The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in ...
The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging...Full Text Available
Despite intensive efforts, the intracellular signaling pathways that mediate apoptosis remain unclear. The human B lymphoma cell line, B104, possesses characteristics that make it an attractive model...Full Text Available
1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 increased the expression and enzymatic ...
beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2)) neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain and B chain. The goal of the present study is to explore the functional contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and intracellular ROS production. Moreover, an activation of p38 MAPK was associated with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N-acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate) effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the inability of A chain, B chain was able to induce cytotoxic effects on ...
BackgroundAlternative splicing is an important mechanismmediating the diversified functions of genes in multicellular organisms, and such event occurs in around 40-60% of human...Full Text Available
Objective: To investigate the mechanism of carbapenem resistance and the occurrence of plasmid-mediated quinolone resistance determinants qnr and aac(6′)-Ib-cr...Full Text Available
A modest reduction in body temperature prolongs longevity and possibly retards aging in both poikilotherm and homeotherm animals. Some of the possible mechanismsmediating these effects are...Full Text Available
Methylation of the arginine residues of histones by methyltransferases has important consequences for chromatin structure and gene regulation; however, the molecular mechanism(s) of methyltransferase...Full Text Available
Female mammals are particularly sensitive to changes in food availability. The mechanisms that affect sexual behavior and food intake are closely related to one another; chief among the mechanisms...Full Text Available
BackgroundNeuropathic pain (NP) is partially mediated by neuroinflammatory mechanisms, and also modulates local neurogenic inflammation. Dietary lipids, in particular the total amount...Full Text Available
SummaryActivating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines...Full Text Available
Plasmid-mediated Qnr and AAC(6′)-Ib-cr have been recognized as new molecular mechanisms affecting fluoroquinolone (FQ) resistance. C316, an Escherichia coli strain demonstrating...Full Text Available
The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin...Full Text Available
Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanismsmediating its beneficial effects are not fully understood. Obesity correlates with increased production...Full Text Available
There is increasing evidence that receptor-mediated events impact one or more stages responsible for tumor development in experimental animals and humans. Although many chemicals and endogenous hormones...Full Text Available
Glycoprotein 60 (gp60) is a normal plasma protein (mean concentration in normal serum 34 micrograms/ml) that is present in increased levels (mean concentration 97 micrograms/ml) in the sera of patients...Full Text Available
Despite the demonstrated clinical efficacy of CD20 monoclonal antibody (mAb) for lymphoma therapy, the in vivo mechanisms of tumor depletion remain controversial and variable. To identify the molecular...Full Text Available
BackgroundSome breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell...Full Text Available
The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic...Full Text Available
Different tombusviruses were able to support the replication of either homologous or heterologous defective interfering (DI) RNAs, and those infected plants usually developed typical attenuated symptoms....Full Text Available
Many plants are known to reduce the toxic effects of high soil boron (B) by reducing uptake of B, but no mechanism for limiting uptake has previously been identified. The B-tolerant cultivar of barley...Full Text Available
Atg9 is a transmembrane protein essential for autophagy which cycles between the Golgi network, late endosomes and LC3-positive autophagosomes in mammalian cells during starvation through a mechanism...Full Text Available
The tendency for some individuals to partake in high-risk behaviors (eg, substance abuse, gambling, risky sexual activities) is a matter of great public health concern, yet the characteristics and neural...Full Text Available
1. To explore mechanisms of urinary obstruction in benign prostatic hyperplasia (BPH), the features of contraction and relaxation in human hyperplastic and non-hyperplastic (control) prostatic tissues...Full Text Available
The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet-On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical- or CVB3-induced upregulation of glucose-regulated protein78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, which further led to the diminished phosphorylation of eIF2?, reduced cleavage/activation of transcription factor SREBP1 and attenuated induction of proapoptotic genes CHOP and GADD34. These data were further supported by experiments using Irgm3 knockout mouse embryonic fibroblasts, in which the ER stress induced by CVB3 was not relieved due to the lack of Irgm3 expression. In addition, the tunicamycin-triggered ER stress promoted the subsequent CVB3 infection. The effect of ...
Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress...Full Text Available
we report an ultrafast synchrotron x-ray phase contrast imaging study of the primary breakup mechanism of a coaxial air-assisted water jet. We demonstrate that there exist great similarities in the phenomenology of primary breakup with that of the secondary breakup. Especially, a membrane-mediated breakup mechanism dominates the breakup process for a wide range of air speeds. This finding reveals the intrinsic connections of these two breakup regimes and has deep implications on the unified theoretical approach in treating the breakup mechanism of high speed liquid jet.
Although caloric restriction (CR) has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro...Full Text Available
Iron, zinc, copper and manganese are essential metals for cellular enzyme functions while cadmium, mercury and the metalloid arsenic lack any biological function. Both, essential metals, at high concentrations, and non-essential metals and metalloids are extremely reactive and toxic. Therefore, plants have acquired specialized mechanisms to sense, transport and maintain essential metals within physiological concentrations and to detoxify non-essential metals and metalloids. This review focuses on the recent identification of transporters that sequester cadmium and arsenic in vacuoles and the mechanismsmediating the partitioning of these metal(loid)s between roots and shoots. We further discuss recent models of phloem-mediated long-distance transport, seed accumulation of Cd and As and rec...
Chinese hamster lung fibroblasts V79 cells were treated with heat stress for 4 weeks with short duration (15 min) heat shock every alternate day in culture. It was observed that Hsp...Full Text Available
Hyperthermia (HT) is a strong adjuvant treatment with radiotherapy and chemotherapy because it causes tumor reoxygenation. However, the detailed molecular mechanisms of how HT enhances tumor oxygenation...Full Text Available
The authors continued their efforts in studying the mechanism of carbalkoxylation of {sigma}-vinyls bound to platinum(II). In this work, the focus was specifically on the reductive elimination of {alpha},{beta}-unsaturated carboxylic esters form the carbonylated, alkoylated intermediates. Crystal structures of the carbonylated (12) and alkoxylated (13) intermediates were reported. Kinetic and NMR studies indicate that reductive elimination proceeds via a preequilibration involving phosphine dissociation, followed by a rate-determining trans-cis isomerization. 35 refs., 3 figs., 5 tabs.
Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases. Epigenetic mechanisms involve chromatin remodeling by relatively generic complexes that catalyze DNA methylation and various types of histone modifications. There is increasing evidence that these complexes are directed to their sites of action by long non-protein-coding RNAs (lncRNAs), of which there are tens if not hundreds of thousands speci...
In this study, we investigated the kinetics of linoleic acid production via lipase-mediated hydrolysis of corn DDGS oil in a batch reactor with continuous mechanical agitation and developed a kinetic model that incorporated the product inhibition to study the complete hydrolysis. The model agreed very well with observed data; though situations with low enzyme dosage or low stirring rates were modeled successfully without product inhibition, actual product concentration in such situations was too low to exert any inhibitory effects. Increasing the enzyme concentration increased hydrolysis, and beyond certain enzyme concentrations, effects tended to fade away because of excessive enzyme desorption from the interface. An enzyme dosage within the range of 40-60KLU/L of oil dispersion could be ...
Hyaluronic acid (HA), a principal matrix molecule in many tissues, is present in high amounts in articular cartilage. HA contributes in unique ways to the physical behavior of the tissue, and has been shown to have beneficial effects on chondrocyte activity. The goal of this study was to incorporate graduated amounts of HA into type I collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis in vitro. The results demonstrated that the amount of contraction of HA/collagen scaffolds by adult canine articular chondrocytes increased with the HA content of the scaffolds. The greatest amount of chondrogenesis after two weeks was found in the scaffolds which had undergone the most contraction. HA can play a useful role in adjusting the mechanical behavior of tissue engineering scaffolds and chondrogenesis in chondrocyte-seeded scaffolds.
Immune thrombocytopenic purpura (ITP), Guillain-Barre syndrome (GBS), and Hashimotos thyroiditis (HT) are autoimmune disorders caused by impaired self-tolerance mechanisms triggered by interaction between genetic and environmental factors. ITP is an immune-mediated destruction of platelets resulting in mucocutaneous bleeding, GBS is an ascending motor paralysis caused by an inflammatory demyelination of peripheral nerves, and HT is characterized by autoimmune-mediated destruction of the thyroid gland. The concurrent development of ITP and GBS has only rarely been reported in the literature, and GBS itself rarely occurs with other autoimmune disorders. We present a 21 year-old patient with known Hashimotos hypothyroidism that simultaneously developed GBS and ITP after an upper respiratory t...
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosi...
Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane fluidity was supported by: ileal contraction that was induced by acetylcholine and ...
The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12?weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished ...
This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers...Full Text Available
A set of equations describing a stress-mediated evolution of the nonequilibrium dopant-defect system has been derived and analyzed. Together with coupled diffusion of dopant atoms and point defects, we consider the drift of all mobile species in different charge states, namely vacancies, self-interstitials, and pairs 'dopant atom-point defect', in the field of stress. It has been shown that stresses may affect the diffusion of dopant atoms mainly in two ways: (1) directly, due to the drift of the pairs in the field of stress; (2) indirectly, by the formation of nonuniform defect distribution due to the drift of point defects. On this basis, various features of doping processes, such as phenomena of 'uphill' impurity diffusion near the surface (within the framework of the first or second mechanisms) and the peculiarities of high concentration phosphorus diffusion (due to the second ...
A set of equations describing a stress-mediated evolution of the nonequilibrium dopant-defect system has been derived and analyzed. Together with coupled diffusion of dopant atoms and point defects, we consider the drift of all mobile species in different charge states, namely vacancies, self-interstitials, and pairs 'dopant atom-point defect', in the field of stress. It has been shown that stresses may affect the diffusion of dopant atoms mainly in two ways: (1) directly, due to the drift of the pairs in the field of stress; (2) indirectly, by the formation of nonuniform defect distribution due to the drift of point defects. On this basis, various features of doping processes, such as phenomena of 'uphill' impurity diffusion near the surface (within the framework of the first or second mechanisms) and the peculiarities of high concentration phosphorus diffusion (due to the second mechanism), can be explained. Numerical ...
Carbalkoxylation of vinyl electrophiles was investigated using platinum complexes. This reaction occurs in two steps: (a) carbonyl insertion of {sigma}-vinyl Pt(II) halides and (b) alcoholysis of vinylic acyl Pt(II) complexes. Alcoholysis of vinylic acyl Pt(II) triflate complexes is investigated kinetically. Vinylic acyl Pt(II) complexes were isolated and characterized. 51 refs., 5 figs., 6 tabs.
Biosorption is an important removal mechanism in treating hydrophobic toxic organics in biological reactors. Equilibrium sorption isotherms and sorption kinetics of 2,4-dichlorophenol on live and chemically inactive anaerobic granules were studied. A metabolic inhibitor was used to inactivate the biological activity of the biomass. Results showed that the difference in the biosorption of live and chemically inactive anaerobic granules is not significant. This would suggest that anaerobic biosorption is mainly a physical-chemical process and that metabolic-mediated diffusion in the process is negligible. 12 refs., 3 tabs., 7 figs.
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism ...
Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate levels of phospho-S6 and the negative immune regulator B7-H1 in tumor cells, Honokiol does not ...
While radiation-pressure cooling is well known, the Brillouin scattering of light from sound is considered an acousto-optical amplification-only process. It was suggested that cooling could be possible in multi-resonance Brillouin systems when phonons experience lower damping than light. However, this regime was not accessible in traditional Brillouin systems since backscattering enforces high acoustical frequencies associated with high mechanical damping. Recently, forward Brillouin scattering in microcavities has allowed access to low-frequency acoustical modes where mechanical dissipation is lower than optical dissipation, in accordance with the requirements for cooling. Here we experimentally demonstrate cooling via such a forward Brillouin process in a microresonator. We show two regimes of operation for the Brillouin process: acoustical amplification as is traditional, but also for the first time, a Brillouin cooling regime. Cooling is ...
PP2B is a Ca2+/calmodulin-dependent protein phosphatase that is ubiquitously expressed in mammals. Among other actions, it is an effector mechanism in NMDA-mediated glutamate neurotransmission as well as a regulator of GSK3? and MAPK signaling cascades. Because all of these mechanisms have demonstrable roles in the control of circadian rhythyms, we hypothesized that PP2B would be a key regulator of rhythm generation and entrainment, and that through inhibition of its phosphatase activity, the circadian system would be affected by immunosuppressant drug therapy. We report here that immunosuppressant drugs (cyclosporin A, FK506) (1) block the circadian responses to light that underlie photic entrainment; (2) produce circadian phase shifts with a characteristic nonphotic profile; and (3) disr...
Resistance (R) protein mediated recognition of pathogen avirulence effectors triggers signaling that induces a very robust form of species-specific immunity in plants. The soybean Rpg1-b protein mediates...Full Text Available
Previous investigations have shown that both the early biological response and the mechanical properties of a porous hydroxyapatite bone graft substitute are highly sensitive to its pore structure. The objective of this study was to evaluate whether the pore structure continued to influence bone integration in the medium to long term. Two screened batches of porous hydroxyapatite (PHA) designated as batch A and batch B, with porosities of approximately 60 and 80%, respectively, were selected for this study and implanted for periods of 5, 13, and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric analysis of the absolute volume of bone ingrowth within batch A and B implants from 5 to 26 weeks showed that the absolute volume of bone ingrowth was consistently lower in batch A (10-21%), compared to batch B implants (24-31%). However, when the volume of bone ingrowth was normalised for the available pore space, this difference was reduced ...
This study describes the chemical composition of the essential oil of Artemisia maritima (Am.Oil) and the pharmacological basis for its medicinal use in gut and airways disorders. Twenty five compounds, composing 93.7% of the oil, were identified; among these, chrysanthenyl propionate and elixene were identified for the first time from any Artemisia species. The Am.Oil (0.3?1.0 mg/mL) suppressed spontaneous and high K+ (80 mM)-induced contractions in isolated rabbit jejunum, suggestive of an antispasmodic effect mediated possibly through calcium channel blockade. The calcium channel blockade activity was confirmed when pre-treatment of the tissue with Am.Oil (0.01?0.03 mg/mL) shifted the Ca++ concentration-response curves to the right, similar to verapamil and papaverine. In isolated trach...
Background and purpose: The aims of this study were to investigate the anti-cancer activity of SZ-685C, an anthracycline analogue isolated from marine-derived mangrove endophytic fungi, and to explore the molecular mechanisms underlying such activity. Experimental approach: The effect of SZ-685C on the viability of cancer cell lines was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. SZ-685C-induced apoptosis was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay and analysis of caspase activation. The effect of SZ-685C on the Akt/FOXO pathway was studied using Western blotting analysis, and the in vivo anti-tumour efficacy was examined in ...
Radiofrequency electromagnetic fields (EMF) are harmful to public health, but the certain anti-irradiation mechanism is not clear yet. The present study was performed to investigate the possible protective effects of green tea polyphenols against electromagnetic radiation-induced injury in the cultured rat cortical neurons. In this study, green tea polyphenols were used in the cultured cortical neurons exposed to 1800?MHz EMFs by the mobile phone. We found that the mobile phone irradiation for 24?h induced marked neuronal cell death in the MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide) and TUNEL (TdT mediated biotin-dUTP nicked-end labeling) assay, and protective effects of green tea polyphenols on the injured cortical neurons were demonstrated by testing the content ...
Pinealectomy completely prevented gonadal regression as well as reduction in body weight and white adipose tissue content of the gonadal and retroperitoneal fat deposits in male meadow voles transferred from long to short day lengths. Pineal influences on pelage characteristics depended on which parameter was assessed. For instance, the increase in guard hair length observed in short-day control voles was blocked by pinealectomy; however, a similar increase in underhair length was unaffected by removal of the pineal gland. Photoperiod-dependent changes in fat deposition, testicular activity, and guard hair length presumably rely on altered pineal secretory activity to transduce the effects of day length on the neuroendocrine axis; however, mechanisms independent of pineal activity may be capable of mediating photoperiodic control of underhair growth. PMID:2979644
Abstract The heterotetrameric K++-channel KCNQ1/KCNE1 is expressed in heart, skeletal muscle, liver and several epithelia including the renal proximal tubule. In the heart, it contributes to the repolarization of cardiomyocytes. The repolarization is impaired in ischemia. Ischemia stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase, sensing energy depletion and stimulating several cellular mechanisms to enhance energy production and to limit energy utilization. AMPK has previously been shown to downregulate the epithelial Na++ channel ENaC, an effect mediated by the ubiquitin ligase Nedd4-2. The present study explored whether AMPK regulates KCNQ1/KCNE1. To this end, cRNA encoding KCNQ1/KCNE1 was injected into Xenopus oocytes with and without additional injection o...
The selection and design of an MEOR process for application in a specific field involves geological, reservoir, and biological characterization. Microbially mediated oil recovery mechanisms (bigenic gas, biopolymers, and biosurfactants) are defined by the types of microorganisms used. The engineering and biological character of a given reservoir must be understood to correctly select a microbial system to enhance oil recovery. This paper discusses the methods used to evaluate three fields with distinct characteristics and production problems for the applicability of MEOR would not be applicable in two of the three fields considered. The development of a microbial oil recovery process for the third field appeared promising. Development of a bacterial consortium capable of producing the desired metabolites was initiated, and field isolates were characterized.
