bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systems biology investigation of the MEP/terpenoid and shikimate/phenylpropanoid pathways points to multiple levels of metabolic control in sweet basil glandular trichomes
Authors: Xie Zhengzhi , Kapteyn Jeremy , Gang David R. 
Published: February 2008

SummaryThe glandular trichome is an excellent model system for investigating plant metabolic processes and their regulation within a single cell type. We utilized a proteomics‐based approach with isolated trichomes of four different sweet basil (Ocimum basilicum L.) lines possessing very different metabolite profiles to clarify the regulation of metabolism in this single cell type. Significant differences in the distribution and accumulation of the 881 highly abundant and non‐redundant protein entries demonstrated that although the proteomes of the glandular trichomes of the four basil lines shared many similarities they were also each quite distinct. Correspondence between proteomic, expressed sequence tag, and metabolic profiling data demonstrated that differential gene expression at major metabolic branch points appears to be responsible for controlling the overall production of phenylpropanoid versus terpenoid constituents in the glandular trichomes of the different basil lines. In contrast, post‐transcriptional and post‐translational regulation of some enzymes appears to contribute significantly to the chemical diversity observed within compound classes for the different basil lines. Differential phosphorylation of enzymes in the 2‐C‐methyl‐d‐erythritol 4‐phosphate (MEP)/terpenoid and shikimate/phenylpropanoid pathways appears to play an important role in regulating metabolism in this single cell type. Additionally, precursors for different classes of terpenoids, including mono‐ and sesquiterpenoids, appear to be almost exclusively supplied by the MEP pathway, and not the mevalonate pathway, in basil glandular trichomes.
AtMKK1 mediates ABA‐induced CAT1 expression and H2O2 production via AtMPK6‐coupled signaling in Arabidopsis
Authors: Xing Yu , Jia Wensuo , Zhang Jianhua 
Published: February 2008

SummaryCatalase controls cellular H2O2 and plays important roles in the adaptation of plants to various stresses, but little is known about the signaling events that lead to the expression of CAT1 and the production of H2O2. Here we report the dependence of CAT1 expression and H2O2 production on a mitogen‐activated protein kinase (MAPK) cascade. CAT1 transcript was induced in an ABA‐dependent way and the induction was abolished in the T‐DNA insertion mutant mkk1 (SALK_015914), while AtMKK1 overexpression significantly enhanced the ABA‐induced CAT1 expression and H2O2 production. AtMPK6, another component in the MAPK cascade, was also involved: mpk6 mutant blocked and overexpressing AtMPK6 enhanced the ABA‐dependent expression of CAT1 and H2O2 production. The activity of AtMPK6 was increased by ABA in an AtMKK1‐dependent manner. These data clearly suggest an ABA‐dependent signaling pathway connecting CAT1 expression through a phosphorelay including AtMKK1 and AtMPK6. In further support of this view, mkk1 mutant reduced both the sensitivity to ABA during germination and the drought tolerance of seedlings, whereas the AtMKK1 overexpression line showed the opposite responses when compared with the wild type. The data suggest AtMKK1–AtMPK6 to be a key module in an ABA‐dependent signaling cascade causing H2O2 production and stress responses.
Evolution of bone mineral density in AIDS patients on treatment with zidovudine/lamivudine plus abacavir or lopinavir/ritonavir
Authors: Rivas P , Górgolas M , García‐Delgado R , Díaz‐Curiel M , Goyenechea A , Fernández‐Guerrero ML 
Published: February 2008

