Showing papers by "University of Louisville published in 2001"
4,461 citations
National Institute of Advanced Industrial Science and Technology1, University of Bari2, Air Products & Chemicals3, University of Delaware4, University of Pittsburgh5, University of California, Berkeley6, California Institute of Technology7, Brookhaven National Laboratory8, Karlsruhe Institute of Technology9, Environmental Molecular Sciences Laboratory10, Tokyo Institute of Technology11, National Renewable Energy Laboratory12, Los Alamos National Laboratory13, University of Louisville14, Texas A&M University15, Sandia National Laboratories16, Northwestern University17, DuPont18, Emory University19, University of Oklahoma20, University of Southern California21, University of Minnesota22, Pennsylvania State University23, Idaho National Laboratory24
TL;DR: The goal of the "Opportunities for Catalysis Research in Carbon Management" workshop was to review within the context of greenhouse gas/carbon issues the current state of knowledge, barriers to further scientific and technological progress, and basic scientific research needs in the areas of H2 generation and utilization.
Abstract: There is increased recognition by the world’s scientific, industrial, and political communities that the concentrations of greenhouse gases in the earth’s
atmosphere, particularly CO_2, are increasing. For
example, recent studies of Antarctic ice cores to
depths of over 3600 m, spanning over 420 000 years,
indicate an 80 ppm increase in atmospheric CO_2 in
the past 200 years (with most of this increase
occurring in the past 50 years) compared to the
previous 80 ppm increase that required 10 000 years.2
The 160 nation Framework Convention for Climate
Change (FCCC) in Kyoto focused world attention on
possible links between CO2 and future climate change
and active discussion of these issues continues.3 In
the United States, the PCAST report4 “Federal
Energy Research and Development for the Challenges
of the Twenty First Century” focused attention
on the growing worldwide demand for energy and the
need to move away from current fossil fuel utilization.
According to the U.S. DOE Energy Information
Administration,5 carbon emission from the transportation
(air, ground, sea), industrial (heavy manufacturing,
agriculture, construction, mining, chemicals,
petroleum), buildings (internal heating, cooling, lighting),
and electrical (power generation) sectors of the
World economy amounted to ca. 1823 million metric
tons (MMT) in 1990, with an estimated increase to
2466 MMT in 2008-2012 (Table 1).
1,220 citations
TL;DR: Review of data from the own laboratory and those in the literature indicate that ERalpha binding affinity does not relate linearly with E(2)-induced transcriptional activation, and it is suggested that the reasons for this discord include cellular amounts of coactivators and adaptor proteins that play roles both in ER binding and transcriptionalactivation; phosphorylation of ER and other proteins involved in transcriptional activated; and sequence-specific and protein-induced alterations in chromatin architecture.
Abstract: The estrogen receptor (ER) is a ligand-activated enhancer protein that is a member of the steroid/nuclear receptor superfamily. Two genes encode mammalian ER: ERα and ERβ. ER binds to specific DNA sequences called estrogen response elements (EREs) with high affinity and transactivates gene expression in response to estradiol (E2). The purpose of this review is to summarize how natural and synthetic variations in the ERE sequence impact the affinity of ER–ERE binding and E2-induced transcriptional activity. Surprisingly, although the consensus ERE sequence was delineated in 1989, there are only seven natural EREs for which both ERα binding affinity and transcriptional activation have been examined. Even less information is available regarding how variations in ERE sequence impact ERβ binding and transcriptional activity. Review of data from our own laboratory and those in the literature indicate that ERα binding affinity does not relate linearly with E2-induced transcriptional activation. We suggest that the reasons for this discord include cellular amounts of coactivators and adaptor proteins that play roles both in ER binding and transcriptional activation; phosphorylation of ER and other proteins involved in transcriptional activation; and sequence-specific and protein-induced alterations in chromatin architecture.
1,010 citations
TL;DR: The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned.