Achievement of transposon mediated germline transgenesis in a basal chordate, Ciona intestinalis, is discussed. A Tc1/mariner superfamily transposon,...Full Text Available
The mechanism of action of Clostridium difficile enterotoxin A (CA), of Escherichia coli enterotoxin (STa) and of cholera toxin (CT), which are known to cause severe diarrhea, were studied in a preparation of ligated jejunal loops of anesthetized rats in vivo. The toxins were administered intraluminally. Pharmacological agents, which were tested for their potency to influence toxin-related effects, were administered subcutaneously. Net fluid transport was determined gravimetrically, prostaglandin (PG) E_2-output into the lumen, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) contents in the mucosa were measured by radioimmunoassay, serotonin-(5-HT)-output into the lumen was determined by high performance liquid chromatography. The histopathological effects of CA and CT were examined by light- and scanning electron microscopy. All three toxins caused net fluid secretion (FS). 5-HT_2-(ketanserin) and 5-HT_3-receptor antagonists ...
Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse ...
1. The benzyl carbamyl analogue of lignocaine [2-(diethylaminoacetamido)-3-carbamyl-4-methyl-5-benzylpyrrole] at an intravenous dose of 4 mg/kg caused a blood pressure decrease of 54 mmHg. 2. A greater hypotensive effect was observed in hypertensive compared to normotensive animals. Anaesthesia magnified the vasodepressor effect in both groups. 3. The analogue did not possess centrally-mediated effects on blood pressure but exerted its hypotensive effect via a peripheral mechanism. 4. The analogue produced a relaxant effect on intestinal and vascular smooth muscle while exerting minimal effects on muscarinic, sympathetic, or ganglionic nicotinic receptors. 5. The analogue exhibited less cardiac depressant action on left ventricular rate (dp/dt) and force of contraction than lignocaine. 6. Lethal effects for the analogue were first observed at 16 mg/kg following intravenous administration and at 500 mg/kg following intraperitoneal ...
The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP_3-mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKC#alpha#) was specified using isotype-specific ...
The mechanisms underlying the pathogenesis of estrogen-induced breast carcinogenesis remain unclear. The present study investigated the roles of estrogen metabolism and oxidative stress in estrogen-mediated mammary carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated with 17b-estradiol (E2), the antioxidant vitamin C, the estrogen metabolic inhibitor a-naphthoflavone (ANF), or cotreated with E2 + vitamin C or E2 + ANF for up to 8 months. E2 (3 mg) was administered as an subcutaneous implant, ANF was given via diet (0.2%) and vitamin C (1%) was added to drinking water. At necropsy, breast tumor incidence in the E2, E2 + vitamin C and E2 + ANF groups was 82, 29 and 0%, respectively. Vitamin C and ANF attenuated E2-induced alterations in oxidative stress markers in b...
Abstract in english Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are e (more) xpressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The ...
Prairie (Microtus ochrogaster) and meadow voles (M. pennsylvanicus) are closely related species that differ in life strategy and social behaviors, and thus provide an excellent comparative model for the study of neuronal and hormonal mechanisms underlying behavior. In the present study using the elevated plus maze (EPM) test, we found that male prairie voles entered the open arms of the EPM more and remained there longer, and showed a higher level of overall locomotor activity than did male meadow voles. In addition, two weeks of social isolation induced an increase in open arm entries in prairie, but not meadow, voles. Prairie voles also had a higher level of circulating corticosterone compared to meadow voles, and the EPM test increased circulating corticosterone in prairie voles. Finally, social isolation coupled with the EPM test influenced Fos-immunoreactive expression in several brain areas, including the medial preoptic area, ventromedial hypothalamus, ...
Understanding risks from exposures to carcinogens and other chemicals depends upon measurement of their dose to target tissues and their reactivity with critical macromolecules. The authors have used AMS detection of radio-isotopes to assess doses and reactivities at low, environmentally relevant doses. Several biomedical investigations show the effectiveness of quantification of biologically important events at extremely high sensitivity with AMS. Specifically, they have measured the addition of environmental carcinogens such as 2-amino-3,8-dimethylimidazo[4,5-f]-quinoaxaline (MelQx), a chemical found in cooked food, to DNA at concentrations relevant to human exposure. Other low level detection problems in biology, such as immunoassay assessment of small environmental chemicals, is being developed with attomole sensitivity. AMS also aids the assessment of genotoxic risks from chemicals by quantifying the binding of labeled chemicals to DNA. The very toxic and potent carcinogen, ...
Emerging evidence suggests that E3 ligases play critical roles in diverse biological processes, including innate immune responses in plants. However, the mechanism of the E3 ligase involvement in plant innate immunity is unclear. We report that a rice gene, OsBBI1, encoding a RING finger protein with E3 ligase activity, mediates broad-spectrum disease resistance. The expression of OsBBI1 was induced by rice blast fungus Magnaporthe oryzae, as well as chemical inducers, benzothiadiazole and salicylic acid. Biochemical analysis revealed that OsBBI1 protein possesses E3 ubiquitin ligase activity in vitro. Genetic analysis revealed that the loss of OsBBI1 function in a Tos17-insertion line increased susceptibility, while the overexpression of OsBBI1 in transgenic plants conferred enhanced resi...
Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT ...
We investigate some aspects of the radiation damage mechanisms in biomolecules, focusing on the modelling of resonant fragmentation caused by the attachment of low-energy electrons (LEEs) initially ejected by biological tissues when exposed to ionizing radiation. Scattering equations are formulated within a symmetry-adapted, single-center expansion of both continuum and bound electrons, and the interaction forces are obtained from a combination of ab initio calculations and a nonempirical model of exchange and correlation effects developed in our group. We present total elastic scattering cross-sections and resonance features obtained for the equilibrium geometries of glycine, alanine, proline and valine. Our results at those geometries of the target molecules are briefly shown to qualitatively explain some of the fragmentation patterns obtained in experiments. We further carry out a one-dimensional (1D) modeling for the dynamics of intramolecular energy transfers ...
Salamanders regenerate their appendages after amputation and nerves are required for this process. Experiments were designed to test the idea that one way nerves could affect blastema cell proliferation is by influencing the metabolism of extracellular matrix (ECM) components and to identify neurotrophic factors which promote blastema cell mitosis. Temporal and spatial differences of glycosaminoglycans (GAGs) synthesis is innervated and denervated limbs were examined. Hyaluronic acid (HA) was found to be the major GAG produced during the proliferative period and chondroitin sulfate during differentiation. Denervation reduced synthesis of both these components by half. Dorsal root ganglia and fibroblast growth factor (FGF), a brain-derived mitogen, similarly doubled GAG synthesis in cultured blastemas, the FGF-effect being primarily on HA production. Histochemical and autoradiographical results confirmed the biochemical data. Autoradiography of the limb tissue showed heaviest labeling ...
Abstract Sam68 (Src-associated protein in mitosis 68-kDa) is a multifunctional protein, known to govern cellular signal transduction, transcription, RNA metabolism, proliferation, apoptosis, and HIV-1 replication. Although intrinsic mechanisms that modulate Sam68 function are beginning to emerge, the regulatory events contributing to its expression remain elusive. We previously reported that heat shock protein-22 (Hsp22) antagonizes Sam68 function in rev-response element (RRE)-mediated gene expression. We now demonstrate that Sam68 levels correlate inversely with Hsp22 in a variety of cells, including U87, Jurkat, 293T, and U-937. In U87 glioblastoma cells, which contained high levels of Hsp22 than other cell lines tested, Hsp22 knockdown dramatically increased both Sam68 mRNA and protein,...
Characteristics of sugar uptake by immature maize embryos were determined in vitro utilizing a /sup 14/C-sugar solution incubation method. Hexose uptake rates were greater than those for sucrose, however, all showed biphasic kinetics. Glucose and fructose saturable components were evidence at <50 mM and sucrose at <5 mM. Chemical inhibitors (CCCP, DNP, NaCN, and PCMBS) and low temperature reduced sugar uptake. Sucrose influx was pH dependent while glucose was not. Embryos maintained a high sucrose to hexose ratio throughout development. At 25 days after pollination sucrose levels exceeded 200 mM while hexose levels remained below 5 mM. Glucose was rapidly converted to sucrose upon transport into the embryo. These circumstantial data indicate that sugar uptake by immature maize embryos is metabolically dependent and carrier mediated. Furthermore, sucrose transport appears to occur against its concentration gradient involving a H+/sucrose cotransport ...
Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding ...
Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) chemicals are antitumor antibiotics inhibiting nucleic acid synthesis. An indole carboxylate-PBD hybrid with six-carbon spacer structure (IN6CPBD) has been previously demonstrated to induce melanoma cell apoptosis and reduce metastasis in mouse lungs. This study aimed at investigating the efficacy of the other hybrid compound with four-carbon spacer (IN4CPBD) and elucidating its anti-metastatic mechanism. Human melanoma A375 cells with IN4CPBD treatment underwent cytotoxicity and apoptosis-associated assays. Transwell migration assay, Western blotting, and ELISA were used for mechanistic study. IN4CPBD exhibited potent melanoma cytotoxicity through interrupting G1/S cell cycle progression, increasing DNA fragmentation and hypodipoidic DNA contents, a...
Somite boundary formation is crucial for segmentation of vertebrate somites and vertebrae and skeletal muscle morphogenesis. Previously, we developed a Tol2 transposon-mediated...Full Text Available
AimsIt is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus.MethodsA...Full Text Available
The purpose of this study was to determine whether resistance exercise training-induced reductions in inflammation are mediated via melanocortin 3 receptor expression in obese (BMI 32.7 ± 3.7)...Full Text Available
The phytochrome-mediated attachment of root tips of mung bean (Phaseolus aureus) and barley (Hordeum vulgare) to glass is affected by the prior exposure of hydrated...Full Text Available
3-Deazaadenosine (deazaAdo) inhibits lymphocyte-mediated cytolysis in vitro at micromolar concentrations and is potentiated markedly in this activity by L-homocysteine thiolactone....Full Text Available
Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies...Full Text Available
Dectin-1, the major β-glucan receptor in leukocytes, triggers an effective immune response upon fungal recognition. Here we use sortase-mediated transpeptidation, a technique that allows placement...Full Text Available
In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced...Full Text Available
Short-hairpin RNA (shRNA)–mediated gene knockdown is a powerful tool for targeted gene silencing and an emerging novel therapeutic strategy. Recent publications, however, reported unexpected...Full Text Available
IntroductionTyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is expressed in numerous cancers and is required for mediating tumorigenesis. Autocrine...Full Text Available
BackgroundThe emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to...Full Text Available
The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at ...
In this paper, the effects of surface mediation on the adsorption isotherm and isosteric heat of adsorption on a graphite surface were investigated, as the surface mediation is known to affect the intermolecular interaction of adsorbed molecules close to the surface. Kim and Steele (Phys. Rev. B 45 (11) (1992) 6226-6233) and others have assumed that the surface mediation is confined only to the first layer. This will be tested in this paper with a combined experimental and Grand Canonical Monte Carlo (GCMC) simulation of adsorption of argon on graphitized thermal carbon black (GTCB) over a range of temperatures (77-95.25K). By matching the simulation results against the experimental data, we have found that the surface mediation is extended up to the fourth layer, rather than only the firs...
The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell loss limited to the ...
The simultaneous diffusion of Si and the dopants B, P, and As has been studied by the use of a multilayer structure of isotopically enriched Si. This structure, consisting of 5 pairs of 120 nm thick natural Si and {sup 28}Si enriched layers, enables the observation of {sup 30}Si self-diffusion from the natural layers into the {sup 28}Si enriched layers, as well as dopant diffusion from an implanted source in an amorphous Si cap layer, via Secondary Ion Mass Spectrometry (SIMS). The dopant diffusion created regions of the multilayer structure that were extrinsic at the diffusion temperatures. In these regions, the Fermi level shift due to the extrinsic condition altered the concentration and charge state of the native defects involved in the diffusion process, which affected the dopant and self-diffusion. The simultaneously recorded diffusion profiles enabled the modeling of the coupled dopant and self-diffusion. From the modeling of the simultaneous diffusion, the dopant diffusion ...
Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological...Full Text Available
The effects of low concentrations (10 nm or less) of indoleacetic acid and abscisic acid on the phytochrome-mediated attachment of barley root (Hordeum vulgare L., var. Compana)...Full Text Available
Temperature is an important modulator of longevity and aging in both poikilotherms and homeotherm animals. In homeotherms, temperature homeostasis is regulated primarily in the preoptic area...Full Text Available
Carbohydrate-directed endocytosis is mediated by a receptor, the hepatic binding protein; it is responsible for the clearance of galactose-terminated glycoproteins from the circulation. This process...Full Text Available
... M. Taylor, T. Kurt Kyser. (2009) Feather isotope analysis discriminates age-classes of Western, Least, and Semipalmated sandpipers when plumage ... ...
Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation....Full Text Available
Background:Alopecia areata (AA) is an immune-mediated form of hair loss that occurs in all ethnic groups, ages, and both sexes. Helicobacter pylori has...Full Text Available
Web Services and mobile data services are the newest trends in information systems engineering in wired and wireless domains, respectively. Web Services have a broad range of service distributions while mobile phones have large and expanding user base. To address the confluence of Web Services and pervasive mobile devices and communication environments, a basic mobile Web Service provider was developed for smart phones. The performance of this Mobile Host was also analyzed in detail. Further analysis of the Mobile Host to provide proper QoS and to check Mobile Host's feasibility in the P2P networks, identified the necessity of a mediation framework. The paper describes the research conducted with the Mobile Host, identifies the tasks of the mediation framework and then discusses the feasible realization details of such a mobile Web Services mediation framework.
Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-#kappa#B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of ...
Single-crystalline nanostructures often exhibit gradients of surface (and/or interface) curvature that emerge from fabrication and growth processes or from thermal fluctuations. Thus, the system-inherent capillary force can initiate morphological transformations during further processing steps or during operation at elevated temperature. Therefore and because of the ongoing miniaturization of functional structures which causes a general rise in surface-to-volume ratios, solid-state capillary phenomena will become increasingly important: On the one hand diffusion-mediated capillary processes can be of practical use in view of non-conventional nanostructure fabrication methods based on self-organization mechanisms, on the other hand they can destroy the integrity of nanostructures which can go along with the failure of functionality. Additionally, capillarity-induced shape transformations are effected and can thereby be controlled by applied ...
Multicellular tumor spheroids (MCTS) are three dimensional cell culture systems induced by suspension culture. MCTS are widely used in cancer research because of their similarity to solid tumors. CaSki cells are derived from a metastatic cervical cancer containing human papillomavirus 16 (HPV16). Cell death of CaSki cells in MCTS has been previously reported, and our model is used to better characterize the mechanisms of cell death of HPV16-positive keratinocytes. In this study, we found that apoptosis of CaSki cells was induced by suspension culture along with the formation of MCTS after 24 h of incubation. In suspended CaSki cells, monoclonal antibodies blocking E-cadherin function inhibited MCTS formation and suppressed suspension-induced apoptosis in a dose-dependent manner. Western blot for E-cadherin detected upregulation of the authentic 120 kDa band from MCTS of CaSki cells as well as a shorter 100 kDa band. Addition of EGF, whose receptor is known to form ...
During the past year, further studies on mAChR were conducted. These studies included verification of the difference in pituitary distribution based on ligand charge. The pituitary localization of TRB. A neutral mAChR ligand, was verified. The lack of QNB blockade of TRB uptake was tested by blockage with scopolamine, another mAChR antagonist and by testing the effect in a different strain of rat. Neither scopolamine or change of rat strain had any effect. We concluded that TRB uptake in pituitary is not a receptor-mediated process. Further studies were conducted with an additional quaternized mAChR ligand: MQNB. Pituitary localization of MQNB, like MTRB, could be blocked by pretreatment with QNB. We have tentatively concluded that permanent charge on a mAChR antagonist changes the mechanism of uptake in the pituitary. Time course studies and the effects of DES on myocardial uptake are reported. A brief report on preliminary results of ...
1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors ...
We studied the effect of extracellular Ca"2"+ concentration ([Ca"2"+]_e) on adipocyte differentiation. Preadipocytes exposed to continuous [Ca"2"+]_e higher than 2.5 mmol/l accumulated little or no cytoplasmic lipid compared to controls in 1.8 mmol/l [Ca"2"+]_e. Differentiation was monitored by Oil Red O staining of cytoplasmic lipid and triglyceride assay of accumulated lipid, by RT-PCR analysis of adipogenic markers, and by the activity of glycerol-3-phosphate dehydrogenase (GPDH). Elevated [Ca"2"+]_e inhibited expression of peroxisome proliferator-activated receptor #gamma#, CCAAT/enhancer binding protein #alpha#, and steroid regulatory binding element protein. High [Ca"2"+]_e significantly inhibited differentiation marker expression including adipocyte fatty acid binding protein, and GPDH. The decrease in Pref-1 expression that accompanied differentiation also was prevented by high [Ca"2"+]_e. Treatment of 3T3-L1 cells with high [Ca"2"+]_e did not significantly affect cell number ...
