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391.
Plasmonics - Hybrid nanocomposites can offer a wide range of opportunities to control the light-matter interaction and electromagnetic energy flow at the nanoscale, leading to exotic optoelectronic... 相似文献
392.
Anjuli M. Timmer John C. Timmer Morgan A. Pence Li-Chung Hsu Mariam Ghochani Terrence G. Frey Michael Karin Guy S. Salvesen Victor Nizet 《The Journal of biological chemistry》2009,284(2):862-871
Group A Streptococcus (GAS) is a leading human bacterial pathogen
capable of producing invasive infections even in previously healthy
individuals. As frontline components of host innate defense, macrophages play
a key role in control and clearance of GAS infections. We find GAS induces
rapid, dose-dependent apoptosis of primary and cultured macrophages and
neutrophils. The cell death pathway involves apoptotic caspases, is partly
dependent on caspase-1, and requires GAS internalization by the phagocyte.
Analysis of GAS virulence factor mutants, heterologous expression, and
purified toxin studies identified the pore-forming cytolysin streptolysin O
(SLO) as necessary and sufficient for the apoptosis-inducing phenotype.
SLO-deficient GAS mutants induced less macrophage apoptosis in vitro
and in vivo, allowed macrophage cytokine secretion, and were less
virulent in a murine systemic infection model. Ultrastructural evidence of
mitochondrial membrane remodeling, coupled with loss of mitochondrial
depolarization and cytochrome c release, suggests a direct attack of
the toxin initiates the intrinsic apoptosis pathway. A general caspase
inhibitor blocked SLO-induced apoptosis and enhanced macrophage killing of
GAS. We conclude that accelerated, caspase-dependent macrophage apoptosis
induced by the pore-forming cytolysin SLO contributes to GAS immune evasion
and virulence.Group A Streptococcus
(GAS)4 is a leading
human pathogen that annually infects hundreds of millions of people worldwide
(1). The last 3 decades have
witnessed a marked increase in severe, invasive forms of GAS infection, many
attributable to a single globally disseminated clone of the M1T1 serotype
(2). Invasive GAS infection
defines a capacity of the pathogen to resist host innate defense mechanisms
designed to prevent microbial spread beyond epithelial surfaces.Macrophages are critical host defense cells involved directly in bacterial
clearance and also in alerting other immune system components to invading
pathogens. Macrophage microbicidal activity is accomplished by phagocytic
uptake coupled with the action of reactive oxygen species, enzymatic
proteolysis, and cationic antimicrobial peptides; their role in amplification
of the innate and adaptive immune responses is achieved through release of
soluble factors such as cytokines and nitric oxide. Mice depleted of
macrophages or treated with inhibitors of macrophage phagocytosis cannot clear
GAS infections even at relatively low challenge doses
(3), demonstrating the
essential first line defense function of these immune cells against the
pathogen.We sought to explore the interaction of the highly virulent GAS M1T1 clone
with macrophages to better understand its propensity to produce invasive human
infection. A prominent regulatory feature of macrophage biology in the context
of infectious disease and inflammation is the process of apoptosis, mediated
by caspase family proteases. Although a number of highly adapted intracellular
bacterial pathogens, including Mycobacterium tuberculosis, Legionella
pneumophila, and Brucella spp., have evolved mechanisms to block
macrophage apoptosis and use the host cell as a vehicle for in vivo
dissemination
(4–6),
a recent study of GAS M1T1 interactions with another host phagocytic cell type
suggested a different outcome. In contrast to other prominent Gram-positive
pathogens, including Staphylococcus aureus and Listeria
monocytogenes, GAS induced an accelerated program of apoptosis in human
neutrophils (7), although the
specific virulence factor(s) involved, effects on caspase activation, and
contribution to disease outcome were not studied.Here we report that GAS rapidly induces macrophage apoptosis through
caspase-dependent pathways, promoted by release of cytochrome c and
permeabilization of mitochondrial outer membranes. GAS-induced macrophage
apoptosis is mediated by the cytolysin streptolysin O (SLO), which is both
necessary and sufficient for the phenotype. SLO-mediated macrophage apoptosis
leads to enhanced GAS survival, dampened cytokine responses, and increased
virulence during systemic infection. 相似文献
393.
