis thaliana) 9-cis-epoxycarotenoid dioxygenase (AtNCED6) coding sequence or an RNA interference (RNAi) sequence of ABA 8′-hydroxylase under the control of a drought-inducible barley promoter. The high levels of ABA and its catabolites in the senescing breeding line under long-term stress were detrimental for assimilate productivity, whereas these levels were not perturbed in the stay-green type that performed better. In transgenic barley, drought-inducible AtNCED expression afforded temporal control in ABA levels such that the ABA levels rose sooner than in wild-type plants but also subsided, unlike as in the wild type , to near-basal levels upon prolonged stress treatment due to down-regulation of endogenous HvNCED genes. Suppressing of ABA catabolism with the RNA interference approach of ABA 8′-hydroxylase caused ABA flux during the entire period of stress. These transgenic plants performed better than the wild type under stress to maintain a favorable instantaneous water use efficiency and better assimilation. Gene expression analysis, protein structural modeling, and protein-protein interaction analyses of the members of the PYRABACTIN RESISTANCE1/PYRABACTIN RESISTANCE1-LIKE/REGULATORY COMPONENT OF ABA RECEPTORS, TYPE 2C PROTEIN PHOSPHATASE Sucrose non-fermenting1-related protein kinase2, and ABA-INSENSITIVE5/ABA-responsive element binding factor family identified specific members that could potentially impact ABA metabolism and stress adaptation in barley. PMID:24610749
Involvement of α(2)-adrenergic receptor in the regulation of the blood glucose level induced by immobilization stress.

PubMed

Kang, Yu-Jung; Sim, Yun-Beom; Park, Soo-Hyun; Sharma, Naveen; Suh, Hong-Won

2015-01-01

The blood glucose profiles were characterized after mice were forced into immobilization stress with various exposure durations. The blood glucose level was significantly enhanced by immobilization stress for 30 min or 1 h, respectively. On the other hand, the blood glucose level was not affected in the groups which were forced into immobilization stress for 2 or 4 h. We further examined the effect of yohimbine (an α2-adrenergic receptor antagonist) administered systemically or centrally in the immobilization stress model. Mice were pretreated intraperitoneally (i.p.; from 0.5 to 5 mg/kg), intracerebroventricularly (i.c.v.; from 1 to 10 µg/5 µl), or intrathecally (i.t.; from 1 to 10 µg/5 µl) with yohimbine for 10 min and then, forced into immobilization stress for 30 min. The blood glucose level was measured right after immobilization stress. We found that up-regulation of the blood glucose level induced by immobilization stress was abolished by i.p. pretreatment with yohimbine. And the immobilization stress-induced blood glucose level was not inhibited by i.c.v. or i.t. pretreatment with yohimbine at a lower dose (1 µg/5 µl). However, immobilization stress-induced blood glucose level was significantly inhibited by i.c.v. or i.t. pretreatment with yohimbine at higher doses (5 and 10 µg/5 µl). In addition, the i.p. (5 mg/kg), i.c.v. (10 µg/5 µl), or i.t. (10 µg/5 µl) pretreatment with yohimbine reduced hypothalamic glucose transporter 4 expression. The involvement of α2-adrenergic receptor in regulation of immobilization stress- induced blood glucose level was further confirmed by the i.p, i.c.v, or i.t pretreatment with idazoxan, another specific α2-adrenergic receptor antagonist. Finally, i.p., i.c.v., or i.t. pretreatment with yohimbine attenuated the blood glucose level in D-glucose-fed model. We suggest that α2-adrenergic receptors located at the peripheral, the brain and the spinal cord play important roles in the up-regulation of the blood glucose level in immobilization stress.
The nucleolus directly regulates p53 export and degradation.

PubMed

Boyd, Mark T; Vlatkovic, Nikolina; Rubbi, Carlos P

2011-09-05

The correlation between stress-induced nucleolar disruption and abrogation of p53 degradation is evident after a wide variety of cellular stresses. This link may be caused by steps in p53 regulation occurring in nucleoli, as suggested by some biochemical evidence. Alternatively, nucleolar disruption also causes redistribution of nucleolar proteins, potentially altering their interactions with p53 and/or MDM2. This raises the fundamental question of whether the nucleolus controls p53 directly, i.e., as a site where p53 regulatory processes occur, or indirectly, i.e., by determining the cellular localization of p53/MDM2-interacting factors. In this work, transport experiments based on heterokaryons, photobleaching, and micronucleation demonstrate that p53 regulatory events are directly regulated by nucleoli and are dependent on intact nucleolar structure and function. Subcellular fractionation and nucleolar isolation revealed a distribution of ubiquitylated p53 that supports these findings. In addition, our results indicate that p53 is exported by two pathways: one stress sensitive and one stress insensitive, the latter being regulated by activities present in the nucleolus.
Adaptive compliant structures for flow regulation

PubMed Central

Brinkmeyer, Alex; Theunissen, Raf; M. Weaver, Paul; Pirrera, Alberto

2017-01-01

This paper introduces conceptual design principles for a novel class of adaptive structures that provide both flow regulation and control. While of general applicability, these design principles, which revolve around the idea of using the instabilities and elastically nonlinear behaviour of post-buckled panels, are exemplified through a case study: the design of a shape-adaptive air inlet. The inlet comprises a deformable post-buckled member that changes shape depending on the pressure field applied by the surrounding fluid, thereby regulating the inlet aperture. By tailoring the stress field in the post-buckled state and the geometry of the initial, stress-free configuration, the deformable section can snap through to close or open the inlet completely. Owing to its inherent ability to change shape in response to external stimuli—i.e. the aerodynamic loads imposed by different operating conditions—the inlet does not have to rely on linkages and mechanisms for actuation, unlike conventional flow-controlling devices. PMID:28878567
Adaptive compliant structures for flow regulation.

PubMed

Arena, Gaetano; M J Groh, Rainer; Brinkmeyer, Alex; Theunissen, Raf; M Weaver, Paul; Pirrera, Alberto

2017-08-01

This paper introduces conceptual design principles for a novel class of adaptive structures that provide both flow regulation and control. While of general applicability, these design principles, which revolve around the idea of using the instabilities and elastically nonlinear behaviour of post-buckled panels, are exemplified through a case study: the design of a shape-adaptive air inlet. The inlet comprises a deformable post-buckled member that changes shape depending on the pressure field applied by the surrounding fluid, thereby regulating the inlet aperture. By tailoring the stress field in the post-buckled state and the geometry of the initial, stress-free configuration, the deformable section can snap through to close or open the inlet completely. Owing to its inherent ability to change shape in response to external stimuli-i.e. the aerodynamic loads imposed by different operating conditions-the inlet does not have to rely on linkages and mechanisms for actuation, unlike conventional flow-controlling devices.
Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling

PubMed Central

Wang, Xiao-Dong; Chen, Yuncai; Wolf, Miriam; Wagner, Klaus V.; Liebl, Claudia; Scharf, Sebastian H.; Harbich, Daniela; Mayer, Bianca; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Müller, Marianne B.; Schmidt, Mathias V.

2011-01-01

Chronic stress evokes profound structural and molecular changes in the hippocampus, which may underlie spatial memory deficits. Corticotropin-releasing hormone (CRH) and CRH receptor 1 (CRHR1) mediate some of the rapid effects of stress on dendritic spine morphology and modulate learning and memory, thus providing a potential molecular basis for impaired synaptic plasticity and spatial memory by repeated stress exposure. Using adult male mice with CRHR1 conditionally inactivated in the forebrain regions, we investigated the role of CRH-CRHR1 signaling in the effects of chronic social defeat stress on spatial memory, the dendritic morphology of hippocampal CA3 pyramidal neurons, and the hippocampal expression of nectin-3, a synaptic cell adhesion molecule important in synaptic remodeling. In chronically stressed wild-type mice, spatial memory was disrupted, and the complexity of apical dendrites of CA3 neurons reduced. In contrast, stressed mice with forebrain CRHR1 deficiency exhibited normal dendritic morphology of CA3 neurons and mild impairments in spatial memory. Additionally, we showed that the expression of nectin-3 in the CA3 area was regulated by chronic stress in a CRHR1-dependent fashion and associated with spatial memory and dendritic complexity. Moreover, forebrain CRHR1 deficiency prevented the down-regulation of hippocampal glucocorticoid receptor expression by chronic stress but induced increased body weight gain during persistent stress exposure. These findings underscore the important role of forebrain CRH-CRHR1 signaling in modulating chronic stress-induced cognitive, structural and molecular adaptations, with implications for stress-related psychiatric disorders. PMID:21296667
Expression of the Hsp23 chaperone during Drosophila embryogenesis: association to distinct neural and glial lineages

PubMed Central

Michaud, Sébastien; Tanguay, Robert M

2003-01-01

Background In addition to their strong induction following stress, small heat shock proteins (Hsp) are also expressed during development in a wide variety of organisms. However, the precise identity of cell(s) expressing these proteins and the functional contribution of small heat shock proteins in such developmental context remain to be determined. The present study provides a detailed description of the Drosophila small heat shock protein Hsp23 expression pattern during embryogenesis and evaluates its functional contribution to central nervous system development. Results Throughout embryogenesis, Hsp23 is expressed in a stage-specific manner by a restricted number of neuronal and glial lineages of the central nervous system. Hsp23 is also detected in the amnioserosa and within a single lateral chordotonal organ. Its expression within the MP2 lineage does not require the presence of a functional midline nor the activity of the Notch signaling pathway. Transactivation assays demonstrate that transcription factors implicated in the differentiation of the midline also regulate hsp23 promoter activity. Phenotypic analysis of a transgenic line exhibiting loss of Hsp23 expression in the central nervous system suggests that Hsp23 is not required for development and function of this tissue. Likewise, its overexpression does not cause deleterious effects, as development remains unaffected. Conclusions Based on the presented data, we suggest that the tightly regulated developmental expression of Hsp23 is not actively involved in cell differentiation and central nervous system development per se but rather reflects a putative role in preventive "pre-stress" neuroprotection or in non-vital process(es) common to the identified cell lineages. PMID:14617383
Self-regulation and recovery: approaching an understanding of the process of recovery from stress.

PubMed

Beckmann, Jürgen; Kellmann, Michael

2004-12-01

Stress has been studied extensively in psychology. Only recently, however, has research started to address the question of how individuals manage to recover from stress. Recovery from stress is analyzed as a process of self-regulation. Several individual difference variables which affect the efficiency of self-regulation have been integrated into a structured model of the recovery process. Such variables are action versus state orientation (a tendency to ruminate, e.g., about a past experience) and volitional components, such as self-determination, self-motivation, emotion control, rumination, and self-discipline. Some of these components are assumed to promote recovery from stress, whereas others are assumed to further the perseverance of stress. The model was supported by the empirical findings of three independent studies (Study 1, N=58; Study 2, N=221; Study 3, N= 105). Kuhl's Action Control Scale measured action versus state orientation. Volitional components were assessed with Kuhl and Fuhrmann's Volitional Components Questionnaire. The amounts of experienced stress and recovery from stress was assessed with Kellmann and Kallus's Recovery-Stress Questionnaire. As hypothesized in the model, the disposition towards action versus state orientation was a more distant determinant of the recovery from stress and perseverance of stress. The volitional components are more proximal determinants in the recovery process. Action orientation promotes recovery from stress via adequate volitional skills, e.g., self-determination, self-motivation, emotion control, whereas state orientation furthers a perseverance of stress through rumination and self-discipline.
Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity

PubMed Central

Panossian, Alexander; Wikman, Georg

2010-01-01

Adaptogens were initially defined as substances that enhance the “state of non-specific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide. PMID:27713248
The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis

PubMed Central

Knippschild, Uwe; Krüger, Marc; Richter, Julia; Xu, Pengfei; García-Reyes, Balbina; Peifer, Christian; Halekotte, Jakob; Bakulev, Vasiliy; Bischof, Joachim

2014-01-01

Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family play major regulatory roles in many cellular processes including DNA-processing and repair, proliferation, cytoskeleton dynamics, vesicular trafficking, apoptosis, and cell differentiation. As a consequence of cellular stress conditions, interaction of CK1 with the mitotic spindle is manifold increased pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is able to alter the activity of key proteins in signal transduction and signal integration molecules. In line with this notion, CK1 is tightly connected to the regulation and degradation of β-catenin, p53, and MDM2. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions, it is not surprising that mutations and alterations in the expression and/or activity of CK1 isoforms are often detected in various tumor entities including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer, adenocarcinomas of the pancreas, and ovarian cancer. Therefore, scientific effort has enormously increased (i) to understand the regulation of CK1 and its involvement in tumorigenesis- and tumor progression-related signal transduction pathways and (ii) to develop CK1-specific inhibitors for the use in personalized therapy concepts. In this review, we summarize the current knowledge regarding CK1 regulation, function, and interaction with cellular proteins playing central roles in cellular stress-responses and carcinogenesis. PMID:24904820
The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells

PubMed Central

Corre, Isabelle; Paris, François; Huot, Jacques

2017-01-01

By gating the traffic of molecules and cells across the vessel wall, endothelial cells play a central role in regulating cardiovascular functions and systemic homeostasis and in modulating pathophysiological processes such as inflammation and immunity. Accordingly, the loss of endothelial cell integrity is associated with pathological disorders that include atherosclerosis and cancer. The p38 mitogen-activated protein kinase (MAPK) cascades are major signaling pathways that regulate several functions of endothelial cells in response to exogenous and endogenous stimuli including growth factors, stress and cytokines. The p38 MAPK family contains four isoforms p38α, p38β, p38γ and p38δ that are encoded by four different genes. They are all widely expressed although to different levels in almost all human tissues. p38α/MAPK14, that is ubiquitously expressed is the prototype member of the family and is referred here as p38. It regulates the production of inflammatory mediators, and controls cell proliferation, differentiation, migration and survival. Its activation in endothelial cells leads to actin remodeling, angiogenesis, DNA damage response and thereby has major impact on cardiovascular homeostasis, and on cancer progression. In this manuscript, we review the biology of p38 in regulating endothelial functions especially in response to oxidative stress and during the metastatic process. PMID:28903453
Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism.

PubMed

Wende, Adam R; Young, Martin E; Chatham, John; Zhang, Jianhua; Rajasekaran, Namakkal S; Darley-Usmar, Victor M

2016-11-01

Understanding molecular mechanisms that underlie the recent emergence of metabolic diseases such as diabetes and heart failure has revealed the need for a multi-disciplinary research integrating the key metabolic pathways which change the susceptibility to environmental or pathologic stress. At the physiological level these include the circadian control of metabolism which aligns metabolism with temporal demand. The mitochondria play an important role in integrating the redox signals and metabolic flux in response to the changing activities associated with chronobiology, exercise and diet. At the molecular level this involves dynamic post-translational modifications regulating transcription, metabolism and autophagy. In this review we will discuss different examples of mechanisms which link these processes together. An important pathway capable of linking signaling to metabolism is the post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc). This is a nutrient regulated protein modification that plays an important role in impaired cellular stress responses. Circadian clocks have also emerged as critical regulators of numerous cardiometabolic processes, including glucose/lipid homeostasis, hormone secretion, redox status and cardiovascular function. Central to these pathways are the response of autophagy, bioenergetics to oxidative stress, regulated by Keap1/Nrf2 and mechanisms of metabolic control. The extension of these ideas to the emerging concept of bioenergetic health will be discussed. Copyright © 2016 Elsevier Inc. All rights reserved.
Central and peripheral nervous systems: master controllers in cancer metastasis.

PubMed

Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

2013-12-01

Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.
Genetic analysis of Physcomitrella patens identifies ABSCISIC ACID NON-RESPONSIVE, a regulator of ABA responses unique to basal land plants and required for desiccation tolerance

DOE PAGES

Stevenson, Sean Ross; Kamisugi, Yasuko; Trinh, Chi H.; ...

2016-05-18

The anatomically simple plants that first colonized land must have acquired molecular and biochemical adaptations to drought stress. Abscisic acid (ABA) coordinates responses leading to desiccation tolerance in all land plants. We identified ABA nonresponsive mutants in the model bryophyte Physcomitrella patens and genotyped a segregating population to map and identify the ABA NON-RESPONSIVE (ANR) gene encoding a modular protein kinase comprising an N-terminal PAS domain, a central EDR domain, and a C-terminal MAPKKK-like domain. anr mutants fail to accumulate dehydration tolerance-associated gene products in response to drought, ABA, or osmotic stress and do not acquire ABA-dependent desiccation tolerance. Themore » crystal structure of the PAS domain, determined to 1.7-Å resolution, shows a conserved PAS-fold that dimerizes through a weak dimerization interface. Targeted mutagenesis of a conserved tryptophan residue within the PAS domain generates plants with ABA nonresponsive growth and strongly attenuated ABA-responsive gene expression, whereas deleting this domain retains a fully ABA-responsive phenotype. ANR orthologs are found in early-diverging land plant lineages and aquatic algae but are absent from more recently diverged vascular plants. Lastly, we propose that ANR genes represent an ancestral adaptation that enabled drought stress survival of the first terrestrial colonizers but were lost during land plant evolution.« less
Genetic analysis of Physcomitrella patens identifies ABSCISIC ACID NON-RESPONSIVE, a regulator of ABA responses unique to basal land plants and required for desiccation tolerance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevenson, Sean Ross; Kamisugi, Yasuko; Trinh, Chi H.

The anatomically simple plants that first colonized land must have acquired molecular and biochemical adaptations to drought stress. Abscisic acid (ABA) coordinates responses leading to desiccation tolerance in all land plants. We identified ABA nonresponsive mutants in the model bryophyte Physcomitrella patens and genotyped a segregating population to map and identify the ABA NON-RESPONSIVE (ANR) gene encoding a modular protein kinase comprising an N-terminal PAS domain, a central EDR domain, and a C-terminal MAPKKK-like domain. anr mutants fail to accumulate dehydration tolerance-associated gene products in response to drought, ABA, or osmotic stress and do not acquire ABA-dependent desiccation tolerance. Themore » crystal structure of the PAS domain, determined to 1.7-Å resolution, shows a conserved PAS-fold that dimerizes through a weak dimerization interface. Targeted mutagenesis of a conserved tryptophan residue within the PAS domain generates plants with ABA nonresponsive growth and strongly attenuated ABA-responsive gene expression, whereas deleting this domain retains a fully ABA-responsive phenotype. ANR orthologs are found in early-diverging land plant lineages and aquatic algae but are absent from more recently diverged vascular plants. Lastly, we propose that ANR genes represent an ancestral adaptation that enabled drought stress survival of the first terrestrial colonizers but were lost during land plant evolution.« less
Distinct Redox Regulation in Sub-Cellular Compartments in Response to Various Stress Conditions in Saccharomyces cerevisiae

PubMed Central

Ayer, Anita; Sanwald, Julia; Pillay, Bethany A.; Meyer, Andreas J.; Perrone, Gabriel G.; Dawes, Ian W.

2013-01-01

Responses to many growth and stress conditions are assumed to act via changes to the cellular redox status. However, direct measurement of pH-adjusted redox state during growth and stress has never been carried out. Organellar redox state (E GSH) was measured using the fluorescent probes roGFP2 and pHluorin in Saccharomyces cerevisiae. In particular, we investigated changes in organellar redox state in response to various growth and stress conditions to better understand the relationship between redox-, oxidative- and environmental stress response systems. E GSH values of the cytosol, mitochondrial matrix and peroxisome were determined in exponential and stationary phase in various media. These values (−340 to −350 mV) were more reducing than previously reported. Interestingly, sub-cellular redox state remained unchanged when cells were challenged with stresses previously reported to affect redox homeostasis. Only hydrogen peroxide and heat stress significantly altered organellar redox state. Hydrogen peroxide stress altered the redox state of the glutathione disulfide/glutathione couple (GSSG, 2H+/2GSH) and pH. Recovery from moderate hydrogen peroxide stress was most rapid in the cytosol, followed by the mitochondrial matrix, with the peroxisome the least able to recover. Conversely, the bulk of the redox shift observed during heat stress resulted from alterations in pH and not the GSSG, 2H+/2GSH couple. This study presents the first direct measurement of pH-adjusted redox state in sub-cellular compartments during growth and stress conditions. Redox state is distinctly regulated in organelles and data presented challenge the notion that perturbation of redox state is central in the response to many stress conditions. PMID:23762325
Conflict Structures in Family Networks of Older Adults and Their Relationship With Health-Related Quality of Life

PubMed Central

Widmer, Eric D.; Girardin, Myriam; Ludwig, Catherine

2017-01-01

This study explores the interrelationships between health-related quality of life and conflict structures in family networks of older adults. Data were derived from a sample of 2,858 elders (aged 65 years and older) from the Vivre/Leben/Vivere study, a large survey addressing family life and health conditions of older people in Switzerland. Conflict density in family networks and the betweenness centrality of respondents in family conflict are significantly associated with health-related quality of life measures. Furthermore, the results demonstrate that conflict–health associations are mediated by the level of perceived individual stress where psychological health is concerned. Family conflict structures depend to a large extent on family composition and age. This study stresses the importance of older adults actively shaping the composition of their family contexts in ways that promote both conflict and stress avoidance. PMID:29593370
Global Analysis of Gene Expression Profiles in Physic Nut (Jatropha curcas L.) Seedlings Exposed to Salt Stress

PubMed Central

Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2014-01-01

Background Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. Methodology/Principal Findings We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many “biological processes” were affected by salt stress, particular those categories belong to “metabolic process”, such as “primary metabolism process”, “cellular metabolism process” and “macromolecule metabolism process”. The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. Conclusions/Significance The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future. PMID:24837971
Global analysis of gene expression profiles in physic nut (Jatropha curcas L.) seedlings exposed to salt stress.

PubMed

Zhang, Lin; Zhang, Chao; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2014-01-01

Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many "biological processes" were affected by salt stress, particular those categories belong to "metabolic process", such as "primary metabolism process", "cellular metabolism process" and "macromolecule metabolism process". The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future.

Acute hypoxia stress induced abundant differential expression genes and alternative splicing events in heart of tilapia.

PubMed

Xia, Jun Hong; Li, Hong Lian; Li, Bi Jun; Gu, Xiao Hui; Lin, Hao Ran

2018-01-10

Hypoxia is one of the critical environmental stressors for fish in aquatic environments. Although accumulating evidences indicate that gene expression is regulated by hypoxia stress in fish, how genes undergoing differential gene expression and/or alternative splicing (AS) in response to hypoxia stress in heart are not well understood. Using RNA-seq, we surveyed and detected 289 differential expressed genes (DEG) and 103 genes that undergo differential usage of exons and splice junctions events (DUES) in heart of a hypoxia tolerant fish, Nile tilapia, Oreochromis niloticus following 12h hypoxic treatment. The spatio-temporal expression analysis validated the significant association of differential exon usages in two randomly selected DUES genes (fam162a and ndrg2) in 5 tissues (heart, liver, brain, gill and spleen) sampled at three time points (6h, 12h, and 24h) under acute hypoxia treatment. Functional analysis significantly associated the differential expressed genes with the categories related to energy conservation, protein synthesis and immune response. Different enrichment categories were found between the DEG and DUES dataset. The Isomerase activity, Oxidoreductase activity, Glycolysis and Oxidative stress process were significantly enriched for the DEG gene dataset, but the Structural constituent of ribosome and Structural molecule activity, Ribosomal protein and RNA binding protein were significantly enriched only for the DUES genes. Our comparative transcriptomic analysis reveals abundant stress responsive genes and their differential regulation function in the heart tissues of Nile tilapia under acute hypoxia stress. Our findings will facilitate future investigation on transcriptome complexity and AS regulation during hypoxia stress in fish. Copyright © 2017 Elsevier B.V. All rights reserved.
Pathway connectivity and signaling coordination in the yeast stress-activated signaling network

PubMed Central

Chasman, Deborah; Ho, Yi-Hsuan; Berry, David B; Nemec, Corey M; MacGilvray, Matthew E; Hose, James; Merrill, Anna E; Lee, M Violet; Will, Jessica L; Coon, Joshua J; Ansari, Aseem Z; Craven, Mark; Gasch, Audrey P

2014-01-01

Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown ‘hubs’ of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology. PMID:25411400
Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue.

PubMed

Kawasaki, Noritaka; Asada, Rie; Saito, Atsushi; Kanemoto, Soshi; Imaizumi, Kazunori

2012-01-01

Adipose tissue plays a central role in maintaining metabolic homeostasis under normal conditions. Metabolic diseases such as obesity and type 2 diabetes are often accompanied by chronic inflammation and adipose tissue dysfunction. In this study, we observed that endoplasmic reticulum (ER) stress and the inflammatory response occurred in adipose tissue of mice fed a high-fat diet for a period of 16 weeks. After 16 weeks of feeding, ER stress markers increased and chronic inflammation occurred in adipose tissue. We found that ER stress is induced by free fatty acid (FFA)-mediated reactive oxygen species (ROS) generation and up-regulated gene expression of inflammatory cytokines in 3T3-L1 adipocytes. Oral administration to obese mice of chemical chaperons, which alleviate ER stress, improved chronic inflammation in adipose tissue, followed by the suppression of increased body weight and improved insulin signaling. These results indicate that ER stress plays important pathophysiological roles in obesity-induced adipose tissue dysfunction.
The unconscious pursuit of emotion regulation: Implications for psychological health

PubMed Central

Hopp, Henrik; Troy, Allison S.; Mauss, Iris B.

2012-01-01

Because of the central involvement of emotion regulation in psychological health and the role that implicit (largely unconscious) processes appear to play in emotion regulation, implicit emotion-regulatory processes should play a vital role in psychological health. We hypothesised that implicitly valuing emotion regulation translates into better psychological health in individuals who use adaptive emotion-regulation strategies. A community sample of 222 individuals (56% women) who had recently experienced a stressful life event completed an implicit measure of emotion regulation valuing (ER-IAT) and reported on their habitual use of an important adaptive emotion-regulation strategy: cognitive reappraisal. We measured three domains of psychological health: well-being, depressive symptoms, and social adjustment. As hypothesised, individuals who implicitly valued emotion regulation exhibited greater levels of psychological health, but only when they were high in cognitive reappraisal use. These findings suggest that salutary effects of unconscious emotion-regulation processes depend on its interplay with conscious emotion-regulation processes. PMID:21432692
Inoculum size-dependent interactive regulation of metabolism and stress response of Saccharomyces cerevisiae revealed by comparative metabolomics.

PubMed

Ding, Ming-Zhu; Tian, Hong-Chi; Cheng, Jing-Sheng; Yuan, Ying-Jin

2009-12-01

To investigate the metabolic regulation against inoculum density and stress response to high cell density, comparative metabolomic analysis was employed on Saccharomyces cerevisiae under fermentations with five different inoculum sizes by gas chromatography time-of-flight mass spectrometry. Samples from these fermentations were clearly distinguished by principal components analysis, indicating that inoculum size had a profound effect on the metabolism of S. cerevisiae. Potential biomarkers responsible for the discrimination were identified as glycerol, phosphoric acid, succinate, glycine, isoleucine, proline, palmitoleic acid, myo-inositol and ethanolamine. It indicated that enhanced stress protectants in glycerol biosynthesis and amino acid metabolism, depressed citric acid cycle intermediates, as well as decreased metabolites relating to membrane structure and function were involved as the inoculum size of yeast increased. Furthermore, significantly higher levels of glycerol and proline in yeast cells of higher inoculum size fermentation (40 g l(-1)) revealed that they played important roles in protecting yeast from stresses in high cell density fermentation. These findings provided new insights into characterizing the metabolic regulation and stress response depending on inoculum density during ethanol fermentation.
Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

PubMed Central

Wilson, Marlene A.; Grillo, Claudia A.; Fadel, Jim R.; Reagan, Lawrence P.

2015-01-01

Neuroplasticity may be defined as the ability of the central nervous system (CNS) to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD) and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior. PMID:26844236
Conservation and Divergence of Circadian Clock Operation in a Stress-Inducible Crassulacean Acid Metabolism Species Reveals Clock Compensation against Stress1

PubMed Central

Boxall, Susanna F.; Foster, Jonathan M.; Bohnert, Hans J.; Cushman, John C.; Nimmo, Hugh G.; Hartwell, James

2005-01-01

One of the best-characterized physiological rhythms in plants is the circadian rhythm of CO2 metabolism in Crassulacean acid metabolism (CAM) plants, which is the focus here. The central components of the plant circadian clock have been studied in detail only in Arabidopsis (Arabidopsis thaliana). Full-length cDNAs have been obtained encoding orthologs of CIRCADIAN CLOCK-ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY), TIMING OF CAB EXPRESSION1 (TOC1), EARLY FLOWERING4 (ELF4), ZEITLUPE (ZTL), FLAVIN-BINDING KELCH REPEAT F-BOX1 (FKF1), EARLY FLOWERING3 (ELF3), and a partial cDNA encoding GIGANTEA in the model stress-inducible CAM plant, Mesembryanthemum crystallinum (Common Ice Plant). TOC1 and LHY/CCA1 are under reciprocal circadian control in a manner similar to their regulation in Arabidopsis. ELF4, FKF1, ZTL, GIGANTEA, and ELF3 are under circadian control in C3 and CAM leaves. ELF4 transcripts peak in the evening and are unaffected by CAM induction. FKF1 shows an abrupt transcript peak 3 h before subjective dusk. ELF3 transcripts appear in the evening, consistent with their role in gating light input to the circadian clock. Intriguingly, ZTL transcripts do not oscillate in Arabidopsis, but do in M. crystallinum. The transcript abundance of the clock-associated genes in M. crystallinum is largely unaffected by development and salt stress, revealing compensation of the central circadian clock against development and abiotic stress in addition to the well-known temperature compensation. Importantly, the clock in M. crystallinum is very similar to that in Arabidopsis, indicating that such a clock could control CAM without requiring additional components of the central oscillator or a novel CAM oscillator. PMID:15734916
Brain oxytocin: a key regulator of emotional and social behaviours in both females and males.

PubMed

Neumann, I D

2008-06-01

In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.
Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.

PubMed

Kocalis, Heidi E; Hagan, Scott L; George, Leena; Turney, Maxine K; Siuta, Michael A; Laryea, Gloria N; Morris, Lindsey C; Muglia, Louis J; Printz, Richard L; Stanwood, Gregg D; Niswender, Kevin D

2014-07-01

Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.
The Redox Proteome*

PubMed Central

Go, Young-Mi; Jones, Dean P.

2013-01-01

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437
Mechanical stress and network structure drive protein dynamics during cytokinesis.

PubMed

Srivastava, Vasudha; Robinson, Douglas N

2015-03-02

Cell-shape changes associated with processes like cytokinesis and motility proceed on several-second timescales but are derived from molecular events, including protein-protein interactions, filament assembly, and force generation by molecular motors, all of which occur much faster [1-4]. Therefore, defining the dynamics of such molecular machinery is critical for understanding cell-shape regulation. In addition to signaling pathways, mechanical stresses also direct cytoskeletal protein accumulation [5-7]. A myosin-II-based mechanosensory system controls cellular contractility and shape during cytokinesis and under applied stress [6, 8]. In Dictyostelium, this system tunes myosin II accumulation by feedback through the actin network, particularly through the crosslinker cortexillin I. Cortexillin-binding IQGAPs are major regulators of this system. Here, we defined the short timescale dynamics of key cytoskeletal proteins during cytokinesis and under mechanical stress, using fluorescence recovery after photobleaching and fluorescence correlation spectroscopy, to examine the dynamic interplay between these proteins. Equatorially enriched proteins including cortexillin I, IQGAP2, and myosin II recovered much more slowly than actin and polar crosslinkers. The mobility of equatorial proteins was greatly reduced at the furrow compared to the interphase cortex, suggesting their stabilization during cytokinesis. This mobility shift did not arise from a single biochemical event, but rather from a global inhibition of protein dynamics by mechanical-stress-associated changes in the cytoskeletal structure. Mechanical tuning of contractile protein dynamics provides robustness to the cytoskeletal framework responsible for regulating cell shape and contributes to cytokinesis fidelity. Copyright © 2015 Elsevier Ltd. All rights reserved.
Replication of Early B-cell Factor 1 (EBF1) Gene-by-psychosocial Stress Interaction Effects on Central Adiposity in a Korean Population.