Background: Recent studies have developed a murine model of IgE-mediated food allergy based on oral coadministration of antigen and cholera toxin (CT) to establish a maximal response for studying immunopathogenic mechanisms and immunotherapeutic strategies. However, for studying subtle immunomodulating factors or factors effective during response initiation, this maximal response-based model is less suitable due to a lack of sensitivity. Therefore, in attempts to identify essential parameters to fine-tune the immune response towards a submaximal level, potentially more sensitive, we were interested in characterizing the individual effects of the parameters in the CT-based model: CT dose, antigen type and dose, and number of immunizations. Methods: BALB/c mice were orally sensitized weekly for 3 or 7 weeks with graded doses of CT and various food antigens (soy-trypsin inhibitor, ovalbumin or ovomucoid). Antigen-specific lgG1, IgG2a, IgA and IgE ...
The mantis shrimp Squilla mantis shows a graded series of avoidance/escape responses to visual and mechanical (vibration and touch) rostral stimuli. A low-threshold response is mediated by the simultaneous protraction of the thoracic walking legs and abdominal swimmerets and telson, producing a backwards 'lurch' or jump that can displace the animal by up to one-third of its body length, but leaves it facing in the same direction. A stronger response starts with similar limb protraction, but is followed by partial abdominal flexion. The maximal response also consists of limb protraction followed by abdominal flexion, but in this case the abdominal flexion is sufficiently vigorous to pull the animal into a tight vertical loop, which leaves it inverted and facing away from the stimulus. The animal then swims forward (away from the stimulus) and rights itself by executing a half-roll. A bilaterally paired, large-diameter, rapidly conducting axon in ...
Abstract in english The aim of the present study was to assess the analgesic activity of the aerial parts of two Hypericum species native to Southern Brazil, H. caprifoliatum and H. polyanthemum. The antinociceptive effect of the H. polyanthemum cyclohexane extract (POL; 180 mg/kg) and of the H. caprifoliatum methanol (MET) and cyclohexane (CH) extracts (90 mg/kg) was evaluated in the hot-plate (ip and po) and writhing (po) tests using male Swiss CF1 mice weighing 22-27 g (N = 10 per group). (more) All extracts displayed antinociceptive effects in the hot-plate test (MET ip = 48%, MET po = 39%, CH ip = 27%, CH po = 50%, POL ip = 74%, and POL po = 49% compared to control). Pretreatment with naloxone (2.5 mg/kg, sc) abolished the effects of CH and POL, and partially prevented the analgesia induced by MET administered by the ip (but not by the po) route. POL and CH (po) significantly reduced the number of writhes induced by acetic acid, while MET was ineffective in this regard. We ...
To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile derivative (HS-1200). Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-19 cells were examined using a trypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. The dose required for the half maximal inhibition (IC_5_0) of the HT-29 cell growth was 100 #approx# 150 #mu# M of HS-1200. Several changes, associated with the apoptosis ...
We report herein that trefoil factor 3 (TFF3) is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in mammary carcinoma cells increased cell proliferation...Full Text Available
The initiation and progression of several forms of retinal degenerations involve excessive, repetitive, and/or sustained oxidative stress that, in turn, mediate photoreceptor cell damage and...Full Text Available
SummaryThe transcriptional co-repressor SMRT utilizes two major receptor interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification....Full Text Available
In diabetes complications, CCN-2 (known originally as CTGF) has been implicated in diabetic nephropathy both as a marker and a mediator of disease. This commentary addresses CCN-2 in diabetic nephropathy, in the context of the recent publication of the first human study to inhibit CCN-2 bioactivity in diabetic kidney disease.
LRP1 is a type-1 transmembrane receptor that mediates the endocytosis of diverse ligands. LRP1 β-chain proteolysis results in release of sLRP1 that is present in human plasma. In this study,...Full Text Available
The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available
Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal transformation uncovered by ...
In this paper, the effects of surface mediation on the adsorption isotherm and isosteric heat of adsorption on a graphite surface were investigated, as the surface mediation is known to affect the intermolecular interaction of adsorbed molecules close to the surface. Kim and Steele (Phys. Rev. B 45 (11) (1992) 6226-6233) and others have assumed that the surface mediation is confined only to the first layer. This will be tested in this paper with a combined experimental and Grand Canonical Monte Carlo (GCMC) simulation of adsorption of argon on graphitized thermal carbon black (GTCB) over a range of temperatures (77-95.25K). By matching the simulation results against the experimental data, we have found that the surface mediation is extended up to the fourth layer, rather than only the first as suggested by Kim and Steele, and the extent of this mediation is reduced with distance ...
Sleep symptoms are a prominent feature of mental health disorders like PTSD and depression. However, it is unknown whether sleep symptoms mediate the relationship between combat stress and these disorders. We examined the mediating role of sleep symptoms on the relationship between combat stress and PTSD; and the relationship between combat stress and depression using data from 576 Army veterans of the Iraq War surveyed in 2004. Correlational analyses revealed that when insomnia was included in the model, the correlation between combat stressors and other depression symptoms decreased by 65%; and when nightmares were included in the model, the correlation between combat stressors and other PTSD symptoms decreased by 69%. We replicated these analyses using individual items assessing PTSD an...
ABSTRACT Aim The study aimed to test simultaneously our understanding of the effects of bupropion sustained-release (SR) treatment on putative mediators and our understanding of determinants of post-quit abstinence, including withdrawal distress, cigarette craving, positive affect and subjective reactions to cigarettes smoked during a lapse. The specificity of bupropion SR effects was also tested in exploratory analyses. Design Data from a randomized, placebo-controlled clinical trial of bupropion SR were submitted to mediation analyses. Setting Center for Tobacco Research and Intervention, Madison, WI, USA. Participants A total of 403 adult, daily smokers without contraindications to bupropion SR use. Intervention Participants were assigned randomly to receive a 9-week course of bupropion...
The rice blast resistance (R) gene Pi-ta mediates gene-for-gene resistance against strains of the fungus Magnaporthe grisea that express avirulent...Full Text Available
Transposons are promising systems for somatic gene integration because they can not only integrate exogenous genes efficiently, but also be delivered to a variety of organs using a range of transfection...Full Text Available
Global acetylation of histone H4 is a mark of gene transcriptional activation. The c-Myc transcription factor binds to specific DNA sites in cellular chromatin and induces the acetylation of...Full Text Available
Sensory rhodopsins (SRs) belong to a subfamily of heptahelical transmembrane proteins containing a retinal chromophore. These photoreceptors mediate the cascade of vision in animal eyes and phototaxis...Full Text Available
Mating signals are often directed at numerous senses and provide information about species identity, gender, receptiveness, individual identity and mate quality. Given the diversity of colourful body...Full Text Available
Flying insects use visual cues to stabilize their heading in a wind stream. Many animals additionally track odors carried in the wind. As such, visual stabilization of upwind tracking directly aids...Full Text Available
In addition to the well documented role of cytokines in mediating tissue-level interactions, it is now clear that matrix macromolecules fulfil a complementary regulatory function. Data highlighted in...Full Text Available
The sequential events and the inflammatory mediators that characterize disease onset and progression of ulcerative colitis (UC) are not well known. In this study, we evaluated the early pathologic events...Full Text Available
Devastating central nervous system injuries and diseases continue to occur in spite of the tremendous efforts of various prevention programs. The enormity of and annual escalation of healthcare...Full Text Available
Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate...Full Text Available
Krabbe disease (KD) is an inherited neurological disorder caused by the deficiency of galactocerebrosidase activity resulting in accumulation of psychosine, which leads to energy depletion,...Full Text Available
Cervical spinal cord hemisection rostral to the phrenic nucleus leads to paralysis of the ipsilateral hemidiaphragm in adult rats. Respiratory function can be restored to the paralyzed hemidiaphragm...Full Text Available
Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen...Full Text Available
BackgroundChromatin insulators or boundary elements are a class of functional elements in the eukaryotic genome. They regulate gene transcription by interfering with promoter-enhancer...Full Text Available
SummaryThe life span of C. elegans can be increased via reduced function of the mitochondria; however, the extent to which mitochondrial alteration in a single,...Full Text Available
BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available
We investigate a method for gene delivery to vascular smooth muscle cells using ultrasound triggered delivery of plasmid DNA from electrostatically coupled cationic microbubbles. Microbubbles...Full Text Available
Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive...Full Text Available
IgA from normal human serum, a myeloma IgA and human colostral IgA were found to inhibit the IgG-dependent phagocytosis of Candida albicans (CA) blastospores by polymorphonuclear leucocytes...Full Text Available
4-Hydroxynonenal (HNE), a major electrophilic product of lipid peroxidation, is regarded as both a marker of oxidative stress and a mediator of oxidative damage. At subtoxic concentrations,...Full Text Available
We show here sodium ion cycling between complex I from Klebsiella pneumoniae and the F1F0 ATP synthase from Ilyobacter tartaricus in a reconstituted...Full Text Available
In utero electroporation is widely used to study neuronal development and function by introducing plasmid DNA into neural progenitors during embryogenesis. This is an effective and...Full Text Available
The study of blocking factors requires in vitro assay of cell mediated immunity that parallels the in vivo response. By microcytotoxicity testing, progressor and immune peripheral blood lymphocytes...Full Text Available
The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2...Full Text Available
The establishment of the primary meristems through proliferation after germination is essential for plant post-embryonic development. Cytokinins have long been considered a key regulator of...Full Text Available
The intracellular bioavailability of lead (Pb) at low dosage levels in major target organs such as the kidney and brain appears to be largely determined by complexation with a group of low molecular...Full Text Available
Green leaf C6-volatiles are among the most important herbivore-induced plant volatiles (HIPVs). They play important roles in mediating the behavior of herbivores and their natural enemies, and in triggering...Full Text Available
Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal...Full Text Available
The secreted Bv8 protein has been recently characterized as a regulator of myeloid cell mobilization and a neutrophil-derived mediator of tumor angiogenesis in several xenografts, but its role in tumor...Full Text Available
PurposeEctopic expression of light-sensitive proteins, such as channelrhodopsin-2, represent a novel approach for restoring light-detection capabilities to degenerated retina. A...Full Text Available
That regulatory T cells (Tregs) have a crucial role in controlling allergic diseases such as asthma is now undisputed. The cytokines most commonly implicated in Treg-mediated suppression of...Full Text Available
Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on...Full Text Available
The Neurofibromatosis-2 (NF2) tumor suppressor merlin negatively regulates cell proliferation in numerous cell types. We have previously shown that the NF2...Full Text Available
Activation of the innate immune system results in a rapid microbicidal response against microorganisms, which needs to be fine-tuned because uncontrolled immune responses can lead to infection and cancer,...Full Text Available
BackgroundThe circadian rhythm in mammals is orchestrated by a central pacemaker in the brain, but most peripheral tissues contain their own intrinsic circadian oscillators. The...Full Text Available
This study was designed to determine the effects of red and far red irradiation on ATP metabolism in etiolated bean buds (Phaseolus vulgaris L. var. Red Kidney). Compared to dark controls,...Full Text Available
Effective small interfering RNA (siRNA)–mediated therapeutics require the siRNA to be delivered into the cellular RNA-induced silencing complex (RISC). Quantitative information of this essential...Full Text Available
SUMMARYSmall bowel epithelium is at the frontline of intestinal barrier function. Restitution is considered to be the major determinant of epithelial repair as function recovers...Full Text Available
BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available
How transcription factors interpret the cis-regulatory logic encoded within enhancers to mediate quantitative changes in spatiotemporally restricted expression patterns during animal...Full Text Available
BackgroundSurrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified.MethodsHIV-infected...Full Text Available
Brief exposures to red light induce far red-reversible changes of 5 to 10 millivolts magnitude in the upper 1 centimeter of etiolated Avena coleoptiles. The changes begin within 15...Full Text Available
Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic...Full Text Available
We have used Western blot analysis and immunocytochemistry to determine the effect of dietary K intake on the expression of protein kinase C (PKC) isoforms in the kidney. Western blot has demonstrated...Full Text Available
Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity...Full Text Available
Acute inflammation is important for tissue repair; however, chronic inflammation contributes to neurodegeneration in Alzheimer’s disease (AD) and occurs when glial cells undergo prolonged...Full Text Available
Background and purpose:The chicken anterior mesenteric artery contains an outer longitudinal smooth muscle layer, whose neural regulation remains to be elucidated. ATP evokes a depolarization...Full Text Available
Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability,...Full Text Available
Experimental metastases in the brain of mice are infiltrated by microglia, and parabiosis experiments of green fluorescent protein (GFP+) and GFP- mice revealed that these microglia...Full Text Available
1. Previous studies have shown that electrical stimulation (ES) of the guinea-pig cochlea causes a neurally mediated increase in cochlear blood flow (CBF). It is known that the centrifugal neuronal...Full Text Available
The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and...Full Text Available
Klebsiella oxytoca can use nitrate and nitrite as sole nitrogen sources. The enzymes required for nitrate and nitrite assimilation are encoded by the nasFEDCBA operon....Full Text Available
BackgroundWe have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial...Full Text Available
Microglia provide immune surveillance for the brain through both the removal of cellular debris and protection against infection by microorganisms and “foreign” molecules. Upon...Full Text Available
Calpains are Ca2+-dependent proteinases that mediate protein turnover in crustacean skeletal muscles. We used an antibody directed against lobster muscle-specific calpain (Ha-CalpM)...Full Text Available
The HTLV-1 Tax protein both activates viral replication and is involved in HTLV-1-mediated transformation of T lymphocytes. The transforming properties of Tax include altering the expression of select...Full Text Available
The Far UpStream Element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream...Full Text Available
Cytoadherence or sequestration is essential for the pathogenesis of the most virulent human malaria species, Plasmodium falciparum (P. falciparum). Similar to leukocyte-endothelium...Full Text Available
Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been implicated in Multiple Sclerosis demyelination through activation of complement and/or macrophage-effector processes. We presented...Full Text Available
We showed recently that secretion of glutamate in biotin-limited cells of Corynebacterium glutamicum is mediated by carrier systems in the plasma membrane (C. Hoischen and R. Krämer, Arch. Microbiol....Full Text Available
Obesity and metabolic syndrome result from excess calorie intake and genetic predisposition and are mechanistically linked to type II diabetes and accelerated body aging; abnormal nutrient and insulin...Full Text Available
Neuronal death is known to trigger reactive microgliosis. However, little is known regarding the manner by which microglia are activated by injured neurons and how microgliosis participates...Full Text Available
We had previously identified a macrophage surface protein whose expression is highly induced, transient, and specific, as it is restricted to actively fusing macrophages in vitro and in vivo. This protein...Full Text Available
In Syrian hamsters (Mesocricetus auratus), the expression of reproductive behavior requires the perception of social odors. The behavioral response to these odors is mediated...Full Text Available
BackgroundHuman immunodeficiency virus type 1 (HIV-1) infection frequently causes neurologic disease, which is the result of viral replication and activation of macrophages and microglia...Full Text Available
Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis....Full Text Available
Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that...Full Text Available
Study objectiveThe study aim was to improve our understanding of the relationships between contextual socioeconomic characteristics and coronary heart disease (CHD)...Full Text Available
Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in...Full Text Available
To investigate the fate of intrinsic factor and cobalamin during cobalamin absorption, we incubated enterocytes isolated from guinea pig ileum for periods of up to 30 min with 57Co-labeled...Full Text Available
Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend...Full Text Available
We present a methodology and database mediator tool for integrating modern knowledge-based systems, such as the Stanford EON architecture for automated guideline-based decision-support, with legacy...Full Text Available
The inhibitory effects of indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) on elongation growth of pea (Pisum sativum L.) seedling roots were investigated...Full Text Available
The phytochrome-mediated attachment of mung bean (Phaseolus vulgaris L., var. Oklahoma 612) root tips on glass is quickly affected by indoleactic acid and abscisic acid at concentrations...Full Text Available
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human...Full Text Available
Activation-induced cytidine deaminase (AID) protein initiates Ig gene mutation by deaminating cytosines, converting them into uracils. Excision of AID-induced uracils by uracil-N-glycosylase...Full Text Available
Background and AimsSulfonylurea (SU) herbicides are used extensively in cereal–livestock farming zones as effective and cheap herbicides with useful levels of residual activity....Full Text Available
ABSTRACTObjectivesTo test the feasibility of human immune globulin (IG, Gamimune N, 10%) as a new treatment for endophthalmitis, the ocular tolerance, distribution,...Full Text Available
IL-4 and IL-13 are up-regulated during in vivo responses to many nematode parasites, but increasing evidence suggests that increases in IL-13 can also occur independently of...Full Text Available
BackgroundThe zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In...Full Text Available
The Dot/Icm type IV translocated Ankyrin B (AnkB) effector of Legionella pneumophila is modified by the host prenylation machinery that anchors it into the outer leaflet of the Legionella-containing...Full Text Available
Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit...Full Text Available
Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally-induced expression of neuronal plasticity utilizes an NMDAR-dependent,...Full Text Available
Following the descovery of its transposition activity in mammalian culture systems, the Sleeping Beauty (SB) transposon has since been applied to achieve germline mutagenesis in mice....Full Text Available
Membrane cofactor protein (MCP or gp45-70) of the complement system is a cofactor for factor I-mediated cleavage of fluid-phase C3b and C3b-like C3, which opens the thioester bond. In the present study...Full Text Available
Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by...Full Text Available
Free radical formation has been implicated in the toxicity of a wide range of xenobiotics. In recent years, particular interest has been paid to compounds which can undergo a one electron reduction...Full Text Available