Irina Kovalchuk Yelena Lyudvikova Mariam Volgina Barbara M. Reed 《Plant Cell, Tissue and Organ Culture》2009,96(2):127-136
The goal of this study was to evaluate the in vitro storage of apple germplasm by screening a range of genotypes followed
by more comprehensive testing of multiple parameters on two genotypes of differing species, Malus domestica cultivar Grushovka Vernenskaya and wild Malus sieversii selection TM-6. Stored plants were rated on a 6 point scale (0 low to 5 high) for plant appearance at 3 month intervals after
storage at 4°C. Combinations of carbon source (sucrose and/or mannitol), nitrate nitrogen content (25, 50 or 100%) and plant
growth regulators (ABA, BAP, IBA) were studied in three types of containers (tissue culture bags, test tubes or jars). An
initial screen of 16 genotypes stored in tissue culture bags indicated that plantlets could be stored at 4°C for 9–14 months
without subculture on standard 3% sucrose Murashige and Skoog (1962) (MS) medium with no plant growth regulators (PGRs). In subsequent in-depth studies on the two genotypes, ANOVA indicated
highly significant interactions of medium, container and genotype. ‘Grushovka Vernenskaya’ shoots with no PGRs and 3% sucrose
remained viable (ratings of ≥1) for 21 months of storage in bags. Storage on reduced nitrogen (MS with 25% nitrogen), PGRs,
and 3% sucrose kept ‘Grushovka Vernenskaya’ shoot condition rated >2 at 21 months. Addition of 0.5 or 1 mg−1 abscisic acid (ABA) also improved plant ratings at 21 months. The longest storage for ‘Grushovka Vernenskaya’ was 33–39 months
with PGRs and 3% sucrose in either tubes or jars. Addition of abscisic acid (ABA) to the medium did not improve storage of
plantlets in jars and tubes at 15 months. TM-6 stored best in tubes on 3% sucrose with PGRs or in jars on 2% mannitol and
2% sucrose. Overall it appears that cold storage of apple shoot cultures can be successful for 21 months in tissue culture
bags with 25% MS nitrate nitrogen, 3% sucrose, and no PGRs or for 33 months in jars or tubes on MS with 3% sucrose and PGRs.
Preliminary RAPD analysis found no significant differences between plants stored for 39 months and non-stored controls. 相似文献
394.
Blankenship JW Varfolomeev E Goncharov T Fedorova AV Kirkpatrick DS Izrael-Tomasevic A Phu L Arnott D Aghajan M Zobel K Bazan JF Fairbrother WJ Deshayes K Vucic D 《The Biochemical journal》2009,417(1):149-160
A family of anti-apoptotic regulators known as IAP (inhibitor of apoptosis) proteins interact with multiple cellular partners and inhibit apoptosis induced by a variety of stimuli. c-IAP (cellular IAP) 1 and 2 are recruited to TNFR1 (tumour necrosis factor receptor 1)-associated signalling complexes, where they mediate receptor-induced NF-kappaB (nuclear factor kappaB) activation. Additionally, through their E3 ubiquitin ligase activities, c-IAP1 and c-IAP2 promote proteasomal degradation of NIK (NF-kappaB-inducing kinase) and regulate the non-canonical NF-kappaB pathway. In the present paper, we describe a novel ubiquitin-binding domain of IAPs. The UBA (ubiquitin-associated) domain of IAPs is located between the BIR (baculovirus IAP repeat) domains and the CARD (caspase activation and recruitment domain) or the RING (really interesting new gene) domain of c-IAP1 and c-IAP2 or XIAP (X-linked IAP) respectively. The c-IAP1 UBA domain binds mono-ubiquitin and Lys(48)- and Lys(63)-linked polyubiquitin chains with low-micromolar affinities as determined by surface plasmon resonance or isothermal titration calorimetry. NMR analysis of the c-IAP1 UBA domain-ubiquitin interaction reveals that this UBA domain binds the classical hydrophobic patch surrounding Ile(44) of ubiquitin. Mutations of critical amino acid residues in the highly conserved MGF (Met-Gly-Phe) binding loop of the UBA domain completely abrogate ubiquitin binding. These mutations in the UBA domain do not overtly affect the ubiquitin ligase activity of c-IAP1 or the participation of c-IAP1 and c-IAP2 in the TNFR1 signalling complex. Treatment of cells with IAP antagonists leads to proteasomal degradation of c-IAP1 and c-IAP2. Deletion or mutation of the UBA domain decreases this degradation, probably by diminishing the interaction of the c-IAPs with the proteasome. These results suggest that ubiquitin binding may be an important mechanism for rapid turnover of auto-ubiquitinated c-IAP1 and c-IAP2. 相似文献
395.