ObjectivesThe aim of the study was to determine the factors that may contribute to decreases in bone mineral density (BMD) in patients with AIDS.MethodsThis was a prospective, non‐randomized study. Dual X‐ray absorptiometry (DXA) was used to determine the BMD of the lumbar spine, femoral neck and distal radius in treatment‐naïve HIV‐infected male patients with AIDS before and after 1 year of treatment with zidovudine (ZDV)/lamivudine (3TC) plus abacavir (ABC) or lopinavir/ritonavir (LPV/r).ResultsBasal DXA was performed in 50 patients with CD4 counts <200 cells/μL and/or any AIDS‐defining condition. Thirty‐two patients completed 1 year with full adherence (17 on ABC and 15 on LPV/r) and a second DXA was then performed. At baseline, 19% had osteopenia at the lumbar spine and 19% at the femoral neck. Low body weight was related to low BMD. After 48 weeks, BMD loss was significant at the three locations. The percentage of BMD loss at the femoral neck tended to be greater in the lopinavir group (5.3 vs. 3.2%, P=0.058). The differences became significant at the lumbar spine (5.7 vs. 2.7%, P=0.044). In the multivariate analysis, the treatment with LPV/r remained associated with bone loss at the lumbar spine.ConclusionsOsteopenia is frequent in treatment‐naïve HIV‐infected men with AIDS. Bone loss is higher with LPV/r‐based regimens compared with triple nucleoside reverse transcriptase inhibitors.
Early changes in adipokine levels and baseline limb fat may predict HIV lipoatrophy over 2 years following initiation of antiretroviral therapy*
Authors: Calmy A , Carey D , Mallon PWG , Wand H , Law M , Cooper DA , Carr A ,   on behalf of the INITIO Trial International Co‐ordinating Committee,   HAMA study coordination team
Published: February 2008

BackgroundNo biological marker has been identified that predicts the development of lipodystrophy (LD). We investigated whether metabolic and body composition parameters could predict the development of LD over 2 years in adults initiating antiretroviral therapy (ART).MethodsWe used stored plasma collected at baseline and weeks 12, 24 and 48 from adults initiating combination ART. Adipocytokine, inflammatory cytokine, lipid and glycaemic parameters were measured and related to subsequent lipoatrophy (loss of limb fat mass of at least 2 kg from weeks 24 to 96 by dual‐energy X‐ray absorptiometry) and an increase in visceral adipose tissue (VAT; an increase of at least 18 cm2 from baseline to week 48 by abdominal computed tomography). Risk factors associated with limb fat loss and VAT gain were analysed by logistic regression.ResultsFifty‐four HIV‐infected, treatment‐naïve adults were included in the study: 53 (98%) of them were men, and they had a median age of 39 years [interquartile range (IQR) 34–48 years] and a median body mass index of 22.6 kg/m2 (IQR 20–24.8 kg/m2). In multivariate analysis, a higher baseline limb fat percentage, and a 1 mmol/L increase in plasma leptin levels during the first 6 months of ART, independently predicted a peripheral fat loss of ≥2 kg [odds ratio (OR) 2.58, 95% confidence interval (CI) 1.04–6.41; OR 3.15, 95% CI 1.34–7.35, respectively). VAT changes showed a borderline association with high baseline tumour necrosis factor‐α levels and hip circumference (OR 1.04, 95% CI 1.00–1.07; OR 1.44, 95% CI 1.07–1.95, respectively).ConclusionsIn ART‐naïve men, higher baseline limb fat and an early increase in leptin concentrations may predict the subsequent development of lipoatrophy. We did not find the same risk factors in the two different groups of patients with peripheral fat loss and central fat gain, suggesting a partially independent pathogenesis.
CD38 expression on CD8 T cells has a weak association with CD4 T‐cell recovery and is a poor marker of viral replication in HIV‐1‐infected patients on antiretroviral therapy
Authors: Steel A , John L , Shamji MH , Henderson DC , Gotch FM , Gazzard BG , Kelleher P 
Published: February 2008

ObjectiveThe aim of the study was to determine whether the expression of CD38 on CD8 T cells can identify patients with virological failure on antiretroviral therapy (ART).DesignThis was a cross‐sectional study of patients attending a single HIV clinic in London.MethodsThe expression of CD38 on CD8 T cells was assessed using a biologically calibrated flow cytometry protocol. Patients were characterized by lymphocyte subset and viral load measurements. Characteristics including historical CD4 T cell counts, therapeutic history, co‐infections and demographics were obtained from medical records.ResultsElevated levels of CD8 CD38high T cells were found in HIV‐1‐infected patients who failed to suppress viral replication with ART; however, this parameter lacked sufficient sensitivity and specificity to replace viral load testing in assessing the efficacy of ART. Increased levels of CD8 CD38high cells were associated with reduced CD4 T cell counts in HIV‐1‐infected patients on ART after correcting for known determinants of CD4 T‐cell recovery.ConclusionsThe expression of CD38 on CD8 T cells lacks sufficient sensitivity and specificity to be used as a surrogate marker for viral load to monitor HIV‐1 infection. T‐cell activation is associated with reduced CD4 T‐cell reconstitution in patients receiving ART.
HIV voluntary counselling and testing in Nakuru, Kenya: findings from a community survey
Authors: Irungu TK , Varkey P , Cha S , Patterson JM 
Published: February 2008