Abstract: Background The conventional treatment strategy for patients with atrial fibrillation who are to undergo electrical cardioversion is to prescribe warfarin for anticoagulation for three weeks before cardioversion. It has been proposed that if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy. Methods In a multicenter, randomized, prospective clinical trial, we enrolled 1222 patients with atrial fibrillation of more than two days' duration and assigned them to either treatment guided by the findings on transesophageal echocardiography or conventional treatment. The composite primary end point was cerebrovascular accident, transient ischemic attack, and peripheral embolism within eight weeks. Secondary end points were functional status, successful restoration and maintenance of sinus rhythm, hemorrhage, and death. Results There was no significant difference between the two treatment groups in the rate of emboli...
827 citations
TL;DR: In this paper, the empirical findings from a survey of US firms with greater environmental risks are reported, which aims to identify variables that either promote or inhibit the successful implementation of green purchasing and to evaluate the effects of green buying on the firm's supplier selection, waste management, packaging, and regulatory compliance.
Abstract: Over the last two decades, growing concerns about eroding ecosystem quality have led to a renewed interest in environmentalism. Such concerns have prompted purchasing professionals to reassess their current purchasing strategy. To help purchasing professionals configure an environmentally conscious (green) purchasing strategy, the empirical findings from a survey of US firms with greater environmental risks are reported. Based on the empirical findings, aims to identify variables that either promote or inhibit the successful implementation of green purchasing and to evaluate the effects of green purchasing on the firm’s supplier selection, waste management, packaging, and regulatory compliance.
699 citations
653 citations
TL;DR: Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.
Abstract: The adipocyte fatty-acid-binding protein, aP2, has an important role in regulating systemic insulin resistance and lipid metabolism. Here we demonstrate that aP2 is also expressed in macrophages, has a significant role in their biological responses and contributes to the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed protection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe-/- mice with Ap2+/+ adipocytes and Ap2-/- macrophages generated by bone-marrow transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.
638 citations
TL;DR: The NO hypothesis of late PC has revealed a cytoprotective function of iNOS in the heart, a novel paradigm which has recently been extended to other tissues, including kidney and intestine.
603 citations
TL;DR: The combination of anesthetic-induced impairment of thermoregulatory control and exposure to a cool operating room environment makes most surgical patients hypothermic.
Abstract: THE combination of anesthetic-induced impairment of thermoregulatory control and exposure to a cool operating room environment makes most surgical patients hypothermic. Several prospective, randomized trials have demonstrated various hypothermia-induced complications. There is no widely accepted definition for the term mild hypothermia. Furthermore, the term is not even used consistently in the literature. For the purpose of this review, mild hypothermia refers to core temperatures between 34 and 36°C.
575 citations
TL;DR: It is demonstrated that two related PKC isozymes have both parallel and opposing effects in the heart, indicating the danger in the use of therapeutics with nonselective isozyme inhibitors and activators.
Abstract: Conflicting roles for protein kinase C (PKC) isozymes in cardiac disease have been reported. Here, deltaPKC-selective activator and inhibitor peptides were designed rationally, based on molecular modeling and structural homology analyses. Together with previously identified activator and inhibitor peptides of epsilonPKC, deltaPKC peptides were used to identify cardiac functions of these isozymes. In isolated cardiomyocytes, perfused hearts, and transgenic mice, deltaPKC and epsilonPKC had opposing actions on protection from ischemia-induced damage. Specifically, activation of epsilonPKC caused cardioprotection whereas activation of deltaPKC increased damage induced by ischemia in vitro and in vivo. In contrast, deltaPKC and epsilonPKC caused identical nonpathological cardiac hypertrophy; activation of either isozyme caused nonpathological hypertrophy of the heart. These results demonstrate that two related PKC isozymes have both parallel and opposing effects in the heart, indicating the danger in the use of therapeutics with nonselective isozyme inhibitors and activators. Moreover, reduction in cardiac damage caused by ischemia by perfusion of selective regulator peptides of PKC through the coronary arteries constitutes a major step toward developing a therapeutic agent for acute cardiac ischemia.