Tissue culture conditions and transformation have been established for both aspen and poplar. The use of previously described culture conditions resulted in shoot tip necrosis in the shoot cultures...Full Text Available
BackgroundLeukotrienes (LTs) belong to the large family of lipid mediators implicated in various inflammatory conditions such as asthma and rheumatoid arthritis. Four distinct types...Full Text Available
Using pharmacological and chromatographic techniques, it was shown that acetylcholine was present in all organs of both light- and dark-grown mung bean seedings (Phaseolus aureus)....Full Text Available
BackgroundEscherichia coli strain EL350 contains chromosomally integrated phage lambda Red recombinase genes enabling this strain to be used for modifying the sequence...Full Text Available
Trypanothione reductase (TryR) is a key enzyme involved in the oxidative stress management of the Trypanosoma and Leishmania parasites, which helps to maintain an intracellular reducing environment...Full Text Available
The hypothesis, that a decrease in metabolic rate mediates the life span prolonging effect of caloric restriction (CR), was tested using two strains of mice, one of which, C57BL/6, exhibits...Full Text Available
B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated...Full Text Available
BackgroundAllergic Contact Dermatitis (ACD) is regarded as a T-cell-mediated delayed-type hypersensitivity reaction. We studied the kinetics of the expression of CS-1 fibronectin,...Full Text Available
SpoIIIE is an FtsK-related protein that transports the forespore chromosome across the Bacillus subtilis sporulation septum. We use membrane photobleaching and protoplast assays to...Full Text Available
The p21-activated kinases (PAKs), immediate downstream effectors of the small G-proteins of the Rac/cdc42 family, are critical mediators of signaling pathways regulating cellular behaviors and...Full Text Available
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR...Full Text Available
Cryptococcus neoformans is a ubiquitously distributed human pathogen. It is also a model system for studying fungal virulence, physiology and differentiation. Light is known to inhibit...Full Text Available
Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available
BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously...Full Text Available
We sought to determine whether the third component of complement (C3) is localized in ischemic baboon myocardium after coronary artery ligation. Furthermore, we assessed the effects of prior C3 depletion...Full Text Available
BackgroundOne virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B....Full Text Available
The mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway plays a key role in mediating estrogen actions in the brain and neuronal sensitization during inflammation....Full Text Available
The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that...Full Text Available
Plasma samples were collected from mice infected with Trypanosoma musculi at different times postinfection and administered to naive recipient mice either before or during T. musculi infection. The...Full Text Available
Cytokinins are distributed through the vascular system and trigger responses of target cells via receptor-mediated signal transduction. Perception and transduction of the signal can occur at the plasma...Full Text Available
Ligature-induced periodontitis was monitored for 6 months in eight Macaca mulatta monkeys to examine clinical status, radiographic bone level, and crevicular fluid (CF) levels of prostaglandin E2 (PGE2),...Full Text Available
The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter...Full Text Available
AimThe goal of this study is to characterize the changes in 33 biomarkers within the gingival crevicular fluid during the 3-week induction and 4-week resolution of...Full Text Available
Medulloblastoma and neuroblastoma belong to a group of neoplasms designated as primitive neuroectodermal tumors (PNETs). Secreted Protein, Acidic and Rich in Cysteine (SPARC) is a matrix-associated...Full Text Available
The flux ratio (influx/efflux) of K+ across the plasmalemma of beet cells at an external potassium concentration of 0.6 mm does not respond to changes of membrane potential in the...Full Text Available
Benzodiazepine withdrawal anxiety is associated with potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) currents in hippocampal CA1 pyramidal...Full Text Available
Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus...Full Text Available
Motor function requires that motor axons extend from the spinal cord at regular intervals and that they are myelinated by Schwann cells. Little attention has been given to another cellular structure,...Full Text Available
The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The subsequent collision of DNA replication forks with these drug-enzyme-DNA...Full Text Available
During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates...Full Text Available
Tooth enamel biomineralization is mediated by enamel proteins synthesized by ameloblast cells. Two classes of proteins have been described: enamelins and amelogenins. In lower vertebrates the absence...Full Text Available
Biosynthesis and uptake of siderophores in Aspergillus nidulans are regulated not only by iron availability but also by ambient pH: expression of this high-affinity iron uptake system...Full Text Available
Average human behavior in cue combination tasks is well predicted by Bayesian inference models. As this capability is acquired over developmental timescales, the question arises, how it is learned....Full Text Available
BackgroundOnline technology is a promising resource for conducting clinical research. While the internet may improve a study's reach, as well as the efficiency of data collection,...Full Text Available
Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and ...Full Text Available
Arabidopsis thaliana SUPERMAN (SUP) plays an important role during flower development by maintaining the boundary between stamens and carpels in the inner two whorls....Full Text Available
A sensitive and specific detection method was developed for Xanthomonas hyacinthi; this method was based on amplification of a subsequence of the type IV fimbrial-subunit gene fimA...Full Text Available
BackgroundFormation of site specific genomic double strand breaks (DSBs), induced by the expression of a pair of engineered zinc-finger nucleases (ZFNs), dramatically increases the...Full Text Available
The aggregation substance (AS) of Enterococcus faecalis, encoded on sex pheromone plasmids, is a surface-bound glycoprotein that mediates aggregation between bacteria thereby facilitating...Full Text Available
Objective:This study examined the role of cognitive factors—such as expectancies regarding the consequences of not drinking and perceptions of peer drinking—in...Full Text Available
BackgroundBacterial constituents, such as Gram-negative derived lipopolysaccharide (LPS), can initiate inflammatory bone loss through induction of host-derived inflammatory...Full Text Available
BackgroundA fundamental requirement for the exploitation of embryonic stem (ES) cells in regenerative medicine is the ability to reproducibly derive sufficient numbers of cells of...Full Text Available
Normal urinary bladder function requires contraction and relaxation of the detrusor smooth muscle (DSM). The DSM undergoes compensatory hypertrophy in response to partial bladder outlet obstruction...Full Text Available
AimsTo compare the theoretical retinal threshold time for endoilluminators and experimental phototoxic effect using A2e laden retinal pigment epithelial (RPE) cells.MethodsThe...Full Text Available
BackgroundThe MYC transcription factors are known to be involved in the biology of many human cancer types. But little is known about the Myc/microRNAs cooperation in the regulation...Full Text Available
The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell ...
Serotonin is one of the neurotransmitters found in the brain and mediates brain functions. It is very well known that serotonin related brain abnormalities are exerted mainly via serotonin receptors in a similar manner to other neurotransmitters found in the brain. Recently, it has also been found that serotonin is involved in Alzheimer's disease either directly or indirectly by its actions on serotonergic neurons. To understand and treat the diseases caused by abnormalities in the serotonergic system in the brain, it is certain that its mechanism of function has to be well investigated. So far several 5-HT receptors and receptor subtypes have been well characterized. Moreover, serotonin agonists and antagonists acting on specific receptors are chemically synthesized and are now available for the prevention or treatment of serotonergic related diseases. In recent years, a great demand for developing neuroimaging agents has emerged for the ...
Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a similar mechanism of functional selectivity for the three serotonin receptors. Interestingly, the ...
Trapped ions are a near ideal system to study quantum information processing due to the high degree of control over the ion's external confinement and internal degrees of freedom. We demonstrate the key steps necessary for trapped ion quantum computing and focus on phonon-mediated entangling gates. We highlight several key algorithms implemented over the last decade with these gates and give a detailed description of Grover's quantum database search implemented with two trapped ion qubits.
Promoted as the first academic conference to be held completely in graphical cyberspace, Avatars 98 took place in November 1998. The virtual conference site was built and inhabited using software that supports multi-party presence over the Internet in a simulated, navigable environment. During the conference, avatar-embodied speakers using text chat performed to virtual audiences, 'webcams' (re)broadcast live video images of CNN and other remote sites, and a 'webcast' sent audiovisual representations captured by video camera of certain key participants in their physical locations. Such a novel and spectacular multi-media event raises many questions. How do we conceive of the recent developments in media technology and social computing that are impacting on what we have traditionally called 'the mass media'? How is interaction and talk mediated and adapted to new media genres? And how do participants construct and maintain senseful talk in a sometimes bewildering, ...
In this paper we investigate the effects of surface mediation on the adsorption behavior of argon at different temperatures on homogeneous graphitized thermal carbon black and on heterogeneous nongraphitized carbon black surface. The grand canonical Monte Carlo (GCMC) simulation is used to study the adsorption, and its performance is tested against a number of experimental data on graphitized thermal carbon black (which is known to be highly homogeneous) that are available in the literature. The surface-mediation effect is shown to be essential in the correct description of the adsorption isotherm because without accounting for that effect the GCMC simulation results are always greater than the experimental data in the region where the monolayer is being completed. This is due to the overestimation of the fluid-fluid interaction between particles in the first layer close to the solid surface. It is the surface mediation ...
Prejudice against overweight people is rife. However, there is a paucity of research on the underlying reasons for it. In two studies the relationship between body image, the tendency to make physical appearance-related comparisons (PACS), and both explicit and implicit anti-fat attitudes was examined. In Study 1 (n = 227) people with a high tendency to make physical appearance-related comparisons (high PACS scorers) reported lower self-appearance evaluation, but higher appearance orientation and explicit anti-fat attitudes. The PACS fully mediated the relationship between appearance orientation and explicit anti-fat attitudes. Study 2 (n = 134) found that the PACS also mediated the relationship between appearance orientation and implicit anti-fat attitudes. Thus, individual differences in factors such as body image and the tendency to make appearance-related comparisons, appear to play a central role in both explicit and implicit anti-fat ...
A novel single-chain immunotoxin was constructed by combining a CD33-specific single chain Fv (scFv) antibody fragment with an engineered variant of Pseudomonas exotoxin A (ETA). The variant toxin carries the KDEL peptide at its C-terminus, a cellular peptide mediating improved retrograde transport to the endoplasmic reticulum. The purified recombinant fusion protein induced potent apoptosis of the human myeloid cell lines U937, HL-60 and THP-1. Up to 98% of U937 cells were eliminated after treatment for 72 h with a single dose of 500 ng/ml (c. 7 nmol/l). Killing was antigen-specific and occurred by apoptosis. A control protein, consisting of a CD19-specific scFv antibody fragment fused to the ETA-KDEL toxin, failed to induce death of the CD19-negative cell lines U937, HL-60 and THP-1. The CD33-ETA toxin also mediated apoptosis of fresh patient-derived acute myeloid leukaemia cells from bone marrow and peripheral blood. The pronounced ...
The immune system modulates many key biological processes in humans. However, the exact role of the immune system in particle-associated periprosthetic osteolysis is controversial. Human tissue retrieval studies, in vivo and in vitro experiments suggest that the immune response to polymer particles is non-specific and macrophage-mediated. Lymphocytes may modulate this response. However direct lymphocyte activation by polymer particle-protein complexes seems unlikely. However, metallic byproducts may complex with serum proteins and lead to a Type IV, lymphocyte-mediated immune reaction. In predisposed individuals, this reaction may rarely lead to persistent painful joint effusions, necessitating debridement and excision of the bearing surfaces of the prosthesis. In these patients, retrieved...
Knowledge and awareness of past and future autobiographical events may be mediated by a common system that supports intentional, goal-directed behavior. The purpose of this study was to assess the correspondence of past and future autobiographical thought. In Experiment 1, 300 undergraduates aged 19 years generated and assigned dates to past and f utu re autobiographical events. Thetemporal distribution of past events replicated a power function for retention as has been described in past research. The intention function of future autobiographical events fit the inverse of this same power function, reflecting a temporality of past and future mental time travel centered around the present moment. In Experiment 2, these findings were extended to young, middle-aged, and older groups. These data provide empirical support for the notion that thinking outside of "now" is mediated by a common system, regardless of whether one is thinking about the ...
Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered regulation of amygdala functioning which is thought to be mediated by the prefrontal cortex, we studied the effects of exogenous testosterone on the interaction between the amygdala and other brain regions. Healthy middle-aged women received a single nasal testosterone dose in a randomized, placebo-controlled, crossover manner, and performed an emotional face matching task while their brain activity was measured with functional MRI. The results show that testosterone rapidly reduced functional co...
Bark beetles that colonize living conifers and their microbial associates encounter constitutive and induced chemical defenses of their host. Monoterpene hydrocarbons comprise a major component of these allelochemicals, and many are antibiotic to insects, fungi, and bacteria. Some bark beetle species exhaust these defenses by killing their host through mass attacks mediated by aggregation pheromones. Others lack adult aggregation pheromones and do not engage in pheromone-mediated mass attacks, but rather have the ability to complete development within live hosts. In the former species, the larvae develop in tissue largely depleted of host terpenes, whereas in the latter exposure to these compounds persists throughout development. A substantial literature exists on how monoterpenes affect b...
Nucleotides released upon brain injury signal to astrocytes and microglia playing an important role in astrogliosis, but the participation of microglia in the purinergic modulation of astrogliosis is still unclear. Highly enriched astroglial cultures and co-cultures of astrocytes and microglia were used to investigate the influence of microglia in the modulation of astroglial proliferation mediated by nucleotides. In highly enriched astroglial cultures, adenosine-5?-triphosphate (ATP), adenosine 5?-O-(3-thio)-triphosphate (ATP?S), adenosine 5?-O-(3-thio)-diphosphate (ADP?S; 0.01?1?mM), and adenosine-5?-diphosphate (ADP; 0.1?1?mM) increased proliferation up to 382%, an effect abolished in co-cultures containing 8% of microglia. The loss of ATP proliferative effect in co-cultures is supporte...
Pneumonia caused by Mannheimia haemolytica is an important disease of domestic sheep (DS, Ovis aries) and cattle (BO). M. haemolytica is a normal commensal of the upper respiratory tract in ruminants, but during stress and viral infection it breaches the host innate mucosal defense and descents into lungs causing fibrinous pleuropneumonia. Leukotoxin (Lkt) produced by M. haemolytica is cytolytic to all subsets of ruminant leukocytes. Earlier, we and others have shown that DS and BO LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) can mediate Lkt-induced cytolysis. It is not clear whether CR4 (CD11c/CD18), which is involved in chemotaxis, phagocytosis and regulates host immune response can also mediate Lkt-induced cytolysis in ruminants. The host innate immune response to M. haemolytica is poorly ...
Objective To evaluate the inhibitory property of de-glycyrrhizinated extract of Glycyrrhiza glabra root and its phytoconstituents (glabridin, isoliquiritigenin and glycyrrhizin) on LPS-induced production of pro-inflammatory mediators. Materials and methods Inhibitory effect of G. glabra extract and its phytoconstituents were studied on lipopolysaccharide (LPS)-induced nitric oxide (NO), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels in J774A.1 murine macrophages. Results G. glabra and isoliquiritigenin significantly inhibited LPS stimulated NO, IL-1 beta and IL-6 production. Glabridin showed significant inhibition of NO and IL-1 beta release, but failed to attenuate IL-6 levels at the tested concentrations. In addition, glycyrrhizin did not exhibit inhibitory response towar...
Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...
We study the rates allowed for the Higgs-mediated decays $B_{s,d}^0\\to\\mu\\tau, e\\tau$ and $\\tau\\to \\mu\\mu\\mu, e\\mu\\mu$ in supersymmetric seesaw models, assuming that the only source of lepton flavour violation (LFV) is the renormalization of soft supersymmetry-breaking terms due to off-diagonal singlet-neutrino Yukawa interactions. These decays are strongly correlated with, and constrained by, the branching ratios for $B_{s,d}^0\\to\\mu\\mu$ and $\\tau\\to \\mu(e)\\gamma.$ Parametrizing the singlet-neutrino Yukawa couplings $Y_\
Abstract Background- Cyclosporine is used for treatment of transplanted patients and for immune-mediated diseases. Cyclosporine is known to cause a combination of metabolic side effects including hypertension, hyperkalemia, hypercalciuria and hypomagnesemia. These side effects except for hypomagnesemia are the cardinal features of familial hyperkalemia and hypertension (FHHt), also called pseudohypoaldosteronism type II (PHA II). FHHt is caused by mutations in the kinases WNK1 and WNK4 resulting in an increase in renal Na-Cl cotransporter (NCC) apical distribution and function. Therefore, we studied whether cyclosporine-s metabolic side effects are mediated by WNK4 and NCC. Design- Sprague-Dawley (SD) rats were treated by cyclosporine 25-mg-kg-1 subcutaneously for 14-days. Blood pressure, ...
We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro.
This study validates a research model that examines usage of instant messaging (IM) from the aspect of online social support. Drawing on the social capital theory, this study postulates that IM usage is indirectly affected by social support via the mediation of the following six dimensions of social capital: commitment, reciprocity, shared codes and language, shared narratives, centrality, and network ties. The model tests data obtained from business organizations in Taiwan, and the results suggest that the indirect influence of social support on IM usage through shared codes and language is significant, and the indirect influence of social support on IM usage through centrality is also significant. Managerial implications and limitations of the empirical findings are provided.
Antisense- or RNAi-mediated suppression of the biosynthesis of nutritionally inferior storage proteins is a promising strategy for improving the amino acid profile of seeds. However, the potential pleiotropic effects of this on interconnected pathways and the agronomic quality traits need to be addressed. In the current study, a transcriptomic analysis of an antisense C-hordein line of barley was performed, using a grain-specific cDNA array. The C-hordein antisense line is characterized by marked changes in storage protein and amino acid profiles, while the seed weight is within the normal range and no external morphological irregularities were observed. The results of the transcriptome analysis showed excellent correlation with data on changes in the relative proportions of storage protei...