PubMed

Kim, Hyun-Jin; Min, Jin-Young; Min, Kyoung-Bok

2016-09-01

Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1) , which was associated with central obesity-related traits via interactions with stress levels. We aimed to evaluate EBF1 gene-by-stress interaction effects on central adiposity traits, including visceral adipose tissue (VAT), in Korean adults. A total of 1467 Korean adults were included in this study. We selected 22 single-nucleotide polymorphisms (SNPs) in the EBF1 gene and analyzed their interactions with stress on central adiposity using additive, dominant, and recessive genetic modeling. The four SNPs that had strong linkage disequilibrium relationships (rs10061900, rs10070743, rs4704967, and rs10056564) demonstrated significant interactions with the waist-hip ratio in the dominant model ( p int <0.007). In addition, two other SNPs (rs6556377 and rs13180086) were associated with VAT by interactions with stress levels, especially in the recessive genetic model ( p int <0.007). As stress levels increased, the mean values of central adiposity traits according to SNP genotypes exhibited gradual but significant changes ( p <0.05). These results suggest that the common genetic variants for EBF1 are associated with central adiposity through interactions with stress levels, emphasizing the importance of managing stress in the prevention of central obesity.
A growing Leaf as a Sheet of an Active Solid

NASA Astrophysics Data System (ADS)

Sharon, Eran

A growing leaf is a thin sheet of active solid, which expands while obeying the laws of mechanics. The effective rheology of this active solid is nontrivial, allowing the leaf to increase its area by orders of magnitude, keeping its ''proper'' geometry. The questions of what the characteristics of the leaf growth field are and how it is regulated without any central ''headquarter'' are still open. I will present measurements of natural leaf growth with high time and space resolution. These show that the growth is a highly fluctuating process in both time and space. We suggest that the entire statistics of the growth field, not just its averages contain information important for the understanding of growth regulation. In another set of experiments we measure the effect of mechanical stress on deformation and growth. The measured effective rheology is viscoelastic with time varying parameters, indicating remodeling of the tissue in response to extended application of mechanical stress.
Identification of Neurodegenerative Factors Using Translatome-Regulatory Network Analysis

PubMed Central

Brichta, Lars; Shin, William; Jackson-Lewis, Vernice; Blesa, Javier; Yap, Ee-Lynn; Walker, Zachary; Zhang, Jack; Roussarie, Jean-Pierre; Alvarez, Mariano J.; Califano, Andrea; Przedborski, Serge; Greengard, Paul

2016-01-01

For degenerative disorders of the central nervous system, the major obstacle to therapeutic advancement has been the challenge of identifying the key molecular mechanisms underlying neuronal loss. We developed a combinatorial approach including translational profiling and brain regulatory network analysis to search for key determinants of neuronal survival or death. Following the generation of transgenic mice for cell type-specific profiling of midbrain dopaminergic neurons, we established and compared translatome libraries reflecting the molecular signature of these cells at baseline or under degenerative stress. Analysis of these libraries by interrogating a context-specific brain regulatory network led to the identification of a repertoire of intrinsic upstream regulators that drive the dopaminergic stress response. The altered activity of these regulators was not associated with changes in their expression levels. This strategy can be generalized for the elucidation of novel molecular determinants involved in the degeneration of other classes of neurons. PMID:26214373
Transcriptional and translational regulation by RNA thermometers, riboswitches and the sRNA DsrA in Escherichia coli O157:H7 Sakai under combined cold and osmotic stress adaptation.

PubMed

Hücker, Sarah Maria; Simon, Svenja; Scherer, Siegfried; Neuhaus, Klaus

2017-01-01

The enteric pathogen Escherichia coli O157:H7 Sakai (EHEC) is able to grow at lower temperatures compared to commensal E. coli Growth at environmental conditions displays complex challenges different to those in a host. EHEC was grown at 37°C and at 14°C with 4% NaCl, a combination of cold and osmotic stress as present in the food chain. Comparison of RNAseq and RIBOseq data provided a snap shot of ongoing transcription and translation, differentiating transcriptional and post-transcriptional gene regulation, respectively. Indeed, cold and osmotic stress related genes are simultaneously regulated at both levels, but translational regulation clearly dominates. Special emphasis was given to genes regulated by RNA secondary structures in their 5 ' UTRs, such as RNA thermometers and riboswitches, or genes controlled by small RNAs encoded in trans The results reveal large differences in gene expression between short-time shock compared to adaptation in combined cold and osmotic stress. Whereas the majority of cold shock proteins, such as CspA, are translationally downregulated after adaptation, many osmotic stress genes are still significantly upregulated mainly translationally, but several also transcriptionally. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of Cryptococcus humicola response to aluminum stress.

PubMed

Zhang, Jingjing; Zhang, Lei; Qiu, Jinkui; Nian, Hongjuan

2015-10-01

Cryptococcus humicola is a highly aluminum (Al) tolerant yeast strain isolated from a tea field. Here the relative changes of protein expression in C. humicola undergoing aluminum stress were analyzed to understand the genetic basis of aluminum tolerance. In this work, iTRAQ-based (isobaric tags for relative and absolute quantification) quantitative proteomic technology was used to detect statistically significant proteins associated with the response to aluminum stress. A total of 625 proteins were identified and were mainly involved in translation/ribosomal structure and biogenesis, posttranslational modification/protein turnover/chaperones, energy production and conversion, and amino acid transport and metabolism. Of these proteins, 59 exhibited differential expression during aluminum stress. Twenty-nine proteins up-regulated by aluminum were mainly involved in translation/ribosomal structure and biogenesis, posttranslational modification/protein turnover and chaperones, and lipid transport and metabolism. Thirty proteins down-regulated by aluminum were mainly associated with energy transport and metabolism, translation/ribosomal structure and biogenesis, posttranslational modification/protein turnover/chaperones, and lipid transport and metabolism. The potential functions of some proteins in aluminum tolerance are discussed. These functional changes may be beneficial for cells to protect themselves from aluminum toxic conditions. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.
Nuclear Proteomics Reveals the Role of Protein Synthesis and Chromatin Structure in Root Tip of Soybean during the Initial Stage of Flooding Stress.

PubMed

Yin, Xiaojian; Komatsu, Setsuko

2016-07-01

To identify the upstream events controlling the regulation of flooding-responsive proteins in soybean, proteomic analysis of nuclear proteins in root tip was performed. By using nuclear fractions, which were highly enriched, a total of 365 nuclear proteins were changed in soybean root tip at initial stage of flooding stress. Four exon-junction complex-related proteins and NOP1/NOP56, which function in upstream of 60S preribosome biogenesis, were decreased in flooded soybean. Furthermore, proteomic analysis of crude protein extract revealed that the protein translation was suppressed by continuous flooding stress. Seventeen chromatin structure-related nuclear proteins were decreased in response to flooding stress. Out of them, histone H3 was clearly decreased with protein abundance and mRNA expression levels at the initial flooding stress. Additionally, a number of protein synthesis-, RNA-, and DNA-related nuclear proteins were decreased in a time-dependent manner. mRNA expressions of genes encoding the significantly changed flooding-responsive nuclear proteins were inhibited by the transcriptional inhibitor, actinomycin D. These results suggest that protein translation is suppressed through inhibition of preribosome biogenesis- and mRNA processing-related proteins in nuclei of soybean root tip at initial flooding stress. In addition, flooding stress may regulate histone variants with gene expression in root tip.
Image log analysis of in situ stress orientation, breakout growth, and natural geologic structures to 2.5 km depth in central Scandinavian Caledonides: Results from the COSC-1 borehole

NASA Astrophysics Data System (ADS)

Wenning, Quinn C.; Berthet, Theo; Ask, Maria; Zappone, Alba; Rosberg, Jan-Erik; Almqvist, Bjarne S. G.

2017-05-01

Stress-induced borehole deformation analysis in the Collisional Orogeny in the Scandinavian Caledonide deep scientific borehole establishes in situ stress orientation in a poorly characterized region in central Sweden. Two acoustic televiewer logging campaigns, with more than 1 year between campaigns, provide detailed images along the full length of the 2.5 km deep borehole for breakout, drilling-induced tensile fracture (DITF), and natural occurring structural analysis. Borehole breakouts occur in 13 distinct zones along total length of 22 m, indicating an average maximum horizontal stress, SHmax, orientation of 127° ± 12°. Infrequent DITFs are constrained within one zone from 786 to 787 m depth (SHmax orientation: 121° ± 07°). These SHmax orientations are in agreement with the general trend in Scandinavia and are in accordance with many mechanisms that generate crustal stress (e.g., ridge push, topographic loading, and mantel driven stresses). The unique acquisition of image logs in two successions allows for analysis of time-dependent borehole deformation, indicating that six breakout zones have crept, both along the borehole axis and radially around the borehole. Strong dynamic moduli measured on core samples and an inferred weak in situ stress anisotropy inhibit the formation of breakouts and DITFs. Natural fracture orientation below 800 m is congruent to extensional or hybrid brittle shear failure along the same trend as the current SHmax. Analysis of foliation in the image logs reinforces the interpretation that the discontinuous seismic reflectors with fluctuating dip observed in seismic profiles are due to recumbent folding and boudinage.
Focal adhesions, stress fibers and mechanical tension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu; Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr

Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discussmore » the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.« less
Angiotensin II AT1 receptor blocker candesartan prevents the fast up-regulation of cerebrocortical benzodiazepine-1 receptors induced by acute inflammatory and restraint stress

PubMed Central

Sánchez-Lemus, Enrique; Honda, Masaru; Saavedra, Juan M.

2012-01-01

Centrally acting Angiotensin II AT1 receptor blockers (ARBs) protect from stress-induced disorders and decrease anxiety in a model of inflammatory stress, the systemic injection of bacterial endotoxin lipopolysaccharide (LPS). In order to better understand the anxiolytic effect of ARBs, we treated rats with LPS (50 µg/kg) with or without three days of pretreatment with the ARB candesartan (1 mg/kg/day), and studied cortical benzodiazepine (BZ) and corticotrophin-releasing factor (CRF) receptors. We compared the cortical BZ and CRF receptors expression pattern induced by LPS with that produced in restraint stress. Inflammation stress produced a generalized increase in cortical BZ1 receptors and reduced mRNA expression of the GABAA receptor γ2 subunit in cingulate cortex; changes were prevented by candesartan pretreatment. Moreover, restraint stress produced similar increases in cortical BZ1 receptor binding, and candesartan prevented these changes. Treatment with candesartan alone increased cortical BZ1 binding, and decreased γ2 subunit mRNA expression in the cingulate cortex. Conversely, we did not find changes in CRF1 receptor expression in any of the cortical areas studied, either after inflammation or restraint stress. Cortical CRF2 receptor binding was undetectable, but CRF2 mRNA expression was decreased by inflammation stress, a change prevented by candesartan. We conclude that stress promotes rapid and widespread changes in cortical BZ1 receptor expression; and that the stress-induced BZ1 receptor expression is under the control of AT1 receptor activity. The results suggest that the anti-anxiety effect of ARBs may be associated with their capacity to regulate stress-induced alterations in cortical BZ1 receptors. PMID:22503782

Alkaline stress and iron deficiency regulate iron uptake and riboflavin synthesis gene expression differently in root and leaf tissue: implications for iron deficiency chlorosis.

PubMed

Hsieh, En-Jung; Waters, Brian M

2016-10-01

Iron (Fe) is an essential mineral that has low solubility in alkaline soils, where its deficiency results in chlorosis. Whether low Fe supply and alkaline pH stress are equivalent is unclear, as they have not been treated as separate variables in molecular physiological studies. Additionally, molecular responses to these stresses have not been studied in leaf and root tissues simultaneously. We tested how plants with the Strategy I Fe uptake system respond to Fe deficiency at mildly acidic and alkaline pH by measuring root ferric chelate reductase (FCR) activity and expression of selected Fe uptake genes and riboflavin synthesis genes. Alkaline pH increased cucumber (Cucumis sativus L.) root FCR activity at full Fe supply, but alkaline stress abolished FCR response to low Fe supply. Alkaline pH or low Fe supply resulted in increased expression of Fe uptake genes, but riboflavin synthesis genes responded to Fe deficiency but not alkalinity. Iron deficiency increased expression of some common genes in roots and leaves, but alkaline stress blocked up-regulation of these genes in Fe-deficient leaves. In roots of the melon (Cucumis melo L.) fefe mutant, in which Fe uptake responses are blocked upstream of Fe uptake genes, alkaline stress or Fe deficiency up-regulation of certain Fe uptake and riboflavin synthesis genes was inhibited, indicating a central role for the FeFe protein. These results suggest a model implicating shoot-to-root signaling of Fe status to induce Fe uptake gene expression in roots. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, Jer-Yuan; Crawley, Suzanne; Chen, Michael

Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure1,2. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand3. Recent studies have identified brain areas outside the hypothalamus that are activated under these ‘non-homeostatic’ conditions4,5,6, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive. Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptormore » for growth and differentiation factor 15 (GDF15). GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses; we show that Gfral knockout mice are hyperphagic under stressed conditions and are resistant to chemotherapy-induced anorexia and body weight loss. GDF15 activates GFRAL-expressing neurons localized exclusively in the area postrema and nucleus tractus solitarius of the mouse brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitute part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions7. GDF15 levels increase in response to tissue stress and injury, and elevated levels are associated with body weight loss in numerous chronic human diseases8,9. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. These findings provide opportunities to develop therapeutic agents for the treatment of disorders with altered energy demand.« less
3D packaging of a microfluidic system with sensory applications

NASA Astrophysics Data System (ADS)

Morrissey, Anthony; Kelly, Gerard; Alderman, John C.

1997-09-01

Among the main benefits of microsystem technology are its contributions to cost reductio, reliability and improved performance. however, the packaging of microsystems, and particularly microsensor, has proven to be one of the biggest limitations to their commercialization and the packaging of silicon sensor devices can be the most costly part of their fabrication. This paper describes the integration of 3D packaging of a microsystem. Central to the operation of the 3D demonstrator is a micromachined silicon membrane pump to supply fluids to a sensing chamber constructed about the active area of a sensor chip. This chip carries ISFET based chemical sensors, pressure sensors and thermal sensors. The electronics required for controlling and regulating the activity of the various sensors ar also available on this chip and as other chips in the 3D assembly. The demonstrator also contains a power supply module with optical fiber interconnections. All of these modules are integrated into a single plastic- encapsulated 3D vertical multichip module. The reliability of such a structure, initially proposed by Val was demonstrated by Barrett et al. An additional module available for inclusion in some of our assemblies is a test chip capable of measuring the packaging-induced stress experienced during and after assembly. The packaging process described produces a module with very high density and utilizes standard off-the-shelf components to minimize costs. As the sensor chip and micropump include micromachined silicon membranes and microvalves, the packaging of such structures has to allow consideration for the minimization of the packaging-induced stresses. With this in mind, low stress techniques, including the use of soft glob-top materials, were employed.
Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.
Stress rotation along pre-Cenozoic basement structures

NASA Astrophysics Data System (ADS)

Reiter, K.; Heidbach, O.; Henk, A.

2017-12-01

The in-situ stress state of the Earth's crust is under investigation since decades for both, scientific and economic purposes. Several methods have been established to indicate the contemporary orientation of the maximum compressive horizontal stress (SHmax). It is assumed that the same forces that drive plate motion are the first order stress sources and one could presume that SHmax is always parallel to plate motion, which is the case for some regions. However, deviations from this general trend occur in many regions. Therefore, second and third order sources of stress have been identified that potentially cause regional and local stress rotation with respect to the long wave-length trend imposed by plate tectonic forces. One group of such subordinate stress sources are lateral heterogeneities based on structures, petrothermal or petrophysical properties. The World Stress Map (WSM) project compiles systematically data records of the present day SHmax orientation. The increasing amount of stress orientation data allows to investigate areas with consistent stress rotation, divergent to the regional stress pattern. In our work we analyse the stress pattern variability and its causes beneath Germany. In the Molasse Basin in the Alpine foreland the SHmax orientation is perpendicular to the Alpine front as a consequence of gravitational potential energy of the orogen. SHmax is oriented in N-S direction in the central Alpine foreland and within the North German Basin. Between both, within the Mid-German Crystalline High, SHmax is divergent oriented in SE-NW direction. Neither gravitational potential energy nor petrothermal effects can be indicated as stress source. But when comparing the stress pattern with the Variscan basement structures it is obvious that SHmax is perpendicular oriented to this Palaeozoic basement structures. Therefore, petrophysical heterogeneities can be expected as reason for the observed stress rotation. Two assumptions can be made for the Mid-German Crystalline High based on this presumption. 1. The magnitude of SHmax and the minimum horizontal stress (Shmin) in the region is close by, allowing local stress rotation. 2. The stiffness contrast perpendicular to the strike of the Variscan basement structures is large enough as stress source to cause significant rotation of the stress pattern.
Mechanisms underlying caloric restriction and life span regulation: implications for vascular aging

PubMed Central

Ungvari, Zoltan; Parrado-Fernandez, Cristina; Csiszar, Anna; de Cabo, Rafael

2008-01-01

This review focuses on the emerging evidence that attenuation of the production of reactive oxygen species (ROS) and inhibition of inflammatory pathways play a central role in the anti-aging cardiovascular effects of caloric restriction (CR). Particular emphasis is placed on the potential role of the plasma membrane redox system in CR-induced pathways responsible for sensing oxidative stress and increasing cellular oxidative stress resistance. We propose that CR increases bioavailability of NO, decreases vascular ROS generation, activates the Nrf2/ARE pathway inducing ROS detoxification systems, exerts anti-inflammatory effects and, thereby, suppresses initiation/progression of vascular disease that accompany aging. PMID:18340017
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway.

PubMed

Le Sage, Valerie; Cinti, Alessandro; Amorim, Raquel; Mouland, Andrew J

2016-05-24

The mammalian target of rapamycin (mTOR) is a central regulator of gene expression, translation and various metabolic processes. Multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mTOR pathway. Viral infection is a significant stress that can activate, reduce or even suppress the mTOR signaling pathway. Consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the mTOR pathway in order to make the host cell a hospitable environment for replication. A more comprehensive knowledge of different viral interactions may provide fruitful targets for new antiviral drugs.
Alterations in the corticotropin-releasing hormone (CRH) neurocircuitry: Insights into post stroke functional impairments.

PubMed

Barra de la Tremblaye, P; Plamondon, H

2016-07-01

Although it is well accepted that changes in the regulation of the hypothalamic-pituitary adrenal (HPA) axis may increase susceptibility to affective disorders in the general population, this link has been less examined in stroke patients. Yet, the bidirectional association between depression and cardiovascular disease is strong, and stress increases vulnerability to stroke. Corticotropin-releasing hormone (CRH) is the central stress hormone of the HPA axis pathway and acts by binding to CRH receptors (CRHR) 1 and 2, which are located in several stress-related brain regions. Evidence from clinical and animal studies suggests a role for CRH in the neurobiological basis of depression and ischemic brain injury. Given its importance in the regulation of the neuroendocrine, autonomic, and behavioral correlates of adaptation and maladaptation to stress, CRH is likely associated in the pathophysiology of post stroke emotional impairments. The goals of this review article are to examine the clinical and experimental data describing (1) that CRH regulates the molecular signaling brain circuit underlying anxiety- and depression-like behaviors, (2) the influence of CRH and other stress markers in the pathophysiology of post stroke emotional and cognitive impairments, and (3) context and site specific interactions of CRH and BDNF as a basis for the development of novel therapeutic targets. This review addresses how the production and release of the neuropeptide CRH within the various regions of the mesocorticolimbic system influences emotional and cognitive behaviors with a look into its role in psychiatric disorders post stroke. Copyright © 2016 Elsevier Inc. All rights reserved.
13C based proteinogenic amino acid (PAA) and metabolic flux ratio analysis of Lactococcus lactis reveals changes in pentose phosphate (PP) pathway in response to agitation and temperature related stresses.

PubMed

Azizan, Kamalrul Azlan; Ressom, Habtom W; Mendoza, Eduardo R; Baharum, Syarul Nataqain

2017-01-01

Lactococcus lactis subsp. cremoris MG1363 is an important starter culture for dairy fermentation. During industrial fermentations, L. lactis is constantly exposed to stresses that affect the growth and performance of the bacterium. Although the response of L. lactis to several stresses has been described, the adaptation mechanisms at the level of in vivo fluxes have seldom been described. To gain insights into cellular metabolism, 13 C metabolic flux analysis and gas chromatography mass spectrometry (GC-MS) were used to measure the flux ratios of active pathways in the central metabolism of L. lactis when subjected to three conditions varying in temperature (30°C, 37°C) and agitation (with and without agitation at 150 rpm). Collectively, the concentrations of proteinogenic amino acids (PAAs) and free fatty acids (FAAs) were compared, and Pearson correlation analysis ( r ) was calculated to measure the pairwise relationship between PAAs. Branched chain and aromatic amino acids, threonine, serine, lysine and histidine were correlated strongly, suggesting changes in flux regulation in glycolysis, the pentose phosphate (PP) pathway, malic enzyme and anaplerotic reaction catalysed by pyruvate carboxylase (pycA). Flux ratio analysis revealed that glucose was mainly converted by glycolysis, highlighting the stability of L. lactis' central carbon metabolism despite different conditions. Higher flux ratios through oxaloacetate (OAA) from pyruvate (PYR) reaction in all conditions suggested the activation of pyruvate carboxylate (pycA) in L. lactis , in response to acid stress during exponential phase. Subsequently, more significant flux ratio differences were seen through the oxidative and non-oxidative pentose phosphate (PP) pathways, malic enzyme, and serine and C1 metabolism, suggesting NADPH requirements in response to environmental stimuli. These reactions could play an important role in optimization strategies for metabolic engineering in L. lactis . Overall, the integration of systematic analysis of amino acids and flux ratio analysis provides a systems-level understanding of how L. lactis regulates central metabolism under various conditions.
Adult cyclical vomiting syndrome: a disorder of allostatic regulation?

PubMed

Levinthal, D J; Bielefeldt, K

2014-08-01

Cyclic vomiting syndrome (CVS) is an idiopathic illness characterized by stereotypic and sudden-onset episodes of intense retching and repetitive vomiting that are often accompanied by severe abdominal pain. Many associated factors that predict CVS attacks, such as prolonged periods of fasting, sleep deprivation, physical and emotional stress, or acute anxiety, implicate sympathetic nervous system activation as a mechanism that may contribute to CVS pathogenesis. Furthermore, adult patients with CVS tend to have a history of early adverse life events, mood disorders, chronic stress, and drug abuse-all associations that may potentiate sympathetic neural activity. In this review, we set forth a conceptual model in which CVS is viewed as a brain disorder involving maladaptive plasticity within central neural circuits important for allostatic regulation of the sympathetic nervous system. This model not only can account for the varied clinical observations that are linked with CVS, but also has implications for potential therapeutic interventions. Thus, it is likely that cognitive behavioral therapy, stress management ("mind-body") interventions, regular exercise, improved sleep, and avoidance of cannabis and opiate use could have positive influences on the clinical course for patients with CVS.
Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System.

PubMed

Burford, Natalie G; Webster, Natalia A; Cruz-Topete, Diana

2017-10-16

The collective of endocrine organs acting in homeostatic regulation-known as the hypothalamic-pituitary-adrenal (HPA) axis-comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart.
Dual leucine zipper kinase-dependent PERK activation contributes to neuronal degeneration following insult

PubMed Central

Larhammar, Martin; Huntwork-Rodriguez, Sarah; Jiang, Zhiyu; Solanoy, Hilda; Sengupta Ghosh, Arundhati; Wang, Bei; Kaminker, Joshua S; Huang, Kevin; Eastham-Anderson, Jeffrey; Siu, Michael; Modrusan, Zora; Farley, Madeline M; Tessier-Lavigne, Marc; Lewcock, Joseph W; Watkins, Trent A

2017-01-01

The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress Response (ISR) is implicated in neurodegenerative disease, although the regulators and consequences of PERK activation following neuronal injury are poorly understood. Here we show that PERK signaling is a component of the mouse MAP kinase neuronal stress response controlled by the Dual Leucine Zipper Kinase (DLK) and contributes to DLK-mediated neurodegeneration. We find that DLK-activating insults ranging from nerve injury to neurotrophin deprivation result in both c-Jun N-terminal Kinase (JNK) signaling and the PERK- and ISR-dependent upregulation of the Activating Transcription Factor 4 (ATF4). Disruption of PERK signaling delays neurodegeneration without reducing JNK signaling. Furthermore, DLK is both sufficient for PERK activation and necessary for engaging the ISR subsequent to JNK-mediated retrograde injury signaling. These findings identify DLK as a central regulator of not only JNK but also PERK stress signaling in neurons, with both pathways contributing to neurodegeneration. DOI: http://dx.doi.org/10.7554/eLife.20725.001 PMID:28440222
Exploring stress tolerance mechanism of evolved freshwater strain Chlorella sp. S30 under 30 g/L salt.

PubMed

Li, Xuyang; Yuan, Yizhong; Cheng, Dujia; Gao, Juan; Kong, Lingzhao; Zhao, Quanyu; Wei, Wei; Sun, Yuhan

2018-02-01

Enhancement of stress tolerance to high concentration of salt and CO 2 is beneficial for CO 2 capture by microalgae. Adaptive evolution was performed for improving the tolerance of a freshwater strain, Chlorella sp. AE10, to 30 g/L salt. A resulting strain denoted as Chlorella sp. S30 was obtained after 46 cycles (138 days). The stress tolerance mechanism was analyzed by comparative transcriptomic analysis. Although the evolved strain could tolerate 30 g/L salt, high salinity caused loss to photosynthesis, oxidative phosphorylation, fatty acid biosynthesis and tyrosine metabolism. The related genes of antioxidant enzymes, CO 2 fixation, amino acid biosynthesis, central carbon metabolism and ABC transporter proteins were up-regulated. Besides the up-regulation of several genes in Calvin-Benson cycle, they were also identified in C4 photosynthetic pathway and crassulacean acid metabolism pathway. They were essential for the survival and CO 2 fixation of Chlorella sp. S30 under 30 g/L salt and 10% CO 2 . Copyright © 2017 Elsevier Ltd. All rights reserved.
Stress perturbation associated with the Amazonas and other ancient continental rifts

USGS Publications Warehouse

Zoback, M.L.; Richardson, R.M.

1996-01-01

The state of stress in the vicinity of old continental rifts is examined to investigate the possibility that crustal structure associated with ancient rifts (specifically a dense rift pillow in the lower crust) may modify substantially the regional stress field. Both shallow (2.0-2.6 km depth) breakout data and deep (20-45 km depth) crustal earthquake focal mechanisms indicate a N to NNE maximum horizontal compression in the vicinity of the Paleozoic Amazonas rift in central Brazil. This compressive stress direction is nearly perpendicular to the rift structure and represents a ???75?? rotation relative to a regional E-W compressive stress direction in the South American plate. Elastic two-dimensional finite element models of the density structure associated with the Amazonas rift (as inferred from independent gravity modeling) indicate that elastic support of this dense feature would generate horizontal rift-normal compressional stresses between 60 and 120 MPa, with values of 80-100 MPa probably most representative of the overall structure. The observed ???75?? stress rotation constrains the ratio of the regional horizontal stress difference to the rift-normal compressive stress to be between 0.25 and 1.0, suggesting that this rift-normal stress may be from 1 to 4 times larger than the regional horizontal stress difference. A general expression for the modification of the normalized local horizontal shear stress (relative to the regional horizontal shear stress) shows that the same ratio of the rift-normal compression relative to the regional horizontal stress difference, which controls the amount of stress rotation, also determines whether the superposed stress increases or decreases the local maximum horizontal shear stress. The potential for fault reactivation of ancient continental rifts in general is analyzed considering both the local stress rotation and modification of horizontal shear stress for both thrust and strike-slip stress regimes. In the Amazonas rift case, because the observed stress rotation only weakly constrains the ratio of the regional horizontal stress difference to the rift-normal compression to be between 0.25 and 1.0, our analysis is inconclusive because the resultant normalized horizontal shear stress may be reduced (for ratios >0.5) or enhanced (for ratios <0.5). Additional information is needed on all three stress magnitudes to predict how a change in horizontal shear stress directly influences the likelihood of faulting in the thrust-faulting stress regime in the vicinity of the Amazonas rift. A rift-normal stress associated with the seismically active New Madrid ancient rift may be sufficient to rotate the horizontal stress field consistent with strike-slip faults parallel to the axis of the rift, although this results in a 20-40% reduction in the local horizontal shear stress within the seismic zone. Sparse stress data in the vicinity of the seismically quiescent Midcontinent rift of the central United States suggest a stress state similar to that of New Madrid, with the local horizontal shear stress potentially reduced by as much as 60%. Thus the markedly different levels of seismic activity associated with these two subparallel ancient rifts is probably due to other factors than stress perturbations due to dense rift pillows. The modeling and analysis here demonstrate that rift-normal compressive stresses are a significant source of stress acting on the lithosphere and that in some cases may be a contributing factor to the association of intraplate seismicity with old zones of continental extension.
BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response

PubMed Central

Castillo, Karen; Rojas-Rivera, Diego; Lisbona, Fernanda; Caballero, Benjamín; Nassif, Melissa; Court, Felipe A; Schuck, Sebastian; Ibar, Consuelo; Walter, Peter; Sierralta, Jimena; Glavic, Alvaro; Hetz, Claudio

2011-01-01

Both autophagy and apoptosis are tightly regulated processes playing a central role in tissue homeostasis. Bax inhibitor 1 (BI-1) is a highly conserved protein with a dual role in apoptosis and endoplasmic reticulum (ER) stress signalling through the regulation of the ER stress sensor inositol requiring kinase 1 α (IRE1α). Here, we describe a novel function of BI-1 in the modulation of autophagy. BI-1-deficient cells presented a faster and stronger induction of autophagy, increasing LC3 flux and autophagosome formation. These effects were associated with enhanced cell survival under nutrient deprivation. Repression of autophagy by BI-1 was dependent on cJun-N terminal kinase (JNK) and IRE1α expression, possibly due to a displacement of TNF-receptor associated factor-2 (TRAF2) from IRE1α. Targeting BI-1 expression in flies altered autophagy fluxes and salivary gland degradation. BI-1 deficiency increased flies survival under fasting conditions. Increased expression of autophagy indicators was observed in the liver and kidney of bi-1-deficient mice. In summary, we identify a novel function of BI-1 in multicellular organisms, and suggest a critical role of BI-1 as a stress integrator that modulates autophagy levels and other interconnected homeostatic processes. PMID:21926971
BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response.

PubMed

Castillo, Karen; Rojas-Rivera, Diego; Lisbona, Fernanda; Caballero, Benjamín; Nassif, Melissa; Court, Felipe A; Schuck, Sebastian; Ibar, Consuelo; Walter, Peter; Sierralta, Jimena; Glavic, Alvaro; Hetz, Claudio

2011-09-16

Both autophagy and apoptosis are tightly regulated processes playing a central role in tissue homeostasis. Bax inhibitor 1 (BI-1) is a highly conserved protein with a dual role in apoptosis and endoplasmic reticulum (ER) stress signalling through the regulation of the ER stress sensor inositol requiring kinase 1 α (IRE1α). Here, we describe a novel function of BI-1 in the modulation of autophagy. BI-1-deficient cells presented a faster and stronger induction of autophagy, increasing LC3 flux and autophagosome formation. These effects were associated with enhanced cell survival under nutrient deprivation. Repression of autophagy by BI-1 was dependent on cJun-N terminal kinase (JNK) and IRE1α expression, possibly due to a displacement of TNF-receptor associated factor-2 (TRAF2) from IRE1α. Targeting BI-1 expression in flies altered autophagy fluxes and salivary gland degradation. BI-1 deficiency increased flies survival under fasting conditions. Increased expression of autophagy indicators was observed in the liver and kidney of bi-1-deficient mice. In summary, we identify a novel function of BI-1 in multicellular organisms, and suggest a critical role of BI-1 as a stress integrator that modulates autophagy levels and other interconnected homeostatic processes.
Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases

NASA Technical Reports Server (NTRS)

Boo, Yong Chool; Jo, Hanjoong

2003-01-01

Vascular endothelial cells are directly and continuously exposed to fluid shear stress generated by blood flow. Shear stress regulates endothelial structure and function by controlling expression of mechanosensitive genes and production of vasoactive factors such as nitric oxide (NO). Though it is well known that shear stress stimulates NO production from endothelial nitric oxide synthase (eNOS), the underlying molecular mechanisms remain unclear and controversial. Shear-induced production of NO involves Ca2+/calmodulin-independent mechanisms, including phosphorylation of eNOS at several sites and its interaction with other proteins, including caveolin and heat shock protein-90. There have been conflicting results as to which protein kinases-protein kinase A, protein kinase B (Akt), other Ser/Thr protein kinases, or tyrosine kinases-are responsible for shear-dependent eNOS regulation. The functional significance of each phosphorylation site is still unclear. We have attempted to summarize the current status of understanding in shear-dependent eNOS regulation.
Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

PubMed

Bryce, Courtney A; Floresco, Stan B

2016-07-01

Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression.
Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor

PubMed Central

Bryce, Courtney A; Floresco, Stan B

2016-01-01

Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression. PMID:26830960
Mapping the Dynamics of Shear Stress—Induced Structural Changes in Endothelial Cells

PubMed Central

Mott, Rosalind E.; Helmke, Brian P.

2009-01-01

Hemodynamic shear stress regulates endothelial cell biochemical processes that govern cytoskeletal contractility, focal adhesion dynamics, and extracellular matrix assembly. Since shear stress causes rapid strain focusing at discrete locations in the cytoskeleton, we hypothesized that shear stress coordinately alters structural dynamics in the cytoskeleton, focal adhesion sites, and extracellular matrix on a time scale of minutes. Using multi-wavelength 4-D fluorescence microscopy, we measured the displacement of rhodamine-fibronectin and of GFP-labeled actin, vimentin, paxillin, and/or vinculin in aortic endothelial cells before and after onset of steady unidirectional shear stress. In the cytoskeleton, the onset of shear stress increased actin polymerization into lamellipodia, altered the angle of lateral displacement of actin stress fibers and vimentin filaments, and decreased centripetal remodeling of actin stress fibers in both subconfluent and confluent cell layers. Shear stress induced the formation of new focal complexes and reduced the centripetal remodeling of focal adhesions in regions of new actin polymerization. The structural dynamics of focal adhesions and the fibronectin matrix varied with cell density. In subconfluent cell layers, shear stress onset decreased the displacement of focal adhesions and fibronectin fibrils. In confluent monolayers, the direction of fibronectin and focal adhesion displacement shifted significantly towards the downstream direction within one minute after onset of shear stress. These spatially coordinated rapid changes in the structural dynamics of cytoskeleton, focal adhesions, and extracellular matrix are consistent with focusing of mechanical stress and/or strain near major sites of shear stress-mediated mechanotransduction. PMID:17855768

Endoplasmic Reticulum Stress in Mice Increases Hepatic Expression of Genes Carrying a Premature Termination Codon via a Nutritional Status-Independent GRP78-Dependent Mechanism.

