bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational Mini-Review Series on Vaccines for HIV: Harnessing innate immunity for HIV vaccine development
Authors: Rhee E G , Barouch D H 
Published: March 2009

Summary
Innate immunity is critical for shaping vaccine-elicited adaptive immune responses. Several classes of immune sensors, including Toll-like receptors, retinoic acid-inducible gene-I-like receptors, nucleotide-binding oligomerization domain-like receptors and cytosolic DNA receptors mediate important innate immune pathways and provide potential targets for novel adjuvant development. Understanding how innate immunity modulates adaptive immune responses will probably be important for optimizing vaccine candidates. Here, we review recent advances in innate immunity, focusing upon their potential applications in developing adjuvants and vectors for HIV vaccines.
Congenital hypopituitarism: clinical, molecular and neuroradiological correlates
Authors: Mehta Ameeta , Hindmarsh Peter C. , Mehta Hiten , Turton James P.G. , Russell‐Eggitt Isabelle , Taylor David , Chong W.K. , Dattani Mehul T. 
Published: March 2009

SummaryObjective  Recent studies have suggested that mutations in genes encoding several hypothalamo–pituitary (H–P) transcription factors result in hypopituitarism [isolated GH deficiency (IGHD) and combined pituitary hormone deficiency (CPHD)], which may in turn be related to the neuroanatomy revealed by magnetic resonance (MR) imaging. Although studies have focused on patients with either optic nerve hypoplasia (ONH) or isolated hypopituitarism with normal optic nerves, few studies have compared the two groups. We aimed to relate the clinical phenotype of a large cohort (n = 170) of children with congenital hypopituitarism including septo‐optic dysplasia (SOD) attending a single centre to the neuroradiological and genetic findings.Design  Clinical, biochemical, MR imaging and molecular data were analysed retrospectively in 170 patients with or ‘at‐risk’ (with ONH) of hypopituitarism to determine predictors of hypopituitarism.Results  The presence of ONH was significantly associated with an absent septum pellucidum [odds ratio (OR) 31·5, 95% confidence intervals (CI) 7·3–136·6, P < 0·001], an abnormal corpus callosum (OR 10·5, 95% CI 3·8–28·6, P < 0·001) and stalk abnormalities (OR 2·3, 95% CI 1·2–4·2, P = 0·009). The risk of hypopituitarism was 27·2 times greater in patients with an undescended posterior pituitary (95% CI 3·6–205·1, P < 0·001). Anterior pituitary hypoplasia (OR 3·1, 95% CI 1·3–7·0, P = 0·006) and an absent pituitary stalk (P < 0·001) were also significantly associated with hypopituitarism. With respect to the type or severity of hypopituitarism, CPHD was more often associated with an abnormal corpus callosum (OR 6·1, 95% CI 1·4–27·4, P = 0·008) and stalk abnormalities (OR 2·8, 95% CI 1·3–6·1, P = 0·006). Male to female ratio was significantly greater in patients with normal optic nerves (3·3:1) as compared with those with ONH (1·2:1). The prevalence of diabetes insipidus, thyrotrophin and ACTH deficiencies was significantly greater in patients with ONH as compared with ‘idiopathic’ hypopituitarism. Mutations in pituitary transcription factors and genes regulating GH secretion were rare (5/170) in this cohort of patients with sporadic hypopituitarism.Conclusion  Our data suggest that individuals presenting with ONH are at high risk for neuroradiologic and endocrine abnormalities. The neuroradiologic features are predictive not only of the presence, but also of the type, of hypopituitarism. The association of midline abnormalities with hypopituitarism in this cohort suggests a common developmental origin for these features, the aetiology of which remains unidentified in the majority of cases.
Should macroprolactin be measured in all hyperprolactinaemic sera?
Authors: Joseph McKenna T. 
Published: March 2009

SummaryMacroprolactin is a nonbioactive prolactin isoform usually composed of a monomer of prolactin and a IgG molecule which has a prolonged clearance rate similar to that of the immunoglobulins. Macroprolactinaemia, hyperprolactinaemia entirely accounted for by the presence of macroprolactin, is estimated to account for approximately 10% of all hyperprolactinaemia coming to clinical attention in the United Kingdom and the United States. Failure to recognize that macroprolactinaemia can explain hyperprolactinaemia, leads to unnecessary investigation, incorrect diagnosis and inappropriate treatment. Screening of hyperprolactinaemic sera for the presence of misleading concentrations of macroprolactin is readily performed in biochemistry laboratories although the procedures have not been automated. The most widely employed method is to treat the hyperprolactinaemic sera with polyethylene glycol which precipitates out high‐molecular weight constituents including immunoglobulins. Re‐assay of the sera for prolactin will then identify those sera which yield values within the relevant normal range indicative of macroprolactinaemia and not true hyperprolactinaemia. The case for the routine screening of all hyperprolactinaemic sera for macroprolactin is compelling. The consequences of failure to recognize macroprolactinaemia are significant, the problem is frequently encountered, the means of addressing it are immediately available and it is cost effective.
Increased C‐reactive protein levels in overweight and obese women taking exogenous hormones: the United Kingdom Women’s Heart Study (UKWHS)
Authors: Kwok See , Canoy Dexter , Ashton William D. , Lowe Gordon D. O. , Wood David , Humphries Stephen E. , Charlton‐Menys Valentine , Durrington Paul N. 
Published: March 2009