A phytase gene (phyA), isolated from Aspergillus ficuum (AF537344), was introduced into cotton (Gossypium hirsutum L.) by Agrobacterium-mediated transformation to increase the phosphorus (P) acquisition efficiency of cotton. Southern and Northern blot analyses showed that the phyA was successfully incorporated into the cotton genome and expressed in transgenic lines. After growing for 45?days with phytate (Po) as the only P source, the shoot and root dry weights of the transgenic plants all increased by nearly 2.0-fold relative to those of wild-type plants, but were similar to those of transgenic plants supplied with inorganic phosphorus. The phytase activities of root extracts prepared from transgenic plants were 2.4- to 3.6-fold higher than those from wild-type plants, and the extracellu...
Contrary to the electronic excitation induced phenomena of desorption and sputtering, we observed incorporation of oxygen in a thin Fe film during its irradiation with swift heavy ions. It is observed that the adsorbed oxygen diffuses in to the Fe film. The incorporation of oxygen and its diffusion in the bulk of the film is a manifestation of extremely large electronic energy deposition by the incident ions. It is shown that the experimentally observed high diffusivity of oxygen in Fe during irradiation is due to the existence of transient melt phase of Fe.
Hypoxia causes abnormal neonatal pulmonary artery remodeling (PAR) and inhibition of alveolar development (IAD). Transforming growth factor (TGF)-β is an important regulator of lung development...Full Text Available
Food animals are a potential source of CTX-M resistance genes for humans. We evaluated the transfer of the blaCTX-M-9 gene from an animal strain of Salmonella enterica...Full Text Available
In both type 1 and type 2 diabetes, pancreatic islet dysfunction results in part from cytokine-mediated inflammation. The ubiquitous eukaryotic translation initiation factor 5A (eIF5A), which is the...Full Text Available
Self-grooming in response to the odors of conspecifics is a form of olfactory communication among meadow voles. The amount of time meadow voles spend self-grooming when they encounter the odors of conspecifics varies seasonally, with males targeting the odors of reproductively active females only during the breeding season. Other odor related behaviors in male voles such as odor preferences for conspecifics and the attractiveness of their odors to conspecifics vary seasonally as well. For male meadow voles, these behaviors are mediated by seasonal variations in testosterone (T) and prolactin (PRL) titers. The objective of this study was to determine whether seasonal differences in the amount of time male meadow voles self-groom in response to odors of conspecifics are mediated by seasonal rhythms in their circulating T and PRL titers. We tested the hypothesis that high titers of both T and PRL are necessary for reproductively active ...
Gastrin and its carboxyl-terminal homolog cholecystokinin (CCK) exert a variety of biological actions in the brain and gastrointestinal tract that are mediated in part through one or more G protein-coupled...Full Text Available
Bacteriocins are an abundant class of antimicrobial molecules that appear to mediate population dynamics within species. The bacteriocins of Escherichia coli have served as a model for exploring the ecological role of these potent toxins. Studies suggest that colicins provide a competitive edge in nutrient-poor environments and that there might be a trade-off between the costs and benefits of colicin production. PMID:10203843
BackgroundOur previous studies indicate that either PEP-1-superoxide dismutase 1 (SOD1) or PEP-1-catalase (CAT) fusion proteins protects myocardium from ischemia-reperfusion-induced...Full Text Available
Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation...Full Text Available
In higher plants, three subfamilies of sucrose nonfermenting-1 (Snf1)-related protein kinases have evolved. While the Snf1-related protein kinase 1 (SnRK1) subfamily has been shown to share pivotal...Full Text Available
We report that the fission yeast nucleoporin Nup124p is required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr. Failure to import Tf1-Gag into the nucleus...Full Text Available
BackgroundCannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB1 and CB2 receptors mediate this therapeutic effect...Full Text Available
RNA interference (RNAi) is an effective tool for studying gene function in oocytes, but no studies have targeted somatic cells of primary cultured cumulus cell-oocyte complexes (COCs). This...Full Text Available
BackgroundThe average nitrogen-to-phosphorus ratio (N∶P) of insect herbivores is less than that of leaves, suggesting that P may mediate plant-insect interactions more often...Full Text Available
Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA...Full Text Available
Bridged monobactam {beta}-lactamase inhibitors were prepared and evaluated as potential partners for combination with imipenem to overcome class C {beta}-lactamase mediated resistance. The (S)-azepine analog 2 was found to be effective in both in vitro and in vivo assays and was selected for preclinical development.
Inhibition of large conductance calcium-activated potassium (BKCa) channels mediates, in part, oxygen sensing by carotid body type I cells. However, BKCa channels remain active...Full Text Available
Scyl1 is an evolutionarily conserved N-terminal protein kinase-like domain protein that plays a role in COP1-mediated retrograde protein trafficking in mammalian cells. Furthermore, loss of Scyl1 function...Full Text Available
The movement of cells and cell fragments in an electric field provided a means for determining the nature of cellular surface charges. We found that changes in ionic strength and particularly changes...Full Text Available
Two millimeter long secondary root tips of etiolated mung bean (Phaseolus aureus) plants were given 4 minute consecutive treatments of darkness, red light, far red light, and acetylcholine...Full Text Available
BackgroundAδ and C fibers are the major pain-conducting nerve fibers, activate only partly the same brain areas, and are differently involved in pain syndromes....Full Text Available
Within 20 min after intraperitoneal injection of Salmonella enteritidis endotoxin in rats, blood platelet-activating factor (PAF) increased from 4.3 +/- 1.3 to 13.7 +/- 2.0 ng/ml (P less than 0.01)...Full Text Available
The properties of a nonviable, aqueous ether-extracted Brucela abortus preparation, Bru-Pel, are described. In addition to inducing a "virus-type" interferon response and protecting mice against challenge with otherwise lethal doses of Semliki Forest virus, Bru-Pel is demonstrated to have potent antitumor properties in mice. These antitumor effects appear to be mediated by an increase in nonspecific resistance similar to that seen with other experimental antitumor agents. PMID:728911
Retinal pigment epithelial (RPE) cells, derived from the neuroectoderm, biosynthesize the novel lipid mediator neuroprotectin D1 (NPD1) from docosahexaenoic acid (DHA) in response to oxidative...Full Text Available
The capacity of bones to adjust their mass and architecture to withstand the loads of everyday activity derives from the ability of their resident cells to respond appropriately to the strains engendered....Full Text Available
Although matrix metalloproteinase-9 (MMP-9) is involved in cardiomyocytes contractility dysfunction, tissue inhibitor of metalloproteinase-4 (TIMP-4) mitigates the effect of MMP-9, and proteinase-activated...Full Text Available
The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated...Full Text Available
The present study demonstrates that tumour necrosis factor (TNF) and FMLP, but not IL-1 or IL-8, enhanced the adherence of polymorphonuclear neutrophil (PMN) to fibronectin, an extracellular matrix...Full Text Available
Helicobacter pylori, a major cause of human gastric disease, is a microaerophilic bacterium that contains neither pyruvate nor 2-oxoglutarate dehydrogenase activity. Previous studies...Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
Summary20 years ago, in 1987, Edelson and co-workers published their first report on the effectiveness of a new procedure, called extracorporeal photochemotherapy (ECP), in patients...Full Text Available
Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction...Full Text Available
Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS)...Full Text Available
Backgroundβ2-Adrenergic receptors (β2AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic...Full Text Available
1. Using a grease-gap recording technique we have investigated the effects of some antagonists of P2-purinoceptors on the depolarization of the rat isolated superior cervical ganglion evoked by 100...Full Text Available
Human Fas/Apo-1 is a cell-surface protein that mediates apoptosis upon ligation with Fas ligand. The gene lies on the long arm of chromosome 10, consists of nine exons, and spans more than 26 kb of...Full Text Available
Neutrophils from people with poorly controlled diabetes present a primed phenotype and secrete excessive superoxide. Phospholipase A2 (PLA2)-derived arachidonic acid (AA)...Full Text Available
Activities of glycogen synthase (GS) and GS phosphatase were determined on human muscle biopsies before and after isometric contraction at 2/3 maximal voluntary force. Total GS activity did not change...Full Text Available
Four Escherichia coli isolates harboring CTX-M-14, with a single Ala231→Val substitution compared to CTX-M-9, had three different ribotypes. Cefotaxime resistance was plasmid...Full Text Available
Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2, can induce persistent nonneoplastic expansion of the CD5+ B-cell population, termed...Full Text Available
A collection of neurons in the upper lumbar spinal cord of male rats projects to the lower lumbar spinal cord, releasing gastrin-releasing peptide (GRP) onto somatic and autonomic centers known to regulate...Full Text Available
Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion....Full Text Available
In superior cervical ganglion (SCG) neurons calcium-induced calcium release (CICR), mediated by ryanodine receptors (RyRs), contributes to stimulation-evoked intracellular calcium ([Ca2+]i)...Full Text Available
Positioning of release factor eRF1 toward adenines and the ribose-phosphate backbone of the UAAA stop signal in the ribosomal decoding site was studied using messenger RNA (mRNA) analogs containing...Full Text Available
This report investigates acute changes in the sensitivity of 5-HT1A receptors in dorsal raphe (dr) neurons in response to elevated serotonin. DR neurons were isolated from adult rats...Full Text Available
Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing...Full Text Available
Arf GTPases control vesicle formation from different intracellular membranes and are regulated by Arf guanine nucleotide exchange factors (GEFs). Outside of their conserved catalytic domains, known...Full Text Available
1-Naphthylphthalamic acid (NPA) is a specific inhibitor of polar auxin transport that blocks carrier-mediated auxin efflux from plant cells. To allow identification of the NPA receptor thought to be...Full Text Available
Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical...Full Text Available
The mechanical properties of laminated window profiles manufactured using two types of adhesives were determined. The objective of this study is to evaluate the effects of heat treatment on some mechanical...Full Text Available
SUMMARYHomeostatic synaptic plasticity is a negative feedback mechanism neurons use to offset excessive excitation or inhibition by adjusting their synaptic strengths. Recent...Full Text Available
The mechanism of hyaluronan biosynthesis in vertebrates had been proposed to occur at the reducing end of growing chains. This mechanism was questioned because a recombinant synthase appeared to add...Full Text Available
The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged ...
The authors present a search for excited and exotic muon states {mu}*, conducted using an integrated luminosity of 371 pb{sup -1} of data collected in p{bar p} collisions at {radical}s = 1.96 TeV at the Tevatron with the CDF II detector. They search for associated production of {mu}{mu}* followed by the decay {mu}* {yields} {mu}{gamma}, resulting in the {mu}{mu}{gamma} final state. They compare the data to model predictions as a function of the mass of the excited muon M{sub {mu}*}, the compositeness energy scale {Lambda}, and the gauge coupling factor f. No signal above the standard model expectation is observed in the {mu}{gamma} mass spectrum. In the contact interaction model, they exclude 107 < M{sub {mu}*} < 853 GeV/c{sup 2} for {Lambda} = M{sub {mu}*}; in the gauge-mediated model, they exclude 100 < M{sub {mu}*} < 410 GeV/c{sup 2} for f/{Lambda} = 10{sup -2} GeV{sup -1}. These 95% confidence level exclusions extend previous limits ...
We investigated the effect of irradiation on the kinetic characteristics of amino acid and glucose transport, and the effect on the activity of the cell membrane-bound enzyme 5'-nucleotidase and on the receptor-mediated stimulation of cyclic adenosine monophosphate synthesis by prostaglandin E1. Irradiation inhibited the sodium-dependent amino acid transport by a reduced binding of the amino acid to the transport unit. The transport of glucose, which appeared to be a sodium-independent process, was temporarily stimulated by increased maximal velocity of the transport. No effect was found on the binding to the transport unit. Irradiation increased the 5'-nucleotidase activity and decreased the prostaglandin E1-stimulated cyclic adenosine monophosphate synthesis 48 h after exposure to 20 Gy. It is concluded that irradiation decreases sodium-dependent transport by impairment of the transport unit, does not impair a sodium-independent process, and has ...
Eribulin is a new anticancer agent currently in Phase III clinical trials for the treatment of metastatic breast cancer. In the current studies, we have investigated the effects of P-glycoprotein (P-gp) on the in vivo disposition of eribulin using CF-1 abcb1a-deficient mice, and the influence of eribulin on P-gp-mediated efflux of digoxin in Caco-2 cells. Eribulin was administered intravenously and orally in both CF-1 wild-type and CF-1 abcb1a-deficient mice. P-gp-mediated efflux of digoxin in Caco-2 cell monolayers was measured in the presence of eribulin. The plasma exposure to eribulin was higher in CF-1 abcb1a-deficient mice than that in CF-1 wild-type mice after intravenous (IV) and oral (PO) administrations. The oral bioavailability of eribulin was 62.3% in CF-1 abcb1a-deficient mice...
The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ 3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activatin observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analyzed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found hypomethylated as ...
As semiconductor device dimensions continue to shrink, the drive beyond 250 nm is creating significant problems for the device processor. In particular, trends toward shallower-junctions, lower thermal budgets and simplified processing steps present severe challenges to ion implantation. In parallel with greater control of the implant process goes the need for a better understanding of the physical processes involved during implantation and subsequent activation annealing. For instance, the need for an understanding of dopant-defect interaction is paramount as defects mediate a number of technologically important phenomena such as transient enhanced diffusion and impurity gettering. This paper will outline the current trends in the ion implantation and some of the challenges it faces in the next decade, as described in the semiconductor roadmap. It will highlight some recent positron annihilation work that has made a contribution to addressing one of these ...
We propose a new scenario that solves the slepton negative mass squared problem of the minimal supersymmetric standard model with anomaly mediated supersymmetry breaking. The solution is achieved by including three trilinear R-parity violating operators in the superpotential. The soft supersymmetry breaking terms satisfy renormalisation group invariant relations in terms of supersymmetric couplings and the overall supersymmetry breaking mass scale. Flavour changing neutral currents are naturally highly suppressed. The model predicts tan beta=4.2 +/- 1.0. Excluding sleptons, the supersymmetric particle spectrum depends upon two remaining free parameters. In the case of the R-parity violating couplings at their quasi-fixed points at a supersymmetric GUT scale, the whole sparticle spectrum approximately depends upon only one free parameter. Imposing experimental limits leads to a constrained and distinctive phenomenology. The lightest CP-even Higgs of mass m_h=118 GeV ...
The online communicative environment is expected to revolutionize political discourse as it expands to cover underrepresented groups and ideas. In this platform, marginalized groups such as indigenous communities from the developing world can articulate claims, strategically mobilize and participate in the forms of meaning-making that constitute them. However, there is skepticism on the actual value of online spaces in effecting agency in an internet-mediated environment. Using James Scott's notion of 'hidden transcripts' and Andrew Feenberg's 'democratic rationalization of technology', the paper explores strategic approaches and historical, social, and political conditions embedded in the construction, negotiation, and transformation of indigenous online activist media. In-depth interview...
Innate immune responses are regulated by microorganisms and cell death, as well as by a third class of stress signal from the nervous and endocrine systems. The innate immune system also feeds back, through the production of cytokines, to regulate the function of the central nervous system (CNS), and this has effects on behaviour. These signals provide an extrinsic regulatory circuit that links physiological, social and environmental conditions, as perceived by the CNS, with transcriptional 'decision-making' in leukocytes. CNS-mediated regulation of innate immune responses optimizes total organism fitness and provides new opportunities for therapeutic control of chronic infectious, inflammatory and neuropsychiatric diseases.
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
Abstract This article summarizes the results of a Nutrient Biomarker Study in the Women's Health Initiative, and its application to studies of the association between energy and protein consumption and the risk of major cancers and cardiovascular diseases. The presentation emphasizes measurement error modeling and related data analysis methods, since addressing measurement issues appears to be central to these topics and to progress in nutritional epidemiology more generally. The manner in which body mass index is modeled in disease association analysis is particularly challenging, since it could serve as a mediator or as a confounder of the association, and at the same time contributes valuably to energy and protein consumption assessment. A hazard ratio parameter estimation procedure tha...
multi-parton interactions and underlying event structure, $\\gamma$-mediated processes and luminosity determination, Monte Carlo tuning and even MSSM Higgs discovery in central exclusive production. In this article, the forward detector instrumentation around the CMS interaction point is described and the prospects for diffractive and forward physics using the CMS forward detectors are summarized. In addition, first observation of forward jets as well as early measurements of the forward energy flow in the pseudorapidity range $3.15
This paper describes the study of kinetically controlled enzymatic coupling of N- and O-glycopeptide fragments using subtilisin BPN' and two of its variants developed for use in high concentrations of dimethylformamide and in aqueous solution, respectively. Glycosyl amino acids were exploited as the P[sub 1], P[sub 2], P[sub 3], P'[sub 1], P'[sub 2], or P'[sub 3] residue in the enzymatic coupling. Glycosyltransferase-mediated glycosylation of the glycopeptide fragments obtained prior to or after enzymatic peptide bond formation is demonstrated. 19 refs., 5 figs., 1 tab.
Environmental computer science is a new partial discipline of applied computer science, which makes use of methods and techniques of information processing in environmental protection. Thanks to the inter-disciplinary nature of environmental problems, computer science acts as a mediator between numerous disciplines and institutions in this sector. The handbook reflects the broad spectrum of state-of-the art environmental computer science. The following important subjects are dealt with: Environmental databases and information systems, environmental monitoring, modelling and simulation, visualization of environmental data and knowledge-based systems in the environmental sector. (orig.).