PubMed

Harada, Nagakatsu; Okuyama, Maiko; Yoshikatsu, Aya; Yamamoto, Hironori; Ishiwata, Saori; Hamada, Chikako; Hirose, Tomoyo; Shono, Masayuki; Kuroda, Masashi; Tsutsumi, Rie; Takeo, Jiro; Taketani, Yutaka; Nakaya, Yutaka; Sakaue, Hiroshi

2017-11-01

Nonsense-mediated mRNA decay (NMD) degrades mRNAs carrying a premature termination codon (PTC) in eukaryotes. Cellular stresses, including endoplasmic reticulum (ER) stress, inhibit NMD, and up-regulate PTC-containing mRNA (PTC-mRNA) levels in several cell lines. However, whether similar effects exist under in vivo conditions that involve systemic nutritional status is unclear. Here, we compared the effects of pharmacological induction of ER stress with those of nutritional interventions on hepatic PTC-mRNA levels in mice. In mouse livers, the ER stress inducer tunicamycin increased PTC-mRNA levels of endogenous marker genes. Tunicamycin decreased body weight and perturbed nutrient metabolism in mice. Food restriction or deprivation mimicked the effect of tunicamycin on weight loss and metabolism, but did not increase PTC-mRNA levels. Hyperphagia-induced obesity also had little effect on hepatic PTC-mRNA levels. Meanwhile, in mouse liver phosphorylation of eIF2α, a factor that regulates NMD, was increased by both tunicamycin and nutritional interventions. Hepatic expression of GRP78, a central chaperone in ER stress responses, was increased by tunicamycin but not by the nutritional interventions. In cultured liver cells (Hepa), exogenous overexpression of a phosphomimetic eIF2α failed to increase PTC-mRNA levels. However, GRP78 overexpression in Hepa cells increased PTC-mRNA and PTC-mRNA-derived protein levels. ER stress promoted localization of GRP78 to mitochondria, and exogenous expression of a GRP78 fusion protein targeted to mitochondria mimicked the effect of wild type GRP78. These results indicate that GRP78, but not nutritional status, is a potent up-regulator of hepatic PTC-mRNA levels during induction of ER stress in vivo. J. Cell. Biochem. 118: 3810-3824, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment

PubMed Central

Kim, Bong Cho; Lee, Hyung Chul; Lee, Je-Jung; Choi, Chang-Min; Kim, Dong-Kwan; Lee, Jae Cheol; Ko, Young-Gyu; Lee, Jae-Seon

2012-01-01

Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA-induced silencing complex (RISC), with target p21 mRNA via binding of the stem-loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA-mediated gene silencing. In addition, these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence. PMID:23085987
Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment.

PubMed

Kim, Bong Cho; Lee, Hyung Chul; Lee, Je-Jung; Choi, Chang-Min; Kim, Dong-Kwan; Lee, Jae Cheol; Ko, Young-Gyu; Lee, Jae-Seon

2012-11-14

Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA-induced silencing complex (RISC), with target p21 mRNA via binding of the stem-loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA-mediated gene silencing. In addition, these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence.
[The role of oxytocin and vasopressin in central nervous system activity and mental disorders].

PubMed

Wójciak, Paweł; Remlinger-Molenda, Agnieszka; Rybakowski, Janusz

2012-01-01

Oxytocin and vasopressin, "peptides of love and fear", except for their classic role in control of labor and breastfeeding and blood pressure regulation, are also implicated in various processes like sexual behaviours, social recognition and stress response. These hormones seems to be essential for appropriate and beneficial social interactions, play a very important role in maternal care and closeness, promote general trust and cooperation and prolong social memory. They also play a very important role in modulating fear and anxiety response, especially by regulating the hypothalamic-pituitary-adrenal axis and amygdala activity by its projections to the brain stem and hypothalamic structures. Both hormones, particularly oxytocin, appears to be activating sexual behaviour or is responsible for increased sexual arousal. Evidence from clinical trials suggests their potential role in pathogenesis of schizophrenia, depression, autism and addiction together with possible therapeutic use in the above conditions. In schizophrenia, patients with higher peripheral oxytocin levels showed less severe positive, general and social symptoms and better prosocial behaviours. Literature suggests that exogenous oxytocin may be effective as an adjunctive therapy for that illness. Some data suggest that naturally occurring autoantibodies reacting with oxytocin and vasopressin are involved in depression, eating disorders and conduct disorder genesis.
Post-Traumatic Stress Avoidance is Attenuated by Corticosterone and Associated with Brain Levels of Steroid Receptor Co-Activator-1 in Rats

PubMed Central

Whitaker, Annie M.; Farooq, Muhammad A.; Edwards, Scott; Gilpin, Nicholas W.

2016-01-01

Individuals with post-traumatic stress disorder (PTSD) avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal (HPA) axis activation at the time of stress. Our laboratory has established a rodent model of stress that mimics the avoidance symptom cluster of PTSD. Rats are classified as ‘Avoiders’ or ‘Non-Avoiders’ post-stress based on avoidance of a predator-odor paired context. Previously, we demonstrated that Avoiders exhibit an attenuated HPA stress response to predator odor. We hypothesized that corticosterone administration prior to stress would reduce magnitude and incidence of avoidance of a stress-paired context. Furthermore, we predicted that Avoiders would exhibit altered expression of GR signaling machinery elements, such as steroid receptor co-activator (SRC)-1. Male Wistar rats (n = 16) were pre-treated with corticosterone (25 mg/kg) or saline and exposed to predator odor stress paired with a context, and tested for avoidance 24 h later, A second group of corticosterone-naïve rats (n = 24) were stressed (or not stressed), indexed for avoidance 24 h later, and killed 48 h post-odor exposure for analysis of phosphorylated GR, FKBP51, and SRC-1 levels in the paraventricular nucleus (PVN), central amygdala (CeA) and ventral hippocampus (VH), all brain sites that express high quantities of GRs and regulate HPA function. Rats pre-treated with corticosterone exhibited lower magnitude and incidence of avoidance. Predator odor exposure also reduced SRC-1 expression in the PVN and CeA of Avoiders, and increased SRC-1 expression in the VH of Avoiders. SRC-1 expression in PVN, CeA, and VH was predicted by prior avoidance behavior. These results suggest that blunted HPA stress response may contribute to stress-induced neuroadaptations in central SRC-1 levels and behavioral dysfunction in Avoider rats. PMID:26482332
A DNA Origami Mechanical Device for the Regulation of Microcosmic Structural Rigidity.

PubMed

Wan, Neng; Hong, Zhouping; Wang, Huading; Fu, Xin; Zhang, Ziyue; Li, Chao; Xia, Han; Fang, Yan; Li, Maoteng; Zhan, Yi; Yang, Xiangliang

2017-11-01

DNA origami makes it feasible to fabricate a tremendous number of DNA nanostructures with various geometries, dimensions, and functionalities. Moreover, an increasing amount of research on DNA nanostructures is focused on biological and biomedical applications. Here, the reversible regulation of microcosmic structural rigidity is accomplished using a DNA origami device in vitro. The designed DNA origami monomer is composed of an internal central axis and an external sliding tube. Due to the external tube sliding, the device transforms between flexible and rigid states. By transporting the device into the liposome, the conformational change of the origami device induces a structural change in the liposome. The results obtained demonstrate that the programmed DNA origami device can be applied to regulate the microcosmic structural rigidity of liposomes. Because microcosmic structural rigidity is important to cell proliferation and function, the results obtained potentially provide a foundation for the regulation of cell microcosmic structural rigidity using DNA nanostructures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Structural Analysis of Helios Filament-Wound Tanks Subjected to Internal Pressure and Cooling

NASA Technical Reports Server (NTRS)

Ko, William L

2005-01-01

A finite-element stress analysis is performed on Helios filament-wound hydrogen tanks to examine the stress field and effect of end dome geometry on the stress field. Each tank is composed of a central circular cylindrical section with either geodesic or hemispherical end domes, which have metallic polar bosses. The tanks are subjected to combined and separate internal pressure and temperature loading conditions, and the stress contributions of each loading component are examined. The tank-wall-polar-boss interfacial meridional tensile stress in the hemispherical dome is found to be approximately 27 percent lower than that in the geodesic dome. The effects of both material anisotropy and the aluminum lining on the intensities of tensile meridional stress at the tank-wall-polar-boss bonding interface are examined.
Glutathionylation of the Bacterial Hsp70 Chaperone DnaK Provides a Link between Oxidative Stress and the Heat Shock Response.

PubMed

Zhang, Hong; Yang, Jie; Wu, Si; Gong, Weibin; Chen, Chang; Perrett, Sarah

2016-03-25

DnaK is the major bacterial Hsp70, participating in DNA replication, protein folding, and the stress response. DnaK cooperates with the Hsp40 co-chaperone DnaJ and the nucleotide exchange factor GrpE. Under non-stress conditions, DnaK binds to the heat shock transcription factor σ(32)and facilitates its degradation. Oxidative stress results in temporary inactivation of DnaK due to depletion of cellular ATP and thiol modifications such as glutathionylation until normal cellular ATP levels and a reducing environment are restored. However, the biological significance of DnaK glutathionylation remains unknown, and the mechanisms by which glutathionylation may regulate the activity of DnaK are also unclear. We investigated the conditions under which Escherichia coli DnaK undergoesS-glutathionylation. We observed glutathionylation of DnaK in lysates of E. coli cells that had been subjected to oxidative stress. We also obtained homogeneously glutathionylated DnaK using purified DnaK in the apo state. We found that glutathionylation of DnaK reversibly changes the secondary structure and tertiary conformation, leading to reduced nucleotide and peptide binding ability. The chaperone activity of DnaK was reversibly down-regulated by glutathionylation, accompanying the structural changes. We found that interaction of DnaK with DnaJ, GrpE, or σ(32)becomes weaker when DnaK is glutathionylated, and the interaction is restored upon deglutathionylation. This study confirms that glutathionylation down-regulates the functions of DnaK under oxidizing conditions, and this down-regulation may facilitate release of σ(32)from its interaction with DnaK, thus triggering the heat shock response. Such a mechanism provides a link between oxidative stress and the heat shock response in bacteria. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
[STUDYING THE ROLE OF BRAIN MELANOCORTIN RECEPTORS IN THE SUPPRESSING OF FOOD INTAKE UNDER ETHER STRESS IN MICE].

PubMed

Bazhan, N M; Kulikova, E V; Makarova, E N; Yakovleva, T V; Kazantseva, A Yu

2015-12-01

Melanocortin (MC) system regulates food intake under the rest conditions. Stress inhibits food intake. It is not clear whether brain MC system is involved in stress-induced anorexia in mice. The aim of the work was to investigate the effect of pharmacological blockade and activation of brain MC receptors on food intake under stress. C57B1/6J male mice were subjected to ether stress (0.5 minute ether anesthesia) before the administration of saline solution or synthetic non-selective blocker (SHU9119) or agonist (Melanotan II) of MC receptors into the lateral brain ventricle. Food intake was pre-stimulated with 17 hours of fasting in all mice. Ether stress decreased food intake, increased the plasma corticosterone level and hypothalamic mRNA AgRP (natural MC receptor antagonist) level at 1 hour after the stress. Pharmacological blockade of the MC receptors weakened stress-induced anorexia and decreased mRNA AgRP level in the hypothalamus. Pharmacological stimulation of the MC receptors enhanced ether stress-induced anorexia and hypercortisolism. Thus, our data demonstrated that the central MC system was involved in the development of stress-induced anorexia in mice.
The Ventromedial Prefrontal Cortex in a Model of Traumatic Stress: Fear Inhibition or Contextual Processing?

ERIC Educational Resources Information Center

Pennington, Zachary T.; Anderson, Austin S.; Fanselow, Michael S.

2017-01-01

The ventromedial prefrontal cortex (vmPFC) has consistently appeared altered in post-traumatic stress disorder (PTSD). Although the vmPFC is thought to support the extinction of learned fear responses, several findings support a broader role for this structure in the regulation of fear. To further characterize the relationship between vmPFC…
The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

PubMed

Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

2016-05-01

Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.
Gene regulation system of vasopressin and corticotropin-releasing hormone.

PubMed

Yoshida, Masanori

2008-03-03

The neurohypophyseal hormones, arginine vasopressin and corticotropin-releasing hormone (CRH), play a crucial role in the physiological and behavioral response to various kinds of stresses. Both neuropeptides activate the hypophysial-pituitary-adrenal (HPA) axis, which is a central mediator of the stress response in the body. Conversely, they receive the negative regulation by glucocorticoid, which is an end product of the HPA axis. Vasopressin and CRH are closely linked to immune response; they also interact with pro-inflammatory cytokines. Moreover, as for vasopressin, it has another important role, which is the regulation of water balance through its potent antidiuretic effect. Hence, it is conceivable that vasopressin and CRH mediate the homeostatic responses for survival and protect organisms from the external world. A tight and elaborate regulation system of the vasopressin and CRH gene is required for the rapid and flexible response to the alteration of the surrounding environments. Several important regulatory elements have been identified in the proximal promoter region in the vasopressin and CRH gene. Many transcription factors and intracellular signaling cascades are involved in the complicated gene regulation system. This review focuses on the current status of the basic research of vasopressin and CRH. In addition to the numerous known facts about their divergent physiological roles, the recent topics of promoter analyses will be discussed.
Examining the intersection of sex and stress in modelling neuropsychiatric disorders.

PubMed

Goel, N; Bale, T L

2009-03-01

Sex-biased neuropsychiatric disorders, including major depressive disorder and schizophrenia, are the major cause of disability in the developed world. Elevated stress sensitivity has been proposed as a key underlying factor in disease onset. Sex differences in stress sensitivity are associated with corticotrophin-releasing factor (CRF) and serotonin neurotransmission, which are important central regulators of mood and coping responses. To elucidate the underlying neurobiology of stress-related disease predisposition, it is critical to develop appropriate animal models of stress pathway dysregulation. Furthermore, the inclusion of sex difference comparisons in stress responsive behaviours, physiology and central stress pathway maturation in these models is essential. Recent studies by our laboratory and others have begun to investigate the intersection of stress and sex where the development of mouse models of stress pathway dysregulation via prenatal stress experience or early-life manipulations has provided insight into points of developmental vulnerability. In addition, examination of the maturation of these pathways, including the functional importance of the organisational and activational effects of gonadal hormones on stress responsivity, is essential for determination of when sex differences in stress sensitivity may begin. In such studies, we have detected distinct sex differences in stress coping strategies where activational effects of testosterone produced females that displayed male-like strategies in tests of passive coping, but were similar to females in tests of active coping. In a second model of elevated stress sensitivity, male mice experiencing prenatal stress early in gestation showed feminised physiological and behavioural stress responses, and were highly sensitive to a low dose of selective serotonin reuptake inhibitors. Analyses of expression and epigenetic patterns revealed changes in CRF and glucocorticoid receptor genes in these mice. Mechanistically, stress early in pregnancy produced a significant sex-dependent effect on placental gene expression that was supportive of altered foetal transport of key growth factors and nutrients. These mouse models examining alterations and hormonal effects on development of stress pathways provide necessary insight into how specific stress responses can be reprogrammed early in development resulting in sex differences in stress sensitivity and neuropsychiatric disease vulnerability.
Examining the intersection of sex and stress in modeling neuropsychiatric disorders

PubMed Central

Goel, Nirupa; Bale, Tracy L.

2009-01-01

Sex-biased neuropsychiatric disorders, including major depressive disorder and schizophrenia, are the major cause of disability in the developed world. Elevated stress sensitivity has been proposed as a key underlying factor in disease onset. Sex differences in stress sensitivity are associated with CRF and serotonin neurotransmission, important central regulators of mood and coping responses. To elucidate the underlying neurobiology of stress-related disease predisposition, it is critical to develop appropriate animal models of stress pathway dysregulation. Further, the inclusion of sex difference comparisons in stress responsive behaviors, physiology, and central stress pathway maturation in these models is essential. Recent studies by our lab and others have begun to investigate the intersection of stress and sex where the development of mouse models of stress pathway dysregulation via prenatal stress experience or early life manipulations has provided insight into points of developmental vulnerability. In addition, examination of the maturation of these pathways including the functional importance of the organizational and activational effects of gonadal hormones on stress responsivity is essential for determination of when sex differences in stress sensitivity may begin. In such studies, we have detected distinct sex differences in stress coping strategies where activational effects of testosterone produced females that displayed male-like strategies in tests of passive coping, but were similar to females in tests of active coping. In a second model of elevated stress sensitivity, male mice experiencing prenatal stress early in gestation showed feminized physiological and behavioral stress responses, and were highly sensitive to a low dose of SSRI. Analyses of expression and epigenetic patterns revealed changes in CRF and glucocorticoid receptor genes in these mice. Mechanistically, stress early in pregnancy produced a significant sex-dependent effect on placental gene expression supportive of altered fetal transport of key growth factors and nutrients. These mouse models examining alterations and hormonal effects on development of stress pathways provide necessary insight into how specific stress responses can be reprogrammed early in development resulting in sex differences in stress sensitivity and neuropsychiatric disease vulnerability. PMID:19187468
Stress field variations in the Swiss Alps and the northern Alpine foreland derived from inversion of fault plane solutions

USGS Publications Warehouse

Kastrup, U.; Zoback, M.L.; Deichmann, N.; Evans, Kenneth F.; Giardini, D.; Michael, A.J.

2004-01-01

This study is devoted to a systematic analysis of the state of stress of the central European Alps and northern Alpine foreland in Switzerland based on focal mechanisms of 138 earthquakes with magnitudes between 1 and 5. The most robust feature of the results is that the azimuth of the minimum compressive stress, S3, is generally well constrained for all data subsets and always lies in the NE quadrant. However, within this quadrant, the orientation of S3 changes systematically both along the structural strike of the Alpine chain and across it. The variation in stress along the mountain belt from NE to SW involves a progressive, counterclockwise rotation of S3 and is most clear in the foreland, where it amounts to 45??-50??. This pattern of rotation is compatible with the disturbance to the stress field expected from the indentation of the Adriatic Block into the central European Plate, possibly together with buoyancy forces arising from the strongly arcuate structure of the Moho to the immediate west of our study area. Across the Alps, the variation in azimuth of S3 is defined by a progressive, counterclockwise rotation of about 45?? from the foreland in the north across the Helvetic domain to the Penninic nappes in the south and is accompanied by a change from a slight predominance of strike-slip mechanisms in the foreland to a strong predominance of normal faulting in the high parts of the Alps. The observed rotation can be explained by the perturbation of the large-scale regional stress by a local uniaxial deviatoric tension with a magnitude similar to that of the regional differential stress and with an orientation perpendicular to the strike of the Alpine belt. The tensile nature and orientation of this stress is consistent with the "spreading" stress expected from lateral density changes due to a crustal root beneath the Alps. Copyright 2004 by the American Geophysical Union.
The arabidopsis polyamine transporter LHRI/AtPUT3 modulates heat responsive gene expression by regulating mRNA stability

USDA-ARS?s Scientific Manuscript database

Polyamines (PA) involve in the gene regulation by interacting with various anionic macromolecules such as DNA, RNA and proteins and modulating their structure and function. Previous studies have showed that changing in polyamine biosynthesis alters plant response to different abiotic stresses. Here,...
Leptin in the interplay of inflammation, metabolism and immune system disorders.

PubMed

Abella, Vanessa; Scotece, Morena; Conde, Javier; Pino, Jesús; Gonzalez-Gay, Miguel Angel; Gómez-Reino, Juan J; Mera, Antonio; Lago, Francisca; Gómez, Rodolfo; Gualillo, Oreste

2017-02-01

Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes. Research on the regulation of different adipose tissues has provided important insights into the intricate network that links nutrition, metabolism and immune homeostasis. The neuroendocrine and immune systems communicate bi-directionally through common ligands and receptors during stress responses and inflammation, and control cellular immune responses in several pathological situations including immune-inflammatory rheumatic diseases. This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis.
The Structural Connectome of the Human Central Homeostatic Network.

PubMed

Edlow, Brian L; McNab, Jennifer A; Witzel, Thomas; Kinney, Hannah C

2016-04-01

Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.
The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription▿

PubMed Central

Dutta, Chaitali; Patel, Prasanta K.; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

2008-01-01

The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF, the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G1/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes. PMID:18662996
The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation.

PubMed Central

Van Der Heide, Lars P; Hoekman, Marco F M; Smidt, Marten P

2004-01-01

FoxO (forkhead box O; forkhead members of the O class) are transcription factors that function under the control of insulin/insulin-like signalling. FoxO factors have been associated with a multitude of biological processes, including cell-cycle, cell death, DNA repair, metabolism and protection from oxidative stress. Central to the regulation of FoxO factors is a shuttling system, which confines FoxO factors to either the nucleus or the cytosol. Shuttling of FoxO requires protein phosphorylation within several domains, and association with 14-3-3 proteins and the nuclear transport machinery. Description of the FoxO-shuttling mechanism contributes to the understanding of FoxO function in relation to signalling and gene regulation. PMID:15005655

Molecular analysis of Hsp70 mechanisms in plants and their function in response to stress.

PubMed

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

2017-04-01

Studying the strategies of improving abiotic stress tolerance is quite imperative and research under this field will increase our understanding of response mechanisms to abiotic stress such as heat. The Hsp70 is an essential regulator of protein having the tendency to maintain internal cell stability like proper folding protein and breakdown of unfolded proteins. Hsp70 holds together protein substrates to help in movement, regulation, and prevent aggregation under physical and or chemical pressure. However, this review reports the molecular mechanism of heat shock protein 70 kDa (Hsp70) action and its structural and functional analysis, research progress on the interaction of Hsp70 with other proteins and their interaction mechanisms as well as the involvement of Hsp70 in abiotic stress responses as an adaptive defense mechanism.
A novel plant ferredoxin-like protein and the regulator Hor are quorum-sensing targets in the plant pathogen Erwinia carotovora.

PubMed

Sjöblom, Solveig; Harjunpää, Heidi; Brader, Günter; Palva, E Tapio

2008-07-01

Quorum sensing (QS), a population-density-sensing mechanism, controls the production of the main virulence determinants, the plant cell-wall-degrading enzymes (PCWDEs) of the soft-rot phytopathogen Erwinia carotovora subsp. carotovora. In this study, we used random transposon mutagenesis with a gusA reporter construct to identify two new QS-controlled genes encoding the regulator Hor and a plant ferredoxin-like protein, FerE. The QS control of the identified genes was executed by the QS regulators ExpR1 and ExpR2 and mediated by the global repressor RsmA. Hor was shown to contribute to bacterial virulence at least partly through its control of PCWDE production. Our results showed that FerE contributes to oxidative stress tolerance and in planta fitness of the bacteria and suggest that QS could be central to control of oxidative stress tolerance. The presence of the FerE protein appears to be rather unique in heterotrophic bacteria and suggests an acquisition of the corresponding gene from plant host by horizontal gene transfer.
Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

PubMed Central

Lee, Wei-Hua; Higuchi, Hitoshi; Ikeda, Sakae; Macke, Erica L; Takimoto, Tetsuya; Pattnaik, Bikash R; Liu, Che; Chu, Li-Fang; Siepka, Sandra M; Krentz, Kathleen J; Rubinstein, C Dustin; Kalejta, Robert F; Thomson, James A; Mullins, Robert F; Takahashi, Joseph S; Pinto, Lawrence H; Ikeda, Akihiro

2016-01-01

While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases. DOI: http://dx.doi.org/10.7554/eLife.19264.001 PMID:27863209
MOF maintains transcriptional programs regulating cellular stress response

PubMed Central

Sheikh, B N; Bechtel-Walz, W; Lucci, J; Karpiuk, O; Hild, I; Hartleben, B; Vornweg, J; Helmstädter, M; Sahyoun, A H; Bhardwaj, V; Stehle, T; Diehl, S; Kretz, O; Voss, A K; Thomas, T; Manke, T; Huber, T B; Akhtar, A

2016-01-01

MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes. PMID:26387537
MOF maintains transcriptional programs regulating cellular stress response.

PubMed

Sheikh, B N; Bechtel-Walz, W; Lucci, J; Karpiuk, O; Hild, I; Hartleben, B; Vornweg, J; Helmstädter, M; Sahyoun, A H; Bhardwaj, V; Stehle, T; Diehl, S; Kretz, O; Voss, A K; Thomas, T; Manke, T; Huber, T B; Akhtar, A

2016-05-01

MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes.
Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala.

PubMed

Li, Ming-Jia; Liu, Ling-Yu; Chen, Lin; Cai, Jie; Wan, You; Xing, Guo-Gang

2017-04-01

Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.
Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

PubMed Central

Bravo, Javier A.; Forsythe, Paul; Chew, Marianne V.; Escaravage, Emily; Savignac, Hélène M.; Dinan, Timothy G.; Bienenstock, John; Cryan, John F.

2011-01-01

There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression. PMID:21876150
Bicuculline, a GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin under an acute stress.

PubMed

Gastón, M S; Cid, M P; Salvatierra, N A

2017-03-01

Ghrelin is a peptide of 28 amino acids with a homology between species, which acts on the central nervous system to regulate different actions, including the control of growth hormone secretion and metabolic regulation. It has been suggested that central ghrelin is a mediator of behavior linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that the anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of the forebrain was blocked by bicuculline (a GABA A receptor competitive antagonist) but not by diazepam (a GABA A receptor allosteric agonist) in neonatal meat-type chicks (Cobb). Numerous studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activation mediates the response to stress in mammals and birds. However, it is still unclear whether this effect of ghrelin is associated with HPA activation. Therefore, we investigated whether anxiety behavior induced by intra-IMM ghrelin and mediated through GABA A receptors could be associated with HPA axis activation in the neonatal chick. In the present study, in an Open Field test, intraperitoneal bicuculline methiodide blocked anxiogenic-like behavior as well as the increase in plasma ACTH and corticosterone levels induced by ghrelin (30pmol) in neonatal chicks. Moreover, we showed for the first time that a competitive antagonist of GABA A receptor suppressed the HPA axis activation induced by an anxiogenic dose of ghrelin. These results show that the anxiogenic ghrelin action involves the activation of the HPA axis, with a complex functional interaction with the GABA A receptor. Copyright © 2016 Elsevier B.V. All rights reserved.
Cell fate control in the developing central nervous system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatmentsmore » of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.« less
Escherichia coli under Ionic Silver Stress: An Integrative Approach to Explore Transcriptional, Physiological and Biochemical Responses

PubMed Central

Saulou-Bérion, Claire; Gonzalez, Ignacio; Enjalbert, Brice; Audinot, Jean-Nicolas; Fourquaux, Isabelle; Jamme, Frédéric; Cocaign-Bousquet, Muriel; Mercier-Bonin, Muriel; Girbal, Laurence

2015-01-01

For a better understanding of the systemic effect of sub-lethal micromolar concentrations of ionic silver on Escherichia coli, we performed a multi-level characterization of cells under Ag+-mediated stress using an integrative biology approach combining physiological, biochemical and transcriptomic data. Physiological parameters, namely bacterial growth and survival after Ag+ exposure, were first quantified and related to the accumulation of intracellular silver, probed for the first time by nano secondary ion mass spectroscopy at sub-micrometer lateral resolution. Modifications in E. coli biochemical composition were evaluated under Ag+-mediated stress by in situ synchrotron Fourier-transform infrared microspectroscopy and a comprehensive transcriptome response was also determined. Using multivariate statistics, correlations between the physiological parameters, the extracellular concentration of AgNO3 and the intracellular silver content, gene expression profiles and micro-spectroscopic data were investigated. We identified Ag+-dependent regulation of gene expression required for growth (e.g. transporter genes, transcriptional regulators, ribosomal proteins), for ionic silver transport and detoxification (e.g. copA, cueO, mgtA, nhaR) and for coping with various types of stress (dnaK, pspA, metA,R, oxidoreductase genes). The silver-induced shortening of the acyl chain of fatty acids, mostly encountered in cell membrane, was highlighted by microspectroscopy and correlated with the down-regulated expression of genes involved in fatty acid transport (fadL) and synthesis/modification of lipid A (lpxA and arnA). The increase in the disordered secondary structure of proteins in the presence of Ag+ was assessed through the conformational shift shown for amides I and II, and further correlated with the up-regulated expression of peptidase (hfq) and chaperone (dnaJ), and regulation of transpeptidase expression (ycfS and ycbB). Interestingly, as these transpeptidases act on the structural integrity of the cell wall, regulation of their expression may explain the morphological damage reported under Ag+-mediated stress. This result clearly demonstrates that the cell membrane is a key target of ionic silver. PMID:26696268
Design and optimization of stress centralized MEMS vector hydrophone with high sensitivity at low frequency

NASA Astrophysics Data System (ADS)

Zhang, Guojun; Ding, Junwen; Xu, Wei; Liu, Yuan; Wang, Renxin; Han, Janjun; Bai, Bing; Xue, Chenyang; Liu, Jun; Zhang, Wendong

2018-05-01

A micro hydrophone based on piezoresistive effect, "MEMS vector hydrophone" was developed for acoustic detection application. To improve the sensitivity of MEMS vector hydrophone at low frequency, we reported a stress centralized MEMS vector hydrophone (SCVH) mainly used in 20-500 Hz. Stress concentration area was actualized in sensitive unit of hydrophone by silicon micromachining technology. Then piezoresistors were placed in stress concentration area for better mechanical response, thereby obtaining higher sensitivity. Static analysis was done to compare the mechanical response of three different sensitive microstructure: SCVH, conventional micro-silicon four-beam vector hydrophone (CFVH) and Lollipop-shaped vector hydrophone (LVH) respectively. And fluid-structure interaction (FSI) was used to analyze the natural frequency of SCVH for ensuring the measurable bandwidth. Eventually, the calibration experiment in standing wave field was done to test the property of SCVH and verify the accuracy of simulation. The results show that the sensitivity of SCVH has nearly increased by 17.2 dB in contrast to CFVH and 7.6 dB in contrast to LVH during 20-500 Hz.
mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging

PubMed Central

Perl, Andras

2015-01-01

The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase that plays pivotal roles in integrating growth signals on a cellular level. To support proliferation and survival under stress, two interacting complexes that harbor mTOR, mTORC1 and mTORC2, promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation, and inhibit autophagy. While rapamycin was originally developed as an inhibitor of T cell proliferation for preventing organ transplant rejection, its molecular target, mTOR, has been subsequently identified as a central regulator of metabolic cues that drive lineage specification in the immune system. Owing to oxidative stress, the activation of mTORC1 has emerged as a central pathway for the pathogenesis of systemic lupus erythematosus and other autoimmune diseases. Paradoxically, mTORC1 has been also identified as a mediator of the Warburg effect that allows cell survival under hypoxia. Rapamycin and new classes of mTOR inhibitors are being developed to block not only transplant rejection and autoimmunity but also to treat obesity and various forms of cancer. Through preventing these diseases, personalized mTOR blockade holds promise to extend life span. PMID:25907074
Role of CRF Receptor Signaling in Stress Vulnerability, Anxiety, and Depression

PubMed Central

Hauger, Richard L.; Risbrough, Victoria; Oakley, Robert H.; Olivares-Reyes, J. Alberto; Dautzenberg, Frank M.

2011-01-01

Markers of hyperactive central corticotropin releasing factor (CRF) systems and CRF-related single nucleotide polymorphisms (SNPs) have been identified in patients with anxiety and depressive disorders. Designing more effective antagonists may now be guided by data showing that small molecules bind to transmembrane domains. Specifically, CRF1 receptor antagonists have been developed as novel anxiolytic and antidepressant treatments. Because CRF1 receptors become rapidly desensitized by G protein-coupled receptor kinase (GRK) and β-arrestin mechanisms in the presence of high agonist concentrations, neuronal hypersecretion of synaptic CRF alone may be insufficient to account for excessive central CRF neurotransmission in stress-induced affective pathophysiology. In addition to desensitizing receptor function, GRK phosphorylation and β-arrestin binding can shift a G protein-coupled receptor (GPCR) to signal selectively via the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK-MAPK) or Akt pathways independent of G proteins. Also, Epac-dependent CRF1 receptor signaling via the ERK-MAPK pathway has been found to potentiate brain-derived neurotrophic factor (BDNF)-stimulated TrkB signaling. Thus, genetic or acquired abnormalities in GRK and β-arrestin function may be involved in the pathophysiology of stress-induced anxiety and depression. PMID:19906236
Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

PubMed

Sun, Hai-Ying; Hu, Yu-Juan; Zhao, Xue-Yan; Zhong, Yi; Zeng, Ling-Ling; Chen, Xu-Bo; Yuan, Jie; Wu, Jing; Sun, Yu; Kong, Wen; Kong, Wei-Jia

2015-07-01

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis. © 2015 FEBS.
Characterization of a Chlamydomonas Insertional Mutant that Disrupts Flagellar Central Pair Microtubule-associated Structures

PubMed Central

Mitchell, David R.; Sale, Winfield S.