533 citations
TL;DR: It is concluded that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions and may underlie components of the learning and memory impairments found in OSA.
Abstract: The role played by chronic episodic hypoxia (EHYP) in the neurocognitive morbidity of obstructive sleep apnea (OSA) is unknown. Sleep recordings, Morris water maze experiments, and immunohistochemistry for NMDA NR1 glutamate receptor, c-fos protein, and apoptosis [nuclear immunoreactivity for single-stranded DNA and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay] were conducted in EHYP-exposed Sprague Dawley male rats. Exposures consisted of up to14 d in an environmental chamber in which O(2) concentrations were cycled between 10 and 21% every 90 sec or 30 min during 12 hr of daylight. For the remaining 12 hr, EHYP rats breathed room air, while controls spent 14 d in room air. Although EHYP induced significant disruption of sleep architecture during the initial day of exposure, sleep patterns normalized thereafter. Marked increases in apoptosis occurred in the CA1 hippocampal region (sevenfold) and cortex (Cx; eightfold) after 1-2 d of EHYP but not in CA3 and were followed by decreases toward normoxic levels by 14 d. Double labeling for NMDA NR1 and c-fos revealed marked architectural disorganization in CA1 and Cx with increases in c-fos over time. Rats exposed to EHYP displayed significantly longer escape latencies and swim path lengths to escape a hidden platform during 12 training trials given over 2 d. Differences in the performances of EHYP and control rats, although reduced, persisted after 14 d of recovery. We conclude that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions. Furthermore, EHYP impaired performance during acquisition of a cognitive spatial task without affecting sensorimotor function. Such changes may underlie components of the learning and memory impairments found in OSA.
TL;DR: It is suggested that in vitro induction prior to transplantation will be necessary for these cells to differentiate into neurons or large numbers of oligodendrocytes, but a differentiated phenotype restricted to glial lineages is suggested.
TL;DR: Two units of quantum conductance 2G(0) = 4e(2)/h are measured for the first time, corresponding to the maximum conductance limit for ballistic transport in two channels of a nanotube.
Abstract: The electron transport properties of well-contacted individual single-walled carbon nanotubes are investigated in the ballistic regime. Phase coherent transport and electron interference manifest as conductance fluctuations as a function of Fermi energy. Resonance with standing waves in finite-length tubes and localized states due to imperfections are observed for various Fermi energies. Two units of quantum conductance ${2G}_{0}{\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}4e}^{2}/h$ are measured for the first time, corresponding to the maximum conductance limit for ballistic transport in two channels of a nanotube.
TL;DR: Constructivist theorists view norms as shared understandings that reflect ''legitimate social purpose'' as discussed by the authors, and the focus is on the ideational building blocks that undergird a community's shared und...
Abstract: Constructivist theorists view norms as shared understandings that reflect `legitimate social purpose'. Because the focus is on the ideational building blocks that undergird a community's shared und...
TL;DR: The heterotrimeric G protein G(s) couples hormone receptors (as well as other receptors) to the effector enzyme adenylyl cyclase and is therefore required for hormone-stimulated intracellular cAMP generation and is shown to be also imprinted in human pituitary glands.
Abstract: The heterotrimeric G protein Gs couples hormone receptors (as well as other receptors) to the effector enzyme adenylyl cyclase and is therefore required for hormone-stimulated intracellular cAMP generation Receptors activate Gs by promoting exchange of GTP for GDP on the Gs α-subunit (Gsα) while an intrinsic GTPase activity of Gsα that hydrolyzes bound GTP to GDP leads to deactivation Mutations of specific Gsα residues (Arg201 or Gln227) that are critical for the GTPase reaction lead to constitutive activation of Gs-coupled signaling pathways, and such somatic mutations are found in endocrine tumors, fibrous dysplasia of bone, and the McCune-Albright syndrome Conversely, heterozygous loss-of-function mutations may lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, brachydactyly, sc ossifications, and mental deficits Similar mutations are also associated with progressive osseous heteroplasia Interestingly, paternal transmission of GNAS1 mutations leads
TL;DR: Children with lower academic performance in middle school are more likely to have snored during early childhood and to require T&A for snoring compared with better performing schoolmates, and the concept that SDB-associated neurocognitive morbidity may be only partially reversible or that a "learning debt" may develop with SDB during early Childhood and hamper subsequent school performance is supported.