Male meadow voles maintained in a long photoperiod (LP) from birth have heavier brains than do females, but in short photoperiods (SP) this sex dimorphism is absent. Testosterone propionate (TP) administration on the second day of postnatal life produced significant increases in brain weight of LP but not SP females at 35 days of age. Short daylengths reduce the responsiveness of the meadow vole nervous system to the masculinizing effects of perinatal testosterone and may, in part, mediate the seasonally reduced sex difference in brain weight. PMID:8446686
Higgs mediated flavor violating electromagnetic interactions, induced at the one-loop level by a nondiagonal Hf_if_j vertex, with f_i and f_j charged leptons or quarks, are studied within the context of a completely general effective Yukawa sector that comprises SU_L(2)xU_Y(1)-invariant operators of up to dimension-six. Exact formulae for the one-loop #gamma#f_if_j and #gamma##gamma#f_if_j couplings are presented and their related processes used to study the phenomena of Higgs mediated lepton flavor violation. The experimental limit on the #mu##->#e#gamma# decay is used to derive a bound on the branching ratio of the #mu##->#e#gamma##gamma# transition, which is 6 orders of magnitude stronger than the current experimental limit. Previous results on the #tau##->##mu##gamma# and #tau##->##mu##gamma##gamma# decays are reproduced. The possibility of detecting signals of lepton flavor violation at #gamma##gamma# colliders is explored ...
Red light stimulates germination in the spores of Onoclea sensibilis L. Phytochrome is confirmed to be the photoreceptor pigment in the germination response by demonstrating red-far-red photoreversibility. External Ca/sup 2 +/ is required for this response with a threshold at a submicromolar concentration. Red light stimulates an increase in the total concentration of intracellular calcium in the spores as determined by atomic absorption spectroscopy. Subsequent exposure to far-red light inhibits the red light-induced increase in intracellular calcium. The majority of the increase occurs 5 minutes after the onset of irradiation. The calcium-antagonist, La/sup 3 +/ inhibits both germination and the red light-induced increase in intracellular calcium. Using /sup 31/P-nuclear magnetic resonance spectroscopy, the author tested the hypothesis that a sustained increase in intracellular pH contributes to the signal transduction chain. He never detected a red light-induced increase in ...
Thioredoxin reductase, lipoamide dehydrogenase, and glutathione reductase are members of the pyridine nucleotide–disulfide oxidoreductase family of dimeric flavoenzymes. The mechanisms and structures...Full Text Available
In this study, a novel compliant mechanism, ''partially compliant spatial slider-crank (RSSP)'' is proposed. All possible configurations of compliant RSSP mechanisms are classified and discussed. A method is derived to determine deflection of the multiple-axis flexural hinge for all positions of the crank. A design procedure for partially compliant RSSP mechanisms is introduced. In order to prove the feasibility of the proposed mathematical model, a real model is built and it is shown that results are consistent.
Detailed chemical kinetic reaction mechanisms have been developed to describe the pyrolysis and oxidation of the n-alkanes, including n-octane (n-C{sub 8}H{sub 18}), n-nonane (n-C{sub 9}H{sub 20}), n-decane (n-C{sub 10}H{sub 22}), n-undecane (n-C{sub 11}H{sub 24}), n-dodecane (n-C{sub 12}H{sub 26}), n-tridecane (n-C{sub 13}H{sub 28}), n-tetradecane (n-C{sub 14}H{sub 30}), n-pentadecane (n-C{sub 15}H{sub 32}), and n-hexadecane (n-C{sub 16}H{sub 34}). These mechanisms include both high temperature and low temperature reaction pathways. The mechanisms are based on previous mechanisms for n-heptane, using the same reaction class mechanism construction developed initially for n-heptane. Individual reaction class rules are as simple as possible in order to focus on the parallelism between all of the n-alkane fuels included in the mechanisms, and there is an intent to ...
Detailed chemical kinetic reaction mechanisms have been developed to describe the pyrolysis and oxidation of nine n-alkanes larger than n-heptane, including n-octane (n-C{sub 8}H{sub 18}), n-nonane (n-C{sub 9}H{sub 20}), n-decane (n-C{sub 10}H{sub 22}), n-undecane (n-C{sub 11}H{sub 24}), n-dodecane (n-C{sub 12}H{sub 26}), n-tridecane (n-C{sub 13}H{sub 28}), n-tetradecane (n-C{sub 14}H{sub 30}), n-pentadecane (n-C{sub 15}H{sub 32}), and n-hexadecane (n-C{sub 16}H{sub 34}). These mechanisms include both high temperature and low temperature reaction pathways. The mechanisms are based on our previous mechanisms for the primary reference fuels n-heptane and iso-octane, using the reaction class mechanism construction first developed for n-heptane. Individual reaction class rules are as simple as possible in order to focus on the parallelism between all of the n-alkane fuels included in ...
Car weight corresponds directly to fuel consumption and driving performance. So in order to improve the fuel efficiency and performance of a car the weight has to be reduced. Magnesium as a light metal offers a wide range of weight saving opportunities, especially Magnesium wrought alloys with their improved mechanical properties have a high potential for structural applications. Mechanical properties in terms of their quality and anisotropy are dependent on the microstructure of the material and can be characterized by their degree of inhomogeneity, their grain size distribution and their crystallographic texture. Therefore the orientation distribution of grains, the grain size, its size distribution, the chemical composition (precipitates) itself influence the mechanical parameters and their anisotropy. In this presentation first results of mechanical anisotropy are given: differences in yield stress, ...
This paper examines the feasibility of returning coal mine wastes to the mined-out areas, as encouraged by PL 95-87, the ''Surface Mining Control and Reclamation Act of 1977'' (SMCRA). Reviews a National Academy of Sciences report which identified alternative backfilling methods. Presents diagram of mechanical backfilling with gravity and mechanical transport, and tables of existing underground mine waste disposal methods and a summary of technical feasibility of alternative disposal systems. Evaluated systems include gravity disposal with mechanical surface transport; gravity disposal with mechanical in-mine transport; complete mechanical disposal; mechanical disposal with gravity surface to underground transport; direct hydraulic disposal; hydraulic disposal with natural head; hydraulic disposal with artificial head; ...
The realization that there existed a G-protein coupled signal transduction mechanism developed gradually and was initially the result of an ill fated quest for uncovering the mechanism of action...Full Text Available
We use a novel normal mode analysis of an elastic network model drawn from configurations generated during microsecond all-atom molecular dynamics simulations to analyze the mechanism of auto-inhibition...Full Text Available
AbstractWe combined atomistic molecular-dynamics simulations with quantum-mechanical calculations to investigate the sequence dependence of the stretching behavior of duplex DNA. Our...Full Text Available
PURPOSEThe purpose of this study was to compare the linear sintering behavior of presintered zirconia blocks of various densities. The mechanical properties of the resulting sintered...Full Text Available
In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual...Full Text Available
The reproducibility of pulmonary mechanics measurements in dairy cattle was examined using two study designs. In design A measurements were made with six cows on two days, and in design B measurements...Full Text Available
Using a new approach to quaternion mechanics based on De Broglie waves, it is shown that such a theory describes tachyons and that the quantum theory of tachyons should be a quaternionic one. (U.K.).
Emphasis was put on the comparative quantitative structure-activity approaches to the exploration of action mechanisms of structurally different classes of compounds showing the same type of activity...Full Text Available
The guide describes a method acceptable to the NRC staff for complying with the Commission's regulations with regard to quality assurance requirements for installation, inspection, and testing of mechanical equipment and systems for water-cooled and high-temperature gas-cooled nuclear power plants.
The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms...Full Text Available
Ion-channels can be activated (gated) by a variety of stimuli including chemicals, voltage, mechanical force or temperature. Whereas molecular mechanisms of ion-channel gating by chemicals and...Full Text Available
Excised sheets of canine myocardium were subjected to cyclic loading and unloading in the predominant fibre and cross-fibre directions to determine passive mechanical properties. Myocardium under biaxial...Full Text Available
Most mechanical forces acting on the skeleton are generated either through impact with the ground (i.e., gravitational loading) or through muscle contractions (i.e., muscle loading). If one...Full Text Available
Bone remodeling is necessary to avoid microdamage accumulation, which could lead to whole-bone failure. Previous studies have shown that this bone-repair mechanism is triggered by osteocyte apoptosis....Full Text Available
Investigation of memory effects in air at 0.7 mbar pressure in the presence of vacuum electrical breakdown mechanism has been performed in this paper. The memory effect has been followed using the time delay method.
The mechanism of chemotherapy-induced acceleration of ovarian aging is not fully understood. We used doxorubicin, a widely used cancer chemotherapeutic, in a variety of in vivo xenograft,...Full Text Available
In this work, coals of various ranks were dissolved in an acid melange. With the use of IR spectroscopy, it was found that the mechanism of coal dissolution consists in the grafting of polar groups to the peripheral benzene rings of graphite-like systems.
Hepatic damage occurs in males and ovariectomized (OVX), not in proestrus (PE), females following trauma-hemorrhage (T-H). The mechanism responsible for hepatoprotection remains unknown. We hypothesized...Full Text Available
DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced...Full Text Available
The mechanism of influenza virus (INFV)-induced immunosuppression and the mode of inosiplex action against INFV infection were studied. INFV suppressed both anti-lipopolysaccharide and anti-sheep erythrocyte...Full Text Available
Catch is a mechanical state occurring in some invertebrate smooth muscles characterized by high force maintenance and resistance to stretch during extremely slow relaxation. During catch, intracellular...Full Text Available
The guiding mechanism is attached by a hinge (swivel) to the supporting frame, and the frame is equipped by hinges (swivels) with hydraulic or pneumatic cylinders mounted on its ends and is attached by hinges (swivels) to the coke ejector and guide respectively. This increases the productivity and efficiency of operating the system.
1. The mechanical power spent to accelerate the limbs relative to the trunk in level walking and running, Ẇint, has been measured at various `constant' speeds (3-33...Full Text Available
In this paper method of constructing quasi-exactly solvable models of quantum mechanics is proposed. This method is based on the use of infinite-dimensional representations of simple and semi-simple Lie algebras.
This dissertation presents the development of the novel mechanical testing technique of in situ nanoindentation in a transmission electron microscope (TEM). This technique makes it possible to simultaneously observe and quantify the mechanical behavior of nano-scale volumes of solids.
The possibility of rapid heat treatment (RHT) application to titanium castings has been studied. It was shown that such treatment provides a significant improvement of intragrain structure and mechanical properties of cast ({alpha}+{beta})-titanium alloys. ((orig.))
Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available
The mechanism by which mechanical force regulates the kinetics of a chemical reaction is unknown. Here, we use single-molecule force–clamp spectroscopy and protein engineering to study the effect...Full Text Available
The effects of Escherichia coli endotoxin on lung mechanics, hemodynamics, gas exchange, and lung fluid and solute exchange were studied in 12 chronically instrumented unanesthetized sheep. A possible...Full Text Available
Mechanism-based inhibition of cytochrome P450 (CYP) 3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive...Full Text Available
Mechanical forces can regulate various functions in living cells. The cytoskeleton is a crucial element for the transduction of forces in cell-internal signals and subsequent biological responses. Accordingly,...Full Text Available
Summary - Hydraulic traits were studied in temperate, woody evergreens in a high-elevation heath community to test for trade-offs between the delivery of water to canopies at rates sufficient to sustain photosynthesis and protection against disruption to vascular transport caused by freeze-thaw-induced embolism. - Freeze-thaw-induced loss in hydraulic conductivity was studied in relation to xylem anatomy, leaf- and sapwood-specific hydraulic conductivity and gas exchange characteristics of leaves. - We found evidence that a trade-off between xylem transport capacity and safety from freeze-thaw-induced embolism affects photosynthetic activity in overwintering evergreens. The mean hydraulically weighted xylem vessel diameter and sapwood-specific conductivity correlated with susceptibility to...
Amyloid precursor protein (APP), a key protein in pathogenesis of Alzheimer's disease (AD), is a type I transmembrane protein which can be cleaved by b- and g-secretase to release the amyloidogenic b-amyloid peptides (Ab) and the APP intracellular domain (AICD). While Ab has been widely believed to initiate pathogenic cascades culminating AD, the physiological functions and regulations of AICD remain elusive. In present study, endogenous AICD was demonstrated to be increased by canonical Wnt signal. Instead of due to g-secretase activity, enhanced AICD expression was found due to the increased protein stability by Wnt/b-catenin. b-Catenin was demonstrated to be an associating partner of AICD, capable of promoting AICD mediated transcriptional activity. Investigation by AICD mutants proved ...
Triacontanol (TRIA) has been realized as a potent plant growth promoting substance for a number of agricultural and horticultural crops. Out of a large number of essential oil bearing plants, mint (Mentha arvensis L.) constitutes the most important source of therapeutic agents used in the alternative systems of medicine. The mint plant has marvelous medicinal properties. In view of enhancing growth, yield and quality of this medicinally important plant, a pot experiment was conducted according to simple randomized block design. The experiment was aimed at studying the effect of four concentrations of TRIA (10?0, 10?7, 10?6 and 10?5?M) on the performance of mint with regard to growth and other physiological attributes, crop yield and quality attributes and the yield and contents of active c...
Short synthetic single-stranded oligodeoxyribonucleotides (ssODNs) can be used to introduce subtle modifications into the genome of mouse embryonic stem cells (ESCs). We have previously shown that effective application of ssODN-mediated gene targeting in ESC requires (transient) suppression of DNA mismatch repair (MMR). However, whereas transient down-regulation of the mismatch recognition protein MSH2 allowed substitution of 3 or 4 nucleotides, 1 or 2 nucleotide substitutions were still suppressed. We now demonstrate that single- or dinucleotide substitution can effectively be achieved by transient down-regulation of the downstream MMR protein MLH1. By exploiting highly specific real-time PCR, we demonstrate the feasibility of substituting a single basepair in a non-selectable gene. Howev...
Thyroid cancer is the most frequently diagnosed endocrine cancer and causes more deaths than all other endocrine cancers combined. Research findings support the concept that a subpopulation of thyroid cancer cells displays properties characteristic of stem cells. These putative cancer-forming entities drive tumorigenesis as a result of their dual ability to undergo self-renewal and to differentiate into various types of cancer cells; they also mediate metastasis and are resistant to the effects of chemotherapy and radiation therapy. This Review discusses the cellular origin of thyroid cancer and the properties of the thyroid cancer stem cell niche. The article critically evaluates the methods used to identify molecular markers expressed by thyroid-cancer-initiating cells and outlines prosp...
l-Carnitine is a critical metabolite indispensable for the metabolism of lipids as it facilitates fatty acid transport into the mitochondrion where b-oxidation occurs. Human astrocytes (CCF-STTG1 cells) and hepatocytes (HepG2 cells) exposed to aluminum (Al) and hydrogen peroxide (H2O2), were characterized with lower levels of l-carnitine, diminished b-oxidation, and increased lipid accumulation compared to the controls. g-Butyrobetainealdehyde dehydrogenase (BADH) and butyrobetaine dioxygenase (BBDOX), two key enzymes mediating the biogenesis of l-carnitine, were sharply reduced during Al and H2O2 challenge. Exposure of the Al and H2O2-treated cells to a-ketoglutarate (KG), led to the recovery of l-carnitine production with the concomitant reduction in ROS levels. It appears that the chann...
Reciprocity is one of the defining features of social exchange and social life, yet exchange theorists have tended to take it for granted. Drawing on work from a decade-long theoretical research program, I argue that reciprocity is structured and variable across different forms of exchange, that these variations in the structure of reciprocity have profound effects on the emergence of integrative bonds of trust and solidarity, and that these effects are explained and mediated by a set of risk- and conflict-based processes. I discuss the consequences of this work for organizational theories of embeddedness and the production of social capital through network ties. Finally, I ask how the structure of networks and the structure of reciprocity are related to one another, and explore possible implications of the structure of reciprocity for exchange theorists' assumptions about actor motivations. (Contains 3 figures and 5 footnotes.)
Mood in humans is a complex phenomenon that integrates emotion (e.g. happiness and sadness), cognition, perception, ideation, and action in a coherent manner. In bipolar disorder extremes of mood (up or down) occur outside the normal range, in which all the above functions are coherently affected. Mood is controlled by a series of separate but interactive brain circuits that involve much of the brain, but particularly the limbic system. The question addressed in this paper is whether the coordination of all these separate systems into one coherent functional mood is mediated by non-linear dynamics acting between these systems as equal participants; or whether it is affected by a single master regulator controlling the others. The possible roles, as master regulators, of non-linear dynamica...
The T cell receptor is a fundamental mediator of the adaptive immune responses, since TR ab on T cells recognize foreign structures (peptides derived from processed antigens) bound to the major histocompatibility complex (MHC) on APC cells. In the present study, we report the cloning of six TRB chains cDNA sequences from gilthead sea bream (Sparus aurata), a fish of high economical impact in South Mediterranean aquaculture. The V-BETA domains have the canonical features of known teleost and mammalian TR V-BETA domains and have been divided in four different subgroups. A multiple alignment of the six sea bream TRB chains with other known TRB sequences was assembled and showed the conservation of the four cysteine residues involved in disulphide bonds and of some amino acids with an importan...