1999-01-01

Two alleles at a new locus, central pair–associated complex 1 (CPC1), were selected in a screen for Chlamydomonas flagellar motility mutations. These mutations disrupt structures associated with central pair microtubules and reduce flagellar beat frequency, but do not prevent changes in flagellar activity associated with either photophobic responses or phototactic accumulation of live cells. Comparison of cpc1 and pf6 axonemes shows that cpc1 affects a row of projections along C1 microtubules distinct from those missing in pf6, and a row of thin fibers that form an arc between the two central pair microtubules. Electron microscopic images of the central pair in axonemes from radial spoke–defective strains reveal previously undescribed central pair structures, including projections extending laterally toward radial spoke heads, and a diagonal link between the C2 microtubule and the cpc1 projection. By SDS-PAGE, cpc1 axonemes show reductions of 350-, 265-, and 79-kD proteins. When extracted from wild-type axonemes, these three proteins cosediment on sucrose gradients with three other central pair proteins (135, 125, and 56 kD) in a 16S complex. Characterization of cpc1 provides new insights into the structure and biochemistry of the central pair apparatus, and into its function as a regulator of dynein-based motility. PMID:9922455
Real-time monitoring of stress erythropoiesis in vivo using Gata1 and beta-globin LCR luciferase transgenic mice.

PubMed

Suzuki, Mikiko; Ohneda, Kinuko; Hosoya-Ohmura, Sakie; Tsukamoto, Saho; Ohneda, Osamu; Philipsen, Sjaak; Yamamoto, Masayuki

2006-07-15

Erythroid progenitors have the potential to proliferate rapidly in response to environmental stimuli. This process is referred to as stress erythropoiesis, with erythropoietin (EPO) playing central roles in its promotion. In this study, we wanted to elucidate the molecular mechanisms governing the regulation of stress erythropoiesis and the maintenance of red-cell homeostasis. This was achieved by our development of a noninvasive real-time monitoring system for erythropoiesis using transgenic mouse lines expressing luciferase under the control of the mouse Gata1 hematopoietic regulatory domain (G1-HRD-luc) or human beta-globin locus control region (Hbb-LCR-luc). Optical bioluminescence images revealed that the luciferase was specifically expressed in spleen and bone marrow and was induced rapidly in response to anemia and hypoxia stimuli. The G1-HRD-luc activity tracked the emergence and disappearance of proerythroblast-stage progenitors, whereas the Hbb-LCR-luc activity tracked erythroblasts and later stage erythroid cells. Increased plasma EPO concentration preceded an increase in G1-HRD-luc, supporting our contention that EPO acts as the key upstream signal in stress erythropoiesis. Hence, we conclude that G1-HRD-luc and Hbb-LCR-luc reporters are differentially activated during stress erythropoiesis and that the transgenic mouse lines used serve as an important means for understanding the homeostatic regulation of erythropoiesis.
Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells

PubMed Central

Panossian, Alexander; Wikman, Georg; Kaur, Punit; Asea, Alexzander

2011-01-01

The beneficial stress–protective effect of adaptogens is related to the regulation of homeostasis via mechanisms of action associated with the hypothalamic–pituitary–adrenal axis and the regulation of key mediators of the stress response, such as molecular chaperones, stress-activated c-Jun N-terminal protein kinase, forkhead box O transcription factor, cortisol, and nitric oxide (NO). However, it still remains unclear what the primary upstream targets are in response to stimulation by adaptogens. The present study addresses this gap in our knowledge and suggests that an important target for adaptogen mediated stress–protective effector functions is the stress hormone neuropeptide Y (NPY). We demonstrated that ADAPT-232, a fixed combination of adaptogens Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract SHR-5, and its active constituent salidroside, stimulated the expression of NPY and 72 kDa heat shock protein (Hsp72) in isolated human neuroglia cells. The central role of NPY was validated in experiments in which pre-treatment of human neuroglia cells with NPY-siRNA and HSF1-siRNA resulted in the significant suppression of ADAPT-232-induced NPY and Hsp72 release. Taken together our studies suggest that the stimulation and release of the stress hormones, NPY and Hsp72, into systemic circulation is an innate defense response against mild stressors (ADAPT-232), which increase tolerance and adaptation to stress. PMID:22347152
Independent Effects of Neighborhood Poverty and Psychosocial Stress on Obesity Over Time.

PubMed

Kwarteng, Jamila L; Schulz, Amy J; Mentz, Graciela B; Israel, Barbara A; Perkins, Denise White

2017-12-01

The objective of the study was to examine the independent effects of neighborhood poverty and psychosocial stress on increases in central adiposity over time. Data are from a community sample of 157 Non-Hispanic Black, Non-Hispanic White, and Hispanic adults collected in 2002-2003 and 2007-2008, and from the 2000 Decennial Census. The dependent variable was waist circumference. Independent variables included neighborhood poverty, perceived neighborhood physical environment, family stress, safety stress, everyday unfair treatment, and a cumulative stress index. Weighted 3-level hierarchical linear regression models for a continuous outcome were used to assess the effects of neighborhood poverty and psychosocial stress on central adiposity over time. We also assessed whether psychosocial stress mediated the association between neighborhood poverty and central adiposity. Neighborhood poverty and everyday unfair treatment at baseline were independently associated with increases in central adiposity over time, accounting for the other indicators of stress. Perceptions of the neighborhood physical environment and cumulative stress mediated associations between neighborhood poverty and central adiposity. Results suggest that residing in neighborhoods with higher concentrations of poverty and exposure to everyday unfair treatment independently heighten risk of increased central adiposity over time. Associations between neighborhood poverty and central adiposity were mediated by perceptions of the neighborhood physical environment and by the cumulative stress index. Public health strategies to reduce obesity should consider neighborhood poverty and exposure to multiple sources of psychosocial stress, including everyday unfair treatment.
Transcriptomic analysis of (group I) Clostridium botulinum ATCC 3502 cold shock response.

PubMed

Dahlsten, Elias; Isokallio, Marita; Somervuo, Panu; Lindström, Miia; Korkeala, Hannu

2014-01-01

Profound understanding of the mechanisms foodborne pathogenic bacteria utilize in adaptation to the environmental stress they encounter during food processing and storage is of paramount importance in design of control measures. Chill temperature is a central control measure applied in minimally processed foods; however, data on the mechanisms the foodborne pathogen Clostridium botulinum activates upon cold stress are scarce. Transcriptomic analysis on the C. botulinum ATCC 3502 strain upon temperature downshift from 37°C to 15°C was performed to identify the cold-responsive gene set of this organism. Significant up- or down-regulation of 16 and 11 genes, respectively, was observed 1 h after the cold shock. At 5 h after the temperature downshift, 199 and 210 genes were up- or down-regulated, respectively. Thus, the relatively small gene set affected initially indicated a targeted acute response to cold shock, whereas extensive metabolic remodeling appeared to take place after prolonged exposure to cold. Genes related to fatty acid biosynthesis, oxidative stress response, and iron uptake and storage were induced, in addition to mechanisms previously characterized as cold-tolerance related in bacteria. Furthermore, several uncharacterized DNA-binding transcriptional regulator-encoding genes were induced, suggesting involvement of novel regulatory mechanisms in the cold shock response of C. botulinum. The role of such regulators, CBO0477 and CBO0558A, in cold tolerance of C. botulinum ATCC 3502 was demonstrated by deteriorated growth of related mutants at 17°C.
Overlapping and distinct roles of AKIN10 and FUSCA3 in ABA and sugar signaling during seed germination.

PubMed

Tsai, Allen Yi-Lun; Gazzarrini, Sonia

2012-10-01

The Arabidopsis B3-domain transcription factor FUSCA3 (FUS3) is a master regulator of seed maturation and also a central modulator of hormonal responses during late embryogenesis and germination. Recently, we have identified AKIN10, the Arabidopsis ortholog of Snf1 (Sucrose Non-Fermenting-1)-Related Kinase1 (SnRK1), as a FUS3-interacting protein. We demonstrated that AKIN10 physically interacts with and phosphorylates FUS3 at its N-terminal region, and genetically interacts with FUS3 to regulate developmental phase transition and lateral organ growth. Snf1/AMPK/SnRK1 kinases are important sensors of the cellular energy level, and they are activated in response to starvation and cellular stress. Here we present findings that indicate FUS3 and AKIN10 functionally overlap in ABA signaling, but play different roles in sugar responses during germination. Seeds overexpressing FUS3 and AKIN10 both display ABA-hypersensitivity and delayed germination. The latter is partly dependent on de novo ABA synthesis in both genotypes, as delayed germination can be partially rescued by the ABA biosynthesis inhibitor, fluridone. However, seeds and seedlings overexpressing FUS3 and AKIN10 show different sugar responses. AKIN10-overexpressing seeds and seedlings are hypersensitive to glucose, while those overexpressing FUS3 display overall defects in osmotic stress, primarily during seedling growth, as they show increased sensitivity toward sorbitol and glucose. Hypersensitivity to sugar and/or osmotic stress during germination are partly dependent on de novo ABA synthesis for both genotypes, although are likely to act through distinct pathways. This data suggests that AKIN10 and FUS3 both act as positive regulators of seed responses to ABA, and that AKIN10 regulates sugar signaling while FUS3 mediates osmotic stress responses.

TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation.

PubMed

Graham, Daniel B; Lefkovith, Ariel; Deelen, Patrick; de Klein, Niek; Varma, Mukund; Boroughs, Angela; Desch, A Nicole; Ng, Aylwin C Y; Guzman, Gaelen; Schenone, Monica; Petersen, Christine P; Bhan, Atul K; Rivas, Manuel A; Daly, Mark J; Carr, Steven A; Wijmenga, Cisca; Xavier, Ramnik J

2016-12-13

Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5-61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Aquaporin structure-function relationships: water flow through plant living cells.

PubMed

Zhao, Chang-Xing; Shao, Hong-Bo; Chu, Li-Ye

2008-04-01

Plant aquaporins play an important role in water uptake and movement-an aquaporin that opens and closes a gate that regulates water movement in and out of cells. Some plant aquaporins also play an important role in response to water stress. Since their discovery, advancing knowledge of their structures and properties led to an understanding of the basic features of the water transport mechanism and increased illumination to water relations. Meanwhile, molecular and functional characterization of aquaporins has revealed the significance of their regulation in response to the adverse environments such as salinity and drought. This paper reviews the structure, species diversity, physiology function, regulation of plant aquaporins, and the relations between environmental factors and plant aquaporins. Complete understanding of aquaporin function and regulation is to integrate those mechanisms in time and space and to well regulate the permeation of water across biological membranes under changing environmental and developmental conditions.
Groundwater withdrawal in the Central Valley, California: implications for San Andreas Fault stressing and lithosphere rheology

NASA Astrophysics Data System (ADS)

Lundgren, P.; Liu, Z.; Ali, S. T.; Farr, T.; Faunt, C. C.

2016-12-01

Anthropogenic perturbations to crustal loading due to groundwater pumping are increasingly recognized as causing changes in nearby fault stresses. We present preliminary analysis of crustal unloading in the Central Valley (CV), California, for the period 2006-2010 to infer Coulomb stress changes on the central San Andreas Fault (CSAF), lithospheric rheology, and system memory due to more than a century of groundwater withdrawal in the southern CV. We use data-driven unloading estimates to drive three-dimensional (3-D) finite element method models and compare model vertical surface deformation rates with observed GPS uplift rates outside the CV. Groundwater level changes are observed through well water elevation changes and through the resultant surface deformation (subsidence) by interferometric synthetic aperture radar (InSAR) and through broader scale changes in gravity from the GRACE satellite time variable gravity data [Famiglietti et al., 2011] that constrain the overall water volume changes. Combining InSAR with well-water data we are able to estimate the aquifer skeletal elastic and inelastic response and through a linear inversion derive the water volume (load) changes across the Central Valley and compare them with GRACE-inferred groundwater changes. Preliminary 3-D finite element method modeling that considers elastic and viscosity structure in the lithosphere gives three interesting results: 1) elastic models poorly fit the uplift rates near the SAF; 2) viscoelastic models that simulate different unloading histories show the past history of groundwater unloading has significant residual uplift rates and fault stress changes; 3) Coulomb stress change varies from inhibited on the locked (Carrizo) section to promoted on the creeping section of the SAF north of Parkfield. Thus, 3D models that account for lithosphere rheology, loading history viscous relaxation, have significant implications for longer-term time-dependent deformation, stress perturbation, and earthquake hazard on the nearby faults. Reference: Famiglietti, J. S., M. Lo, S. L. Ho, J. Bethune, K. J. Anderson, T. H. Syed, S. C. Swenson, C. R. de Linage, and M. Rodell, 2011, Satellites measure recent rates of groundwater depletion in California's Central Valley, Geophys. Res. Lett., 38, L03403, doi:10.1029/2010GL046442.
Central Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure

PubMed Central

Tupone, Domenico

2014-01-01

SUMMARY Thermogenesis, the production of heat energy, is the specific, neurally-regulated, metabolic function of brown adipose tissue (BAT) and contributes to the maintenance of body temperature during cold exposure and to the elevated core temperature during several behavioral states, including wakefulness, the acute phase response (fever), and stress. BAT energy expenditure requires metabolic fuel availability and contributes to energy balance. This review summarizes the functional organization and neurochemical influences within the CNS networks governing the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolically-driven alterations in BAT thermogenesis and energy expenditure that contribute to overall energy homeostasis. PMID:24630813
PTP1B Regulates Cortactin Tyrosine Phosphorylation by Targeting Tyr446*S⃞

PubMed Central

Stuible, Matthew; Dubé, Nadia; Tremblay, Michel L.

2008-01-01

The emergence of protein-tyrosine phosphatase 1B (PTP1B) as a potential drug target for treatment of diabetes, obesity, and cancer underlies the importance of understanding its full range of cellular functions. Here, we have identified cortactin, a central regulator of actin cytoskeletal dynamics, as a substrate of PTP1B. A trapping mutant of PTP1B binds cortactin at the phosphorylation site Tyr446, the regulation and function of which have not previously been characterized. We show that phosphorylation of cortactin Tyr446 is induced by hyperosmolarity and potentiates apoptotic signaling during prolonged hyperosmotic stress. This study advances the importance of Tyr446 in the regulation of cortactin and provides a potential mechanism to explain the effects of PTP1B on processes including cell adhesion, migration, and tumorigenesis. PMID:18387954
Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system

PubMed Central

Imanaka-Yoshida, Kyoko; Aoki, Hiroki

2014-01-01

Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non-structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines, and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection (AAD) under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation, or pathological tissue remodeling. PMID:25120494
Epigenetic mechanisms involved in the effects of stress exposure: focus on 5-hydroxymethylcytosine.

PubMed

Hack, Laura M; Dick, Alec L W; Provençal, Nadine

2016-08-01

5-hydroxymethylcytosine (5hmC) is a recently re-discovered transient intermediate in the active demethylation pathway that also appears to play an independent role in modulating gene function. Epigenetic marks, particularly 5-methylcytosine, have been widely studied in relation to stress-related disorders given the long-lasting effect that stress has on these marks. 5hmC is a good candidate for involvement in the etiology of these disorders given its elevated concentration in mammalian neurons, its dynamic regulation during development of the central nervous system, and its high variability among individuals. Although we are unaware of any studies published to date examining 5 hmC profiles in human subjects who have developed a psychiatric disorder after a life stressor, there is emerging evidence from the animal literature that 5hmC profiles are altered in the context of fear-conditioning paradigms and stress exposure, suggesting a possible role for 5hmC in the biological underpinnings of stress-related disorders. In this review, the authors examine the available approaches for profiling 5hmC and describe their advantages and disadvantages as well as discuss the studies published thus far investigating 5hmC in the context of fear-related learning and stress exposure in animals. The authors also highlight the global versus locus-specific regulation of 5hmC in these studies. Finally, the limitations of the current studies and their implications are discussed.
Comparative transcriptome and gene co-expression network analysis reveal genes and signaling pathways adaptively responsive to varied adverse stresses in the insect fungal pathogen, Beauveria bassiana.

PubMed

He, Zhangjiang; Zhao, Xin; Lu, Zhuoyue; Wang, Huifang; Liu, Pengfei; Zeng, Fanqin; Zhang, Yongjun

2018-01-01

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. Beauveria bassiana is an economically important insect-pathogenic fungus which is widely used as a biocontrol agent to control a variety of insect pests. The fungal pathogen unavoidably encounters a variety of adverse environmental stresses and defense response from the host insects during application of the fungal agents. However, few are known about the transcription response of the fungus to respond or adapt varied adverse stresses. Here, we comparatively analyzed the transcriptome of B. bassiana in globe genome under the varied stationary-phase stresses including osmotic agent (0.8 M NaCl), high temperature (32 °C), cell wall-perturbing agent (Congo red), and oxidative agents (H 2 O 2 or menadione). Total of 12,412 reads were obtained, and mapped to the 6767 genes of the B. bassiana. All of these stresses caused transcription responses involved in basal metabolism, cell wall construction, stress response or cell rescue/detoxification, signaling transduction and gene transcription regulation, and likely other cellular processes. An array of genes displayed similar transcription patterns in response to at least two of the five stresses, suggesting a shared transcription response to varied adverse stresses. Gene co-expression network analysis revealed that mTOR signaling pathway, but not HOG1 MAP kinase pathway, played a central role in regulation the varied adverse stress responses, which was verified by RNAi-mediated knockdown of TOR1. Our findings provided an insight of transcription response and gene co-expression network of B. bassiana in adaptation to varied environments. Copyright © 2017 Elsevier Inc. All rights reserved.
Staphylococcus aureus CymR Is a New Thiol-based Oxidation-sensing Regulator of Stress Resistance and Oxidative Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji, Quanjiang; Zhang, Liang; Sun, Fei

As a human pathogen, Staphylococcus aureus must cope with oxidative stress generated by the human immune system. Here, we report that CymR utilizes its sole Cys-25 to sense oxidative stress. Oxidation followed by thiolation of this cysteine residue leads to dissociation of CymR from its cognate promoter DNA. In contrast, the DNA binding of the CymRC25S mutant was insensitive to oxidation and thiolation, suggesting that CymR senses oxidative stress through oxidation of its sole cysteine to form a mixed disulfide with low molecular weight thiols. The determined crystal structures of the reduced and oxidized forms of CymR revealed that Cys-25more » is oxidized to Cys-25-SOH in the presence of H{sub 2}O{sub 2}. Deletion of cymR reduced the resistance of S. aureus to oxidative stresses, and the resistance was restored by expressing a C25S mutant copy of cymR. In a C25S substitution mutant, the expression of two genes, tcyP and mccB, was constitutively repressed and did not respond to hydrogen peroxide stress, whereas the expression of the genes were highly induced under oxidative stress in a wild-type strain, indicating the critical role of Cys-25 in redox signaling in vivo. Thus, CymR is another master regulator that senses oxidative stress and connects stress responses to virulence regulation in S. aureus.« less
The stressed eyewitness: the interaction of thematic arousal and post-event stress in memory for central and peripheral event information

PubMed Central

Echterhoff, Gerald; Wolf, Oliver T.

2012-01-01

Both arousal during the encoding of stimuli and subsequent stress can affect memory, often by increasing memory for important or central information. We explored whether event-based (thematic) arousal and post-event stress interact to selectively enhance eyewitnesses' memory for the central aspects of an observed incident. Specifically, we argue that memory for stimuli should be enhanced when (1) the stimuli are encoded under arousal (vs. non-arousal), and (2) stress is experienced soon after the encoding episode. We designed an experiment that extended previous research by manipulating arousal without changing the stimulus material, distinguishing between central and peripheral event information, and using a dynamic, life-like event instead of static pictures. After watching a video depicting a burglary under high or low thematic arousal, psychosocial stress was induced or not induced by the Trier Social Stress Test (TSST). Salivary cortisol was measured at standard intervals. Consistent with our prediction, we found a significant post-event stress × thematic arousal × centrality interaction, indicating that the recognition advantage for central event items over peripheral event items was most pronounced under both high thematic arousal and post-event stress. Because stress was induced after encoding this interaction cannot be explained by possible differences at encoding, such as narrowed attention. The centrality effect of post-event stress under high thematic arousal was statistically mediated by the cortisol increase, which suggests a key role of the stress hormone. We discuss implications of our findings for psychological and neuroscientific theories of emotional memory formation. PMID:22936900
The stressed eyewitness: the interaction of thematic arousal and post-event stress in memory for central and peripheral event information.

PubMed

Echterhoff, Gerald; Wolf, Oliver T

2012-01-01

Both arousal during the encoding of stimuli and subsequent stress can affect memory, often by increasing memory for important or central information. We explored whether event-based (thematic) arousal and post-event stress interact to selectively enhance eyewitnesses' memory for the central aspects of an observed incident. Specifically, we argue that memory for stimuli should be enhanced when (1) the stimuli are encoded under arousal (vs. non-arousal), and (2) stress is experienced soon after the encoding episode. We designed an experiment that extended previous research by manipulating arousal without changing the stimulus material, distinguishing between central and peripheral event information, and using a dynamic, life-like event instead of static pictures. After watching a video depicting a burglary under high or low thematic arousal, psychosocial stress was induced or not induced by the Trier Social Stress Test (TSST). Salivary cortisol was measured at standard intervals. Consistent with our prediction, we found a significant post-event stress × thematic arousal × centrality interaction, indicating that the recognition advantage for central event items over peripheral event items was most pronounced under both high thematic arousal and post-event stress. Because stress was induced after encoding this interaction cannot be explained by possible differences at encoding, such as narrowed attention. The centrality effect of post-event stress under high thematic arousal was statistically mediated by the cortisol increase, which suggests a key role of the stress hormone. We discuss implications of our findings for psychological and neuroscientific theories of emotional memory formation.
Centrality of women's multiple roles: beneficial and detrimental consequences for psychological well-being.

PubMed

Martire, L M; Stephens, M A; Townsend, A L

2000-03-01

Theorists have proposed that greater centrality (personal importance) of a social role is associated with better psychological well-being but that role centrality exacerbates the negative effects of stress in that same social role on well-being. The present study found evidence to support both hypotheses in a sample of 296 women who simultaneously occupied the roles of parent care provider, mother, wife, and employee. Greater centrality of all four roles was related to better psychological well-being. As predicted, wife centrality exacerbated the effects of wife stress on life satisfaction, and employee centrality exacerbated the effects of employee stress on depressive symptoms. Contrary to prediction, centrality of the mother role buffered women from the negative effects of mother stress on depressive symptoms. These findings point to an aspect of role identity that can benefit well-being but that has complex effects in the context of role stress.
Schizothorax prenanti corticotropin-releasing hormone (CRH): molecular cloning, tissue expression, and the function of feeding regulation.

PubMed

Wang, Tao; Zhou, Chaowei; Yuan, Dengyue; Lin, Fangjun; Chen, Hu; Wu, Hongwei; Wei, Rongbin; Xin, Zhiming; Liu, Ju; Gao, Yundi; Li, Zhiqiong

2014-10-01

Corticotropin-releasing hormone (CRH) is a potent mediator of endocrine, autonomic, behavioral, and immune responses to stress. For a better understanding of the structure and function of the CRH gene and to study its effect on feeding regulation in cyprinid fish, the cDNA of the CRH gene from the brain of Schizothorax prenanti was cloned and sequenced. The full-length CRH cDNA consisted of 1,046 bp with an open reading frame of 489 bp encoding a protein of 162 amino acids. Real-time quantitative PCR analyses revealed that CRH was widely expressed in central and peripheral tissues. In particular, high expression level of CRH was detected in brain. Furthermore, CRH mRNA expression was examined in different brain regions, especially high in hypothalamus. In addition, there was no significant change in CRH mRNA expression in fed group compared with the fasted group in the S. prenanti hypothalamus during short-term fasting. However, CRH gene expression presented significant decrease in the hypothalamus in fasted group compared with the fed group (P < 0.05) on day 7; thereafter, re-feeding could lead to a significant increase in CRH mRNA expression in fasted group on day 9. The results suggest that the CRH may play a critical role in feeding regulation in S. prenanti.
Heme Oxygenase in the Regulation of Vascular Biology: From Molecular Mechanisms to Therapeutic Opportunities

PubMed Central

Kim, Young-Myeong; Pae, Hyun-Ock; Park, Jeong Euy; Lee, Yong Chul; Woo, Je Moon; Kim, Nam-Ho; Choi, Yoon Kyung; Lee, Bok-Soo; Kim, So Ri

2011-01-01

Abstract Heme oxygenases (HOs) are the rate-limiting enzymes in the catabolism of heme into biliverdin, free iron, and carbon monoxide. Two genetically distinct isoforms of HO have been characterized: an inducible form, HO-1, and a constitutively expressed form, HO-2. HO-1 is a kind of stress protein, and thus regarded as a sensitive and reliable indicator of cellular oxidative stress. The HO system acts as potent antioxidants, protects endothelial cells from apoptosis, is involved in regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in angiogenesis and vasculogenesis. Endothelial integrity and activity are thought to occupy the central position in the pathogenesis of cardiovascular diseases. Cardiovascular disease risk conditions converge in the contribution to oxidative stress. The oxidative stress leads to endothelial and vascular smooth muscle cell dysfunction with increases in vessel tone, cell growth, and gene expression that create a pro-thrombotic/pro-inflammatory environment. Subsequent formation, progression, and obstruction of atherosclerotic plaque may result in myocardial infarction, stroke, and cardiovascular death. This background provides the rationale for exploring the potential therapeutic role for HO system in the amelioration of vascular inflammation and prevention of adverse cardiovascular outcomes. Antioxid. Redox Signal. 14, 137–167. PMID:20624029
Effect of implant number and distribution on load transfer in implant-supported partial fixed dental prostheses for the anterior maxilla: A photoelastic stress analysis study.

PubMed

Lee, Jae-In; Lee, Yoon; Kim, Yu-Lee; Cho, Hye-Won

2016-02-01

The 4-, 3- or even 2-implant-supported partial fixed dental prosthesis (PFDP) designs have been used to rehabilitate the anterior edentulous maxilla. The purpose of this in vitro study was to compare the stress distribution in the supporting tissues surrounding implants placed in the anterior maxilla with 5 PFDP designs. A photoelastic model of the human maxilla with an anterior edentulous region was made with photoelastic resin (PL-2; Vishay Micro-Measurements), and 6 straight implants (OsseoSpeed; Astra Tech AB) were placed in the 6 anterior tooth positions. The 5 design concepts based on implant location were as follows: model 6I: 6 implants; model 2C2CI: 4 implants (2 canines and 2 central incisors); model 2C2LI: 4 implants (2 canines and 2 lateral incisors); model 2C1CI: 3 implants (2 canines and 1 central incisor); and model 2C: 2 canines. A load of 127.4 N was applied on the cingulum of 3 teeth at a 30-degree angle to the long axis of the implant. Stresses that developed in the supporting structure were recorded photographically. The 6-implant-supported PFDP exhibited the most even and lowest distribution of stresses in all loading conditions. When the canine was loaded, the 2- or 3-implant-supported PFDP showed higher stresses around the implant at the canine position than did the 4- or 6-implant-supported PFDP. When the central incisor or lateral incisor was loaded, the two 4-implant-supported PFDPs exhibited similar levels of stresses around the implants and showed lower stresses than did the 2- or 3-implant-supported PFDP. Implant number and distribution influenced stress distribution around the implants in the anterior maxilla. With a decrease in implant number, the stresses around the implants increased. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.
Structure of the second RRM domain of Nrd1, a fission yeast MAPK target RNA binding protein, and implication for its RNA recognition and regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobayashi, Ayaho; Kanaba, Teppei; Satoh, Ryosuke

Highlights: •Solution structure of the second RRM of Nrd1 was determined. •RNA binding site of the second RRM was estimated. •Regulatory mechanism of RNA binding by phosphorylation is discussed. -- Abstract: Negative regulator of differentiation 1 (Nrd1) is known as a negative regulator of sexual differentiation in fission yeast. Recently, it has been revealed that Nrd1 also regulates cytokinesis, in which physical separation of the cell is achieved by a contractile ring comprising many proteins including actin and myosin. Cdc4, a myosin II light chain, is known to be required for cytokinesis. Nrd1 binds and stabilizes Cdc4 mRNA, and therebymore » suppressing the cytokinesis defects of the cdc4 mutants. Interestingly, Pmk1 MAPK phosphorylates Nrd1, resulting in markedly reduced RNA binding activity. Furthermore, Nrd1 localizes to stress granules in response to various stresses, and Pmk1 phosphorylation enhances the localization. Nrd1 consists of four RRM domains, although the mechanism by which Pmk1 regulates the RNA binding activity of Nrd1 is unknown. In an effort to delineate the relationship between Nrd1 structure and function, we prepared each RNA binding domain of Nrd1 and examined RNA binding to chemically synthesized oligo RNA using NMR. The structure of the second RRM domain of Nrd1 was determined and the RNA binding site on the second RRM domain was mapped by NMR. A plausible mechanism pertaining to the regulation of RNA binding activity by phosphorylation is also discussed.« less
Classroom Learning Environments and the Mental Health of First Grade Children

ERIC Educational Resources Information Center

Milkie, Melissa A.; Warner, Catharine H.

2011-01-01

Sociological research focuses on how poverty, family, and neighborhood dynamics shape children's problems, but knowledge about how school is related to children's mental health is underdeveloped, despite its central presence in children's lives. Using a social structure and personality-stress contagion perspective, the authors use a nationally…
Men, hearts and minds: developing and piloting culturally specific psychometric tools assessing psychosocial stress and depression in central Australian Aboriginal men.

PubMed

Brown, Alex; Mentha, Ricky; Howard, Michael; Rowley, Kevin; Reilly, Rachel; Paquet, Catherine; O'Dea, Kerin

2016-02-01

The health inequalities experienced by Aboriginal and Torres Strait Islander Australians are well documented but there are few empirical data outlining the burden, consequences, experience and expression of depressive illness. This paper seeks to address the lack of accessible, culturally specific measures of psychosocial stress, depression or quality of life developed for, and validated within, this population. Building on an extensive qualitative phase of research, a psychosocial questionnaire comprising novel and adapted scales was developed and piloted with 189 Aboriginal men across urban and remote settings in central Australia. With a view to refining this tool for future use, its underlying structure was assessed using exploratory factor analysis, and the predictive ability of the emergent psychosocial constructs assessed with respect to depressive symptomatology. The latent structure of the psychosocial questionnaire was conceptually aligned with the components of the a priori model on which the questionnaire was based. Regression modelling indicated that depressive symptoms were driven by a sense of injury and chronic stress and had a non-linear association with socioeconomic position. This represents the first community-based survey of psychosocial stress and depression in Aboriginal men. It provides both knowledge of, and an appropriate process for, the further development of psychometric tools, including quality of life, in this population. Further research with larger and more diverse samples of Aboriginal people is required to refine the measurement of key constructs such as chronic stress, socioeconomic position, social support and connectedness. The further refinement, validation against criterion-based methods and incorporation within primary care services is essential.
Application experience of grade 10Kh9MFB chromium steel for steam shutoff and control valve bodies

NASA Astrophysics Data System (ADS)

Skorobogatykh, V. N.; Schenkova, I. A.; Danyushevskiy, I. A.; Grin', E. A.; Levkov, L. Ya.; Prudnikov, D. A.; Zhuravlev, D. N.; Bazhenov, A. M.

2017-04-01

In 2014-2015, the engineers of JSC "NPO "TsNIITMash", in cooperation with JSC "Energomash (Chekhov)—ChZEM", developed a technology for manufacturing D u = 250 mm valve bodies from 10Kh9MFB chromium steel by electroslag melting (ESM) and produced their pilot copies within the frame of import substitution program. This article provides results of research into determining the design values of metal characteristics, including short-term mechanical properties at working temperatures and impact and long-term strength. The test specimens have been sampled from the following four zones: bottom, central, branch-pipe, and head. Tensile short-term rupture testing has been performed at temperatures of 350, 450, 500, 550, 600, and 650°C. Testing for long-term strength has been carried out at temperatures of 550, 575, 600, and 625°C and stresses of 156.8, 137.2, 117.6, and 98 MPa. To estimate brittle fracture resistance, impact-strength tests have been run at temperatures of-20 and-10°C; 20 and 50°C. The specimens have been sampled from the middle of the blank section. All short-term mechanical properties and impact strength are in agreement with the requirements imposed on the metal of hot-deformed steam piping made of 10Kh9MFB steel as per TU (Technical Conditions) 14-3R-55-2001. The absence of microliquation of alloying elements and the high homogeneity of chemical composition (as demonstrated with nine specimens) have also been experimentally confirmed. Metallographic analysis has shown that the structure of the tested metal is that of tempered martensite with local areas of tempered bainite. Overall, the microscopic structure of metal is practically the same in all the studied zones. Service-life calculation of pilot valve bodies has proved conformity with the safety-margin regulations. Such properties of electroslag melting blank as long-term strength and allowable stress correspond to the level of deformed metal and to regulations.
Structural basis of dual Ca2+/pH regulation of the endolysosomal TRPML1 channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Minghui; Zhang, Wei K.; Benvin, Nicole M.