Yassine Sakar Corinne Nazaret Philippe Lettéron Amal Ait Omar Mathilde Avenati Beno?t Viollet Robert Ducroc André Bado 《PloS one》2009,4(11)
Background and Aims
The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences.Methodology
Wistar rats, wild type and AMPKα2 −/− mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver.Principal Findings
First, in vitro luminal leptin activating its receptors coupled to PKCβII and AMPKα, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver.Conclusion/Significance
These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates metabolic functions in the liver. This loop appears to be a new mechanism (possibly pathogenic) by which fructose consumption rapidly becomes highly lipogenic and deleterious. 相似文献396.
Unfavourable conditions throughout the period of parental care can severely affect growth, reproductive performance, and survival. Yet, individuals may be affected differently, depending on the developmental period during which constraints are experienced. Here we tested whether the nestling phase compared to the fledgling phase is more susceptible to nutritional stress by considering biometry, physiology, sexually selected male ornaments and survival using zebra finches (Taeniopygia guttata) as a model species. As nestlings (day 0–17) or fledglings (day 17–35), subjects were raised either on low or high quality food. A low quality diet resulted in significantly elevated baseline corticosterone titres in both nestlings and fledglings. Subjects showed substantial compensatory growth after they had experienced low quality food as nestlings but catch-up growth did neither lead to elevated baseline corticosterone titres nor did we detect long term effects on biometry, male cheek patch, or survival. The compensation for temporally unfavourable environmental conditions reflects substantial phenotypic plasticity and the results show that costs of catch-up growth were not mediated via corticosterone as a physiological correlate of allostatic load. These findings provide new insights into the mechanisms and plasticity with which animals respond to periods of constraints during development as they may occur in a mistiming of breeding. 相似文献
397.
Faezeh Ebrahimi Farzaneh Pirouzmand Renzon Daniel Cosme Pecho Mariam Alwan Mohammed Yassen Mohamed Mohammed Shnain Ali Arezoo Hormozi Sajedeh Hasanzadeh Narges Daei Zahra Hajimortezayi Majid Zamani 《Biotechnology progress》2023,39(6):e3374
Mesenchymal Stem Cells (MSCs) are non-hematopoietic and multipotent stem cells, which have been considered in regenerative medicine. These cells are easily separated from different sources, such as bone marrow (BM), umbilical cord (UC), adipose tissue (AT), and etc. MSCs have the differentiation capability into chondrocytes, osteocytes, and adipocytes; This differentiation potential along with the paracrine properties have made them a key choice for tissue repair. MSCs also have various advantages over other stem cells, which is why they have been extensively studied in recent years. The effectiveness of MSCs-based therapies depend on several factors, including differentiation status at the time of use, concentration per injection, delivery method, the used vehicle, and the nature and extent of the damage. Although, MSCs have emerged promising sources for regenerative medicine, there are potential risks regarding their safety in their clinical use, including tumorigenesis, lack of availability, aging, and sensitivity to toxic environments. In this study, we aimed to discuss how MSCs may be useful in treating defects and diseases. To this aim, we will review recent advances of MSCs action mechanisms in regenerative medicine, as well as the most recent clinical trials. We will also have a brief overview of MSCs resources, differences between their sources, culture conditions, extraction methods, and clinical application of MSCs in various fields of regenerative medicine. 相似文献
398.