Abstract: Objectives. Obstructive sleep apnea syndrome in young children is associated with an adverse effect on learning. However, the long-term impact of sleep-disordered breathing (SDB) during early childhood on learning remains unknown. Methods. Questionnaires were mailed to seventh and eighth graders attending public schools whose class ranking was either in the top 25% (high performance [HP]) or bottom 25% of their class (low performance [LP]), and who were matched for age, gender, race, school, and street of residence. Snoring frequency and loudness at 2 to 6 years of age, tonsillectomy and adenoidectomy (T&A) for snoring or recurrent infection, school grades, and parental smoking and snoring were assessed. Results. The questionnaire response rate was 82.8%. Because of ongoing snoring, 13 responders were excluded, such that 1588 questionnaires could be analyzed (797 in LP and 791 in HP group). Frequent and loud snoring during early childhood was reported in 103 LP children (12.9%) compared with 40 HP children (5.1%; odds ratio: 2.79; confidence interval: 1.88–4.15). Furthermore, 24 LP and 7 HP children underwent TA confidence interval: 1.47–7.84), while 21 LP and 19 HP children required surgery for recurrent tonsillitis. Conclusions. Children with lower academic performance in middle school are more likely to have snored during early childhood and to require T&A for snoring compared with better performing schoolmates. These findings support the concept that SDB-associated neurocognitive morbidity may be only partially reversible or that a “learning debt” may develop with SDB during early childhood and hamper subsequent school performance.
TL;DR: Estradiol and progesterone replacement therapy in females and testosterone replacement in males, to determine whether phenotype and biochemical changes were a consequence of decreased gonadal steroid levels or due to a loss of LH signaling, revealed complete restoration of some and partial restoration of others, Nevertheless, the animals remained infertile.
Abstract: LH/hCG receptors were disrupted by gene targeting in embryonic stem cells. The disruption resulted in infertility in both sexes. The gonads contained no receptor mRNA or receptor protein. Serum LH levels were greatly elevated, and FSH levels were moderately elevated in both sexes; estradiol and progesterone levels decreased but were not totally suppressed in females; testosterone levels were dramatically decreased and estradiol levels moderately elevated in males. The external and internal genitalia were grossly underdeveloped in both sexes. Abnormalities included ambiguous vaginal opening, abdominal testes, micropenis, dramatically decreased weights of the gonads and reproductive tract, arrested follicular growth beyond antral stage, disarray of seminiferous tubules, diminished number and hypotrophy of Leydig cells, and spermatogenic arrest beyond the round spermatid stage. LH/hCG receptor gene disruption had no effect on FSH receptor mRNA levels in ovaries and testes, progesterone receptor (PR) levels in ovaries and androgen receptor (AR) levels in testes. However, it caused a dramatic decrease in StAR and estrogen receptor-alpha (ERalpha) mRNA levels and an increase in ERbeta mRNA levels in both ovaries and testes. Estradiol and progesterone replacement therapy in females and testosterone replacement in males, to determine whether phenotype and biochemical changes were a consequence of decreased gonadal steroid levels or due to a loss of LH signaling, revealed complete restoration of some and partial restoration of others. Nevertheless, the animals remained infertile. It is anticipated that the LH receptor knockout animals will increase our current understanding of gonadal and nongonadal actions of LH and hCG.
University of Toronto1, Abbott Laboratories2, Children's Mercy Hospital3, University of Louisville4, University of Chile5, Oregon Health & Science University6, MetroHealth7, City University of New York8, Cornell University9, University of Nottingham10, University of Arkansas for Medical Sciences11, Yeshiva University12
TL;DR: These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months' CA.