The activities of organellar ion channels are often regulated by Ca2+ and H+, which are present in high concentrations in many organelles. Here we report a structural element critical for dual Ca2+/pH regulation of TRPML1, a Ca2+-release channel crucial for endolysosomal function. TRPML1 mutations cause mucolipidosis type IV (MLIV), a severe lysosomal storage disorder characterized by neurodegeneration, mental retardation and blindness. We obtained crystal structures of the 213-residue luminal domain of human TRPML1 containing three missense MLIV-causing mutations. This domain forms a tetramer with a highly electronegative central pore formed by a novel luminal pore loop. Cysteine cross-linking and cryo-EMmore » analyses confirmed that this architecture occurs in the full-length channel. Structure–function studies demonstrated that Ca2+ and H+ interact with the luminal pore and exert physiologically important regulation. The MLIV-causing mutations disrupt the luminal-domain structure and cause TRPML1 mislocalization. Our study reveals the structural underpinnings of TRPML1's regulation, assembly and pathogenesis.« less

Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

PubMed

Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

2014-01-01

Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.
Long-Term Effects of Acute Stress on the Prefrontal-Limbic System in the Healthy Adult

PubMed Central

Wei, Dongtao; Du, Xue; Zhang, Qinglin; Liu, Guangyuan; Qiu, Jiang

2017-01-01

Most people are exposed to at least one traumatic event during the course of their lives, but large numbers of people do not develop posttraumatic stress disorders. Although previous studies have shown that repeated and chronic stress change the brain’s structure and function, few studies have focused on the long-term effects of acute stressful exposure in a nonclinical sample, especially the morphology and functional connectivity changes in brain regions implicated in emotional reactivity and emotion regulation. Forty-one months after the 5/12 Wenchuan earthquake, we investigated the effects of trauma exposure on the structure and functional connectivity of the brains of trauma-exposed healthy individuals compared with healthy controls matched for age, sex, and education. We then used machine-learning algorithms with the brain structural features to distinguish between the two groups at an individual level. In the trauma-exposed healthy individuals, our results showed greater gray matter density in prefrontal-limbic brain systems, including the dorsal anterior cingulate cortex, medial prefrontal cortex, amygdala and hippocampus, than in the controls. Further analysis showed stronger amygdala-hippocampus functional connectivity in the trauma-exposed healthy compared to the controls. Our findings revealed that survival of traumatic experiences, without developing PTSD, was associated with greater gray matter density in the prefrontal-limbic systems related to emotional regulation. PMID:28045980
The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways.

PubMed

Chen, Xubo; Zhao, Xueyan; Cai, Hua; Sun, Haiying; Hu, Yujuan; Huang, Xiang; Kong, Wen; Kong, Weijia

2017-08-01

Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H 2 S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H 2 S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKβ and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKβ and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD), declined. These effects were also achieved by activating CaMKKβ/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKβ and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKβ and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Tetrameres (Tetrameres) grusi (Shumakovich, 1946) (Nematoda: Tetrameridae) in Eurasian cranes (Grus grus) in central Iran.

PubMed

Mowlavi, G R; Massoud, J; Mobedi, I; Gharagozlou, M J; Rezaian, M; Solaymani-Mohammadi, S

2006-04-01

The proventriculi of 11 Eurasian cranes (Grus grus) from central Iran were examined for the existence of parasitic helminths. Preliminary reports suggested that the death of these birds was related to untimely cold weather. Nine proventriculi (82%) were heavily infected by the nematode Tetrameres grusi. Glandular structure of the infected proventriculi was replaced by epithelial atrophy but significant inflammatory reactions were not observed in any of the infected organs. In serious infections, the nematode produced vast structural and functional changes, causing organ dysfunction and glandular necrosis. The coincidence of heavy helminth infection at times of environmental stress may lead to debilitation, wasting, and perhaps mortality in migratory cranes.
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway

PubMed Central

Le Sage, Valerie; Cinti, Alessandro; Amorim, Raquel; Mouland, Andrew J.

2016-01-01

The mammalian target of rapamycin (mTOR) is a central regulator of gene expression, translation and various metabolic processes. Multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mTOR pathway. Viral infection is a significant stress that can activate, reduce or even suppress the mTOR signaling pathway. Consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the mTOR pathway in order to make the host cell a hospitable environment for replication. A more comprehensive knowledge of different viral interactions may provide fruitful targets for new antiviral drugs. PMID:27231932
Infant negative reactivity defines the effects of parent-child synchrony on physiological and behavioral regulation of social stress.

PubMed

Pratt, Maayan; Singer, Magi; Kanat-Maymon, Yaniv; Feldman, Ruth

2015-11-01

How infants shape their own development has puzzled developmentalists for decades. Recent models suggest that infant dispositions, particularly negative reactivity and regulation, affect outcome by determining the extent of parental effects. Here, we used a microanalytic experimental approach and proposed that infants with varying levels of negative reactivity will be differentially impacted by parent-infant synchrony in predicting physiological and behavioral regulation of increasing social stress during an experimental paradigm. One hundred and twenty-two mother-infant dyads (4-6 months) were observed in the face-to-face still face (SF) paradigm and randomly assigned to three experimental conditions: SF with touch, standard SF, and SF with arms' restraint. Mother-infant synchrony and infant negative reactivity were observed at baseline, and three mechanisms of behavior regulation were microcoded; distress, disengagement, and social regulation. Respiratory sinus arrhythmia baseline, reactivity, and recovery were quantified. Structural equation modeling provided support for our hypothesis. For physiological regulation, infants high in negative reactivity receiving high mother-infant synchrony showed greater vagal withdrawal, which in turn predicted comparable levels of vagal recovery to that of nonreactive infants. In behavioral regulation, only infants low in negative reactivity who received high synchrony were able to regulate stress by employing social engagement cues during the SF phase. Distress was reduced only among calm infants to highly synchronous mothers, and disengagement was lowest among highly reactive infants experiencing high mother-infant synchrony. Findings chart two pathways by which synchrony may bolster regulation in infants of high and low reactivity. Among low reactive infants, synchrony builds a social repertoire for handling interpersonal stress, whereas in highly reactive infants, it constructs a platform for repeated reparation of momentary interactive "failures" and reduces the natural tendency of stressed infants to disengage from source of distress. Implications for the construction of synchrony-focused interventions targeting infants of varying dispositions are discussed.
Targeting ion channels for the treatment of gastrointestinal motility disorders

PubMed Central

Beyder, Arthur

2012-01-01

Gastrointestinal (GI) functional and motility disorders are highly prevalent and responsible for long-term morbidity and sometimes mortality in the affected patients. It is estimated that one in three persons has a GI functional or motility disorder. However, diagnosis and treatment of these widespread conditions remains challenging. This partly stems from the multisystem pathophysiology, including processing abnormalities in the central and peripheral (enteric) nervous systems and motor dysfunction in the GI wall. Interstitial cells of Cajal (ICCs) are central to the generation and propagation of the cyclical electrical activity and smooth muscle cells (SMCs) are responsible for electromechanical coupling. In these and other excitable cells voltage-sensitive ion channels (VSICs) are the main molecular units that generate and regulate electrical activity. Thus, VSICs are potential targets for intervention in GI motility disorders. Research in this area has flourished with advances in the experimental methods in molecular and structural biology and electrophysiology. However, our understanding of the molecular mechanisms responsible for the complex and variable electrical behavior of ICCs and SMCs remains incomplete. In this review, we focus on the slow waves and action potentials in ICCs and SMCs. We describe the constituent VSICs, which include voltage-gated sodium (NaV), calcium (CaV), potassium (KV, KCa), chloride (Cl–) and nonselective ion channels (transient receptor potentials [TRPs]). VSICs have significant structural homology and common functional mechanisms. We outline the approaches and limitations and provide examples of targeting VSICs at the pores, voltage sensors and alternatively spliced sites. Rational drug design can come from an integrated view of the structure and mechanisms of gating and activation by voltage or mechanical stress. PMID:22282704
Visceral obesity: a "civilization syndrome".

PubMed

Björntorp, P

1993-05-01

The controversial question of the relationship between obesity and disease has been considerably clearer after the demonstration in several prospective, epidemiological studies that the subgroup of central, visceral obesity is particularly prone to develop cardiovascular disease, stroke, and non-insulin dependent diabetes mellitus. Visceral obesity is associated with multiple central endocrine aberrations. The hypothalamo-adrenal axis is apparently sensitive to stimuli, sex steroid hormone secretion blunted, and hyperandrogenicity is found in women. In addition, there seem to be signs of central dysfunctions in the regulation of hemodynamic factors after stress, and growth hormone secretion appears to be particularly blunted. Several of these endocrine abnormalities are associated with insulin resistance, particularly glycogen synthesis in muscle. Fiber composition with low type I/type II ratio might be secondary to the prevailing hyperinsulinemia, but low capillary density in muscle may well be of importance. In combination with elevated turn-over of free fatty acids (FFA) this will probably provide powerful mechanisms whereby insulin resistance is created. Portal FFA, from the highly lipolytic visceral depots may, in addition, affect hepatic metabolism to induce increased gluconeogenesis, production of very low density lipoproteins as well as to perhaps inhibit clearance of insulin. By these mechanisms a Metabolic Syndrome Visceral adipocytes seem to have a high density of several steroid hormone receptors, directing steroid hormone effects particularly to these depots. The net effect of cortisol is apparently a stimulation of lipid storage, with opposing effects of sex steroid hormones which also facilitate lipid mobilization, regulations most often found at the gene transcription level. Growth hormone inhibits cortisol effects on lipid accumulation, and amplifies the lipid mobilizing effects of steroid hormones. The combined perturbations of hormonal secretions will therefore probably direct triglycerides toward visceral depots. Circulatory and nervous regulatory mechanisms require, however, more attention. The multiple central endocrine and nervous aberrations of visceral obesity suggest neuroendocrine dysregulations, and have features characteristic of the hypothalamic arousal seen after certain types of stress, alcohol intake, and smoking. Such factors can be traced to subjects with visceral fat accumulation. Standardized stress, eliciting a "defeat reaction" in primates is followed by an apparently identical syndrome. This integrated picture of the multiple symptoms of visceral obesity is based on epidemiological, clinical, experimental, cellular, and molecular evidence. The ingredients of positive energy balance, including physical inactivity, stress, smoking, and alcohol consumption are frequent features of modern, urbanized society. Visceral obesity may therefore be an expression of a "Civilization Syndrome."
Altered Exocytosis in Chromaffin Cells from Mouse Models of Neurodegenerative Diseases.

PubMed

de Diego, Antonio M G; García, Antonio G

2018-05-09

Chromaffin cells from the adrenal gland (CCs) have extensively been used to explore the molecular structure and function of the exocytotic machinery, neurotransmitter release and synaptic transmission. The CC is integrated in the sympathoadrenal axis that helps the body maintain homeostasis during both routine life and in acute stress conditions. This function is exquisitely controlled by the cerebral cortex and the hypothalamus. We propose the hypothesis that damage undergone by the brain during neurodegenerative diseases is also affecting the neurosecretory function of adrenal medullary CCs. In this context we review here the following themes: (i) how the discharge of catecholamines is centrally and peripherally regulated at the sympatho-adrenal axis; (ii) which are the intricacies of the amperometric techniques used to study the quantal release of single-vesicle exocytotic events; (iii) which are the alterations of the exocytotic fusion pore so far reported, in CCs of mouse models of neurodegenerative diseases; (iv) how some proteins linked to neurodegenerative pathologies affects the kinetics of exocytotic events; (v) finally we try to integrate available data into a hypothesis to explain how the centrally originated neurodegenerative diseases may alter the kinetics of single-vesicle exocytotic events in peripheral adrenal medullary CCs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Hypoxia and fetal heart development.

PubMed

Patterson, A J; Zhang, L

2010-10-01

Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.
On the central charge for the W algebras

NASA Astrophysics Data System (ADS)

Hornfeck, K.

1991-02-01

For the W algebra that is built besides by the stress-energy tensor T by one additional field W we translate the (WWW) Jacobi-identity (that restricts in general the allowed values for the central charge) into a set of conditions on the structure constants CWWΦ and CΦWW with quasi-primary fields Φ. For the case where the additional field has half-integer dimension >3/2 we give a restriction on the possible central charges that includes that in this case c must be less than one. Address after 1 November 1990: Department of Mathematics, King's College, Strand, London WC2R 2LS, UK.
Magmatic control along a strike-slip volcanic arc: The central Aeolian arc (Italy)

NASA Astrophysics Data System (ADS)

Ruch, J.; Vezzoli, L.; De Rosa, R.; Di Lorenzo, R.; Acocella, V.

2016-02-01

The regional stress field in volcanic areas may be overprinted by that produced by magmatic activity, promoting volcanism and faulting. In particular, in strike-slip settings, the definition of the relationships between the regional stress field and magmatic activity remains elusive. To better understand these relationships, we collected stratigraphic, volcanic, and structural field data along the strike-slip central Aeolian arc (Italy): here the islands of Lipari and Vulcano separate the extensional portion of the arc (to the east) from the contractional one (to the west). We collected >500 measurements of faults, extension fractures, and dikes at 40 sites. Most structures are NNE-SSW to NNW-SSE oriented, eastward dipping, and show almost pure dip-slip motion, consistent with an E-W extension direction, with minor dextral and sinistral shear. Our data highlight six eruptive periods during the last 55 ka, which allow considering both islands as a single magmatic system, in which tectonic and magmatic activities steadily migrated eastward and currently focus on a 10 km long × 2 km wide active segment. Faulting appears to mostly occur in temporal and spatial relation with magmatic events, supporting that most of the observable deformation derives from transient magmatic activity (shorter term, days to months), rather than from steady longer-term regional tectonics (102-104 years). More in general, the central Aeolian case shows how magmatic activity may affect the structure and evolution of volcanic arcs, overprinting any strike-slip motion with magma-induced extension at the surface.
The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blom, Magdalena; Reis, Katarina; Heldin, Johan

RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as corticalmore » actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.« less
Structure of the BTB Domain of Keap1 and Its Interaction with the Triterpenoid Antagonist CDDO

PubMed Central

Cleasby, Anne; Yon, Jeff; Day, Philip J.; Richardson, Caroline; Tickle, Ian J.; Williams, Pamela A.; Callahan, James F.; Carr, Robin; Concha, Nestor; Kerns, Jeffrey K.; Qi, Hongwei; Sweitzer, Thomas; Ward, Paris; Davies, Thomas G.

2014-01-01

The protein Keap1 is central to the regulation of the Nrf2-mediated cytoprotective response, and is increasingly recognized as an important target for therapeutic intervention in a range of diseases involving excessive oxidative stress and inflammation. The BTB domain of Keap1 plays key roles in sensing environmental electrophiles and in mediating interactions with the Cul3/Rbx1 E3 ubiquitin ligase system, and is believed to be the target for several small molecule covalent activators of the Nrf2 pathway. However, despite structural information being available for several BTB domains from related proteins, there have been no reported crystal structures of Keap1 BTB, and this has precluded a detailed understanding of its mechanism of action and interaction with antagonists. We report here the first structure of the BTB domain of Keap1, which is thought to contain the key cysteine residue responsible for interaction with electrophiles, as well as structures of the covalent complex with the antagonist CDDO/bardoxolone, and of the constitutively inactive C151W BTB mutant. In addition to providing the first structural confirmation of antagonist binding to Keap1 BTB, we also present biochemical evidence that adduction of Cys 151 by CDDO is capable of inhibiting the binding of Cul3 to Keap1, and discuss how this class of compound might exert Nrf2 activation through disruption of the BTB-Cul3 interface. PMID:24896564
Boreal Tree Light- and Water-Use: Asynchronous, Diverging, yet Complementary

NASA Astrophysics Data System (ADS)

Pappas, C.; Baltzer, J. L.; Barr, A.; Black, T. A.; Bohrer, G.; Detto, M.; Maillet, J.; Matheny, A. M.; Roy, A.; Sonnentag, O.; Stephens, J.

2017-12-01

Water stress has been suggested as a key mechanism behind the contemporary increase in tree mortality rates in northwestern North America. However, a detailed analysis of boreal tree light- and water-use strategies as well as their interspecific differences are still lacking. Here, we examine the tree hydraulic behaviour of co-occurring larch (Larix laricina) and black spruce (Picea mariana), two characteristic boreal tree species, near the southern limit of the boreal ecozone in central Canada. Sap flux density (Js) and concurrently recorded stem radius fluctuations and meteorological conditions are used to quantify tree hydraulic functioning and to scrutinize tree light- and water-use strategies. Our analysis reveals an asynchrony in the diel hydrodynamics of the two species with the initial rise in Js occurring two hours earlier in larch than in black spruce. Structural differences in the crown architecture of larch and black spruce lead to interspecific differences in light harvesting that can explain the observed asynchrony in their hydraulic function. Furthermore, the two species exhibit diverging stomatal regulation strategies with larch employing relatively isohydric whereas black spruce anisohydric behaviour. Such asynchronous and diverging tree-level light- and water-use strategies provide new insights into the ecosystem-level complementarity of tree form and function, with implications for understanding boreal forests' water and carbon dynamics and resilience to environmental stress.
γ-Aminobutyric acid transaminase deficiency impairs central carbon metabolism and leads to cell wall defects during salt stress in Arabidopsis roots.

PubMed

Renault, Hugues; El Amrani, Abdelhak; Berger, Adeline; Mouille, Grégory; Soubigou-Taconnat, Ludivine; Bouchereau, Alain; Deleu, Carole

2013-05-01

Environmental constraints challenge cell homeostasis and thus require a tight regulation of metabolic activity. We have previously reported that the γ-aminobutyric acid (GABA) metabolism is crucial for Arabidopsis salt tolerance as revealed by the NaCl hypersensitivity of the GABA transaminase (GABA-T, At3g22200) gaba-t/pop2-1 mutant. In this study, we demonstrate that GABA-T deficiency during salt stress causes root and hypocotyl developmental defects and alterations of cell wall composition. A comparative genome-wide transcriptional analysis revealed that expression levels of genes involved in carbon metabolism, particularly sucrose and starch catabolism, were found to increase upon the loss of GABA-T function under salt stress conditions. Consistent with the altered mutant cell wall composition, a number of cell wall-related genes were also found differentially expressed. A targeted quantitative analysis of primary metabolites revealed that glutamate (GABA precursor) accumulated while succinate (the final product of GABA metabolism) significantly decreased in mutant roots after 1 d of NaCl treatment. Furthermore, sugar concentration was twofold reduced in gaba-t/pop2-1 mutant roots compared with wild type. Together, our results provide strong evidence that GABA metabolism is a major route for succinate production in roots and identify GABA as a major player of central carbon adjustment during salt stress. © 2012 Blackwell Publishing Ltd.
Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

PubMed

Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

2018-06-06

Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.
Central neuropeptide Y plays an important role in mediating the adaptation mechanism against chronic stress in male rats.

PubMed

Yang, Yu; Babygirija, Reji; Zheng, Jun; Shi, Bei; Sun, Weinan; Zheng, Xiaojiao; Zhang, Fan; Cao, Yu

2018-02-07

Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF), and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days, 1-5, of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, while central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism, and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, over-expressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress. Copyright © 2018 Endocrine Society.
Histone H3 lysine 9 methyltransferase FvDim5 regulates fungal development, pathogenicity and osmotic stress responses in Fusarium verticillioides.

PubMed

Gu, Qin; Ji, Tiantian; Sun, Xiao; Huang, Hai; Zhang, Hao; Lu, Xi; Wu, Liming; Huo, Rong; Wu, Huijun; Gao, Xuewen

2017-10-16

Histone methylation plays important biological roles in eukaryotic cells. Methylation of lysine 9 at histone H3 (H3K9me) is critical for regulating chromatin structure and gene transcription. Dim5 is a lysine histone methyltransferase (KHMTase) enzyme, which is responsible for the methylation of H3K9 in eukaryotes. In the current study, we identified a single ortholog of Neurospora crassa Dim5 in Fusarium verticillioides. In this study, we report that FvDim5 regulates the trimethylation of H3K9 (H3K9me3). The FvDIM5 deletion mutant (ΔFvDim5) showed significant defects in conidiation, perithecium production and fungal virulence. Unexpectedly, we found that deletion of FvDIM5 resulted in increased tolerance to osmotic stresses and upregulated FvHog1 phosphorylation. These results indicate the importance of FvDim5 for the regulation of fungal development, pathogenicity and osmotic stress responses in F. verticillioides. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Angiostrongylus cantonensis daf-2 regulates dauer, longevity and stress in Caenorhabditis elegans.

PubMed

Yan, Baolong; Sun, Weiwei; Shi, Xiaomeng; Huang, Liyang; Chen, Lingzi; Wang, Suhua; Yan, Lanzhu; Liang, Shaohui; Huang, Huicong

2017-06-15

The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity. Copyright © 2017. Published by Elsevier B.V.

Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.

PubMed

Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M

2015-10-01

Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.
Regulation of AKT Phosphorylation at Ser473 and Thr308 by Endoplasmic Reticulum Stress Modulates Substrate Specificity in a Severity Dependent Manner

PubMed Central

Yung, Hong Wa

2011-01-01

Endoplasmic reticulum (ER) stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473) confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308). The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling. PMID:21445305
Depletion of norepinephrine of the central nervous system Down-regulates the blood glucose level in d-glucose-fed and restraint stress models.

PubMed

Park, Soo-Hyun; Kim, Sung-Su; Lee, Jae-Ryeong; Sharma, Naveen; Suh, Hong-Won

2016-05-04

DSP-4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d-glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10-40μg) for 3days, and d-glucose (2g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120min after d-glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d-glucose-fed model. Plasma corticosterone level was downregulated in the d-glucose-fed model, whereas plasma insulin level increased in the d-glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d-glucose. In addition, the d-glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d-glucose-fed and restraint stress models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
The missing link: does tunnelling nanotube-based supercellularity provide a new understanding of chronic and lifestyle diseases?

PubMed

Rustom, Amin

2016-06-01

Tunnelling nanotubes (TNTs) are increasingly recognized as central players in a multitude of cellular mechanisms and diseases. Although their existence and functions in animal organisms are still elusive, emerging evidence suggests that they are involved in developmental processes, tissue regeneration, viral infections or pathogen transfer, stem cell differentiation, immune responses as well as initiation and progression of neurodegenerative disorders and cancer (see Sisakhtnezhad & Khosravi 2015 Eur. J. Cell Biol. 94, 429-443. (doi:10.1016/j.ejcb.2015.06.010)). A broader field of vision, including their striking functional and structural resemblance with nanotube-mediated phenomena found throughout the phylogenetic tree, from plants down to bacteria, points to a universal, conserved and tightly regulated mechanism of cellular assemblies. Based on our initial definition of TNTs as open-ended channels mediating membrane continuity between connected cells (Rustom et al. 2004 Science 303, 1007-1010. (doi:10.1126/science.1093133)), it is suggested that animal tissues represent supercellular assemblies that-besides opening discrete communication pathways-balance diverse stress factors caused by pathological changes or fluctuating physiological and environmental conditions, such as oxidative stress or nutrient shortage. By combining current knowledge about nanotube formation, intercellular transfer and communication phenomena as well as associated molecular pathways, a model evolves, predicting that the linkage between reactive oxygen species, TNT-based supercellularity and the intercellular shuttling of materials will have significant impact on diverse body functions, such as cell survival, redox/metabolic homeostasis and mitochondrial heteroplasmy. It implies that TNTs are intimately linked to the physiological and pathological state of animal cells and represent a central joint element of diverse diseases, such as neurodegenerative disorders, diabetes or cancer. © 2016 The Authors.
Environmental-stress-induced Chromatin Regulation and its Heritability

PubMed Central

Fang, Lei; Wuptra, Kenly; Chen, Danqi; Li, Hongjie; Huang, Shau-Ku; Jin, Chunyuan; Yokoyama, Kazunari K

2014-01-01

Chromatin is subject to proofreading and repair mechanisms during the process of DNA replication, as well as repair to maintain genetic and epigenetic information and genome stability. The dynamic structure of chromatin modulates various nuclear processes, including transcription and replication, by altering the accessibility of the DNA to regulatory factors. Structural changes in chromatin are affected by the chemical modification of histone proteins and DNA, remodeling of nucleosomes, incorporation of variant histones, noncoding RNAs, and nonhistone DNA-binding proteins. Phenotypic diversity and fidelity can be balanced by controlling stochastic switching of chromatin structure and dynamics in response to the environmental disruptors and endogenous stresses. The dynamic chromatin remodeling can, therefore, serve as a sensor, through which environmental and/or metabolic agents can alter gene expression, leading to global cellular changes involving multiple interactive networks. Furthermore its recent evidence also suggests that the epigenetic changes are heritable during the development. This review will discuss the environmental sensing system for chromatin regulation and genetic and epigenetic controls from developmental perspectives. PMID:25045581
Structural model of an mRNA in complex with the bacterial chaperone Hfq

DOE PAGES

Peng, Yi; Curtis, Joseph E.; Fang, Xianyang; ...

2014-11-17

The Sm-like protein Hfq (host factor Q-beta phage) facilitates regulation by bacterial small noncoding RNAs (sRNAs) in response to stress and other environmental signals. In this paper, we present a low-resolution model of Escherichia coli Hfq bound to the rpoS mRNA, a bacterial stress response gene that is targeted by three different sRNAs. Selective 2'-hydroxyl acylation and primer extension, small-angle X-ray scattering, and Monte Carlo molecular dynamics simulations show that the distal face and lateral rim of Hfq interact with three sites in the rpoS leader, folding the RNA into a compact tertiary structure. These interactions are needed for sRNAmore » regulation of rpoS translation and position the sRNA target adjacent to an sRNA binding region on the proximal face of Hfq. Finally, our results show how Hfq specifically distorts the structure of the rpoS mRNA to enable sRNA base pairing and translational control.« less
Maternal regulation of the infant's HPA axis stress response: Seymour 'Gig' Levine's legacy to Neuroendocrinology.

PubMed

Suchecki, Deborah

2018-05-18

Thirty years ago, Seymour 'Gig' Levine published a serendipitous, yet, seminal finding on the regulatory role of maternal presence on the corticosterone stress response of neonatal rats, during the developmental period know as stress hyporesponsive period. At the same time, his group of students also studied the stress response of infant monkeys to maternal separation, as a means to understand the stressful nature of disruptions of attachment to the primary caregiver. Gig and his group of students and collaborators, mainly in the USA and the Netherlands, investigated how initial social relationships buffer the stress response of non-human primate and rodent infants. His work in rodents revolved on determining how prolonged deprivation of maternal care disinhibits the stress response of neonates and how maternal behaviours regulate specific aspects of the hypothalamic-pituitary-adrenal axis. The 24 h maternal deprivation was useful to determine the importance of nutrition to suppress the corticosterone stress response, whilst anogenital licking and grooming inhibited stress-induced ACTH release and the combination of both behaviours prevented the effects of maternal deprivation on the central hypothalamic stress response. Levine's group also studied the consequences of maternal deprivation on basal and stress-induced activity of the HPA axis in juveniles' and the persistent effects of replacement of maternal behaviours on these parameters. Gig's legacy allowed many groups around the world to use the 24 h maternal deprivation paradigm as an animal model of vulnerability and resilience to stress-related psychiatric disorders and to study the neurobiological underpinnings of disruption of the mother-infant relationship and loss of parental care, a highly prevalent condition in humans. This review pays homage to a great scientist and mentor, whose discoveries paved the way for the understanding of how early social relations build resilience or lead to susceptibility to emotional disorders later in life. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
The heart as a self-regulating system: integration of homeodynamic mechanisms.

PubMed

Kresh, J Y; Armour, J A

1997-04-01

In the past the study of mechanical and electrical properties of the heart has been disjointed with minimal overlap and unification. The fact remains that these features are tightly coupled and central to the functioning heart. The maintenance of adequate cardiac output relies upon the highly integrated autoregulatory mechanisms and modulation of cardiac myocyte function. Regional ventricular mechanics and energetics are dependent upon muscle fiber stress-strain rate, the passive properties of myocardial collagen matrix, adequate vascular perfusion, transcapillary transport and electrical activation pattern. Intramural hydraulic "loading" is regulated by coronary arterial and venous dynamics. All of these components are under the constant influence of intrinsic cardiac and extracardiac autonomic neurons, as well as circulating hormones. A brief overview of the putative regulation of these various components is presented in this paper.
Mitochondrial morphology transitions and functions: implications for retrograde signaling?

PubMed Central

Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

2013-01-01

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527
Oxidative stress signaling to chromatin in health and disease

PubMed Central

Kreuz, Sarah; Fischle, Wolfgang

2016-01-01

Oxidative stress has a significant impact on the development and progression of common human pathologies, including cancer, diabetes, hypertension and neurodegenerative diseases. Increasing evidence suggests that oxidative stress globally influences chromatin structure, DNA methylation, enzymatic and non-enzymatic post-translational modifications of histones and DNA-binding proteins. The effects of oxidative stress on these chromatin alterations mediate a number of cellular changes, including modulation of gene expression, cell death, cell survival and mutagenesis, which are disease-driving mechanisms in human pathologies. Targeting oxidative stress-dependent pathways is thus a promising strategy for the prevention and treatment of these diseases. We summarize recent research developments connecting oxidative stress and chromatin regulation. PMID:27319358
30 CFR 250.509 - Well-completion structures on fixed platforms.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false Well-completion structures on fixed platforms. 250.509 Section 250.509 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND... stresses to the platform. [53 FR 10690, Apr. 1, 1988, as amended at 54 FR 50616, Dec. 8, 1989. Redesignated...
The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins.

PubMed

Norman, Michael; Rivers, Caroline; Lee, Youn-Bok; Idris, Jalilah; Uney, James

2016-12-01

RNA-binding proteins play a central role in cellular metabolism by orchestrating the complex interactions of coding, structural and regulatory RNA species. The SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM), which are highly conserved evolutionarily, were first identified on the basis of their ability to bind scaffold attachment region DNA elements, but attention has subsequently shifted to their RNA-binding and protein-protein interactions. Initial studies identified the involvement of these proteins in the cellular stress response and other aspects of gene regulation. More recently, the multifunctional capabilities of SAFB proteins have shown that they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as well as in interaction with chromatin-modifying complexes. With the advent of new techniques for identifying RNA-binding sites, enumeration of individual RNA targets has now begun. This review aims to summarise what is currently known about the functions of SAFB proteins. © 2016 The Author(s).
Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

PubMed Central

Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

2015-01-01

K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142
Substrate phosphorylation and feedback regulation in JFK-promoted p53 destabilization.

PubMed

Sun, Luyang; Shi, Lei; Wang, Feng; Huangyang, Peiwei; Si, Wenzhe; Yang, Jie; Yao, Zhi; Shang, Yongfeng

2011-02-11

The p53 tumor suppressor plays a central role in integrating cellular responses to various stresses. Tight regulation of p53 is thus essential for the maintenance of genome integrity and normal cell proliferation. Previously, we reported that JFK, the only Kelch domain-containing F-box protein in human, promotes ubiquitination and degradation of p53 and that unlike the other E3 ligases for p53, all of which possess an intrinsic ubiquitin ligase activity, JFK destabilizes p53 through the assembly of a Skp1-Cul1-F-box complex. Here, we report that the substrate recognition by JFK requires phosphorylation of p53 in its central core region by CSN (COP9 signalosome)-associated kinase. Significantly, inhibition of CSN-associated kinase activity or knockdown of CSN5 impairs JFK-promoted p53 degradation, enhances p53-dependent transcription, and promotes cell growth suppression, G(1) arrest, and apoptosis. Moreover, we showed that JFK is transcriptionally regulated by p53 and forms an auto-regulatory negative feedback loop with p53. These data may shed new light on the functional connection between CSN, Skp1-Cul1-F-box ubiquitin ligase, and p53 and provide a molecular mechanism for the regulation of JFK-promoted p53 degradation.
Substrate Phosphorylation and Feedback Regulation in JFK-promoted p53 Destabilization*

PubMed Central

Sun, Luyang; Shi, Lei; Wang, Feng; Huangyang, Peiwei; Si, Wenzhe; Yang, Jie; Yao, Zhi; Shang, Yongfeng

2011-01-01

The p53 tumor suppressor plays a central role in integrating cellular responses to various stresses. Tight regulation of p53 is thus essential for the maintenance of genome integrity and normal cell proliferation. Previously, we reported that JFK, the only Kelch domain-containing F-box protein in human, promotes ubiquitination and degradation of p53 and that unlike the other E3 ligases for p53, all of which possess an intrinsic ubiquitin ligase activity, JFK destabilizes p53 through the assembly of a Skp1-Cul1-F-box complex. Here, we report that the substrate recognition by JFK requires phosphorylation of p53 in its central core region by CSN (COP9 signalosome)-associated kinase. Significantly, inhibition of CSN-associated kinase activity or knockdown of CSN5 impairs JFK-promoted p53 degradation, enhances p53-dependent transcription, and promotes cell growth suppression, G1 arrest, and apoptosis. Moreover, we showed that JFK is transcriptionally regulated by p53 and forms an auto-regulatory negative feedback loop with p53. These data may shed new light on the functional connection between CSN, Skp1-Cul1-F-box ubiquitin ligase, and p53 and provide a molecular mechanism for the regulation of JFK-promoted p53 degradation. PMID:21127074
Ecological genomics of natural plant populations: the Israeli perspective.