Two no-carrier-added "1"2"5I-labelled photoaffinity rapamycin analogs were prepared: 7-demethoxy-7-(4-azido-3-"1"2"5I-benzyloxy) rapamycin and its C_2_8-C_2_9 seco analog. The key reactions of the synthesis were substitution of the C_7 methoxyl of rapamycin with 4-azido-3-tributylstannylbenzyloxy group, exchange of tributyltin with "1"2"5I using Na"1"2"5I and Chloramine-T, and a ZnCl_2 mediated retro-Aldol cleavage of the C_2_8-C_2_9 bond of rapamycin. (author).
An attempt is made to induce in mud crab (Scylla serrata) epileptiform activities that resemble the generalized epileptic seizures. Cerebral ganglion of crab was exposed in situ, to a convulsant drug pentylenetetrazole (PTZ) 100?mM, for induction of seizures. Also, crabs were pretreated with antiepileptic drug viz sodium valproate (120??mol/l) to inhibit epileptiform activities. The surface electrical discharges of cerebral ganglion were recorded using Unkelscope (MIT, USA) in control as well as experimental animals. The cerebral ganglion of crab showed a pattern of high cerebral electrical discharges after PTZ treatment compared to control. The sodium valproate promoted sedative action in control and prevented PTZ-mediated epileptiform discharges. Glutamate and GABA contents in cerebral g...
In vulnerable individuals, exposure to stressors can result in chronic disorders such as generalized anxiety disorder (GAD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). The extended amygdala is critically implicated in mediating acute and chronic stress responsivity and anxiety-like behaviors. The bed nucleus of the stria terminalis (BNST), a subregion of the extended amygdala, serves as a relay of corticolimbic information to the paraventricular nucleus of the hypothalamus (PVN) to directly influence the stress response. To investigate the influence of the corticosteroid milieu and housing conditions on BNST function, adult C57Bl/6J were either acutely or chronically administered corticosterone (CORT, 25mg/kg in sesame oil) or vehicle (sesame oil) or were g...
The Mediated Electrochemical Oxidation (MEO) system is an aqueous process which treats low-level mixed wastes by oxidizing the organic components of he waste into carbon dioxide and water. As MEO system continues to run, dissolved ash and radionuclides slowly accumulate in the anolyte and must be removed to maintain process efficiency. At such time, all of the anolyte is pumped into a still feed tank, and the silver ions need to be removed before sending the solution to a thin-film evaporator for further concentration. The efficiency of removing silver ions in the solution needs to be high enough such that the residual silver sent to Final Forms would be less than 1% wt. The purpose of this work is to develop an efficient process to remove silver ions during the MEO cleanout and to demonstrate the capability of centrifugation for separating small silver chloride particles from the solution. This development work includes lab scale experiments and bench scale tests. ...
Abstract Capillary permeability is a tightly regulated feature of microcirculation in all organ beds. In sepsis, this feature is fundamentally altered. We have previously reported elevated levels of angiopoietin-2 in patients with septic shock, and have investigated tumor necrosis factor (TNF)-related and weak inducer of apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20 patients with septic shock, all of whom were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls. The TWEAK levels were higher in patients with septic shock (192.8--230.5-pg/mL) than in controls (84.1--28.7-pg/mL, P-=-0.043). Between 11 survivors and 1...
Abstract The treatment of advanced colorectal cancer with 5-fluorouracil has two major problems: development of tumor resistance and toxicity toward normal tissues. The aim of this study was to investigate the possible advantages of combining 5-fluorouracil (5-FU) with resveratrol (trans-3, 4prime, 5-trihydroxystilbene) for treating HT-29 and SW-620 colorectal carcinoma cell lines. Since combined treatment using 5-FU with resveratrol resulted in a significant decrease in long-term cell survival, we investigated the possible basis of this synergistic interaction at a molecular level, focusing on oxidative stress as a possible mediator of cell death. Resveratrol established interactions with the mitochondria of cancer cells and induced an imbalance in cellular antioxidant activities, leading...
Insect attraction to host plants may be partly mediated by visual stimuli. In the present study, the responses of adult Hycleus apicicornis (Gur.) (Coleoptera: Meloidae) to plant models of different colours, different combinations of two colours, or three hues of blue of different shapes are compared. Single-colour models comprised the colours sky blue, bright green, yellow, red, white and black. Sky blue (reflecting light in the 440-500 nm region) is the most attractive, followed by white, which reflects light over a broader range (400-700 nm). On landing on sky blue targets, beetles exhibit feeding behaviour immediately. When different hues of blue (of different shapes) are compared, sky blue is preferred over turquoise, followed by dark blue, indicating that H. apicicornis is more attra...
C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid to regulation of the ANP and BNP genes. CNP expression in vitro is regulated by TGF-b and recepto...
The ability of the R46 R factor and its derivative pKM101 to modify sensitivity to "6"0Co #gamma# radiation was studied. In Escherichia coli K12 both plasmids enhanced bacterial survival after "6"0Co #gamma# irradiation. This effect was dependent on recA"+ genotype but not on recB"+, recB"+recC"+, and recF"+ genotypes. 5-Fluorouracil eliminated the R46 R factor from the parent and its rec"- mutant strains. These strains lost not only the antibiotic resistance coded for R46 R factor but their radioresistance as well.
Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NFkB-induced PLD1 expression vi...
This research proposes that the concept of emotional attachment, and specifically the independent constructs of psychological ownership and affective reaction, can help explain many of the endowment effect findings documented in the literature. We define these constructs and then test them across a set of nine studies in which we both replicate previous and generate new endowment effect findings, and then show that psychological ownership and affective reaction can mediate the effects. In doing so, we offer direct empirical support for the idea of emotional attachment as a driver of loss aversion while also providing practitioners and future endowment effect researchers with new insights about the psychological processes that underlie the endowment effect.
The effects of exposure to sublethal levels of microwaves were studied. Young albino rats of both sexes were exposed for 60 days to 7.5-GHz microwaves (1.0-KHz square wave modulation, average power 0.6 mW/cm2) for 3 h daily. During and after microwave exposure several physiological parameters were measured in both control and exposed animals. It was found that the animals exposed to microwaves tended to eat and drink less and thus showed a smaller gain in body weight. Some of the hematological parameters and organ weights were also significantly different. It is proposed that a nonspecific stress response due to microwave exposure and mediated through the central nervous system is responsible for the observed physiological changes.
The generation and control of quantum states of light constitute fundamental tasks in cavity quantum electrodynamics (QED). The superconducting realization of cavity QED, circuit QED, enables on-chip microwave photonics, where superconducting qubits control and measure individual photon states. A long-standing issue in cavity QED is the coherent transfer of photons between two or more resonators. Here, we use circuit QED to implement a three-resonator architecture on a single chip, where the resonators are interconnected by two superconducting phase qubits. We use this circuit to shuffle one- and two-photon Fock states between the three resonators, and demonstrate qubit-mediated vacuum Rabi swaps between two resonators. This illustrates the potential for using multi-resonator circuits as photon quantum registries and for creating multipartite entanglement between delocalized bosonic modes.
Protein kinase C activity has been identified in the rat brown adipocyte. About 60% of this activity is found in the cytosolic fraction under basal conditions, and 12-O-tetradecanoylphorbol 13-acetate (TPA) causes a rapid shift from the cytosol to the particulate fraction. Norepinephrine and phenylephrine causes a similar redistribution that can be blocked by prazosin but not by alprenolol. {alpha}{sub 1}-Adrenergic agonists cause three- to fivefold stimulation of type 2 iodothyronine 5{prime}-deiodinase activity in brown adipocytes. TPA has no effect on basal deiodinase activity and reduces the response of the enzyme to {alpha}{sub 1}-adrenergic agonists. These results suggest that the translocation of protein kinase C from cytosol to particulate fraction is not sufficient to increase deiodinase activity but can modulate the {alpha}{sub 1}-adrenergic agonist-mediated responses in these cells.
Summary Background Current management of egg allergy relies on egg elimination from the diet. It does not protect patients from reactions after accidental ingestion of the food and it has a negative influence on quality of life. To solve these problems, some desensitization protocols have been described that are safe and effective, but only one study of a rush regimen for egg with a small patient sample has been published. Objective To evaluate the safety, efficacy and immunologic effects of an oral rush desensitization protocol for immediate egg allergy. Methods Subjects aged 5 years or older with symptomatic IgE-mediated allergy to hen's egg underwent a 5-day oral tolerance induction regimen and were subsequently maintained on a regular egg intake. The variables studied were the reaction...
Abstract People with a physical disability are a population who for a number of reasons may be vulnerable to social isolation. Research into Internet based support sites has found that social support and an online sense of community can be developed through computer mediated communication channels. This study aims to gain an understanding of the benefits that membership of disability specific online communities may have for people with a physical disability. An online survey was administered to a sample of users of such sites (N = 160). Results indicated that users did receive moral support and personal advice through participating in such online communities. Further, results indicated that online social support and feeling a sense of community online were positively associated with partic...
The growth of thin Pd[sub 2]Si films on Si(111) surfaces is studied using [ital in] [ital situ] transmission electron microscope under ultrahigh vacuum conditions. No immediate reaction of deposited Pd with Si is observed at room temperature. At [similar to]200 [degree]C, uniform Pd[sub 2]Si films can be formed. The thin Pd[sub 2]Si films are found to grow into strained islands at elevated temperatures. Interfacial misfit dislocations associated with interfacial steps propagate across the strained islands, causing the islands to grow layer-by-layer at the interface. The strain fields associated with the misfit dislocations are believed to be responsible for this behavior.
In the paper we investigate a mathematical model describing the growth of tumor in the presence of immune response of a host organism. The dynamics of tumour and immune cells is based on the generic Michaelis-Menten kinetics describing interaction and competition between the tumour and the immune system. The appropriate phenomenological equation modeling cell-mediated immune surveillance against cancer is of the predator-prey form and within a given choice of parameters exhibits bistability. Under the influence of spontaneous weak fluctuations, the model may be analyzed in terms of a stochastic differential equation bearing the form of an overdamped Langevin-like dynamics in the external quasi-potential represented by a double well. We analyze properties of the system within the range of parameters for which the potential wells are of the same depth and when the additional perturbation describing a periodic treatment is insufficient to overcome the barrier height ...
By choosing appropriate microemulsion systems, hexagonal cobalt (Co) and cobalt-nickel (1:1) alloy nanoparticles have been obtained with cetyltrimethylammonium bromide as a cationic surfactant at 500degreeC. This method thus stabilizes the hcp cobalt even at sizes (<10nm) at which normally fcc cobalt is predicted to be stable. On annealing the hcp cobalt nanoparticles in H2 at 700degreeC we could transform them to fcc cobalt nanoparticles. Microscopy studies show the formation of spherical nanoparticles of hexagonal and cubic forms of cobalt and Co-Ni (1:1) alloy nanoparticles with the average size of 4, 8 and 20nm, respectively. Electrochemical studies show that the catalytic property towards oxygen evolution is dependent on the applied voltage. At low voltage (less than 0.65V) the Co (he...
Manganese toxicity can cause a neurodegenerative disorder affecting cortical and basal ganglia structures with a neurological presentation resembling features of Parkinson's disease. Children are more sensitive to Mn-induced neurological dysfunction than adults, and recent studies from our laboratory revealed a marked sensitivity of male juvenile mice to neuroinflammatory injury from Mn, relative to females. To determine the role of estrogen (E2) in mediating sex-dependent vulnerability to Mn-induced neurotoxicity, we exposed transgenic mice expressing an NF-kB-driven enhanced green fluorescent protein (EGFP) reporter construct (NF-kB-EGFP mice) to Mn, postulating that supplementing male mice with E2 during juvenile development would attenuate neuroinflammatory changes associated with glia...
Heme peroxidases are a class of multifunctional redox-active proteins found in all organisms. We recently cloned, expressed, and characterized an ascorbate peroxidase from Leishmania major (LmAPX) that was capable of detoxifying hydrogen peroxide. Localization studies using green fluorescent protein fusions revealed that LmAPX was localized within the mitochondria by its N-terminal signal sequence. Subcellular fractionation analysis of the cell homogenate by the Percoll density-gradient method and subsequent Western blot analysis with anti-LmAPX antibody further confirmed the mitochondrial localization of mature LmAPX. Submitochondrial fractionation analysis showed that the mature enzyme (?3.6?kDa shorter than the theoretical value of the whole gene) was present in the intermembrane space ...
Isolation of functional and intact mitochondria from solid tissue is crucial for studies that focus on the elucidation of normal mitochondrial physiology and/or mitochondrial dysfunction in conditions such as aging, diabetes, and cancer. There is growing recognition of the importance of mitochondria both as targets for drug development and as off-target mediators of drug side effects. Unfortunately, mitochondrial isolation from tissue is generally carried out using homogenizer-based methods that require extensive operator experience to obtain reproducible high-quality preparations. These methods limit dissemination, impede scale-up, and contribute to difficulties in reproducing experimental results over time and across laboratories. Here we describe semiautomated methods to disrupt tissue ...
The response regulator protein is a core element of two-component signaling pathway. In this study, we investigated functions of BRRG-1 of Botrytis cinerea, a gene that encodes a putative response regulator protein, which is homologous to Rrg-1 in Neurospora crassa. The BRRG-1 gene deletion mutant ?Brrg1-62 was unable to produce conidia. The mutant showed increased sensitivity to osmotic stress mediated by NaCl and KCl, and to oxidative stress generated by H2O2. Additionally, the mutant was more sensitive to the fungicides iprodione, fludioxonil, and triadimefon than the parental strain. Western-blot analysis showed that the Bos-2 protein, the putative downstream component of Brrg-1, was not phosphorylated in the ?Brrg1-62. Real-time polymerase chain reaction assays showed that expression ...
Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunize...
This paper investigates the dynamics of excitonic transport in photocomplex LHCII, the primary component of the photosynthetic apparatus in green plants. The dynamics exhibits a strong interplay between coherent processes mediated by the excitonic Hamiltonian, and incoherent processes due to interactions with the environment. The spreading of the exciton over a single monomer is well described by a proper measure of delocalization that allows one to identify two relevant time scales. An exciton initially localized in one chromophore first spreads coherently to neighboring chromophores. During this initial coherent spreading, quantum effects such as entanglement play a role. As the effects of a decohering environment come into play, coherence and decoherence interact to give rise to efficient and robust excitonic transport, reaching a maximum efficiency at the levels of decoherence found in physiological conditions. We analyze the efficiency for different possible ...
In QCD the spontaneous breaking of chiral symmetry and the U(1) axial anomaly can be understood considering instantons as the gauge configurations mediating quark-quark interaction. The existence of an exact zero mode solution of the Dirac equation in the field of a single instanton is the fundamental ingredient of this analysis. Explicit expressions for psi_0 are available for T different from 0 and mu=0, and mu different from 0 and T=0. In this paper we derive the solution for the most general case T different from 0 and mu different from 0. This new result opens the possibility of investigating the QCD dynamics associated with instantons in the full phase diagram. As a first step in this direction we will study the dependence of the instanton density from the thermodynamic coordinates.
The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test t...
Based on terror management theory, previous research has shown that terrorism threat increases prejudice against Muslims and is mediated by death-related thoughts. Because this effect was found on a correlational level, it remains unclear whether terrorism threat increases prejudice against Muslims because of enhanced death-related thoughts or the opposite: terrorism threat increases death-related thoughts because of stronger prejudice against Muslims. To disentangle this shortcoming, we varied death-related thoughts by systematically manipulating the belief in literal immortality. Using two studies, we found that participants exposed to terrorism pictures (vs. controls) had increased prejudice against both Muslims (Study 1) and immigrants (Study 2) when they were led to believe that liter...
Computer vision imposes unique requirements on the representation and manipulation of image data and knowledge. At a vision system's lowest level are sensors that represent an image with purely numeric image arrays, while at the highest level are semantic world models that provide the final interpretation of the scene. In between are thousands of intermediate descriptions, many of which must be repeatedly accessed and processed during interpretation. In this article, the authors describe a representation and management system for use at the intermediate (symbolic) level of vision. Based on database management methodology, the intermediate symbolic representation (ISR) mediates access to intermediate-level vision data and forms an active interface to the higher-level inference processes that construct an image's interpretation. The system supports important types of data and operations and can be adapted to the changing needs of ongoing research. ...
In this work, a highly-sensitive polymeric membrane ion selective electrode for determination of tetracycline was constructed by using molecularly imprinted polymer (MIP) particles as quasi-ionophore. The water-compatible MIP particles targeting tetracycline were synthesized with tetracycline as a template molecule, methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, 2,2?-azobisisobutyronitrile as an initiator and lanthanum ion as a mediator. Benefited from the distinctive performance of the quasi-ionophore and the optimized composition of the membrane and the inner filling solution, the lower detection limit of the electrode was decreased to about 1 ? 10?8 mol/l. It exhibited a good electrode slope 59.8 mV/decade near the theoretical Nernstian one, ...
The function of selenium in an organism is mediated mostly by selenoproteins including glutathione peroxidase. Glutathione peroxidase is a potent anti-oxidative enzyme, scavenging a variety of peroxides. The green alga Scenedesmus quadricauda was used to investigate the relationship between the toxicity of selenium and the glutathione peroxidase activity. Selenium resistant strains SeIV and SeVI were synchronized and grown in high concentrations of Se (selenite or selenate). As a measure of selenium toxicity the EC50 values were determined. During growth of the untreated wild type, glutathione peroxidase activity increased slightly and then declined gradually until the end of the cell cycle. A similar pattern was observed in untreated resistant strains and when resistant strains were grown...