ObjectivesHIV voluntary counselling and testing (VCT) is important for prevention, detection and treatment of HIV infection. A study was conducted to determine the extent of utilization of VCT, and to study the attitudes and preferences of the community regarding VCT.MethodsA total of 301 adults, aged 18–49 years, residing in Nakuru, Kenya were randomly selected using a two‐stage sampling process. A self‐administered questionnaire delivered during home visits was used to collect data over a 4‐week period.ResultsThe majority of study participants (184 of 287; 64.1%) had never been tested for HIV; 77 (26.8%) had received VCT, and 26 (9.1%) had received HIV testing without counselling. A total of 219 (78.2%) of the 280 responding participants expressed readiness to have VCT. The majority of participants (216 of 296; 73%) preferred VCT, while 46 (15.5%) preferred testing without counselling. The majority (227; 76.7%) preferred couple testing and dedicated clinics and private doctors' offices as testing facilities. The choice of a nearby facility was ranked above the provision of anonymity by most participants (162 of 298; 54.4%; vice versa for 136 of 298; 45.6%).ConclusionsWith HIV/AIDS continuing to be a major public health concern in Kenya, the issues surrounding acceptance and use of VCT need to be addressed. Enhancing community awareness of the benefits of early HIV diagnosis, providing couple‐based VCT as an integral part of VCT and increasing access to VCT testing sites may enhance utilization of VCT.
Age‐related intrinsic changes in human bone‐marrow‐derived mesenchymal stem cells and their differentiation to osteoblasts
Authors: Zhou Shuanhu , Greenberger Joel S. , Epperly Michael W. , Goff Julie P. , Adler Carolyn , LeBoff Meryl S. , Glowacki Julie 
Published: February 2008

Summary In vivo and in vitro studies indicate that a subpopulation of human marrow‐derived stromal cells (MSCs, also known as mesenchymal stem cells) has potential to differentiate into multiple cell types, including osteoblasts. In this study, we tested the hypothesis that there are intrinsic effects of age in human MSCs (17–90 years). We tested the effect of age on senescence‐associated β‐galactosidase, proliferation, apoptosis, p53 pathway genes, and osteoblast differentiation in confluent monolayers by alkaline phosphatase activity and osteoblast gene expression analysis. There were fourfold more human bone MSCs (hMSCs) positive for senescence‐associated β‐galactosidase in samples from older than younger subjects (P < 0.001; n = 17). Doubling time of hMSCs was 1.7‐fold longer in cells from the older than the younger subjects, and was positively correlated with age (P = 0.002; n = 19). Novel age‐related changes were identified. With age, more cells were apoptotic (P = 0.016; n = 10). Further, there were age‐related increases in expression of p53 and its pathway genes, p21 and BAX. Consistent with other experiments, there was a significant age‐related decrease in generation of osteoblasts both in the STRO‐1+ cells (P = 0.047; n = 8) and in adherent MSCs (P < 0.001; n = 10). In sum, there is an age‐dependent decrease in proliferation and osteoblast differentiation, and an increase in senescence‐associated β‐galactosidase‐positive cells and apoptosis in hMSCs. Up‐regulation of the p53 pathway with age may have a critical role in mediating the reduction in both proliferation and osteoblastogenesis of hMSCs. These findings support the view that there are intrinsic alterations in human MSCs with aging that may contribute to the process of skeletal aging in humans.
Neuropsychological Deficits in Alcoholics: Facts and Fancies
Authors: Parsons Oscar A. 
Published: February 2008