PubMed

Nevo, Eviatar

2009-01-01

The genomic era revolutionized evolutionary population biology. The ecological genomics of the wild progenitors of wheat and barley reviewed here was central in the research program of the Institute of Evolution, University of Haifa, since 1975 ( http://evolution.haifa.ac.il ). We explored the following questions: (1) How much of the genomic and phenomic diversity of wild progenitors of cultivars (wild emmer wheat, Triticum dicoccoides, the progenitor of most wheat, plus wild relatives of the Aegilops species; wild barley, Hordeum spontaneum, the progenitor of cultivated barley; wild oat, Avena sterilis, the progenitor of cultivated oats; and wild lettuce species, Lactuca, the progenitor and relatives of cultivated lettuce) are adaptive and processed by natural selection at both coding and noncoding genomic regions? (2) What is the origin and evolution of genomic adaptation and speciation processes and their regulation by mutation, recombination, and transposons under spatiotemporal variables and stressful macrogeographic and microgeographic environments? (3) How much genetic resources are harbored in the wild progenitors for crop improvement? We advanced ecological genetics into ecological genomics and analyzed (regionally across Israel and the entire Near East Fertile Crescent and locally at microsites, focusing on the "Evolution Canyon" model) hundreds of populations and thousands of genotypes for protein (allozyme) and deoxyribonucleic acid (DNA) (coding and noncoding) diversity, partly combined with phenotypic diversity. The environmental stresses analyzed included abiotic (climatic and microclimatic, edaphic) and biotic (pathogens, demographic) stresses. Recently, we introduced genetic maps, cloning, and transformation of candidate genes. Our results indicate abundant genotypic and phenotypic diversity in natural plant populations. The organization and evolution of molecular and organismal diversity in plant populations, at all genomic regions and geographical scales, are nonrandom and are positively correlated with, and partly predictable by, abiotic and biotic environmental heterogeneity and stress. Biodiversity evolution, even in small isolated populations, is primarily driven by natural selection including diversifying, balancing, cyclical, and purifying selection regimes interacting with, but, ultimately, overriding the effects of mutation, migration, and stochasticity. The progenitors of cultivated plants harbor rich genetic resources and are the best hope for crop improvement by both classical and modern biotechnological methods. Future studies should focus on the interplay between structural and functional genome organization focusing on gene regulation.
Long-range comparison of human and mouse Sprr loci to identify conserved noncoding sequences involved in coordinate regulation

PubMed Central

Martin, Natalia; Patel, Satyakam; Segre, Julia A.

2004-01-01

Mammalian epidermis provides a permeability barrier between an organism and its environment. Under homeostatic conditions, epidermal cells produce structural proteins, which are cross-linked in an orderly fashion to form a cornified envelope (CE). However, under genetic or environmental stress, specific genes are induced to rapidly build a temporary barrier. Small proline-rich (SPRR) proteins are the primary constituents of the CE. Under stress the entire family of 14 Sprr genes is upregulated. The Sprr genes are clustered within the larger epidermal differentiation complex on mouse chromosome 3, human chromosome 1q21. The clustering of the Sprr genes and their upregulation under stress suggest that these genes may be coordinately regulated. To identify enhancer elements that regulate this stress response activation of the Sprr locus, we utilized bioinformatic tools and classical biochemical dissection. Long-range comparative sequence analysis identified conserved noncoding sequences (CNSs). Clusters of epidermal-specific DNaseI-hypersensitive sites (HSs) mapped to specific CNSs. Increased prevalence of these HSs in barrier-deficient epidermis provides in vivo evidence of the regulation of the Sprr locus by these conserved sequences. Individual components of these HSs were cloned, and one was shown to have strong enhancer activity specific to conditions when the Sprr genes are coordinately upregulated. PMID:15574822
Iron metabolism: current facts and future directions

PubMed Central

Tandara, Leida; Salamunic, Ilza

2012-01-01

Iron metabolism has been intensively examined over the last decade and there are many new players in this field which are worth to be introduced. Since its discovery many studies confirmed role of liver hormone hepcidin as key regulator of iron metabolism and pointed out liver as the central organ of system iron homeostasis. Liver cells receive multiple signals related to iron balance and respond by transcriptional regulation of hepcidin expression. This liver hormone is negative regulator of iron metabolism that represses iron efflux from macrophages, hepatocytes and enterocytes by its binding to iron export protein ferroportin. Ferroportin degradation leads to cellular iron retention and decreased iron availability. At level of a cell IRE/IRP (iron responsive elements/iron responsive proteins) system allows tight regulation of iron assimilation that prevents an excess of free intracellular iron which could lead to oxidative stress and damage of DNA, proteins and lipid membranes by ROS (reactive oxygen species). At the same time IRE/IRP system provides sufficient iron in order to meet the metabolic needs. Recently a significant progress in understanding of iron metabolism has been made and new molecular participants have been characterized. Article gives an overview of the current understanding of iron metabolism: absorption, distribution, cellular uptake, release, and storage. We also discuss mechanisms underlying systemic and cellular iron regulation with emphasis on central regulatory hormone hepcidin. PMID:23092063
Does sex have an independent effect on thermoeffector responses during exercise in the heat?

PubMed Central

Gagnon, Daniel; Kenny, Glen P

2012-01-01

Although a number of studies have examined potential differences in temperature regulation between males and females during heat stress, conclusions have remained limited as to whether reported differences are due to confounding physical characteristics or to actual differences in the physiological variables of temperature regulation. Recent observations suggest that sex differences in temperature regulation, particularly in sudomotor activity, go beyond those associated with physical characteristics. Females have recently been shown to have a lower sudomotor activity, as well as a lower thermosensitivity of the response compared to males during exercise performed at a fixed rate of metabolic heat production. Furthermore, sex differences in local and whole-body sudomotor activity are only evident above a certain combination of environmental conditions and rate of metabolic heat production. In contrast, both the onset threshold and thermosensitivity of cutaneous vasodilatation are similar between males and females. In theory, differences in the thermosensitivity of sudomotor activity could be related to either a central (neural activity/integration) and/or peripheral (effector organ) modulation of temperature regulation. Based on recent findings, sex differences in sudomotor activity appear to be mediated peripherally, although a central modulation has yet to be conclusively ruled out. Here we present a brief yet comprehensive review of the current state of knowledge pertaining to sex differences in temperature regulation during exercise in the heat. PMID:23045336
Tasco®, a Product of Ascophyllum nodosum, Imparts Thermal Stress Tolerance in Caenorhabditis elegans

PubMed Central

Kandasamy, Saveetha; Fan, Di; Sangha, Jatinder Singh; Khan, Wajahatullah; Evans, Franklin; Critchley, Alan T.; Prithiviraj, Balakrishnan

2011-01-01

Tasco®, a commercial product manufactured from the brown alga Ascophyllum nodosum, has been shown to impart thermal stress tolerance in animals. We investigated the physiological, biochemical and molecular bases of this induced thermal stress tolerance using the invertebrate animal model, Caenorhabiditis elegans. Tasco® water extract (TWE) at 300 μg/mL significantly enhanced thermal stress tolerance as well as extended the life span of C. elegans. The mean survival rate of the model animals under thermal stress (35 °C) treated with 300 μg/mL and 600 μg/mL TWE, respectively, was 68% and 71% higher than the control animals. However, the TWE treatments did not affect the nematode body length, fertility or the cellular localization of daf-16. On the contrary, TWE under thermal stress significantly increased the pharyngeal pumping rate in treated animals compared to the control. Treatment with TWE also showed differential protein expression profiles over control following 2D gel-electrophoresis analysis. Furthermore, TWE significantly altered the expression of at least 40 proteins under thermal stress; among these proteins 34 were up-regulated while six were down-regulated. Mass spectroscopy analysis of the proteins altered by TWE treatment revealed that these proteins were related to heat stress tolerance, energy metabolism and a muscle structure related protein. Among them heat shock proteins, superoxide dismutase, glutathione peroxidase, aldehyde dehydrogenase, saposin-like proteins 20, myosin regulatory light chain 1, cytochrome c oxidase RAS-like, GTP-binding protein RHO A, OS were significantly up-regulated, while eukaryotic translation initiation factor 5A-1 OS, 60S ribosomal protein L18 OS, peroxiredoxin protein 2 were down regulated by TWE treatment. These results were further validated by gene expression and reporter gene expression analyses. Overall results indicate that the water soluble components of Tasco® imparted thermal stress tolerance in the C. elegans by altering stress related biochemical pathways. PMID:22163185

Transcriptome responses of an ungrafted Phytophthora root rot tolerant avocado (Persea americana) rootstock to flooding and Phytophthora cinnamomi.

PubMed

Reeksting, B J; Olivier, N A; van den Berg, N

2016-09-22

Avocado (Persea americana Mill.) is a commercially important fruit crop worldwide. A major limitation to production is the oomycete Phytophthora cinnamomi, which causes root rot leading to branch-dieback and tree death. The decline of orchards infected with P. cinnamomi occurs much faster when exposed to flooding, even if flooding is only transient. Flooding is a multifactorial stress compromised of several individual stresses, making breeding and selection for tolerant varieties challenging. With more plantations occurring in marginal areas, with imperfect irrigation and drainage, understanding the response of avocado to these stresses will be important for the industry. Maintenance of energy production was found to be central in the response to flooding, as seen by up-regulation of transcripts related to glycolysis and induction of transcripts related to ethanolic fermentation. Energy-intensive processes were generally down-regulated, as evidenced by repression of transcripts related to processes such as secondary cell-wall biosynthesis as well as defence-related transcripts. Aquaporins were found to be down-regulated in avocado roots exposed to flooding, indicating reduced water-uptake under these conditions. The transcriptomic response of avocado to flooding and P. cinnamomi was investigated utilizing microarray analysis. Differences in the transcriptome caused by the presence of the pathogen were minor compared to transcriptomic perturbations caused by flooding. The transcriptomic response of avocado to flooding reveals a response to flooding that is conserved in several species. This data could provide key information that could be used to improve selection of stress tolerant rootstocks in the avocado industry.
HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1.

PubMed

Shamalnasab, Mehrnaz; Dhaoui, Manel; Thondamal, Manjunatha; Harvald, Eva Bang; Færgeman, Nils J; Aguilaniu, Hugo; Fabrizio, Paola

2017-07-27

In yeast, the broadly conserved acyl-CoA-binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene expression studies we have demonstrated that HIF-1, a master transcriptional regulator of adaptation to hypoxia, plays a central role in orchestrating the anti-aging response induced by MAA-1 deficiency. This response relies on the activation of molecular chaperones known to contribute to maintenance of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1 -deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins in the age-associated decline in proteostasis in mammals.
Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic-Pituitary-Adrenal Axis.

PubMed

Borrow, A P; Stranahan, A M; Suchecki, D; Yunes, R

2016-07-01

The central nervous system regulates and responds to endocrine signals, and this reciprocal relationship determines emotional processing and behavioural anxiety. Although the hypothalamic-pituitary-adrenal (HPA) axis remains the best-characterised system for this relationship, other steroid and peptide hormones are increasingly recognised for their effects on anxiety-like behaviour and reward. The present review examines recent developments related to the role of a number of different hormones in anxiety, including pregnane neurosteroids, gut peptides, neuropeptides and hormonal signals derived from fatty acids. Findings from both basic and clinical studies suggest that these alternative systems may complement or occlude stress-induced changes in anxiety and anxiety-like behaviour. By broadening the scope of mechanisms for depression and anxiety, it may be possible to develop novel strategies to attenuate stress-related psychiatric conditions. The targets for these potential therapies, as discussed in this review, encompass multiple circuits and systems, including those outside of the HPA axis. © 2016 British Society for Neuroendocrinology.
AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells.

PubMed

Pei, Shanshan; Minhajuddin, Mohammad; Adane, Biniam; Khan, Nabilah; Stevens, Brett M; Mack, Stephen C; Lai, Sisi; Rich, Jeremy N; Inguva, Anagha; Shannon, Kevin M; Kim, Hyunmin; Tan, Aik-Choon; Myers, Jason R; Ashton, John M; Neff, Tobias; Pollyea, Daniel A; Smith, Clayton A; Jordan, Craig T

2018-06-06

Leukemia stem cells (LSCs) are thought to drive the genesis of acute myeloid leukemia (AML) as well as relapse following chemotherapy. Because of their unique biology, developing effective methods to eradicate LSCs has been a significant challenge. In the present study, we demonstrate that intrinsic overexpression of the mitochondrial dynamics regulator FIS1 mediates mitophagy activity that is essential for primitive AML cells. Depletion of FIS1 attenuates mitophagy and leads to inactivation of GSK3, myeloid differentiation, cell cycle arrest, and a profound loss of LSC self-renewal potential. Further, we report that the central metabolic stress regulator AMPK is also intrinsically activated in LSC populations and is upstream of FIS1. Inhibition of AMPK signaling recapitulates the biological effect of FIS1 loss. These data suggest a model in which LSCs co-opt AMPK/FIS1-mediated mitophagy as a means to maintain stem cell properties that may be otherwise compromised by the stresses induced by oncogenic transformation. Copyright © 2018 Elsevier Inc. All rights reserved.
Peculiarities of Thermal Treatment of Monolithic Reinforced Concrete Structures

NASA Astrophysics Data System (ADS)

Kuchin, V. N.; Shilonosova, N. V.

2017-11-01

A mathematical program has been developed that allows one to determine the parameters of heat treatment of monolithic structures. One of the quality indicators of monolithic reinforced concrete structures is the level of temperature stresses arising in the process of heat treatment and further operation of structures. In winter at heat treatment the distribution of temperatures along the cross-section of the structure is uneven. A favorable thermo-stressed state in a concrete massif occurs when using the preheating method, providing the concrete temperature in the center of the structure is greater than at the periphery. In this case, after the strength is set and the temperature is later equalized along the cross-section, the central part of the structure tends to decrease its dimensions more but the extreme zones prevent it. Therefore, the center is in a state of tension, and the extreme zones on the periphery are compressed. In compressed concrete there is a lesser chance of cracks or defects. The temperature gradient over the section of the structure, the stress in the concrete and its strength are determined. When calculating the temperature and strength fields, the stress level was determined - a value equal to the ratio of the tensile stresses in the section under consideration to the tensile strength of the concrete in this section at the same time. The nature of the change in stress level is determined by the massive structure and power of the formwork heaters. It is shown that under unfavorable conditions the stress level is close to the critical value. The greatest temperature gradient occurs in the outer layers adjacent to the heating formwork. A technology for concrete conditioning is proposed which makes it possible to reduce the temperature stresses along the cross-section of the structure. The time for concrete conditioning in the formwork is reduced. In its turn, it further reduces labor costs and the cost of concrete work along with the cost of heat treatment. The authors conduct the technical and economic comparison of heat treatment options for the structures. The duration of monolithic structures erection with the use of combined heat treatment decreases in comparison with the method of peripheral heating. The economic effect consists of the reduction of the cost to organize and perform temperature control, insulation, electricity.
Static Tensile and Transient Dynamic Response of Cracked Aluminum Plate Repaired with Composite Patch - Numerical Study

NASA Astrophysics Data System (ADS)

Khalili, S. M. R.; Shariyat, M.; Mokhtari, M.

2014-06-01

In this study, the central cracked aluminum plates repaired with two sided composite patches are investigated numerically for their response to static tensile and transient dynamic loadings. Contour integral method is used to define and evaluate the stress intensity factors at the crack tips. The reinforcement for the composite patches is carbon fibers. The effect of adhesive thickness and patch thickness and configuration in tensile loading case and pre-tension, pre-compression and crack length effect on the evolution of the mode I stress intensity factor (SIF) (KI) of the repaired structure under transient dynamic loading case are examined. The results indicated that KI of the central cracked plate is reduced by 1/10 to 1/2 as a result of the bonded composite patch repair in tensile loading case. The crack length and the pre-loads are more effective in repaired structure in transient dynamic loading case in which, the 100 N pre-compression reduces the maximum KI for about 40 %, and the 100 N pre-tension reduces the maximum KI after loading period, by about 196 %.
Deformation behavior of micro-indentation defects under uniaxial and biaxial loads

NASA Astrophysics Data System (ADS)

Ma, Zhichao; Zhao, Hongwei; Lu, Shuai; Li, Hailian; Liu, Changyi; Liu, Xianhua

2015-09-01

The microdefects of structure frequently act as the source to generate initial cracks and lead to the fracture failure. Study on the deformation behaviors of embedded defects would be conducive to better understand the failure mechanisms of structural materials. Micro-indentation technique was applied to prepare the initial indentations as embedded surface defects at the gauge length section and central section of a cross-shaped AZ31B magnesium alloy specimen. A novel in situ biaxial tensile device was developed to apply the synchronous biaxial loads. Via the observation by an optical microscope with three-dimensional imaging and measurement functions, the changing laws of the indentation topographies under uniaxial and biaxial tensile loads were discussed. Compared with the gauge length section, the increasing trend of the indentation length of the central section was relatively flat, and the decreasing trend of the indentation depth was more significant. The changes of indentation topographies were explained by the Poisson effect, and the significant plastic tensile stress has led to the releasing of the residual stress around the indentation location and also promoted the planarization of the pileup.
Deformation behavior of micro-indentation defects under uniaxial and biaxial loads.

PubMed

Ma, Zhichao; Zhao, Hongwei; Lu, Shuai; Li, Hailian; Liu, Changyi; Liu, Xianhua

2015-09-01

The microdefects of structure frequently act as the source to generate initial cracks and lead to the fracture failure. Study on the deformation behaviors of embedded defects would be conducive to better understand the failure mechanisms of structural materials. Micro-indentation technique was applied to prepare the initial indentations as embedded surface defects at the gauge length section and central section of a cross-shaped AZ31B magnesium alloy specimen. A novel in situ biaxial tensile device was developed to apply the synchronous biaxial loads. Via the observation by an optical microscope with three-dimensional imaging and measurement functions, the changing laws of the indentation topographies under uniaxial and biaxial tensile loads were discussed. Compared with the gauge length section, the increasing trend of the indentation length of the central section was relatively flat, and the decreasing trend of the indentation depth was more significant. The changes of indentation topographies were explained by the Poisson effect, and the significant plastic tensile stress has led to the releasing of the residual stress around the indentation location and also promoted the planarization of the pileup.
A cotton Raf-like MAP3K gene, GhMAP3K40, mediates reduced tolerance to biotic and abiotic stress in Nicotiana benthamiana by negatively regulating growth and development.

PubMed

Chen, Xiaobo; Wang, Ji; Zhu, Ming; Jia, Haihong; Liu, Dongdong; Hao, Lili; Guo, Xingqi

2015-11-01

Mitogen-activated protein kinase (MAPK) cascades mediate various responses in plants. As the top component, MAP3Ks deserve more attention; however, little is known about the role of MAP3Ks, especially in cotton, a worldwide economic crop. In this study, a gene encoding a putative Raf-like MAP3K, GhMAP3K40, was isolated. GhMAP3K40 expression was induced by stress and multiple signal molecules. The plants overexpressing GhMAP3K40 had an enhanced tolerance to drought and salt stress at the germination stage. However, at the seedling stage, the transgenic plants suffered more severe damage after drought, exposure to pathogens and oxidative stress. The defence-related genes and the antioxidant system were activated in transgenic palnts, suggesting that GhMAP3K40 positively regulate the defence response. The transgenic plants were less able to prevent pathogenic invasion, which was due to defects in the cell structure of the leaves. The root system of the control plants were stronger compared with the transgenic plants. These results indicated a negative role of GhMAP3K40 in growth and development and GhMAP3K40 possibly caused the defects by down-regulating the lignin biosynthesis. Overall, these results suggest that GhMAP3K40 may positively regulate defence response but cause reduced tolerance to biotic and abiotic stress by negatively regulating growth and development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Mechanical consequences of core drilling and bone-grafting on osteonecrosis of the femoral head.

PubMed

Brown, T D; Pedersen, D R; Baker, K J; Brand, R A

1993-09-01

We employed an anatomically realistic three-dimensional finite-element model to explore several biomechanical variables involved in coring or bone-grafting of a segmentally necrotic femoral head. The mechanical efficacy of several variants of these procedures was indexed in terms of their alteration of the stress:strength ratio in at-risk necrotic cancellous bone. For coring alone, the associated structural compromise was generally modest, provided that the tract did not extend near the subchondral plate. Cortical bone-grafting was potentially of great structural benefit for femoral heads in which the graft penetrated deeply into the superocentral or lateral aspect of the lesion, ideally with abutment against the subchondral plate. By contrast, central or lateral grafts that stopped well short of the subchondral plate were contraindicated biomechanically because they caused marked elevations in stress on the necrotic cancellous bone. Calculated levels of stress were relatively insensitive to variations in the diameter of the graft.
Genome-wide identification and characterization of Glyceraldehyde-3-phosphate dehydrogenase genes family in wheat (Triticum aestivum).

PubMed

Zeng, Lingfeng; Deng, Rong; Guo, Ziping; Yang, Shushen; Deng, Xiping

2016-03-16

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a central enzyme in glycolysi, we performed genome-wide identification of GAPDH genes in wheat and analyzed their structural characteristics and expression patterns under abiotic stress in wheat. A total of 22 GAPDH genes were identified in wheat cv. Chinese spring; the phylogenetic and structure analysis showed that these GAPDH genes could be divided into four distinct subfamilies. The expression profiles of GAPDH genes showed tissue specificity all over plant development stages. The qRT-PCR results revealed that wheat GAPDHs were involved in several abiotic stress response. Wheat carried 22 GAPDH genes, representing four types of plant GAPDHs (gapA/B, gapC, gapCp and gapN). Whole genome duplication and segmental duplication might account for the expansion of wheat GAPDHs. Expression analysis implied that GAPDHs play roles in plants abiotic stress tolerance.
The Self-Liking Brain: A VBM Study on the Structural Substrate of Self-Esteem

PubMed Central

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource. PMID:24489727
The self-liking brain: a VBM study on the structural substrate of self-esteem.

PubMed

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource.
Uncovering the Salt Response of Soybean by Unraveling Its Wild and Cultivated Functional Genomes Using Tag Sequencing

PubMed Central

Ali, Zulfiqar; Zhang, Da Yong; Xu, Zhao Long; Xu, Ling; Yi, Jin Xin; He, Xiao Lan; Huang, Yi Hong; Liu, Xiao Qing; Khan, Asif Ali; Trethowan, Richard M.; Ma, Hong Xiang

2012-01-01

Soil salinity has very adverse effects on growth and yield of crop plants. Several salt tolerant wild accessions and cultivars are reported in soybean. Functional genomes of salt tolerant Glycine soja and a salt sensitive genotype of Glycine max were investigated to understand the mechanism of salt tolerance in soybean. For this purpose, four libraries were constructed for Tag sequencing on Illumina platform. We identify around 490 salt responsive genes which included a number of transcription factors, signaling proteins, translation factors and structural genes like transporters, multidrug resistance proteins, antiporters, chaperons, aquaporins etc. The gene expression levels and ratio of up/down-regulated genes was greater in tolerant plants. Translation related genes remained stable or showed slightly higher expression in tolerant plants under salinity stress. Further analyses of sequenced data and the annotations for gene ontology and pathways indicated that soybean adapts to salt stress through ABA biosynthesis and regulation of translation and signal transduction of structural genes. Manipulation of these pathways may mitigate the effect of salt stress thus enhancing salt tolerance. PMID:23209559
Shear Stress Induced Reorganization of the Keratin Intermediate Filament Network Requires Phosphorylation by Protein Kinase C ζ

PubMed Central

Sivaramakrishnan, Sivaraj; Schneider, Jaime L.; Sitikov, Albert; Goldman, Robert D.

2009-01-01

Keratin intermediate filaments (KIFs) form a fibrous polymer network that helps epithelial cells withstand external mechanical forces. Recently, we established a correlation between the structure of the KIF network and its local mechanical properties in alveolar epithelial cells. Shear stress applied across the cell surface resulted in the structural remodeling of KIF and a substantial increase in the elastic modulus of the network. This study examines the mechanosignaling that regulates the structural remodeling of the KIF network. We report that the shear stress–mediated remodeling of the KIF network is facilitated by a twofold increase in the dynamic exchange rate of KIF subunits, which is regulated in a PKC ζ and 14-3-3–dependent manner. PKC ζ phosphorylates K18pSer33, and this is required for the structural reorganization because the KIF network in A549 cells transfected with a dominant negative PKC ζ, or expressing the K18Ser33Ala mutation, is unchanged. Blocking the shear stress–mediated reorganization results in reduced cellular viability and increased apoptotic levels. These data suggest that shear stress mediates the phosphorylation of K18pSer33, which is required for the reorganization of the KIF network, resulting in changes in mechanical properties of the cell that help maintain the integrity of alveolar epithelial cells. PMID:19357195
Global Regulatory Mutations in csrA and rpoS Cause Severe Central Carbon Stress in Escherichia coli in the Presence of Acetate

PubMed Central

Wei, Bangdong; Shin, Sooan; LaPorte, David; Wolfe, Alan J.; Romeo, Tony

2000-01-01

The csrA gene encodes a small RNA-binding protein, which acts as a global regulator in Escherichia coli and other bacteria (T. Romeo, Mol. Microbiol. 29:1321–1330, 1998). Its key regulatory role in central carbon metabolism, both as an activator of glycolysis and as a potent repressor of glycogen biosynthesis and gluconeogenesis, prompted us to examine the involvement of csrA in acetate metabolism and the tricarboxylic acid (TCA) cycle. We found that growth of csrA rpoS mutant strains was very poor on acetate as a sole carbon source. Surprisingly, growth also was inhibited specifically by the addition of modest amounts of acetate to rich media (e.g., tryptone broth). Cultures grown in the presence of ≥25 mM acetate consisted substantially of glycogen biosynthesis (glg) mutants, which were no longer inhibited by acetate. Several classes of glg mutations were mapped to known and novel loci. Several hypotheses were examined to provide further insight into the effects of acetate on growth and metabolism in these strains. We determined that csrA positively regulates acs (acetyl-coenzyme A synthetase; Acs) expression and isocitrate lyase activity without affecting key TCA cycle enzymes or phosphotransacetylase. TCA cycle intermediates or pyruvate, but not glucose, galactose, or glycerol, restored growth and prevented the glg mutations in the presence of acetate. Furthermore, amino acid uptake was inhibited by acetate specifically in the csrA rpoS strain. We conclude that central carbon flux imbalance, inhibition of amino acid uptake, and a deficiency in acetate metabolism apparently are combined to cause metabolic stress by depleting the TCA cycle. PMID:10692369
The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

PubMed Central

Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato

2011-01-01

The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents. PMID:21814209
Transcriptome profiling of Vitis amurensis, an extremely cold-tolerant Chinese wild Vitis species, reveals candidate genes and events that potentially connected to cold stress.

PubMed

Xu, Weirong; Li, Ruimin; Zhang, Ningbo; Ma, Fuli; Jiao, Yuntong; Wang, Zhenping

2014-11-01

Vitis amurensis Rupr. is an exceptional wild-growing Vitis (grape) species that can safely survive a wide range of cold conditions, but the underlying cold-adaptive mechanism associated with gene regulation is poorly investigated. We have analyzed the physiochemical and transcriptomic changes caused by cold stress in a cold-tolerant accession, 'Heilongjiang seedling', of Chinese wild V. amurensis. We statistically determined that a total of 6,850 cold-regulated transcripts were involved in cold regulation, including 3,676 up-regulated and 3,174 down-regulated transcripts. A global survey of messenger RNA revealed that skipped exon is the most prevalent form of alternative spicing event. Importantly, we found that the total splicing events increased with the prolonged cold stress. We also identified thirty-eight major TF families that were involved in cold regulation, some of which were previously unknown. Moreover, a large number of candidate pathways for the metabolism or biosynthesis of secondary metabolites were found to be regulated by cold, which is of potential importance in coordinating cold tolerance with growth and development. Several heat shock proteins and heat shock factors were also detected to be intensively cold-regulated. Furthermore, we validated the expression profiles of 16 candidates using qRT-PCR to further confirm the accuracy of the RNA-seq data. Our results provide a genome-wide view of the dynamic changes in the transcriptome of V. amurensis, in which it is evident that various structural and regulatory genes are crucial for cold tolerance/adaptation. Moreover, our robust dataset advances our knowledge of the genes involved in the complex regulatory networks of cold stress and leads to a better understanding of cold tolerance mechanisms in this extremely cold-tolerant Vitis species.
Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction.

PubMed

Chu, Alison; Thamotharan, Shanthie; Ganguly, Amit; Wadehra, Madhuri; Pellegrini, Matteo; Devaskar, Sherin U

2016-10-01

Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long-term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate (1) key cytokines (eg, IL-10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and endoplasmic reticulum [ER] stress) that are immunologically mediated and important for cellular survival and functioning, and (3) the resulting IUGR phenotype and placental histopathology in this animal model. After subjecting pregnant mice to mild and moderate FR from gestational day 10 to 19, we collected placentas and embryos at gestational day 19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated messenger RNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared with control mice, including a considerable subset that regulates immune tolerance, inflammation, and cellular integrity. In summary, maternal FR decreases the anti-inflammatory effect of IL-10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR. Copyright © 2016 Elsevier Inc. All rights reserved.
Structure and State of Stress of the Chilean Subduction Zone from Terrestrial and Satellite-Derived Gravity and Gravity Gradient Data

NASA Astrophysics Data System (ADS)

Gutknecht, B. D.; Götze, H.-J.; Jahr, T.; Jentzsch, G.; Mahatsente, R.; Zeumann, St.

2014-11-01

It is well known that the quality of gravity modelling of the Earth's lithosphere is heavily dependent on the limited number of available terrestrial gravity data. More recently, however, interest has grown within the geoscientific community to utilise the homogeneously measured satellite gravity and gravity gradient data for lithospheric scale modelling. Here, we present an interdisciplinary approach to determine the state of stress and rate of deformation in the Central Andean subduction system. We employed gravity data from terrestrial, satellite-based and combined sources using multiple methods to constrain stress, strain and gravitational potential energy (GPE). Well-constrained 3D density models, which were partly optimised using the combined regional gravity model IMOSAGA01C (Hosse et al. in Surv Geophys, 2014, this issue), were used as bases for the computation of stress anomalies on the top of the subducting oceanic Nazca plate and GPE relative to the base of the lithosphere. The geometries and physical parameters of the 3D density models were used for the computation of stresses and uplift rates in the dynamic modelling. The stress distributions, as derived from the static and dynamic modelling, reveal distinct positive anomalies of up to 80 MPa along the coastal Jurassic batholith belt. The anomalies correlate well with major seismicity in the shallow parts of the subduction system. Moreover, the pattern of stress distributions in the Andean convergent zone varies both along the north-south and west-east directions, suggesting that the continental fore-arc is highly segmented. Estimates of GPE show that the high Central Andes might be in a state of horizontal deviatoric tension. Models of gravity gradients from the Gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite mission were used to compute Bouguer-like gradient anomalies at 8 km above sea level. The analysis suggests that data from GOCE add significant value to the interpretation of lithospheric structures, given that the appropriate topographic correction is applied.

The Dysfunctions of Bureaucratic Structure.

ERIC Educational Resources Information Center

Duttweiler, Patricia Cloud

1988-01-01

Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…
Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats.

PubMed

Bülbül, Mehmet; İzgüt-Uysal, V Nimet; Sinen, Osman; Birsen, İlknur; Tanrıöver, Gamze

2016-02-15

Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress-induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF-independent pathway. Copyright © 2016 the American Physiological Society.
Exogenous spermidine is enhancing tomato tolerance to salinity-alkalinity stress by regulating chloroplast antioxidant system and chlorophyll metabolism.