Abstract: Objectives. A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4n6), and docosahexaenoic acid (DHA; 22:6n3) on growth, visual acuity, and multiple indices of development. Methods. Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months9 CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. Results. Visual acuity measured by acuity cards at 2, 4, and 6 months9 CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] ± standard error [SE; octaves] 11.4 ± 0.1) and AA+DHA (egg-TG/fish; 12.5 ± 0.1) than control (8.4 ± 0.1) and closer to that of the EHM-T group (16.0 ± 0.2) at 6 months9 CA. Visual acuity improved from 4 to 6 months9 CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means ± SE, 59.4 ± 7.7) than AA+DHA (fish/fungal; 57.0 ± 7.5) and control (57.5 ± 7.4) at 6 months9 CA, but not at 9 months9 CA. There were no differences in the Bayley Mental Development Index at 12 months9 CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means ± SE, 90.6 ± 4.4) than control (81.8 ± 4.3) for infants ≤1250 g. When Spanish-speaking infants and twins were excluded from the analyses, the MacArthur Communicative Development Inventory revealed that control infants (LS means ± SE, 94.1 ± 2.9) had lower vocabulary comprehension at 14 months9 CA than AA+DHA (fish/fungal) infants (100.6 ± 2.9) or AA+DHA (egg-TG/fish) infants (102.2 ± 2.8). There were no consistent differences in weight, length, head circumference, or anthropometric gains. Conclusion. These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months9 CA.
TL;DR: This work provides support for the hypothesis that the visual system uses the angular declination below the horizon for distance judgement, and shows that the distance overestimation as an after-effect of prism adaptation was due to a lowered perceived eye level, which reduced the object's angular Declinationbelow the horizon.
Abstract: A biological system is often more efficient when it takes advantage of the regularities in its environment1,2. Like other terrestrial creatures, our spatial sense relies on the regularities associated with the ground surface2,3,4,5,6. A simple, but important, ecological fact is that the field of view of the ground surface extends upwards from near (feet) to infinity (horizon)2. It forms the basis of a trigonometric relationship wherein the further an object on the ground is, the higher in the field of view it looks, with an object at infinity being seen at the horizon. Here, we provide support for the hypothesis that the visual system uses the angular declination below the horizon for distance judgement. Using a visually directed action task7,8,9,10, we found that when the angular declination was increased by binocularly viewing through base-up prisms, the observer underestimated distance. After adapting to the same prisms, however, the observer overestimated distance on prism removal. Most significantly, we show that the distance overestimation as an after-effect of prism adaptation was due to a lowered perceived eye level, which reduced the object's angular declination below the horizon.
TL;DR: Five additional patients with FVS and autism are presented and there was evidence of cognitive deficits, manifestations of autism, and typical phenotypic characteristics of FVS.
Abstract: Autism has been described in association with a variety of medical and genetic conditions. We previously reported on a patient whose clinical phenotype was compatible with both fetal valproate syndrome (FVS) and autism. Here we present five additional patients with FVS and autism. In all five of our patients, there was evidence of cognitive deficits, manifestations of autism, and typical phenotypic characteristics of FVS. The association between this known teratogen and autism has both clinical and research implications.
TL;DR: It appears that adrenergic and renin-angiotensin system overactivity contributes to the early chronic elevated blood pressure in rat intermittent hypoxia and perhaps to human hypertension associated with obstructive sleep apnea.