SUMMARYFive facts and complementary “fancies” have been examined. Brain damage is found in alcoholics but whether alcohol directly causes the damage is not clear at this time. Cortical and subcortical atrophy is found in 50%‐70% of unselected alcoholics coming for treatment but a substantial minority of alcoholics do not have such changes. Brain changes in alcoholics are associated significantly with neuropsychological deficits but the magnitude of the correlations leaves much of the variance unexplained. Neuropsychological deficits in alcoholics (who do not have “mental deterioration”) are relatively specific and in most instances functions can be recovered but there are some suggestions of more permanent, if limited, deficits. While specific neuropsychological deficits in alcoholics have been recurrently established, their relationship to therapeutic strategies and therapeutic outcome remains to be explored. Finally, it is abundantly clear that implicit and explicit criteria for patient selection in neuropsychological studies are major, if not critical, variables in work in this field.
Elevation of the Hemoglobin Al Fraction in Alcoholism
Authors: Hoberman Henry D. , Chiodo Sandra M. 
Published: February 2008

The proportion of hemoglobin A1 was measured in 43 normoglycemic men and women admitted consecutively to an alcohol treatment center and in 41 healthy volunteers. On the average, the size of the fraction was significantly greater in the alcoholic patients than in the healthy subjects. The results of hemoglobin A1c determinations added independent evidence that this difference was not due to formation of any of the known glycosylated hemoglobins despite the fact that the alcohol‐related hemoglobin was found to cochromatograph with hemoglobin A1 c.The size of the hemoglobin A1 fraction was unrelated to the presence or absence of alcoholic hepatitis, although most patients having abnormally high serum hepatic enzyme activities were also found to have abnormal elevations of the A1 fraction. However, some patients with normal serum enzyme activities were among those having the highest values of the A1 fraction, indicating that the latter was a more sensitive indicator of excessive alcohol intake than were hepatic enzyme activities. The proportion of hemoglobin A1 in a patient followed over a period of 9 months rose to a maximum as the patient continued to drink. In a patient who abstained from drinking while under hospital care, the A1 fraction decreased towards normal with a half‐time of 11 days. These observations are interpreted as evidence that alcohol‐related hemoglobin is a product of a readily reversible reaction occurring at a maximal rate of 0.038 mm day‐1, about 4 times as rapid as is the formation of hemoglobin A1c.
The Interaction of Chronic Alcohol Consumption and Aging on Brain Structure and Function
Authors: Freund Gerhard 
Published: February 2008

Cognitive performance declines moderately with normal aging and severely with pathological aging. A similar range of intellectual impairment has been described in association with prolonged alcohol consumption. It is doubtful that all types and degrees of alcohol‐associated impairments of cognitive function are attributable only to thiamin deficiency. Evidence from human and animal data indicates increasingly that alcohol per se has direct CNS toxic effects as well, and it is dangerous to suggest that adequate thiamin consumption alone would prevent all CNS toxic effects of chronic alcohol consumption.If a direct role of ethanol in CNS toxicity is accepted, it becomes important to study the molecular basis of the behavioral impairment caused by both aging and alcohol abuse in order to develop rational treatment and prevention. An entire spectrum of relationships is possible between aging and alcohol‐related CNS changes. At the one end of the spectrum could simply be deficits additive at the behavioral level but caused by different molecular events. Conversely, molecular processes of biological aging could interact with molecular effects of ethanol, potentiating each other and culminating in an accelerated aging process. Many pathological mechanisms could lead to an irreversible loss of neuronal cell bodies. However, changes in peripheral cell processes, including the synapses, may be equally important in limiting interneuronal communications that result in behavioral deficits. Some changes could even be limited to a decrease of numbers or affinity of synaptic receptor molecules of a particular region. From the human and animal data reviewed, chronic ethanol consumption appears to increase some behavioral deficits caused by aging. What the exact interrelationships are at the molecular basis for the behavioral changes is not yet clear.
Examination of Alcoholics by Computed Tomographic (CT) Scans: A Critical Review
Authors: Wilkinson D. Adrian 
Published: February 2008