PubMed

Li, Jianming; Hu, Lipan; Zhang, Li; Pan, Xiongbo; Hu, Xiaohui

2015-12-29

Salinity-alkalinity stress is known to adversely affect a variety of processes in plants, thus inhibiting growth and decreasing crop yield. Polyamines protect plants against a variety of environmental stresses. However, whether exogenous spermidine increases the tolerance of tomato seedlings via effects on chloroplast antioxidant enzymes and chlorophyll metabolism is unknown. In this study, we examined the effect of exogenous spermidine on chlorophyll synthesis and degradation pathway intermediates and related enzyme activities, as well as chloroplast ultrastructure, gene expression, and antioxidants in salinity-alkalinity-stressed tomato seedlings. Salinity-alkalinity stress disrupted chlorophyll metabolism and hindered uroorphyrinogen III conversion to protoporphyrin IX. These effects were more pronounced in seedlings of cultivar Zhongza No. 9 than cultivar Jinpengchaoguan. Under salinity-alkalinity stress, exogenous spermidine alleviated decreases in the contents of total chlorophyll and chlorophyll a and b in seedlings of both cultivars following 4 days of stress. With extended stress, exogenous spermidine reduced the accumulation of δ-aminolevulinic acid, porphobilinogen, and uroorphyrinogen III and increased the levels of protoporphyrin IX, Mg-protoporphyrin IX, and protochlorophyllide, suggesting that spermidine promotes the conversion of uroorphyrinogen III to protoporphyrin IX. The effect occurred earlier in cultivar Jinpengchaoguan than in cultivar Zhongza No. 9. Exogenous spermidine also alleviated the stress-induced increases in malondialdehyde content, superoxide radical generation rate, chlorophyllase activity, and expression of the chlorophyllase gene and the stress-induced decreases in the activities of antioxidant enzymes, antioxidants, and expression of the porphobilinogen deaminase gene. In addition, exogenous spermidine stabilized the chloroplast ultrastructure in stressed tomato seedlings. The tomato cultivars examined exhibited different capacities for responding to salinity-alkalinity stress. Exogenous spermidine triggers effective protection against damage induced by salinity-alkalinity stress in tomato seedlings, probably by maintaining chloroplast structural integrity and alleviating salinity-alkalinity-induced oxidative damage, most likely through regulation of chlorophyll metabolism and the enzymatic and non-enzymatic antioxidant systems in chloroplast. Exogenous spermidine also exerts positive effects at the transcription level, such as down-regulation of the expression of the chlorophyllase gene and up-regulation of the expression of the porphobilinogen deaminase gene.
Glucose Regulation of Load‐Induced mTOR Signaling and ER Stress in Mammalian Heart

PubMed Central

Sen, Shiraj; Kundu, Bijoy K.; Wu, Henry Cheng‐Ju; Hashmi, S. Shahrukh; Guthrie, Patrick; Locke, Landon W.; Roy, R. Jack; Matherne, G. Paul; Berr, Stuart S.; Terwelp, Matthew; Scott, Brian; Carranza, Sylvia; Frazier, O. Howard; Glover, David K.; Dillmann, Wolfgang H.; Gambello, Michael J.; Entman, Mark L.; Taegtmeyer, Heinrich

2013-01-01

Background Changes in energy substrate metabolism are first responders to hemodynamic stress in the heart. We have previously shown that hexose‐6‐phosphate levels regulate mammalian target of rapamycin (mTOR) activation in response to insulin. We now tested the hypothesis that inotropic stimulation and increased afterload also regulate mTOR activation via glucose 6‐phosphate (G6P) accumulation. Methods and Results We subjected the working rat heart ex vivo to a high workload in the presence of different energy‐providing substrates including glucose, glucose analogues, and noncarbohydrate substrates. We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation). The histone deacetylase inhibitor 4‐phenylbutyrate, which relieves ER stress, also improved contractile function. In contrast, adding the glucose analogue 2‐deoxy‐d‐glucose, which is phosphorylated but not further metabolized, to the perfusate resulted in mTOR activation and contractile dysfunction. Next we tested our hypothesis in vivo by transverse aortic constriction in mice. Using a micro‐PET system, we observed enhanced glucose tracer analog uptake and contractile dysfunction preceding dilatation of the left ventricle. In contrast, in hearts overexpressing SERCA2a, ER stress was reduced and contractile function was preserved with hypertrophy. Finally, we examined failing human hearts and found that mechanical unloading decreased G6P levels and ER stress markers. Conclusions We propose that glucose metabolic changes precede and regulate functional (and possibly also structural) remodeling of the heart. We implicate a critical role for G6P in load‐induced mTOR activation and ER stress. PMID:23686371
Rice Ribosomal Protein Large Subunit Genes and Their Spatio-temporal and Stress Regulation

PubMed Central

Moin, Mazahar; Bakshi, Achala; Saha, Anusree; Dutta, Mouboni; Madhav, Sheshu M.; Kirti, P. B.

2016-01-01

Ribosomal proteins (RPs) are well-known for their role in mediating protein synthesis and maintaining the stability of the ribosomal complex, which includes small and large subunits. In the present investigation, in a genome-wide survey, we predicted that the large subunit of rice ribosomes is encoded by at least 123 genes including individual gene copies, distributed throughout the 12 chromosomes. We selected 34 candidate genes, each having 2–3 identical copies, for a detailed characterization of their gene structures, protein properties, cis-regulatory elements and comprehensive expression analysis. RPL proteins appear to be involved in interactions with other RP and non-RP proteins and their encoded RNAs have a higher content of alpha-helices in their predicted secondary structures. The majority of RPs have binding sites for metal and non-metal ligands. Native expression profiling of 34 ribosomal protein large (RPL) subunit genes in tissues covering the major stages of rice growth shows that they are predominantly expressed in vegetative tissues and seedlings followed by meiotically active tissues like flowers. The putative promoter regions of these genes also carry cis-elements that respond specifically to stress and signaling molecules. All the 34 genes responded differentially to the abiotic stress treatments. Phytohormone and cold treatments induced significant up-regulation of several RPL genes, while heat and H2O2 treatments down-regulated a majority of them. Furthermore, infection with a bacterial pathogen, Xanthomonas oryzae, which causes leaf blight also induced the expression of 80% of the RPL genes in leaves. Although the expression of RPL genes was detected in all the tissues studied, they are highly responsive to stress and signaling molecules indicating that their encoded proteins appear to have roles in stress amelioration besides house-keeping. This shows that the RPL gene family is a valuable resource for manipulation of stress tolerance in rice and other crops, which may be achieved by overexpressing and raising independent transgenic plants carrying the genes that became up-regulated significantly and instantaneously. PMID:27605933
Structure of the novel monomeric glyoxalase I from Zea mays

PubMed Central

Turra, Gino L.; Agostini, Romina B.; Fauguel, Carolina M.; Presello, Daniel A.; Andreo, Carlos S.; González, Javier M.; Campos-Bermudez, Valeria A.

2015-01-01

The glyoxalase system is ubiquitous among all forms of life owing to its central role in relieving the cell from the accumulation of methylglyoxal, a toxic metabolic byproduct. In higher plants, this system is upregulated under diverse metabolic stress conditions, such as in the defence response to infection by pathogenic microorganisms. Despite their proven fundamental role in metabolic stresses, plant glyoxalases have been poorly studied. In this work, glyoxalase I from Zea mays has been characterized both biochemically and structurally, thus reporting the first atomic model of a glyoxalase I available from plants. The results indicate that this enzyme comprises a single polypeptide with two structurally similar domains, giving rise to two lateral concavities, one of which harbours a functional nickel(II)-binding active site. The putative function of the remaining cryptic active site remains to be determined. PMID:26457425
Structure of the novel monomeric glyoxalase I from Zea mays.

PubMed

Turra, Gino L; Agostini, Romina B; Fauguel, Carolina M; Presello, Daniel A; Andreo, Carlos S; González, Javier M; Campos-Bermudez, Valeria A

2015-10-01

The glyoxalase system is ubiquitous among all forms of life owing to its central role in relieving the cell from the accumulation of methylglyoxal, a toxic metabolic byproduct. In higher plants, this system is upregulated under diverse metabolic stress conditions, such as in the defence response to infection by pathogenic microorganisms. Despite their proven fundamental role in metabolic stresses, plant glyoxalases have been poorly studied. In this work, glyoxalase I from Zea mays has been characterized both biochemically and structurally, thus reporting the first atomic model of a glyoxalase I available from plants. The results indicate that this enzyme comprises a single polypeptide with two structurally similar domains, giving rise to two lateral concavities, one of which harbours a functional nickel(II)-binding active site. The putative function of the remaining cryptic active site remains to be determined.
Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

PubMed Central

Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

2015-01-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470
Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

PubMed

Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

2015-11-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).
Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

PubMed

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2016-03-25

The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.
The nucleolus—guardian of cellular homeostasis and genome integrity.

PubMed

Grummt, Ingrid

2013-12-01

All organisms sense and respond to conditions that stress their homeostasis by downregulating the synthesis of rRNA and ribosome biogenesis, thus designating the nucleolus as the central hub in coordinating the cellular stress response. One of the most intriguing roles of the nucleolus, long regarded as a mere ribosome-producing factory, is its participation in monitoring cellular stress signals and transmitting them to the RNA polymerase I (Pol I) transcription machinery. As rRNA synthesis is a most energy-consuming process, switching off transcription of rRNA genes is an effective way of saving the energy required to maintain cellular homeostasis during acute stress. The Pol I transcription machinery is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production which, in turn, guides cell growth and proliferation. This review focuses on the mechanisms that link cell physiology to rDNA silencing, a prerequisite for nucleolar integrity and cell survival.
Multivariate assessment of the central-cardiorespiratory network structure in neuropathological disease.

PubMed

Schulz, Steffen; Haueisen, Jens; Bär, Karl-Juergen; Voss, Andreas

2018-06-22

The new interdisciplinary field of network physiology is getting more and more into the focus of interest in medicine. The autonomic nervous system (ANS) dysfunction is well described in schizophrenia (SZO). However, the linear and nonlinear coupling between the ANS and central nervous system (CNS) is only partly addressed until now. This coupling can be assumed as a feedback-feedforward network, reacting with flexible and adaptive responses to internal and external factors. Approach: For the first time, in this study, we investigated linear and nonlinear short-term central-cardiorespiratory couplings of 17 patients suffering from paranoid schizophrenia (SZO) in comparison to 17 age-gender matched healthy subjects (CON) analyzing heart rate (HR), respiration (RESP) and the power of frontal EEG activity (PEEG). The objective is to determine how the different regulatory aspects of the CNS-ANS compose the central-cardiorespiratory network (CCRN). To quantify these couplings within the CCRN the normalized short time partial directed coherence (NSTPDC) and the new multivariate high-resolution joint symbolic dynamics (mHRJSD) were applied. Main results: We found that the CCRN in SZO is characterized as a bidirectional one, with stronger central driving mechanisms (PEEG→HR) towards HR regulation than vice versa, and with stronger respiratory influence (RESP→PEEG) on central activity than vice versa. This suggests that the central-cardiorespiratory process (closed-loop) is mainly focusing on adapting the HR via the sinoatrial node than focusing on respiratory regulation. On the other side, the feedback-loop from ANS to CNS is strongly dominated via respiratory activity. Significance: We could demonstrate a considerably significantly different central-cardiorespiratory network structure in schizophrenia with strong central influence on the cardiac system and a strong respiratory influence on the central nervous system. Moreover, this study provides a more in-depth understanding of the interplay of the central and autonomic regulatory network in healthy subjects and schizophrenic patients. . © 2018 Institute of Physics and Engineering in Medicine.
Involvement of Abscisic Acid in the Coordinated Regulation of a Stress-Inducible Hexose Transporter (VvHT5) and a Cell Wall Invertase in Grapevine in Response to Biotrophic Fungal Infection[W

PubMed Central

Hayes, Matthew A.; Feechan, Angela; Dry, Ian B.

2010-01-01

Biotrophic fungal and oomycete pathogens alter carbohydrate metabolism in infected host tissues. Symptoms such as elevated soluble carbohydrate concentrations and increased invertase activity suggest that a pathogen-induced carbohydrate sink is established. To identify pathogen-induced regulators of carbohydrate sink strength, quantitative real-time polymerase chain reaction was used to measure transcript levels of invertase and hexose transporter genes in biotrophic pathogen-infected grapevine (Vitis vinifera) leaves. The hexose transporter VvHT5 was highly induced in coordination with the cell wall invertase gene VvcwINV by powdery and downy mildew infection. However, similar responses were also observed in response to wounding, suggesting that this is a generalized response to stress. Analysis of the VvHT5 promoter region indicated the presence of multiple abscisic acid (ABA) response elements, suggesting a role for ABA in the transition from source to sink under stress conditions. ABA treatment of grape leaves was found to reproduce the same gene-specific transcriptional changes as observed under biotic and abiotic stress conditions. Furthermore, the key regulatory ABA biosynthetic gene, VvNCED1, was activated under these same stress conditions. VvHT5 promoter::β-glucuronidase-directed expression in transgenic Arabidopsis (Arabidopsis thaliana) was activated by infection with powdery mildew and by ABA treatment, and the expression was closely associated with vascular tissue adjacent to infected regions. Unlike VvHT1 and VvHT3, which appear to be predominantly involved in hexose transport in developing leaves and berries, VvHT5 appears to have a specific role in enhancing sink strength under stress conditions, and this is controlled through ABA. Our data suggest a central role for ABA in the regulation of VvcwINV and VvHT5 expression during the transition from source to sink in response to infection by biotrophic pathogens. PMID:20348211
Acceptance lowers stress reactivity: Dismantling mindfulness training in a randomized controlled trial.

PubMed

Lindsay, Emily K; Young, Shinzen; Smyth, Joshua M; Brown, Kirk Warren; Creswell, J David

2018-01-01

Mindfulness interventions, which train practitioners to monitor their present-moment experience with a lens of acceptance, are known to buffer stress reactivity. Little is known about the active mechanisms driving these effects. We theorize that acceptance is a critical emotion regulation mechanism underlying mindfulness stress reduction effects. In this three-arm parallel trial, mindfulness components were dismantled into three structurally equivalent 15-lesson smartphone-based interventions: (1) training in both monitoring and acceptance (Monitor+Accept), (2) training in monitoring only (Monitor Only), or (3) active control training (Coping control). 153 stressed adults (mean age=32years; 67% female; 53% white, 21.5% black, 21.5% Asian, 4% other race) were randomly assigned to complete one of three interventions. After the intervention, cortisol, blood pressure, and subjective stress reactivity were assessed using a modified Trier Social Stress Test. As predicted, Monitor+Accept training reduced cortisol and systolic blood pressure reactivity compared to Monitor Only and control trainings. Participants in all three conditions reported moderate levels of subjective stress. This study provides the first experimental evidence that brief smartphone mindfulness training can impact stress biology, and that acceptance training drives these effects. We discuss implications for basic and applied research in contemplative science, emotion regulation, stress and coping, health, and clinical interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.
Genome-Wide Survey on Genomic Variation, Expression Divergence, and Evolution in Two Contrasting Rice Genotypes under High Salinity Stress

PubMed Central

Jiang, Shu-Ye; Ma, Ali; Ramamoorthy, Rengasamy; Ramachandran, Srinivasan

2013-01-01

Expression profiling is one of the most important tools for dissecting biological functions of genes and the upregulation or downregulation of gene expression is sufficient for recreating phenotypic differences. Expression divergence of genes significantly contributes to phenotypic variations. However, little is known on the molecular basis of expression divergence and evolution among rice genotypes with contrasting phenotypes. In this study, we have implemented an integrative approach using bioinformatics and experimental analyses to provide insights into genomic variation, expression divergence, and evolution between salinity-sensitive rice variety Nipponbare and tolerant rice line Pokkali under normal and high salinity stress conditions. We have detected thousands of differentially expressed genes between these two genotypes and thousands of up- or downregulated genes under high salinity stress. Many genes were first detected with expression evidence using custom microarray analysis. Some gene families were preferentially regulated by high salinity stress and might play key roles in stress-responsive biological processes. Genomic variations in promoter regions resulted from single nucleotide polymorphisms, indels (1–10 bp of insertion/deletion), and structural variations significantly contributed to the expression divergence and regulation. Our data also showed that tandem and segmental duplication, CACTA and hAT elements played roles in the evolution of gene expression divergence and regulation between these two contrasting genotypes under normal or high salinity stress conditions. PMID:24121498
Nitric oxide in the stress axis.

PubMed

López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

1998-10-01

In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.
The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders

PubMed Central

Pokusa, Michal

2017-01-01

Traditionally, oxidative stress as a biological aspect is defined as an imbalance between the free radical generation and antioxidant capacity of living systems. The intracellular imbalance of ions, disturbance in membrane dynamics, hypoxic conditions, and dysregulation of gene expression are all molecular pathogenic mechanisms closely associated with oxidative stress and underpin systemic changes in the body. These also include aspects such as chronic immune system activation, the impairment of cellular structure renewal, and alterations in the character of the endocrine secretion of diverse tissues. All of these mentioned features are crucial for the correct function of the various tissue types in the body. In the present review, we summarize current knowledge about the common roots of metabolic and neurodegenerative disorders induced by oxidative stress. We discuss these common roots with regard to the way that (1) the respective metal ions are involved in the maintenance of oxidative balance and (2) the metabolic and signaling disturbances of the most important biometals, such as Mg2+, Zn2+, Se2+, Fe2+, or Cu2+, can be considered as the central connection point between the pathogenesis of both types of disorders and oxidative stress. PMID:28751933
Stress Energy tensor in LCFT and the Logarithmic Sugawara construction

NASA Astrophysics Data System (ADS)

Kogan, Ian I.; Nichols, Alexander

2002-01-01

We discuss the partners of the stress energy tensor and their structure in Logarithmic conformal field theories. In particular we draw attention to the fundamental differences between theories with zero and non-zero central charge. However they are both characterised by at least two independent parameters. We show how, by using a generalised Sugawara construction, one can calculate the logarithmic partner of T. We show that such a construction works in the c = -2 theory using the conformal dimension one primary currents which generate a logarithmic extension of the Kac-Moody algebra.
The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress

NASA Astrophysics Data System (ADS)

Mitić, M.; Simić, I.; Djordjević, J.; Radojčić, M. B.; Adžić, M.

2011-12-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study.
Seismicity and seismogenic structures of Central Apennines (Italy): constraints on the present-day stress field from focal mechanisms - The SLAM (Seismicity of Lazio-Abruzzo and Molise) project

NASA Astrophysics Data System (ADS)

Frepoli, Alberto; Battista Cimini, Giovanni; De Gori, Pasquale; De Luca, Gaetano; Marchetti, Alessandro; Montuori, Caterina; Pagliuca, Nicola

2016-04-01

We present new results for the microseismic activity in the Central Apennines recorded from a total of 81seismic stations. The large number of recording sites derives from the combination of temporary and permanent seismic networks operating in the study region. Between January 2009 and October 2013 we recorded 6923 earthquakes with local magnitudes ML ranging from 0.1 to 4.8. We located hypocentres by using a refined 1D crustal velocity model. The majority of the hypocenters are located beneath the axes of the Apenninic chain, while the seismic activity observed along the peri-Tyrrhenian margin is lower. The seismicity extends to a depth of 32 km; the hypocentral depth distribution exhibits a pronounced peak of seismic energy release in the depth range between 8 and 20 km. During the observation period we recorded two major seismic swarms and one seismic sequence in the Marsica-Sorano area in which we have had the largest detected magnitude (ML = 4.8). Fault plane solutions for a total of 600 earthquakes were derived from P-polarities. This new data set consists of a number of focal plane solutions that is about four times the data so far available for regional stress field study. The majority of the focal mechanisms show predominantly normal fault solutions. T-axis trends are oriented NE-SW confirming that the area is in extension. We also derived the azimuths of the principal stress axes by inverting the fault plane solutions and calculated the direction of the maximum horizontal stress, which is mainly sub-vertical oriented. The study region has been historically affected by many strong earthquakes, some of them very destructive. This work can give an important contribution to the seismic hazard assessment in an area densely populated as the city of Rome which is distant around 60 km from the main seismogenic structures of Central Apennine.

Lipidomics: the function of vital lipids in embryogenesis preventing autism spectrum disorders, treating sterile inflammatory diatheses with a lymphopoietic central nervous system component.

PubMed

Tallberg, Thomas; Dabek, Jan; Hallamaa, Raija; Atroshi, Faik

2011-01-01

The central role performed by billions of vital central nervous system (CNS) lipids "lipidomics" in medical physiology is usually overlooked. A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.
Structural analysis of a Petri net model of oxidative stress in atherosclerosis.

PubMed

Kozak, Adam; Formanowicz, Dorota; Formanowicz, Piotr

2018-06-01

Atherosclerosis is a complex process of gathering sub-endothelial plaques decreasing lumen of the blood vessels. This disorder affects people of all ages, but its progression is asymptomatic for many years. It is regulated by many typical and atypical factors including the immune system response, a chronic kidney disease, a diet rich in lipids, a local inflammatory process and a local oxidative stress that is here one of the key factors. In this study, a Petri net model of atherosclerosis regulation is presented. This model includes also some information about stoichiometric relationships between its components and covers all mentioned factors. For the model, a structural analysis based on invariants was made and biological conclusions are presented. Since the model contains inhibitor arcs, a heuristic method for analysis of such cases is presented. This method can be used to extend the concept of feasible t -invariants.
Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson's Disease.

PubMed

Rodríguez-Arribas, M; Yakhine-Diop, S M S; Pedro, J M Bravo-San; Gómez-Suaga, P; Gómez-Sánchez, R; Martínez-Chacón, G; Fuentes, J M; González-Polo, R A; Niso-Santano, M

2017-10-01

Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by PARK genes and some of neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this regulation. In this regard, MAM alteration is associated with neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD) and contributes to the appearance of the pathogenesis features, i.e., autophagy dysregulation, mitochondrial dysfunction, oxidative stress, and lately, neuronal death. Moreover,, ER stress and/or damaged mitochondria can be the cause of these disruptions. Therefore, ER-mitochondria contact structure and function are crucial to multiple cellular processes. This review is focused on the molecular interaction between ER and mitochondria indispensable to MAM formation and on MAM alteration-induced etiology of neurodegenerative diseases.
Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction.

PubMed

Ramsden, David B; Ho, Philip W-L; Ho, Jessica W-M; Liu, Hui-Fang; So, Danny H-F; Tse, Ho-Man; Chan, Koon-Ho; Ho, Shu-Leong

2012-07-01

Uncoupling proteins (UCPs) belong to a large family of mitochondrial solute carriers 25 (SLC25s) localized at the inner mitochondrial membrane. UCPs transport protons directly from the intermembrane space to the matrix. Of five structural homologues (UCP1 to 5), UCP4 and 5 are principally expressed in the central nervous system (CNS). Neurons derived their energy in the form of ATP that is generated through oxidative phosphorylation carried out by five multiprotein complexes (Complexes I-V) embedded in the inner mitochondrial membrane. In oxidative phosphorylation, the flow of electrons generated by the oxidation of substrates through the electron transport chain to molecular oxygen at Complex IV leads to the transport of protons from the matrix to the intermembrane space by Complex I, III, and IV. This movement of protons to the intermembrane space generates a proton gradient (mitochondrial membrane potential; MMP) across the inner membrane. Complex V (ATP synthase) uses this MMP to drive the conversion of ADP to ATP. Some electrons escape to oxygen-forming harmful reactive oxygen species (ROS). Proton leakage back to the matrix which bypasses Complex V resulting in a major reduction in ROS formation while having a minimal effect on MMP and hence, ATP synthesis; a process termed "mild uncoupling." UCPs act to promote this proton leakage as means to prevent excessive build up of MMP and ROS formation. In this review, we discuss the structure and function of mitochondrial UCPs 4 and 5 and factors influencing their expression. Hypotheses concerning the evolution of the two proteins are examined. The protective mechanisms of the two proteins against neurotoxins and their possible role in regulating intracellular calcium movement, particularly with regard to the pathogenesis of Parkinson's disease are discussed.
Rumination, event centrality, and perceived control as predictors of post-traumatic growth and distress: The Cognitive Growth and Stress model.

PubMed

Brooks, Matthew; Graham-Kevan, Nicola; Lowe, Michelle; Robinson, Sarita

2017-09-01

The Cognitive Growth and Stress (CGAS) model draws together cognitive processing factors previously untested into a single model. Intrusive rumination, deliberate rumination, present and future perceptions of control, and event centrality were assessed as predictors of post-traumatic growth (PTG) and post-traumatic stress (PTS). The CGAS model is tested on a sample of survivors (N = 250) of a diverse range of adverse events using structural equation modelling techniques. Overall, the best fitting model was supportive of the theorized relations between cognitive constructs and accounted for 30% of the variance in PTG and 68% of the variance in PTS across the sample. Rumination, centrality, and perceived control factors are significant determinants of positive and negative psychological change across the wide spectrum of adversarial events. In its first phase of development, the CGAS model also provides further evidence of the distinct processes of growth and distress following adversity. Clinical implications People can experience positive change after adversity, regardless of life background or types of events experienced. While growth and distress are possible outcomes after adversity, they occur through distinct processes. Support or intervention should consider rumination, event centrality, and perceived control factors to enhance psychological well-being. Cautions/limitations Longitudinal research would further clarify the findings found in this study. Further extension of the model is recommended to include other viable cognitive processes implicated in the development of positive and negative changes after adversity. © 2017 The British Psychological Society.
Expression of Stipa purpurea SpCIPK26 in Arabidopsis thaliana Enhances Salt and Drought Tolerance and Regulates Abscisic Acid Signaling

PubMed Central

Zhou, Yanli; Sun, Xudong; Yang, Yunqiang; Li, Xiong; Cheng, Ying; Yang, Yongping

2016-01-01

Stipa purpurea (S. purpurea) is the dominant plant species in the alpine steppe of the Qinghai-Tibet Plateau, China. It is highly resistant to cold and drought conditions. However, the underlying mechanisms regulating the stress tolerance are unknown. In this study, a CIPK gene from S. purpurea (SpCIPK26) was isolated. The SpCIPK26 coding region consisted of 1392 bp that encoded 464 amino acids. The protein has a highly conserved catalytic structure and regulatory domain. The expression of SpCIPK26 was induced by drought and salt stress. SpCIPK26 overexpression in Arabidopsis thaliana (A. thaliana) plants provided increased tolerance to drought and salt stress in an abscisic acid (ABA)-dependent manner. Compared with wild-type A. thaliana plants, SpCIPK26-overexpressing plants had higher survival rates, water potentials, and photosynthetic efficiency (Fv/Fm), as well as lower levels of reactive oxygen species (ROS) following exposure to drought and salt stress. Gene expression analyses indicated stress-inducible genes (RD29A, RD29B, and ABF2) and a ROS-scavenger gene (CAT1) were upregulated in SpCIPK26-overexpressing plants after stress treatments. All of these marker genes are associated with ABA-responsive cis-acting elements. Additionally, the similarities in the gene expression patterns following ABA, mannitol, and NaCl treatments suggest SpCIPK26 has an important role during plant responses to drought and salt stress and in regulating ABA signaling. PMID:27338368
mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging.

PubMed

Perl, Andras

2015-06-01

The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase, which plays pivotal roles in integrating growth signals on a cellular level. To support proliferation and survival under stress, two interacting complexes that harbor mTOR, mTORC1 and mTORC2, promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation, and inhibit autophagy. Although rapamycin was originally developed as an inhibitor of T cell proliferation for preventing organ transplant rejection, its molecular target, mTOR, has been subsequently identified as a central regulator of metabolic cues that drive lineage specification in the immune system. Owing to oxidative stress, the activation of mTORC1 has emerged as a central pathway for the pathogenesis of systemic lupus erythematosus and other autoimmune diseases. Paradoxically, mTORC1 has also been identified as a mediator of the Warburg effect that allows cell survival under hypoxia. Rapamycin and new classes of mTOR inhibitors are being developed to block not only transplant rejection and autoimmunity but also to treat obesity and various forms of cancer. Through preventing these diseases, personalized mTOR blockade holds promise to extend life span. © 2015 New York Academy of Sciences.
Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice

PubMed Central

Wu, Yuwei; Tu, Qisheng; Valverde, Paloma; Zhang, Jin; Murray, Dana; Dong, Lily Q.; Cheng, Jessica; Jiang, Hua; Rios, Maribel; Morgan, Elise; Tang, Zhihui

2014-01-01

Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C) expressions but decreased hypothalamic cannabinoid receptor-1 expression. Treatment of immortalized mouse neurons with APN demonstrated that APN-mediated effects on TPH2, CART, and Htr2C expression levels were abolished by downregulating adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL)-1 expression. Pharmacological increase in sympathetic activity stimulated adipogenic differentiation of bone marrow stromal cells (BMSC) and reversed APN-induced expression of the lysine-specific demethylases involved in regulating their commitment to the osteoblastic lineage. In conclusion, we found that APN regulates bone metabolism via central and peripheral mechanisms to decrease sympathetic tone, inhibit osteoclastic differentiation, and promote osteoblastic commitment of BMSC. PMID:24780611
Race and Gender Matter: A Multidimensional Approach to Conceptualizing and Measuring Stress in African American Women

PubMed Central

Woods-Giscombé, Cheryl L.; Lobel, Marci

2008-01-01

Based on prior research and theory, the authors constructed a multidimensional model of stress in African American women comprised of race-related, gender-related, and generic stress. Exposure to and appraisal of these three types of stress were combined into a higher-order global stress factor. Using structural equation modeling, the fit of this stress factor and its ability to predict distress symptoms were examined in 189 socioeconomically diverse African American women aged 21 to 78. Results support the multidimensional conceptualization and operationalization of stress. Race-related, gender-related, and generic stress contributed equally to the global stress factor, and global stress predicted a significant amount of variance in distress symptoms and intensity. This model exhibited better fit than a model without a global stress factor, in which each stress component predicted distress directly. Furthermore, race-related, gender-related, and generic stress did not contribute to distress beyond their representation in the global stress factor. These findings illustrate that stress related to central elements of identity, namely race and gender, cohere with generic stress to define the stress experience of African American women. PMID:18624581
Race and gender matter: a multidimensional approach to conceptualizing and measuring stress in African American women.

PubMed

Woods-Giscombé, Cheryl L; Lobel, Marci

2008-07-01

Based on prior research and theory, the authors constructed a multidimensional model of stress in African American women comprised of race-related, gender-related, and generic stress. Exposure to and appraisal of these three types of stress were combined into a higher-order global stress factor. Using structural equation modeling, the fit of this stress factor and its ability to predict distress symptoms were examined in 189 socioeconomically diverse African American women aged 21 to 78. Results support the multidimensional conceptualization and operationalization of stress. Race-related, gender-related, and generic stress contributed equally to the global stress factor, and global stress predicted a significant amount of variance in distress symptoms and intensity. This model exhibited better fit than a model without a global stress factor, in which each stress component predicted distress directly. Furthermore, race-related, gender-related, and generic stress did not contribute to distress beyond their representation in the global stress factor. These findings illustrate that stress related to central elements of identity, namely race and gender, cohere with generic stress to define the stress experience of African American women. Copyright (c) 2008 APA, all rights reserved.
Pediatric oncologists' attitudes towards involving adolescents in decision-making concerning research participation.

PubMed

de Vries, Martine C; Wit, Jan M; Engberts, Dirk P; Kaspers, Gertjan J L; van Leeuwen, Evert

2010-07-15

Various regulations and guidelines stipulate the importance of involving adolescents in decision-making concerning research participation. Several studies have shown that in the context of pediatric oncology this involvement is difficult to achieve due to emotional stress, the complexity of research protocols and limited time. Still, up to 80% of adolescents with cancer enter onto a trial during their illness. The aim of this study was to determine clinicians' views and attitudes towards enrolling adolescents in research, considering the difficulties surrounding their involvement in decision-making. A qualitative multicenter study was performed, using in-depth semi-structured interviews on the informed consent process with 15 pediatric hemato-oncologists. Four central themes emerged that characterize clinicians' attitudes towards involving adolescents in the decision-making process: (1) clinicians regard most adolescents as not capable of participating meaningfully in discussions regarding research; (2) clinicians do not always provide adolescents with all information; (3) proxy consent from parents is obtained and is deemed sufficient; (4) clinician-investigator integrity: clinicians judge research protocols as not being harmful and even in the best interest of the adolescent. Clinicians justify not involving adolescents in research discussions by referring to best interest arguments (adolescents' incompetence, proxy consent, and investigator integrity), although this is not in line with legal regulations and ethical guidelines.
[Features of seasonal reorganizations of the central mechanisms of regulation in children northerners with different level of social risk].

PubMed

Soroko, S I; Rozhkov, V P; Bekshaev, S S

2013-12-01

The paper presents a comparative analysis of frequency, spatial-temporal parameters and three-dimensional localization of EEG sources that characterize changes of cortical-subcortical interactions processes in autumn and spring periods at northern schoolchildren living in satisfactory and disadvantaged (risk group) conditions of the social (family) environment. Seasonal rearrangement of interaction between wave components of main EEG rhythms was revealed. School students present regressive changes in the EEG pattern temporal organization in spring compared to autumn, and this effect was more expressed at adolescents from group of risk. Data EEDS-tomography showed increased activity in the prefrontal, cingular and subcallosal areas of the cortex in the autumn period that could be related to the mechanisms of season depression caused by the significant reduction of the day length in the North. The increased activity of the limbic system structures which is persisted in the spring in adolescents from risk group narrows the range of regulation of adaptive reactions. Unfavorable conditions of the family environment are an additional stress factor to increased load on the regulatory mechanisms that have a negative impact on the emotional-motivation behavior of children and adolescents, thus increasing the risk of the school and of social disadaptation.
Redox signaling in cardiac myocytes

PubMed Central

Santos, Celio X.C.; Anilkumar, Narayana; Zhang, Min; Brewer, Alison C.; Shah, Ajay M.

2011-01-01

The heart has complex mechanisms that facilitate the maintenance of an oxygen supply–demand balance necessary for its contractile function in response to physiological fluctuations in workload as well as in response to chronic stresses such as hypoxia, ischemia, and overload. Redox-sensitive signaling pathways are centrally involved in many of these homeostatic and stress-response mechanisms. Here, we review the main redox-regulated pathways that are involved in cardiac myocyte excitation–contraction coupling, differentiation, hypertrophy, and stress responses. We discuss specific sources of endogenously generated reactive oxygen species (e.g., mitochondria and NADPH oxidases of the Nox family), the particular pathways and processes that they affect, the role of modulators such as thioredoxin, and the specific molecular mechanisms that are involved—where this knowledge is available. A better understanding of this complex regulatory system may allow the development of more specific therapeutic strategies for heart diseases. PMID:21236334
Dehydration responsive element binding transcription factors and their applications for the engineering of stress tolerance.