Plaisancie P Ducroc R El Homsi M Tsocas A Guilmeau S Zoghbi S Thibaudeau O Bado A 《American journal of physiology. Gastrointestinal and liver physiology》2006,290(4):G805-G812
Leptin has been suggested to be involved in tissue injury and/or mucosal defence mechanisms. Here, we studied the effects of leptin on colonic mucus secretion and rat mucin 2 (rMuc2) expression. Wistar rats and ob/ob mice were used. Secretion of mucus was followed in vivo in the rat perfused colon model. Mucus secretion was quantified by ELISA, and rMuc2 mRNA levels were quantified by real-time RT PCR. The effects of leptin alone or in association with protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) inhibitors on mucin secreted by human mucus-secreting HT29-MTX cells were determined. Leptin was detected in the rat colonic lumen at substantial levels. Luminal perfusion of leptin stimulates mucus-secreting goblet cells in a dose-dependent manner in vivo in the rat. Leptin (10 nmol/l) increased mucus secretion by a factor of 3.5 and doubled rMuc2 mRNA levels in the colonic mucosa. There was no damage to mucosa 24 h after leptin, but the number of stained mucus cells significantly increased. Leptin-deficient ob/ob mice have abnormally dense mucus-filled goblet cells. In human colonic goblet-like HT29-MTX cells expressing leptin receptors, leptin increased mucin secretion by activating PKC- and PI3K-dependent pathways. This is the first demonstration that leptin, acting from the luminal side, controls the function of mucus-secreting goblet cells. Because the gel layer formed by mucus at the surface of the intestinal epithelium has a barrier function, our data may be relevant physiologically in defence mechanisms of the gastrointestinal tract. 相似文献
399.
Tamoxifen is currently used as adjuvant therapy for estrogen receptor (ER) positive breast cancer patients and as a chemopreventative agent. Although ER is a predictive marker for tamoxifen response, ER status fails to predict tamoxifen response in a significant number of patients highlighting the need to identify new pathways for tamoxifen sensitivity/resistance. To identify novel proteins induced by tamoxifen in breast cancer cells sensitive to tamoxifen growth inhibition, two-dimensional (2D) gel electrophoresis was used to profile proteins in T47D breast cancer cells. Six proteins were identified that were differentially regulated by 17beta-estradiol, 4-hydroxytamoxifen and the pure antagonist acolbifene (EM-652); calreticulin, synapse associated protein 1 (SYAP1), CD2 antigen binding protein 2 (CD2BP2), nucleosome assembly protein 1 like 1 (NAP1L1), d-3-phosphoglycerate dehydrogenase (3-PHGDH) and pyridoxine 5' phosphate oxidase (PNPO). At the mRNA level, these ligands differentially regulated expression of mRNAs encoding the identified proteins in T47D and MCF7 cells but had no effect on mRNA in ERalpha-negative MDA-MB-231 breast cancer cells. These novel SERM-regulated proteins may participate in new or existing pathways for sensitivity or resistance to SERMs. 相似文献
400.
In an investigation of the communication between specialist hospital departments and general practitioners 97 general practitioners were asked to say how important selected items of information that the hospital could pass on would be for management of a patient receiving chemotherapy. In addition, the records of 68 patients were examined for coverage of these topics. General practitioners considered technical topics to be more important than social ones. Hospital letters covered technical topics well, apart from details of possible side effects, but did not do the same even for the two social topics that most doctors considered to be essential--namely, what patients have been told about their diagnosis and prognosis. Letters from hospitals to general practitioners cover technical topics well but should include more information relating to the social aspects of the patient''s disease. 相似文献