Abstract: One of the major manifestations of obstructive sleep apnea is profound and repeated hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn increases sympathetic outflow, acutely increasing blood pressure. The chronic effect of these repeated episodic or intermittent periods of hypoxia in humans is difficult to study because chronic cardiovascular changes may take many years to manifest. Rodents have been a tremendous source of information in short- and long-term studies of hypertension and other cardiovascular diseases. Recurrent short cycles of normoxia-hypoxia, when administered to rats for 35 days, allows examination of the chronic cardiovascular response to intermittent hypoxia patterned after the episodic desaturation seen in humans with sleep apnea. The result of this type of intermittent hypoxia in rats is a 10- to 14-mmHg increase in resting (unstimulated) mean blood pressure that lasts for several weeks after cessation of the daily cyclic hypoxia. Carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and angiotensin II receptor blockade block the blood pressure increase. It appears that adrenergic and renin-angiotensin system overactivity contributes to the early chronic elevated blood pressure in rat intermittent hypoxia and perhaps to human hypertension associated with obstructive sleep apnea.
TL;DR: The results strongly suggest that Nkx2.2 regulates the differentiation and/or maturation, but not the initial specification, of oligodendrocyte progenitors, and that overproduction of Nk X.2 protein in fibroblast cells can induce gene expression from the proteolipid protein promoter.
Abstract: Oligodendrocytes are derived from glial precursors that arise from the ventral neural tube early in development. In the developing chicken CNS, oligodendrocyte progenitors selectively express Nkx2.2 homeodomain transcription factor, raising the possibility that Nkx2.2 may directly regulate oligogliogenesis. In this study, we have examined Nkx2.2 expression in rodent glial precursors and studied the effect of a loss of Nkx2.2 on oligodendrocyte and astrocyte differentiation. We show that Nkx2.2 is also expressed in mammalian oligodendrocyte progenitors and that the differentiation of MBP-positive and PLP-DM20-positive oligodendrocytes is dramatically retarded in Nkx2.2-null mutants along the entire rostrocaudal axis. In contrast, no effect is seen on astrocytic differentiation. Interestingly, absence of Nkx2.2 expression leads to a ventral expansion of the Olig1/Olig2 expression in neuroepithelial cells into the Nkx2.2 domain and a consequent increase in the production of Olig1/Olig2-positive and platelet-derived growth factor receptor alpha-positive oligodendrocyte progenitors. These results strongly suggest that Nkx2.2 regulates the differentiation and/or maturation, but not the initial specification, of oligodendrocyte progenitors. Consistent with this suggestion, overproduction of Nkx2.2 protein in fibroblast cells can induce gene expression from the proteolipid protein promoter.
Journal Article•
TL;DR: Green tea polyphenols are an effective inhibitor of IKK activity, which may explain, at least in part, some of the reported anti-inflammatory and anticancer effects of green tea.
Abstract: The IκB kinase complex (IKK) mediates activation of the transcription factor nuclear factor-κB (NF-κB). We previously showed that green tea polyphenols inhibited endotoxin-mediated tumor necrosis factor-α (TNFα) production by blocking NF-κB activation. In this study, we evaluated whether green tea polyphenols inhibit NF-κB by blocking IKK activity. We assessed IKK activity by detecting changes in phosphorylation of an IκBα-glutathioneS-transferase (GST) fusion protein. IEC-6 cells pretreated with an extract of green tea polyphenols (GrTPs; 0–0.4 mg/ml) had diminished TNFα-induced IKK and NF-κB activity. Of the various GrTPs, (−)-epigallocatechin-3-gallate (EGCG) was the most potent inhibitor. We next examined whether EGCG inhibited activated IKK. In cytosolic extracts of TNFα-stimulated cells, EGCG inhibited phosphorylation of IκBα-GST (IC50 > 18 μM) consistent with inhibition of IKK activity. Using other polyphenols, we showed that the gallate group was essential for inhibition, and antioxidants were ineffective in blocking activated IKK. Importantly, EGCG decreased IKK activity in cytosolic extracts of NIK transiently transfected cells. This latter finding showed that our findings were not related to nonspecific kinase activity. In conclusion, EGCG is an effective inhibitor of IKK activity. This may explain, at least in part, some of the reported anti-inflammatory and anticancer effects of green tea.
TL;DR: It is shown that serum and the serum lipid, lysophosphatidic acid (LPA), increased Cdc42 GTP levels and triggeredMTOC reorientation in serum-starved wounded monolayers of 3T3 fibroblasts, establishing an LPA/Cdc42 signaling pathway that regulates MTOC re orientation in a dynein-dependent manner.