The objective of this work was to combine asymmetric somatic hybridization (donor-recipient fusion or gamma fusion) to microprotoplast-mediated chromosome transfer, as a tool to be used for chromosome mapping in Citrus. Swinglea glutinosa micro protoplasts were irradiated either with 50, 70, 100 or 200 gamma rays and fused to cv. Ruby Red grapefruit or Murcott tangor protoplasts. Cell colonies were successfully formed and AFLP analyses confirmed presence of S. glutinosa in both 'Murcott' tangor and 'Ruby Red' grapefruit genomes. (author)
Five arylethylenes with 1-naphthyl, 2-naphthyl, and phenyl groups in 1,2-positions have been studied for singlet-mediated charge-transfer interactions with several amines and paraquat dication. 1-Phenyl-2-(2-naphthyl)ethylene and 1,2-di(2-naphthyl)ethylene exhibit distinct dependence of exciplex emission maxima and lifetimes, and fluorescence quenching constants, on excitation and/or monitoring wavelengths; this is in conformity with the existence of ground-state rotamers for these systems, wtih distinguishable absorption-emission spectra and fluorescence lifetimes. The fluorescence quenching by aromatic amines and paraquat dication occurs with rate constants in the limit of diffusion control and is accompanied by the formation of radical ions in polar solvents (acetonitrile). The transient spectra and kinetics associated with the radical ions, observed by 337.1- and 355-nm laser flash photolysis, are also reported. 10 figures, 4 tables.
Three in vivo assays were used to measure the immunocompetence of chickens in two generations of a selection experiment. The obtained data were used to estimate the variance components for sire and dam for antibody production to Pasteurella multocida and Mycoplasma gallisepticum vaccines, for T-cell-mediated immunity evaluated by a phytohemagglutinin wing web assay, and for clearance of foreign particles from the circulatory system. Heritabilities of and genetic correlations among these immunological traits were calculated from the sire variance components. Heritability estimates of the immunological traits based on the sire component of variance ranged from .06 to .53, and genetic correlations among immunological traits were generally negative. PMID:1956847
New nanofibers containing poly(vinyl pyrrolidone)-iodine complex (PVP-iodine) were obtained by electrospinning in order to prepare materials suitable for wound dressings. Different approaches were used: a one-step method based on electrospinning of PVP-iodine or poly(ethylene oxide)/PVP-iodine solutions and a three-step method based on electrospinning of PVP or poly(ethylene oxide)/PVP mixed solutions followed by photo-mediated crosslinking of the obtained nanofibers and subsequent complexation with iodine. The average diameters of the fibers were in the range 150-470nm depending on the composition and on the applied field strength (AFS) and increased with increasing the amount of PEO in the spinning solutions. Higher AFS resulted in greater fiber diameter and in size distribution broadeni...
One proposed solution to the problem of ballast-mediated aquatic invasions involves chemically treating ballast water to kill key target organisms. Here, we examine the efficacy of three commercially available ballast water biocides using vegetative microalgae, dinoflagellate resting cysts and bacteria as test organisms. Chemicals tested were the ballast water biocides SeaKleen and Peraclean Ocean, and the chlorine dioxide biocide Vibrex. Results demonstrate that the applicability of each of the three chemical biocides as a routine ballast water treatment is limited by factors such as cost, biological effectiveness and possible residual toxicity of the discharged ballast water (assessed on the basis of impact on motility of vegetative marine microalgae). Of the three biocides tested, Perac...
Purpose - Based upon the E-VALUE model developed, this paper aims to investigate the impact of e-commerce usage on business performance in the tourism sector. Design/methodology/approach - A cross-sectional survey is carried out on 165 Malaysian firms involved in the tourism sector (hotels, resorts, and hospitals engaged in health tourism) through the use of a structured questionnaire. Findings - The structural equation modeling results indicate that technology competency, firm size, firm scope, web-technology investment, pressure intensity, and back-end usage have significant influence on e-commerce usage. Among these variables, back-end integration is found to function as a mediator. E-commerce experience (in years) is found to moderate the relationship between e-commerce usage and busin...
We investigate the effect of the intrinsic spin of a fundamental spinor field on the surrounding spacetime geometry. We show that despite the lack of a rotating stress-energy source (and despite claims to the contrary) the intrinsic spin of a spin-half fermion gives rise to a frame-dragging effect analogous to that of orbital angular momentum, even in Einstein-Hilbert gravity where torsion is constrained to be zero. This resolves a paradox regarding the counter-force needed to restore Newton's third law in the well known spin-orbit interaction. In addition, the frame-dragging effect gives rise to a {\\it long-range} gravitationally mediated spin-spin dipole interaction coupling the {\\it internal} spins of two sources. We argue that despite the weakness of the interaction, the spin-spin interaction will dominate over the ordinary inverse square Newtonian interaction in any process of sufficiently high-energy for quantum field theoretical effects to be ...
Summary 1.-Traditional views of ecological disturbance emphasize the role that physical disturbances play in reducing competition between populations and maintaining species coexistence. I present an alternative view that employs a simple Lotka-Volterra model to demonstrate how disturbance resistance, disturbance resilience and resource storage can increase competition between individual perennial plants of similar growth form along a resource supply gradient. 2.-In contrasting the growth of individual genets of two hypothetical species, I assumed that traits associated with inherently low module (i.e. plant part) mortality in infertile soils resulted in greater resource storage, but traded off with maximum potential net photosynthesis rates and thus disturbance resilience. 3.-The species ...
Objective Multiple sclerosis (MS) and its animal counterpart experimental autoimmune encephalomyelitis (EAE) have a major inflammatory component that drives and orchestrates both diseases. One particular group of mediators are the prostaglandins (PGs), which we have previously shown, through quantitation and pharmacological intervention, to be closely involved in the pathology of MS and EAE. The aim of the current study was to determine the expression of the PG-generating cyclooxygenase (COX) enzymes and the profile of PGE2 and PGD2, in selected central nervous system (CNS) tissues, with the development of the chronic relapsing (CR) form of EAE. In particular, the work investigates the possible relationship between the expression of COX isoenzymes and PG levels during the neurological phas...
The adhesion of microorganisms onto materials surface mediated by extracellular polymeric substances (EPS) lead to an important modification of the metal-solution interface. The requirement of modern civilization with the heightened sense of environmental responsibilities and quality of life can be met by using some eco-friendly microbiocides with different spectra of activity. Some N{sub 2}O{sub 2} donor Schiff base compounds were synthesized and characterized by IR, NMR and ESR spectroscopy. These compounds were found effective in controlling the growth of biofilm of E. coli, Pseudomonas fluorescens and Thiobacillus thiooxidans on copper surface. The optimum concentration of these compounds are in the range of 1--10 ppm. Various electrochemical, microbiological and surface-analytical techniques were used to monitor the biofilm in the presence of microbiocides.
Objective Over recent years the Internet has become an increasingly popular source of support and information for infertility, with a growing number of online support groups now available to individuals affected by fertility problems. The aims of the present study were therefore to explore the online experiences of individuals accessing infertility support groups via the Internet. Methods Ninety-five participants who were recruited from several online infertility support groups completed an online questionnaire containing a series of open-ended questions. Responses to the open-ended questions were analysed using inductive thematic analysis. Results The thematic analysis revealed five recurrent themes, which were labelled: `unique features of online social support', `improved relationship w...
The talk will focus on spin-dependent competition between oblate and prolate shape minima in the potential energy landscape of "1"8"0Hf (the most neutron-rich stable isotope), mediated via the alignment of valence nucleons. Results of a prompt spectroscopic study, using deep inelastic reactions with Gammasphere and CHICO, bombarding a thin "2"3"2Th target with a "1"8"0Hf beam #approx#25% above the Coulomb barrier, will be presented. Nucleon alignments in both prolate and oblate minima will be discussed, as well as the favoring of oblate collective rotation at high spins, observed through a mixing with gamma vibrations built on the prolate shape.
Transgenic plants offer advantages for biomolecule production because plants can be grown on a large scale and the recombinant macromolecules can be easily harvested and extracted. We introduced an Aspergillus phytase gene into canola (Brassica napus) (line 9412 with low erucic acid and low glucosinolates) by Agrobacterium-mediated transformation. Phytase expression in transgenic plant was enhanced with a synthetic phytase gene according to the Brassica codon usage and an endoplasmic reticulum (ER) retention signal KDEL that confers an ER accumulation of the recombinant phytase. Secretion of the phytase to the extracellular fluid was also established by the use of the tobacco PR-S signal peptide. Phytase accumulation in mature seed accounted for 2.6% of the total soluble proteins. The enzy...
It is uncertain if downregulation of ?-adrenoceptor signaling pathway is promoted by an enhanced adrenergic tone at an early stage of cardiac disease, or it develops secondary to detrimental local myocardial changes in advanced heart failure. We examined the integrity of ?-adrenoceptor signaling pathway upon chronic infusion of isoproterenol, a ?-adrenoceptor agonist, at a dose producing no structural left ventricular (LV) remodeling and systolic dysfunction. Subcutaneous isoproterenol infusion (400??g?kg?1?h?1 over 16?days) to guinea pigs using osmotic minipumps produced no change in cardiac weights, LV internal dimensions, myocyte cross-sectional area, extent of interstitial fibrosis, and basal contractile function. Isolated, perfused heart preparations from isoproterenol-treated guinea ...
Colorectal cancer is the second most common cause of cancer death in the world and about half of the patients with colorectal cancer require adjuvant therapy after surgical resection. Therefore, the eradication of cancer cells via chemotherapy constitutes a viable approach to treating patients with colorectal cancer. In this study, the effects of bufalin isolated from a traditional Chinese medicine were evaluated and characterized in HT-29 and Caco-2 human colon cancer cells. Contrary to its well-documented apoptosis-promoting activity in other cancer cells, bufalin did not cause caspase-dependent cell death in colon cancer cells, as indicated by the absence of significant early apoptosis as well as poly(ADP-ribose) polymerase and caspase-3 cleavage. Instead, bufalin activated an autophagy...
Potential of spent biomass of a cyanobacterium, Nostoc linckia HA 46, from a hydrogen bioreactor was studied for biosorption of a textile dye, reactive red 198. The waste biomass was immobilized in calcium alginate and used for biosorption of the dye from aqueous solution using response surface methodology (RSM). Kinetics of the dye in aqueous solution was studied in batch mode. Interactive effects of initial dye concentration (100-500mg/L), pH (2-6) and temperature (25-45^oC) on dye removal were examined using Box-Behnken design. Maximum adsorption capacity of the immobilized biomass was 93.5mg/g at pH 2.0, initial concentration of 100mg/L and 35^oC temperature, when 94% of the dye was removed. Fourier transform infrared (FT-IR) studies revealed that biosorption was mainly mediated by fun...
Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency that affects premature newborns. This disease often has a rapid onset with few, if any, antecedent signs that can be used to reliably predict its occurrence. Its rapid onset and progression to death, as well as its severe morbidity when the infant survives, begs for early diagnostic tools that may be used in determining those infants who would be at greatest risk for development of the disease and for whom early preventative measures could be targeted. Although studies have suggested efficacy of several techniques such as breath hydrogen, inflammatory mediators in blood, urine or stool, and genetic markers, these all have drawbacks limiting their use. The application of newly developed "omic" approaches may provide biomarkers for early diagnosis and targeted prevention of this disease. PMID:19190533
Gold nanoparticles were synthesized by using banana peel extract (BPE) as a simple, non-toxic, eco-friendly 'green material'. The boiled, crushed, acetone precipitated, air-dried peel powder was used to reduce chloroauric acid. A variety of nanoparticles were formed when the reaction conditions were altered with respect to pH, BPE content, chloroauric acid concentration and temperature of incubation. The reaction mixtures displayed vivid colors and UV-vis spectra characteristic of gold nanoparticles. Dynamic light scattering (DLS) studies revealed that the average size of the nanoparticles under standard synthetic conditions was around 300nm. Scanning electron microscopy and energy dispersive spectrometry (EDS) confirmed these results. A coffee ring phenomenon, led to the aggregation of th...
Bio-inspired silver nanoparticles were synthesized with the aid of a novel, non-toxic, eco-friendly biological material namely, banana peel extract (BPE). Boiled, crushed, acetone precipitated, air-dried peel powder was used for reducing silver nitrate. Silver nanoparticles were formed when the reaction conditions were altered with respect to pH, BPE content, concentration of silver nitrate and incubation temperature. The colorless reaction mixtures turned brown and displayed UV-visible spectra characteristic of silver nanoparticles. Scanning electron microscope (SEM) observations revealed the predominance of silver nanosized crystallites after short incubation periods. When the reaction mixtures were incubated for 15 days, some micro-aggregates were also observed. Energy dispersive spectr...
Bio-inspired palladium nanoparticles were synthesized by using banana peel extract (BPE), a non-toxic eco-friendly material. Boiled, crushed, acetone precipitated, air-dried peel powder was used to reduce palladium chloride. The palladium nanoparticles were characterized by using UV-Visible spectroscopy, scanning electron microscope-energy dispersive spectra (SEM-EDS) and X-ray diffraction (XRD) analysis. Dynamic light scattering (DLS) studies revealed the average size of nanoparticles to be 50nm. Fourier transform infra red spectroscopy (FTIR) implicated the role of carboxyl, amine and hydroxyl groups in the synthetic process. This paper thus describes a novel green method for the synthesis of palladium nanoparticles.
Coral populations have precipitously declined on Caribbean reefs while algal abundance has increased, leading to enhanced competitive damage to corals, which likely is mediated by the potent allelochemicals produced by both macroalgae and benthic cyanobacteria. Allelochemicals may affect the composition and abundance of coral-associated microorganisms that control host responses and adaptations to environmental change, including susceptibility to bacterial diseases. Here, we demonstrate that extracts of six Caribbean macroalgae and two benthic cyanobacteria have both inhibitory and stimulatory effects on bacterial taxa cultured from the surfaces of Caribbean corals, macroalgae, and corals exposed to macroalgal extracts. The growth of 54 bacterial isolates was monitored in the presence of l...
Ab initio lattice dynamics based on linear response method are performed for high pressure phase of yttrium to describe electron-phonon coupling and subsequent superconducting behavior. The critical temperature Tc in fcc-Y increases monotonically with pressure up to 9.25 K at 31 GPa, which is quantitatively in excellent agreement with two quasihydrostatic experiments and is qualitatively compatible with recent experiments. The excellent agreement with experiments gives us a better understanding of the effective pseudopotential ?* as well as spectral function ?2(?)F(?) in yttrium. These results demonstrate that there exists strong electron-phonon coupling in Y within the studied pressure regime, and for lower pressure electron correlation becomes stronger. Generally, it is found that superconductivity in yttrium under pressure can be described quantitatively within standard theory of phonon-mediated superconductivity.
Abstract Gelatinization temperature (GT) is an important parameter in evaluating the cooking and eating quality of rice. Indeed, the phenotype, biochemistry and inheritance of GT have been widely studied in recent times. Previous map-based cloning revealed that GT was controlled by ALK gene, which encodes a putative soluble starch synthase II-3. Complementation vector and RNAi vector were constructed and transformed into Nipponbare mediated by Agrobacterium. Phenotypic and molecular analyses of transgenic lines provided direct evidence for ALK as a key gene for GT. Meanwhile, amylose content, gel consistency and pasting properties were also affected in transgenic lines. Two of four nonsynonymous single nucleotide polymorphisms in coding sequence of ALK were identified as essential for GT. ...
It has been shown by recent experiments that bulk immiscible metals (e.g. Ag/Cu, Ag/Co and Au/Ni) can form binary alloys on certain surfaces where the substrate mediates the elastic misfits between the two components, thus relieving the elastic strain in the overlayer. These novel surface alloys exhibit a rich phase structure. We formulate a two-component Frenkel-Kontorova model in one dimension to study surface alloy formation. This model can naturally incorporate dislocation formation that plays a crucial role in determining the actual structure of the system. Using energy minimization calculations we provide a phase diagram in terms of average alloy composition and the energy of mixing. Monte Carlo simulations were also performed to study the structure and interaction of the emerging dislocations.
Abstract Despite the fact that oxidation is the second most frequent degradation pathway for pharmaceuticals, means of evaluating the oxidative stability of pharmaceutical solids, especially effective stress testing, are still lacking. This paper describes a novel experimental method for peroxide-mediated oxidative stress testing on pharmaceutical solids. The method utilizes urea-hydrogen peroxide, a molecular complex that undergoes solid-state decomposition and releases hydrogen peroxide vapor at elevated temperatures (e.g., 30C), as a source of peroxide. The experimental setting for this method is simple, convenient, and can be operated routinely in most laboratories. The fundamental parameter of the system, that is, hydrogen peroxide vapor pressure, was determined using a modified spect...
A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling reaction. Most of these compounds were found to exhibit excellent activity against the colon cancer cell lines HT-29 and Caco-2, whilst not showing significant toxicity against white blood cells. Our studies have shown that the proteolytic phase of apoptosis was initiated 2 h after treatment with these imidazo-[1,2-a]pyridines. The data suggests that the imidazo[1,2-a]pyridine-induced cell death in HT-29 and Caco-2 cells is mediated via pathway(s) that include the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase 3 and caspase 8.