PubMed

Agarwal, Pradeep K; Gupta, Kapil; Lopato, Sergiy; Agarwal, Parinita

2017-04-01

Dehydration responsive element binding (DREB) factors or CRT element binding factors (CBFs) are members of the AP2/ERF family, which comprises a large number of stress-responsive regulatory genes. This review traverses almost two decades of research, from the discovery of DREB/CBF factors to their optimization for application in plant biotechnology. In this review, we describe (i) the discovery, classification, structure, and evolution of DREB genes and proteins; (ii) induction of DREB genes by abiotic stresses and involvement of their products in stress responses; (iii) protein structure and DNA binding selectivity of different groups of DREB proteins; (iv) post-transcriptional and post-translational mechanisms of DREB transcription factor (TF) regulation; and (v) physical and/or functional interaction of DREB TFs with other proteins during plant stress responses. We also discuss existing issues in applications of DREB TFs for engineering of enhanced stress tolerance and improved performance under stress of transgenic crop plants. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Dissecting Regional Variations in Stress Fiber Mechanics in Living Cells with Laser Nanosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanner, Kandice; Boudreau, Aaron; Bissell, Mina J

The ability of a cell to distribute contractile stresses across the extracellular matrix in a spatially heterogeneous fashion underlies many cellular behaviors, including motility and tissue assembly. Here we investigate the biophysical basis of this phenomenon by using femtosecond laser nanosurgery to measure the viscoelastic recoil and cell-shape contributions of contractile stress fibers (SFs) located in specific compartments of living cells. Upon photodisruption and recoil, myosin light chain kinase-dependent SFs located along the cell periphery display much lower effective elasticities and higher plateau retraction distances than Rho-associated kinase-dependent SFs located in the cell center, with severing of peripheral fibers uniquelymore » triggering a dramatic contraction of the entire cell within minutes of fiber irradiation. Image correlation spectroscopy reveals that when one population of SFs is pharmacologically dissipated, actin density flows toward the other population. Furthermore, dissipation of peripheral fibers reduces the elasticity and increases the plateau retraction distance of central fibers, and severing central fibers under these conditions triggers cellular contraction. Together, these findings show that SFs regulated by different myosin activators exhibit different mechanical properties and cell shape contributions. They also suggest that some fibers can absorb components and assume mechanical roles of other fibers to stabilize cell shape.« less
Silicon mitigates heavy metal stress by regulating P-type heavy metal ATPases, Oryza sativa low silicon genes, and endogenous phytohormones

PubMed Central

2014-01-01

Background Silicon (Si) application has been known to enhance the tolerance of plants against abiotic stresses. However, the protective mechanism of Si under heavy metals contamination is poorly understood. The aim of this study was to assess the role of Si in counteracting toxicity due to cadmium (Cd) and copper (Cu) in rice plants (Oryza sativa). Results Si significantly improved the growth and biomass of rice plants and reduced the toxic effects of Cd/Cu after different stress periods. Si treatment ameliorated root function and structure compared with non-treated rice plants, which suffered severe root damage. In the presence of Si, the Cd/Cu concentration was significantly lower in rice plants, and there was also a reduction in lipid peroxidation and fatty acid desaturation in plant tissues. The reduced uptake of metals in the roots modulated the signaling of phytohormones involved in responses to stress and host defense, such as abscisic acid, jasmonic acid, and salicylic acid. Furthermore, the low concentration of metals significantly down regulated the mRNA expression of enzymes encoding heavy metal transporters (OsHMA2 and OsHMA3) in Si-metal-treated rice plants. Genes responsible for Si transport (OsLSi1 and OsLSi2), showed a significant up-regulation of mRNA expression with Si treatment in rice plants. Conclusion The present study supports the active role of Si in the regulation of stresses from heavy metal exposure through changes in root morphology. PMID:24405887
Regulation in the Air: Price and Frequency Cap

NASA Technical Reports Server (NTRS)

deVillemeur, Etienne Billette

2003-01-01

Despite deregulation on the air-transportation markets, many connections are still operated by a single operator. Regulation is thus a central issue in this industry. There is however a great concern for the (possibly negative) consequences of price regulation on the quality of services. We argue that both aspects should be considered jointly and propose a mechanism that allow to decentralize the optimal structure of services in this industry. The regulatory procedure is robust to the introduction of heterogeneity in the travellers' valuation of the connections' frequency.
The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response

PubMed Central

Dedic, Nina; Chen, Alon; Deussing, Jan M.

2018-01-01

Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and conse-quently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2. Objective: Here we review the past and current state of the CRF/CRFR field, ranging from pharmacologi-cal studies to genetic mouse models and virus-mediated manipulations. Results: Although it is well established that CRF/CRFR1 signaling mediates aversive responses, includ-ing anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiol-ogy and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions. Conclusion: A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mecha-nisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely un-derstood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of adaptive and maladaptive stress responses. PMID:28260504
Impaired Voluntary Control in PTSD: Probing Self-Regulation of the ACC With Real-Time fMRI

PubMed Central

Zweerings, Jana; Pflieger, Eliza M.; Mathiak, Krystyna A.; Zvyagintsev, Mikhail; Kacela, Anastasia; Flatten, Guido; Mathiak, Klaus

2018-01-01

Background: Post-traumatic stress disorder (PTSD) is characterized by deficits in the self-regulation of cognitions and emotions. Neural networks of emotion regulation may exhibit reduced control mediated by the anterior cingulate cortex (ACC), contributing to aberrant limbic responses in PTSD. Methods: Real-time fMRI neurofeedback (rt-fMRI NF) assessed self-regulation of the ACC in nine patients with PTSD after single trauma exposure and nine matched healthy controls. All participants were instructed to train ACC upregulation on three training days. Results: Both groups achieved regulation, which was associated with wide-spread brain activation encompassing the ACC. Compared to the controls, regulation amplitude and learning rate was lower in patients, correlating with symptom severity. In addition, a frontopolar activation cluster was associated with self-regulation efforts in patients. Conclusions: For the first time, we tested self-regulation of the ACC in patients with PTSD. The observed impairment supports models of ACC-mediated regulation deficits that may contribute to the psychopathology of PTSD. Controlled trials in a larger sample are needed to confirm our findings and to directly investigate whether training of central regulation mechanisms improves emotion regulation in PTSD. PMID:29899712
Impaired Voluntary Control in PTSD: Probing Self-Regulation of the ACC With Real-Time fMRI.

PubMed

Zweerings, Jana; Pflieger, Eliza M; Mathiak, Krystyna A; Zvyagintsev, Mikhail; Kacela, Anastasia; Flatten, Guido; Mathiak, Klaus

2018-01-01

Background: Post-traumatic stress disorder (PTSD) is characterized by deficits in the self-regulation of cognitions and emotions. Neural networks of emotion regulation may exhibit reduced control mediated by the anterior cingulate cortex (ACC), contributing to aberrant limbic responses in PTSD. Methods: Real-time fMRI neurofeedback (rt-fMRI NF) assessed self-regulation of the ACC in nine patients with PTSD after single trauma exposure and nine matched healthy controls. All participants were instructed to train ACC upregulation on three training days. Results: Both groups achieved regulation, which was associated with wide-spread brain activation encompassing the ACC. Compared to the controls, regulation amplitude and learning rate was lower in patients, correlating with symptom severity. In addition, a frontopolar activation cluster was associated with self-regulation efforts in patients. Conclusions: For the first time, we tested self-regulation of the ACC in patients with PTSD. The observed impairment supports models of ACC-mediated regulation deficits that may contribute to the psychopathology of PTSD. Controlled trials in a larger sample are needed to confirm our findings and to directly investigate whether training of central regulation mechanisms improves emotion regulation in PTSD.

Temporal and spatial patterns in wind stress and wind stress curl over the central Southern California Bight

USGS Publications Warehouse

Noble, Marlene A.; Rosenberger, Kurt J.; Rosenfeld, Leslie K.; Robertson, George L.

2012-01-01

In 2001, the U.S. Geological Survey, together with several other federal and municipal agencies, began a series of field programs to determine along and cross-shelf transport patterns over the continental shelves in the central Southern California Bight. As a part of these programs, moorings that monitor winds were deployed off the Palos Verdes peninsula and within San Pedro Bay for six 3–4 month summer and winter periods between 2001 and 2008. In addition, nearly continuous records of winds for this 7-year period were obtained from a terrestrial site at the coast and from a basin site offshore of the long-term coastal site. The mean annual winds are downcoast at all sites. The alongshelf components of wind stress, which are the largest part of the low-frequency wind stress fields, are well correlated between basin, shelf and coastal sites. On average, the amplitude of alongshelf fluctuations in wind stress are 3–4 times larger over the offshore basin, compared to the coastal site, irrespective of whether the fluctuations represent the total, or just the correlated portion of the wind stress field. The curl in the large-scale wind stress tends to be positive, especially in the winter season when the mean wind stress is downcoast and larger at the offshore basin site than at the beach. However, since the fluctuation in wind stress amplitudes are usually larger than the mean, periods of weak negative curl do occur, especially in the summer season when the largest normalized differences in the amplitude of wind stress fluctuations are found in the nearshore region of the coastal ocean. Even though the low-frequency wind stress field is well-correlated over the continental shelf and offshore basins, out to distances of 35 km or more from the coast, winds even 10 km inshore of the beach do not represent the coastal wind field, at least in the summer months. The seasonal changes in the spatial structures in wind stress amplitudes suggest that an assessment of the amplitude of the responses of coastal ocean processes to wind forcing is complex and that the responses may have significant seasonal structures.
Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases.

PubMed

Kumar, Hemant; Kim, In-Su; More, Sandeep Vasant; Kim, Byung-Wook; Choi, Dong-Kug

2014-01-01

Covering: 2000 to 2013. Oxidative stress is the central component of chronic diseases. The nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway is vital in the up-regulation of cytoprotective genes and enzymes in response to oxidative stress and treatment with certain dietary phytochemicals. Herein, we classify bioactive compounds derived from natural products that are Nrf2/ARE pathway activators and recapitulate the molecular mechanisms for inducing Nrf2 to provide favorable effects in experimental models of chronic diseases. Moreover, pharmacological inhibition of Nrf2 signalling has emerged as promising strategy against multi-drug resistance thereby improving the treatment efficacy. We have also enlisted natural product-derived inhibitors of Nrf2/ARE pathway.
Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior

PubMed Central

Wohleb, Eric S.; McKim, Daniel B.; Sheridan, John F.; Godbout, Jonathan P.

2015-01-01

HIGHLIGHTS Psychological stress activates neuroendocrine pathways that alter immune responses.Stress-induced alterations in microglia phenotype and monocyte priming leads to aberrant peripheral and central inflammation.Elevated pro-inflammatory cytokine levels caused by microglia activation and recruitment of monocytes to the brain contribute to development and persistent anxiety-like behavior.Mechanisms that mediate interactions between microglia, endothelial cells, and macrophages and how these contribute to changes in behavior are discussed.Sensitization of microglia and re-distribution of primed monocytes are implicated in re-establishment of anxiety-like behavior. Psychological stress causes physiological, immunological, and behavioral alterations in humans and rodents that can be maladaptive and negatively affect quality of life. Several lines of evidence indicate that psychological stress disrupts key functional interactions between the immune system and brain that ultimately affects mood and behavior. For example, activation of microglia, the resident innate immune cells of the brain, has been implicated as a key regulator of mood and behavior in the context of prolonged exposure to psychological stress. Emerging evidence implicates a novel neuroimmune circuit involving microglia activation and sympathetic outflow to the peripheral immune system that further reinforces stress-related behaviors by facilitating the recruitment of inflammatory monocytes to the brain. Evidence from various rodent models, including repeated social defeat (RSD), revealed that trafficking of monocytes to the brain promoted the establishment of anxiety-like behaviors following prolonged stress exposure. In addition, new evidence implicates monocyte trafficking from the spleen to the brain as key regulator of recurring anxiety following exposure to prolonged stress. The purpose of this review is to discuss mechanisms that cause stress-induced monocyte re-distribution in the brain and how dynamic interactions between microglia, endothelial cells, and brain macrophages lead to maladaptive behavioral responses. PMID:25653581
Precision of Sensitivity in the Design Optimization of Indeterminate Structures

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.; Pai, Shantaram S.; Hopkins, Dale A.

2006-01-01

Design sensitivity is central to most optimization methods. The analytical sensitivity expression for an indeterminate structural design optimization problem can be factored into a simple determinate term and a complicated indeterminate component. Sensitivity can be approximated by retaining only the determinate term and setting the indeterminate factor to zero. The optimum solution is reached with the approximate sensitivity. The central processing unit (CPU) time to solution is substantially reduced. The benefit that accrues from using the approximate sensitivity is quantified by solving a set of problems in a controlled environment. Each problem is solved twice: first using the closed-form sensitivity expression, then using the approximation. The problem solutions use the CometBoards testbed as the optimization tool with the integrated force method as the analyzer. The modification that may be required, to use the stiffener method as the analysis tool in optimization, is discussed. The design optimization problem of an indeterminate structure contains many dependent constraints because of the implicit relationship between stresses, as well as the relationship between the stresses and displacements. The design optimization process can become problematic because the implicit relationship reduces the rank of the sensitivity matrix. The proposed approximation restores the full rank and enhances the robustness of the design optimization method.
Perceiving a negative event as central to one's identity partially mediates age differences in posttraumatic stress disorder symptoms.

PubMed

Boals, Adriel; Hayslip, Bert; Knowles, Laura R; Banks, Jonathan B

2012-04-01

Older adults report fewer posttraumatic stress disorder (PTSD) symptoms than younger adults, but the reasons for this age difference are unclear. In the current study, the authors explored the extent to which they may be due to age differences in event centrality (the extent to which a person construes a stressful event as central to their identity). A sample of older and younger adults nominated their most stressful event and completed measures of PTSD symptoms and event centrality. The results revealed that older adults were less likely to construe a stressful event as central to identity, even after controlling for type of event, how long ago the event occurred, and gender. In addition, the results of a mediation analysis indicated that age-related differences in event centrality partially mediated age-related differences in PTSD symptoms. The results are consistent with the Socioemotional Selectivity Theory view that older adults tend to use cognitive strategies designed to protect emotional health.
The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast

PubMed Central

Sanz, Ana Belén; García, Raúl; Rodríguez-Peña, José M.; Arroyo, Javier

2017-01-01

Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI) pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies. PMID:29371494
Transcription Factor CBF4 Is a Regulator of Drought Adaptation in Arabidopsis1

PubMed Central

Haake, Volker; Cook, Daniel; Riechmann, José Luis; Pineda, Omaira; Thomashow, Michael F.; Zhang, James Z.

2002-01-01

In plants, low temperature and dehydration activate a set of genes containing C-repeat/dehydration-responsive elements in their promoter. It has been shown previously that the Arabidopsis CBF/DREB1 transcription activators are critical regulators of gene expression in the signal transduction of cold acclimation. Here, we report the isolation of an apparent homolog of the CBF/DREB1 proteins (CBF4) that plays the equivalent role during drought adaptation. In contrast to the three already identified CBF/DREB1 homologs, which are induced under cold stress, CBF4 gene expression is up-regulated by drought stress, but not by low temperature. Overexpression of CBF4 in transgenic Arabidopsis plants results in the activation of C-repeat/dehydration-responsive element containing downstream genes that are involved in cold acclimation and drought adaptation. As a result, the transgenic plants are more tolerant to freezing and drought stress. Because of the physiological similarity between freezing and drought stress, and the sequence and structural similarity of the CBF/DREB1 and the CBF4 proteins, we propose that the plant's response to cold and drought evolved from a common CBF-like transcription factor, first through gene duplication and then through promoter evolution. PMID:12376631
Structure-based functional characterization of repressor of toxin (Rot), a central regulator of staphylococcus aureus virulence

DOE PAGES

Killikelly, April; Jakoncic, Jean; Benson, Meredith A.; ...

2014-10-20

Staphylococcus aureus is responsible for a large number of diverse infections worldwide. In order to support its pathogenic lifestyle, S. aureus has to regulate the expression of virulence factors in a coordinated fashion. One of the central regulators of the S. aureus virulence regulatory networks is the transcription factor repressor of toxin (Rot). Rot plays a key role in regulating S. aureus virulence through activation or repression of promoters that control expression of a large number of critical virulence factors. However, the mechanism by which Rot mediates gene regulation has remained elusive. Here, we have determined the crystal structure ofmore » Rot and used this information to probe the contribution made by specific residues to Rot function. Rot was found to form a dimer, with each monomer harboring a winged helix-turn-helix (WHTH) DNA-binding motif. Despite an overall acidic pI, the asymmetric electrostatic charge profile suggests that Rot can orient the WHTH domain to bind DNA. Structure-based site-directed mutagenesis studies demonstrated that R 91, at the tip of the wing, plays an important role in DNA binding, likely through interaction with the minor groove. We also found that Y 66, predicted to bind within the major groove, contributes to Rot interaction with target promoters. Evaluation of Rot binding to different activated and repressed promoters revealed that certain mutations on Rot exhibit promoter-specific effects, suggesting for the first time that Rot differentially interacts with target promoters. As a result, this work provides insight into a precise mechanism by which Rot controls virulence factor regulation in S. aureus.« less
Structure-based functional characterization of repressor of toxin (Rot), a central regulator of staphylococcus aureus virulence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Killikelly, April; Jakoncic, Jean; Benson, Meredith A.

Staphylococcus aureus is responsible for a large number of diverse infections worldwide. In order to support its pathogenic lifestyle, S. aureus has to regulate the expression of virulence factors in a coordinated fashion. One of the central regulators of the S. aureus virulence regulatory networks is the transcription factor repressor of toxin (Rot). Rot plays a key role in regulating S. aureus virulence through activation or repression of promoters that control expression of a large number of critical virulence factors. However, the mechanism by which Rot mediates gene regulation has remained elusive. Here, we have determined the crystal structure ofmore » Rot and used this information to probe the contribution made by specific residues to Rot function. Rot was found to form a dimer, with each monomer harboring a winged helix-turn-helix (WHTH) DNA-binding motif. Despite an overall acidic pI, the asymmetric electrostatic charge profile suggests that Rot can orient the WHTH domain to bind DNA. Structure-based site-directed mutagenesis studies demonstrated that R 91, at the tip of the wing, plays an important role in DNA binding, likely through interaction with the minor groove. We also found that Y 66, predicted to bind within the major groove, contributes to Rot interaction with target promoters. Evaluation of Rot binding to different activated and repressed promoters revealed that certain mutations on Rot exhibit promoter-specific effects, suggesting for the first time that Rot differentially interacts with target promoters. As a result, this work provides insight into a precise mechanism by which Rot controls virulence factor regulation in S. aureus.« less
Mindfulness meditation improves emotion regulation and reduces drug abuse.

PubMed

Tang, Yi-Yuan; Tang, Rongxiang; Posner, Michael I

2016-06-01

The core clinical symptoms of addiction include an enhanced incentive for drug taking (craving), impaired self-control (impulsivity and compulsivity), emotional dysregulation (negative mood) and increased stress reactivity. Symptoms related to impaired self-control involve reduced activity in anterior cingulate cortex (ACC), adjacent prefrontal cortex (mPFC) and other brain areas. Behavioral training such as mindfulness meditation can increase the function of control networks including those leading to improved emotion regulation and thus may be a promising approach for the treatment of addiction. In a series of randomized controlled trials (RCTs), we tested whether increased ACC/mPFC activity is related to better self-control abilities in executive functions, emotion regulation and stress response in healthy and addicted populations. After a brief mindfulness training (Integrative Body-Mind Training, IBMT), we used the Positive and Negative Affect Schedule (PANAS) and Profile of Mood States (POMS) to measure emotion regulation, salivary cortisol for the stress response and fMRI for brain functional and DTI structural changes. Relaxation training was used to serve as an active control. In both smokers and nonsmokers, improved self-control abilities in emotion regulation and stress reduction were found after training and these changes were related to increased ACC/mPFC activity following training. Compared with nonsmokers, smokers showed reduced ACC/mPFC activity in the self-control network before training, and these deficits were ameliorated after training. These results indicate that promoting emotion regulation and improving ACC/mPFC brain activity can help for addiction prevention and treatment. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
The Redox Stress Hypothesis of Aging

PubMed Central

Sohal, Rajindar S.; Orr, William C.

2011-01-01

The main objective of this review is to examine the role of the endogenous reactive oxygen/nitrogen species (ROS) in the aging process. Until relatively recently, ROS were considered to be potentially toxic by-products of aerobic metabolism, which, if not eliminated, may inflict structural damage on various macromolecules. Accrual of such damage over time was postulated to be responsible for the physiological deterioration in the post-reproductive phase of life and eventually the death of the organism. This “structural damage-based oxidative stress” hypothesis has received support from the age-associated increases in the rates of ROS production and the steady-state amounts of oxidized macromolecules; however, there are increasing indications that structural damage alone is insufficient to satisfactorily explain the age-associated functional losses. The level of oxidative damage, accrued during aging, often does not match the magnitude of functional losses. Although experimental augmentations of antioxidant defenses tend to enhance resistance to induced oxidative stress, such manipulations are generally ineffective in the extension of life span of long-lived strains of animals. More recently, in a major conceptual shift, ROS have been found to be physiologically vital for signal transduction, gene regulation and redox regulation, among others, implying that their complete elimination would be harmful. An alternative notion, advocated here, termed “redox stress hypothesis”, proposes that aging-associated functional losses are primarily caused by a progressive pro-oxidizing shift in the redox state of the cells, which leads to the over-oxidation of redox-sensitive protein thiols and the consequent disruption of the redox-regulated signaling mechanisms. PMID:22080087
Maternal neglect with reduced depressive-like behavior and blunted c-fos activation in Brattleboro mothers, the role of central vasopressin.

PubMed

Fodor, Anna; Klausz, Barbara; Pintér, Ottó; Daviu, Nuria; Rabasa, Cristina; Rotllant, David; Balazsfi, Diana; Kovacs, Krisztina B; Nadal, Roser; Zelena, Dóra

2012-09-01

Early mother-infant relationships exert important long-term effects in offspring and are disturbed by factors such as postpartum depression. We aimed to clarify if lack of vasopressin influences maternal behavior paralleled by the development of a depressive-like phenotype. We compared vasopressin-deficient Brattleboro mothers with heterozygous and homozygous normal ones. The following parameters were measured: maternal behavior (undisturbed and separation-induced); anxiety by the elevated plus maze; sucrose and saccharin preference and forced swim behavior. Underlying brain areas were examined by c-fos immunocytochemistry among rest and after swim-stress. In another group of rats, vasopressin 2 receptor agonist was used peripherally to exclude secondary changes due to diabetes insipidus. Results showed that vasopressin-deficient rats spend less time licking-grooming their pups through a centrally driven mechanism. There was no difference between genotypes during the pup retrieval test. Vasopressin-deficient mothers tended to explore more the open arms of the plus maze, showed more preference for sucrose and saccharin and struggled more in the forced swim test, suggesting that they act as less depressive. Under basal conditions, vasopressin-deficient mothers had more c-fos expression in the medial preoptic area, shell of nucleus accumbens, paraventricular nucleus of the hypothalamus and amygdala, but not in other structures. In these areas the swim-stress-induced activation was smaller. In conclusion, vasopressin-deficiency resulted in maternal neglect due to a central effect and was protective against depressive-like behavior probably as a consequence of reduced activation of some stress-related brain structures. The conflicting behavioral data underscores the need for more sex specific studies. Copyright © 2012 Elsevier Inc. All rights reserved.
Impact of Acute Metal Stress in Saccharomyces cerevisiae

PubMed Central

Lichtenberg-Fraté, Hella; Glaser, Walter; Schüller, Christoph; Klipp, Edda

2014-01-01

Although considered as essential cofactors for a variety of enzymatic reactions and for important structural and functional roles in cell metabolism, metals at high concentrations are potent toxic pollutants and pose complex biochemical problems for cells. We report results of single dose acute toxicity testing in the model organism S. cerevisiae. The effects of moderate toxic concentrations of 10 different human health relevant metals, Ag+, Al3+, As3+, Cd2+, Co2+, Hg2+, Mn2+, Ni2+, V3+, and Zn2+, following short-term exposure were analyzed by transcription profiling to provide the identification of early-on target genes or pathways. In contrast to common acute toxicity tests where defined endpoints are monitored we focused on the entire genomic response. We provide evidence that the induction of central elements of the oxidative stress response by the majority of investigated metals is the basic detoxification process against short-term metal exposure. General detoxification mechanisms also comprised the induction of genes coding for chaperones and those for chelation of metal ions via siderophores and amino acids. Hierarchical clustering, transcription factor analyses, and gene ontology data further revealed activation of genes involved in metal-specific protein catabolism along with repression of growth-related processes such as protein synthesis. Metal ion group specific differences in the expression responses with shared transcriptional regulators for both, up-regulation and repression were also observed. Additionally, some processes unique for individual metals were evident as well. In view of current concerns regarding environmental pollution our results may support ongoing attempts to develop methods to monitor potentially hazardous areas or liquids and to establish standardized tests using suitable eukaryotic a model organism. PMID:24416162
Impact of acute metal stress in Saccharomyces cerevisiae.

PubMed

Hosiner, Dagmar; Gerber, Susanne; Lichtenberg-Fraté, Hella; Glaser, Walter; Schüller, Christoph; Klipp, Edda

2014-01-01

Although considered as essential cofactors for a variety of enzymatic reactions and for important structural and functional roles in cell metabolism, metals at high concentrations are potent toxic pollutants and pose complex biochemical problems for cells. We report results of single dose acute toxicity testing in the model organism S. cerevisiae. The effects of moderate toxic concentrations of 10 different human health relevant metals, Ag(+), Al(3+), As(3+), Cd(2+), Co(2+), Hg(2+), Mn(2+), Ni(2+), V(3+), and Zn(2+), following short-term exposure were analyzed by transcription profiling to provide the identification of early-on target genes or pathways. In contrast to common acute toxicity tests where defined endpoints are monitored we focused on the entire genomic response. We provide evidence that the induction of central elements of the oxidative stress response by the majority of investigated metals is the basic detoxification process against short-term metal exposure. General detoxification mechanisms also comprised the induction of genes coding for chaperones and those for chelation of metal ions via siderophores and amino acids. Hierarchical clustering, transcription factor analyses, and gene ontology data further revealed activation of genes involved in metal-specific protein catabolism along with repression of growth-related processes such as protein synthesis. Metal ion group specific differences in the expression responses with shared transcriptional regulators for both, up-regulation and repression were also observed. Additionally, some processes unique for individual metals were evident as well. In view of current concerns regarding environmental pollution our results may support ongoing attempts to develop methods to monitor potentially hazardous areas or liquids and to establish standardized tests using suitable eukaryotic a model organism.
A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress.

PubMed

Chaudhari, Namrata; Talwar, Priti; Parimisetty, Avinash; Lefebvre d'Hellencourt, Christian; Ravanan, Palaniyandi

2014-01-01

Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress.
Systems Mechanobiology: Tension-Inhibited Protein Turnover Is Sufficient to Physically Control Gene Circuits

PubMed Central

Dingal, P.C. Dave P.; Discher, Dennis E.

2014-01-01

Mechanotransduction pathways convert forces that stress and strain structures within cells into gene expression levels that impact development, homeostasis, and disease. The levels of some key structural proteins in the nucleus, cytoskeleton, or extracellular matrix have been recently reported to scale with tissue- and cell-level forces or mechanical properties such as stiffness, and so the mathematics of mechanotransduction becomes important to understand. Here, we show that if a given structural protein positively regulates its own gene expression, then stresses need only inhibit degradation of that protein to achieve stable, mechanosensitive gene expression. This basic use-it-or-lose-it module is illustrated by application to meshworks of nuclear lamin A, minifilaments of myosin II, and extracellular matrix collagen fibers—all of which possess filamentous coiled-coil/supercoiled structures. Past experiments not only suggest that tension suppresses protein degradation mediated and/or initiated by various enzymes but also that transcript levels vary with protein levels because key transcription factors are regulated by these structural proteins. Coupling between modules occurs within single cells and between cells in tissue, as illustrated during embryonic heart development where cardiac fibroblasts make collagen that cardiomyocytes contract. With few additional assumptions, the basic module has sufficient physics to control key structural genes in both development and disease. PMID:25468352
Bacterial differentiation via gradual activation of global regulators.

PubMed

Kovács, Ákos T

2016-02-01

Bacteria have evolved to adapt to various conditions and respond to certain stress conditions. The ability to sense and efficiently reply to these environmental effects involve versatile array of sensors and global or specific regulators. Interestingly, modulation of the levels of active global regulators enables bacteria to respond to diverse signals via a single central transcriptional regulator and to activate or repress certain differentiation pathways at a spatio-temporal manner. The Gram-positive Bacillus subtilis is an ideal bacterium to study how membrane bound and cytoplasmic sensor kinases affect the level of phosphorylated global regulator, Spo0A which in response activates genes related to sliding, biofilm formation, and sporulation. In addition, other global regulators, including the two-component system DegS-DegU, modulate overlapping and complementary genes in B. subtilis related to surface colonization and biofilm formation. The intertwinement of global regulatory systems also allows the accurate modulation of differentiation pathways. Studies in the last decade enable us to get a deeper insight into the role of global regulators on the smooth transition of developmental processes in B. subtilis.
The Role of zinc in the disulphide stress-regulated anti-sigma factor RsrA from Streptomyces coelicolor.

PubMed

Li, Wei; Bottrill, Andrew R; Bibb, Maureen J; Buttner, Mark J; Paget, Mark S B; Kleanthous, Colin

2003-10-17

The regulation of disulphide stress in actinomycetes such as Streptomyces coelicolor is known to involve the zinc-containing anti-sigma factor RsrA that binds and inactivates the redox-regulated sigma factor sigmaR. However, it is not known how RsrA senses disulphide stress nor what role the metal ion plays. Using in vitro assays, we show that while zinc is not required for sigmaR binding it is required for functional anti-sigma factor activity, and that it plays a critical role in modulating the reactivity of RsrA cysteine thiol groups towards oxidation. Apo-RsrA is easily oxidised and, while the Zn-bound form is relatively resistant, the metal ion is readily expelled when the protein is treated with strong oxidants such as diamide. We also show, using a combination of proteolysis and mass spectrometry, that the first critical disulphide to form in RsrA involves Cys11 and one of either Cys41 or Cys44, all previously implicated in metal binding. Circular dichroism spectroscopy was used to follow structural changes during oxidation of RsrA, which indicated that concomitant with formation of this critical disulphide bond is a major restructuring of the protein where its alpha-helical content increases. Our data demonstrate that RsrA can only bind sigmaR in the reduced state and that this state is stabilised by zinc. Redox stress induces disulphide bond formation amongst zinc-ligating residues, expelling the metal ion and stabilising a structure incapable of binding the sigma factor.
Differential expression and alternative splicing of rice sulphate transporter family members regulate sulphur status during plant growth, development and stress conditions.

PubMed

Kumar, Smita; Asif, Mehar Hasan; Chakrabarty, Debasis; Tripathi, Rudra Deo; Trivedi, Prabodh Kumar

2011-06-01

Sulphur, an essential nutrient required for plant growth and development, is mainly taken up by the plants as inorganic sulphate from the soil and assimilated into the sulphur reductive pathway. The uptake and transport of sulphate in plants is carried out by transporters encoded by the sulphate transporter gene family. Plant sulphate transporters have been classified with respect to their protein sequences, kinetic properties and tissue-specific localization in Arabidopsis. Though sulphate transporter genes from few other plants have also been characterized, no detailed study with respect to the structure and expression of this family from rice has been carried out. Here, we present genome-wide identification, structural and expression analyses of the rice sulphate transporter gene family. Our analysis using microarray data and MPSS database suggests that 14 rice sulphate transporters are differentially expressed during growth and development in various tissues and during biotic and abiotic stresses. Our analysis also suggests differential accumulation of splice variants of OsSultr1;1 and OsSultr4;1 transcripts during these processes. Apart from known spliced variants, we report an unusual alternative splicing of OsSultr1;1 transcript related to sulphur supply in growth medium and during stress response. Taken together, our study suggests that differential expression and alternative splicing of members of the sulphate transporter family plays an important role in regulating cellular sulphur status required for growth and development and during stress conditions. These findings significantly advance our understanding of the posttranscriptional regulatory mechanisms operating to regulate sulphur demand by the plant.
mTOR Pathways in Cancer and Autophagy.

PubMed

Paquette, Mathieu; El-Houjeiri, Leeanna; Pause, Arnim

2018-01-12

TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase, acts as a central regulator of cell growth, proliferation and survival in response to nutritional status, growth factor, and stress signals. It plays a crucial role in coordinating the balance between cell growth and cell death, depending on cellular conditions and needs. As such, TOR has been identified as a key modulator of autophagy for more than a decade, and several deregulations of this pathway have been implicated in a variety of pathological disorders, including cancer. At the molecular level, autophagy regulates several survival or death signaling pathways that may decide the fate of cancer cells; however, the relationship between autophagy pathways and cancer are still nascent. In this review, we discuss the recent cellular signaling pathways regulated by TOR, their interconnections to autophagy, and the clinical implications of TOR inhibitors in cancer.

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