TL;DR: A comprehensive understanding of the mechanisms of diabetic cardiomyopathy is urgently needed to develop approaches for the prevention and treatment of diabetic cardiac complications and advances in the application of various strategies for targeting the prevention of hyperglycemia-induced oxidative myocardial injury may be fruitful.
Abstract: Diabetes is a serious public health problem. Improvements in the treatment of noncardiac complications from diabetes have resulted in heart disease becoming a leading cause of death in diabetic patients. Several cardiovascular pathological consequences of diabetes such as hypertension affect the heart to varying degrees. However, hyperglycemia, as an independent risk factor, directly causes cardiac damage and leads to diabetic cardiomyopathy. Diabetic cardiomyopathy can occur independent of vascular disease, although the mechanisms are largely unknown. Previous studies have paid little attention to the direct effects of hyperglycemia on cardiac myocytes, and most studies, especially in vitro, have mainly focused on the molecular mechanisms underlying pathogenic alterations in vascular smooth-muscle cells and endothelial cells. Thus, a comprehensive understanding of the mechanisms of diabetic cardiomyopathy is urgently needed to develop approaches for the prevention and treatment of diabetic cardiac complications. This review provides a survey of current understanding of diabetic cardiomyopathy. Current consensus is that hyperglycemia results in the production of reactive oxygen and nitrogen species, which leads to oxidative myocardial injury. Alterations in myocardial structure and function occur in the late stage of diabetes. These chronic alterations are believed to result from acute cardiac responses to suddenly increased glucose levels at the early stage of diabetes. Oxidative stress, induced by reactive oxygen and nitrogen species derived from hyperglycemia, causes abnormal gene expression, altered signal transduction, and the activation of pathways leading to programmed myocardial cell deaths. The resulting myocardial cell loss thus plays a critical role in the development of diabetic cardiomyopathy. Advances in the application of various strategies for targeting the prevention of hyperglycemia-induced oxidative myocardial injury may be fruitful.
TL;DR: It is demonstrated that S-nitrosothiol biochemistry is of central importance to the regulation of breathing, and plasma from deoxygenated, but not from oxygenated, blood produces the ventilatory effect of both SNOs and hypoxia.
Abstract: Increased ventilation in response to hypoxia has been appreciated for over a century1, but the biochemistry underlying this response remains poorly understood. Here we define a pathway in which increased minute ventilation (VE ) is signalled by deoxyhaemoglobin-derived S-nitrosothiols (SNOs). Specifically, we demonstrate that S-nitrosocysteinyl glycine (CGSNO) and S-nitroso-l-cysteine (l-CSNO)—but not S-nitroso-d-cysteine (d-CSNO)—reproduce the ventilatory effects of hypoxia at the level of the nucleus tractus solitarius (NTS). We show that plasma from deoxygenated, but not from oxygenated, blood produces the ventilatory effect of both SNOs and hypoxia. Further, this activity is mediated by S-nitrosoglutathione (GSNO), and GSNO activation by γ-glutamyl transpeptidase (γ-GT) is required. The normal response to hypoxia is impaired in a knockout mouse lacking γ-GT. These observations suggest that S-nitrosothiol biochemistry is of central importance to the regulation of breathing.
TL;DR: The maternal, placental, and fetal neuroendocrine, immune/inflammatory, and vascular processes that may bridge the experience of social adversity before and during pregnancy and the biological outcome of preterm birth are discussed.
Abstract: A growing literature suggests that maternal psychological and social stress is a significant and independent risk factor for a range of adverse reproductive outcomes including preterm birth. Several issues remain to be addressed about stress and vulnerability to stress during pregnancy. Of these, perhaps one of the most important questions relates to biologic plausibility. Parturition, the process that results in birth, is a biological phenomenon. Very little empirical research to date, however, has examined the role of biological processes, if any, as mediators of the relationship between stress and preterm birth. In this paper we discuss the maternal, placental, and fetal neuroendocrine, immune/inflammatory, and vascular processes that may bridge the experience of social adversity before and during pregnancy and the biological outcome of preterm birth.