SummaryObjective  Women’s cardiovascular risk factors, including inflammatory markers such as C‐reactive protein (CRP) which is emerging as a major association with cardiovascular disease (CVD) risk, can be influenced by the oral contraceptive (OC) pill in premenopausal and hormone replacement (HR) in postmenopausal women and by central adiposity which is associated with a heightened inflammatory state. The interaction between central obesity and different hormone use in both pre and postmenopausal women has not previously been reported in a study spanning the whole age range associated with hormone use.Design  Observational, cross‐sectional study.Patients  Only healthy women were included in this study.Measurements  A total of 21,310 women aged 30–64 employed by Marks & Spencer participated. They completed a health questionnaire and were screened for CVD risk factors including blood pressure, weight, height, waist and hip circumference, lipids and lipoproteins, CRP and fibrinogen.Results  Compared with non‐users, women who took the OC or HR had significantly higher CRP levels. This was more marked than effects on other CVD risk factors. It was further compounded by the independent effect of increased waist circumference. The CRP increase was greatest (more than twice that of nonhormone users) in premenopausal women with the highest quartile of waist circumference who took the combined contraceptive pill.Conclusions  Women who received first the combined OC and then HR may be exposed over much of their life to high CRP levels aggravated by central obesity. The health consequences of this require further investigation.
A safe hydraulic architecture as wood anatomical explanation for the difference in distribution of the mangroves Avicennia and Rhizophora
Authors: Robert Elisabeth M R , Koedam Nico , Beeckman Hans , Schmitz Nele 
Published: March 2009

Summary

Wood anatomical characteristics are an important source of information about how trees are coping with the conflicting requirements of optimal hydraulic conductivity and safety. In this study we compared the vessel characteristics of Avicennia marina and Rhizophora mucronata to contribute to a better understanding of the difference in distribution of these two mangrove species.
Density, grouping and diameters of vessels together with vessel element length of A. marina trees growing on seven different study sites in Gazi Bay (Kenya) were measured and compared with the vessel characteristics of R. mucronata of the same research area. Furthermore, the relation of environmental factors related to the water relations of mangrove trees to the wood anatomy of both species was tested.
Vessel density of both species and vessel grouping of A. marina are higher with higher salinity. In addition, A. marina was shown to have a higher vessel density, a higher vessel grouping, smaller vessel diameters and shorter vessel element lengths as compared to R. mucronata.
As the vessel characteristics of A. marina are related to protection against cavitation or the effects of cavitation, we can infer that this species has a water transport system which can be considered safer under water limiting conditions than that of R. mucronata.
The contrast in the safety of the water transport system between the two mangrove species studied is reflected in their distribution at local scale, over the land‐sea ecotone, and it may also explain the wide latitudinal distribution of A. marina as compared to R mucronata.
This conclusion emphasizes the importance of the anatomy of the water transport system for survival under diverse environmental conditions. In general it is shown that dominant species of a single ecosystem can deal with the stressful conditions they live in by contrasting ecological strategies.
Life history correlates of oxidative damage in a free‐living mammal population
Authors: Nussey Daniel H. , Pemberton Josephine M. , Pilkington Jill G. , Blount Jonathan D. 
Published: March 2009

Summary

Reactive oxygen species, produced as a by‐product of normal metabolism, can cause intracellular damage and negatively impact on cell function. Such oxidative damage has been proposed as an evolutionarily important cost of growth and reproduction and as a mechanistic explanation for organismal senescence, although few tests of these ideas have occurred outside the laboratory.
Here, we examined correlations between a measure of phospholipid oxidative damage in plasma samples and age, growth rates, parasite burden and investment in reproduction in a population of wild Soay sheep on St. Kilda, Scotland.
We found that, amongst females of different ages, lambs had significantly elevated levels of oxidative damage compared to all other age classes and there was no evidence of increasing damage with age amongst adult sheep.
Amongst lambs, levels of oxidative damage increased significantly with increasing growth rates over the first 4 months of life. Neither mean damage nor the effect of growth rate on damage differed between male and female lambs.
Amongst adult female sheep, there was no evidence that body mass, current parasite burden or metrics of recent and past reproductive effort significantly predicted oxidative damage levels.
This study is the first to examine age variation in an assay of oxidative damage and correlations between oxidative damage, growth and reproduction in a wild mammal. Our results suggest strong links between early conditions and oxidative damage in lambs, but also serve to highlight the limitations of cross‐sectional data for studies examining associations between oxidative stress, ageing and life history in free‐living populations.
Linking movement behaviour, dispersal and population processes: is individual variation a key?
Authors: Hawkes Colin 
Published: March 2009