Neuroradiological studies have consistently demonstrated that alcoholics have morphological abnormalities of cortical, ventricular, and cerebellar structures suggesting brain atrophy. This atrophy is weakly correlated with impaired psychological test performance. Because brain atrophy and intellectual impairment can also be found in normal aging it is necessary to compare alcoholics with age‐matched control subjects.It is currently unknown if alcohol‐associated brain atrophy and intellectual impairment are the result of conditions preceding alcohol consumption or conditions only indirectly related such as head trauma or other associated diseases. Direct alcohol toxicity would be supported by quantitative alcohol‐atrophy dose‐response relationships and by a partial reversal of atrophy and functional impairment following abstinence from alcohol.Because of methodological difficulties inherent in neuroradiological research, data on the exact pathogenesis of abnormalities in alcoholics have not been produced. The design of such studies can be improved to increase the probability that the causes of brain atrophy will be elucidated.
Human Blood Acetaldehyde Levels: With Improved Methods, a Clearer Picture Emerges
Authors: Lindros Kai O. 
Published: February 2008

New reliable methods for the determination of acetaldehyde in human blood, either from separated plasma or from acidprecipitated whole blood, demonstrate that the blood of healthy Caucasians contains at most only extremely small amounts of acetaldehyde (>1 μM) after moderate alcohol intoxication. On the other hand, among about 50% of the Japanese population ethanol ingestion results in elevated blood acetaldehyde levels (10–50 μM) with consequent unpleasant cardiovascular responses such as facial flushing and tachycardia, apparently because of a lack of one of the acetaldehyde‐oxidizing aldehyde dehydrogenase isozymes.Elevated acetaldehyde levels may eventually occur also among intoxicated Caucasian alcoholics, primarily as a consequence of abuse‐induced loss of hepatic aldehyde dehydrogenase activity, but accentuated by an accelerated ethanol oxidation rate. The elevation is probably reversible, since no acetaldehyde IS seen In alcoholics after abstinence and hospital treatment. There is thus little evidence that an elevation of acetaldehyde could serve as a marker for predisposition for alcoholism.
Studies on the Differences in NaK‐ATPase and Lipid Properties of Liver Plasma Membranes in Long Sleep and Short Sleep Mice
Authors: Zysset Thomas , Sutherland Eileen , Simon Francis R. 
Published: February 2008

Activity of NaK‐ATPase, the biochemical equivalent of the sodium pump, may be reguiated by several factors including hormones, drugs, and inheritance. To evaluate further the possibility of genetic control, we investigated hepatic NaK‐ATPase in mice selectively bred for differences in ethanol‐induced sleep time, designated long sleep (LS) and short sleep (SS). In SS mice, specific acitivity of NaK‐ATPase was 65% higher than in LS. Other plasma membrane enzymes were also increased in SS including alkaline phosphatase (176%), leucine aminopeptidase (115%), 5′‐nucleotidase (49%). In contrast, basal adenylate cyclase and insulin binding, sodium do‐decyl sulfate polyacrylamide gel electrophoresis patterns, and the cytosolic enzyme tyrosine aminotransferase were similar. Altered membrane lipid composition did not account for these differences since the cholesterol:phospholipid ratio and the enzyme activity response after addition of benzyl alcohol to membrane preparation were similar in both strains.Kinetic analysis of NaK‐ATPase activity showed a similar Km, but Vmax was 60% increased in SS mice. Using sodium‐dependent binding of [γ32P]ATP, a comparable increase in enzyme units was demonstrated. Since half‐maximal ouabain inhibition was similar, differences in NaK‐ATPase isoenzymes are unlikely. Differences in NaK‐ATPase between LS and SS appear to be specific to the liver since activities were not different in kidneys and muscles. Induction of NaK‐ATPase with tri‐iodothyronine (T3) showed greater responses in LS (+53%) than in SS (+13%). These changes may relate to a post‐receptor abnormality, since malic enzyme, a thyroid‐responsive enzyme, was higher basally in LS mice, but similar to NaK‐ATPase, the response to T3 administration was blunted in SS mice.To evaluate a possible link between NaK‐ATPase activity and resistance to the hypnotic effect of ethanol, we examined inbred strains of mice with shorter (C57BL/6J) and longer (DBA/2J) ethanol sleep times. In contrast to LS/SS mice, NaK‐ATPaae was higher In DBA and lower in C57. Our study adds an animal model of genetically controlled differences in NaK‐ATPase, which is localized only to the liver. Although there seems to be no relationship between the different NaK‐ATPase activity in LS and SS mice and their different response to ethanol, this model is of potential interest for the study of mechanisms leading to ethanol‐induced liver disease.