TL;DR: Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization.
Abstract: Background Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function. Methods We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood–brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients — including 1 whose surgery was canceled — to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated th...
TL;DR: In this paper, the authors demonstrate a low-temperature vapor-liquid-solid synthesis method that uses liquid-metal solvents with low solubility for silicon and other elemental semiconductor materials.
Abstract: Silicon nanowires will find applications in nanoscale electronics and optoelectronics both as active and passive components. Here, we demonstrate a low-temperature vapor–liquid–solid synthesis method that uses liquid-metal solvents with low solubility for silicon and other elemental semiconductor materials. This method eliminates the usual requirement of quantum-sized droplets in order to obtain quantum-scale one-dimensional structures. Specifically, we synthesized silicon nanowires with uniform diameters distributed around 6 nm using gallium as the molten solvent, at temperatures less than 400 °C in hydrogen plasma. The potential exists for bulk synthesis of silicon nanowires at temperatures significantly lower than 400 °C. Gallium forms a eutectic with silicon near room temperature and offers a wide temperature range for bulk synthesis of nanowires. These properties are important for creating monodispersed one-dimensional structures capable of yielding sharp hetero- or homointerfaces.
TL;DR: It is demonstrated that ischemic PC induces isoform-selective activation of JAK1, JAK2, STAT1, and STAT3, and that ablation of this response impedes the up-regulation of iNOS and the concurrent acquisition of isChemic tolerance.
Abstract: The goal of this study was to determine the role of the Janus tyrosine kinase (JAK)–signal transducers and activators of transcription (STAT) pathway in the late phase of ischemic preconditioning (PC). A total of 230 mice were used. At 5 min after ischemic PC (induced with six cycles of 4-min coronary occlusion/4-min reperfusion), immunoprecipitation with anti-phosphotyrosine (anti-pTyr) antibodies followed by immunoblotting with anti-JAK antibodies revealed increased tyrosine phosphorylation of JAK1 (+257 ± 53%) and JAK2 (+238 ± 35%), indicating rapid activation of these two kinases. Similar results were obtained by immunoblotting with anti-pTyr-JAK1 and anti-pTyr-JAK2 antibodies. Western analysis with anti-pTyr-STAT antibodies demonstrated a marked increase in nuclear pTyr-STAT1 (+301 ± 61%) and pTyr-STAT3 (+253 ± 60%) 30 min after ischemic PC, which was associated with redistribution of STAT1 and STAT3 from the cytosolic to the nuclear fraction and with an increase in STAT1 and STAT3 γ-IFN activation site DNA-binding activity (+606 ± 64%), indicating activation of STAT1 and STAT3. No nuclear translocation or tyrosine phosphorylation of STAT2, STAT4, STAT5A, STAT5B, or STAT6 was observed. Pretreatment with the JAK inhibitor AG-490 20 min before the six occlusion/reperfusion cycles blocked the enhanced tyrosine phosphorylation of JAK1 and JAK2 and the increased tyrosine phosphorylation, nuclear translocation, and enhanced DNA-binding activity of STAT1 and STAT3. The same dose of AG-490 abrogated the protection against myocardial infarction and the concomitant up-regulation of inducible NO synthase (iNOS) protein and activity observed 24 h after ischemic PC. Taken together, these results demonstrate that ischemic PC induces isoform-selective activation of JAK1, JAK2, STAT1, and STAT3, and that ablation of this response impedes the up-regulation of iNOS and the concurrent acquisition of ischemic tolerance. This study demonstrates that the JAK-STAT pathway plays an essential role in the development of late PC. The results reveal a signaling mechanism that underlies the transcriptional up-regulation of the cardiac iNOS gene and the adaptation of the heart to ischemic stress.