SummaryMovement behaviour has become increasingly important in dispersal ecology and dispersal is central to the development of spatially explicit population ecology. The ways in which the elements have been brought together are reviewed with particular emphasis on dispersal distance distributions and the value of mechanistic models.There is a continuous range of movement behaviours and in some species, dispersal is a clearly delineated event but not in others. The biological complexities restrict conclusions to high‐level generalizations but there may be principles that are common to dispersal and other movements.Random walk and diffusion models when appropriately elaborated can provide an understanding of dispersal distance relationships on spatial and temporal scales relevant to dispersal. Leptokurtosis in the relationships may be the result of a combination of factors including population heterogeneity, correlation, landscape features, time integration and density dependence. The inclusion in diffusion models of individual variation appears to be a useful elaboration. The limitations of the negative exponential and other phenomenological models are discussed.The dynamics of metapopulation models are sensitive to what appears to be small differences in the assumptions about dispersal. In order to represent dispersal realistically in population models, it is suggested that phenomenological models should be replaced by those based on movement behaviour incorporating individual variation.The conclusions are presented as a set of candidate principles for evaluation. The main features of the principles are that uncorrelated or correlated random walk, not linear movement, is expected where the directions of habitat patches are unpredictable and more complex behaviour when organisms have the ability to orientate or navigate. Individuals within populations vary in their movement behaviour and dispersal; part of this variation is a product of random elements in movement behaviour and some of it is heritable. Local and metapopulation dynamics are influenced by population heterogeneity in dispersal characteristics and heritable changes in dispersal propensity occur on time‐scales short enough to impact population dynamics.
Global gene regulation by Fusarium transcription factors Tri6 and Tri10 reveals adaptations for toxin biosynthesis
Authors: Seong Kye‐Yong , Pasquali Matias , Zhou Xiaoying , Song Jongwoo , Hilburn Karen , McCormick Susan , Dong Yanhong , Xu Jin‐Rong , Kistler H. Corby 
Published: March 2009

SummaryTrichothecenes are isoprenoid mycotoxins produced in wheat infected with the filamentous fungus Fusarium graminearum. Some fungal genes for trichothecene biosynthesis (Tri genes) are known to be under control of transcription factors encoded by Tri6 and Tri10. Tri6 and Tri10 deletion mutants were constructed in order to discover additional genes regulated by these factors in planta. Both mutants were greatly reduced in pathogenicity and toxin production and these phenotypes were largely restored by genetic complementation with the wild‐type gene. Transcript levels for over 200 genes were altered ≥ twofold for Δtri6 or Δtri10 mutants including nearly all known Tri genes. Also reduced were transcript levels for enzymes in the isoprenoid biosynthetic pathway leading to farnesyl pyrophosphate, the immediate molecular precursor of trichothecenes. DNA sequences 5′ to isoprenoid biosynthetic genes were enriched for the Tri6p DNA binding motif, YNAGGCC, in F. graminearum but not in related species that do not produce trichothecenes. To determine the effect of trichothecene metabolites on gene expression, cultures were treated with trichodiene, the first metabolic intermediate specific to the trichothecene biosynthetic pathway. A total of 153 genes were upregulated by added trichodiene and were significantly enriched for genes likely involved in cellular transport. Differentially regulated genes will be targeted for functional analysis to discover additional factors involved in toxin biosynthesis, toxin resistance and pathogenesis.
The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase‐1 and blocks mitotic progression in bloodstream forms
Authors: Jetton Neal , Rothberg Karen G. , Hubbard James G. , Wise John , Li Yan , Ball Haydn L. , Ruben Larry 
Published: March 2009

SummaryAurora kinase family members co‐ordinate a range of events associated with mitosis and cytokinesis. Anti‐cancer therapies are currently being developed against them. Here, we evaluate whether Aurora kinase‐1 (TbAUK1) from pathogenic Trypanosoma brucei might be targeted in anti‐parasitic therapies as well. Conditional knockdown of TbAUK1 within infected mice demonstrated its essential contribution to infection. An in vitro kinase assay was developed which used recombinant trypanosome histone H3 as a substrate. Tandem mass spectroscopy identified a novel phosphorylation site in the carboxyl‐tail of recombinant trypanosome histone H3. Hesperadin, an inhibitor of human Aurora B, prevented the phosphorylation of substrate with IC50 of 40 nM. Growth of cultured bloodstream forms was also sensitive to Hesperadin (IC50 of 50 nM). Hesperadin blocked nuclear division and cytokinesis but not other aspects of the cell cycle. Consequently, growth arrested cells accumulated multiple kinetoplasts, flagella and nucleoli, similar to the effects of RNAi‐dependent knockdown of TbAUK1 in cultured bloodstream forms cells. Molecular models predicted high‐affinity binding of Hesperadin to both conserved and novel sites in TbAUK1. Collectively, these data demonstrate that cell cycle progression is essential for infections with T. brucei and that parasite Aurora kinases can be targeted with small‐molecule inhibitors.
RNase E autoregulates its synthesis in Escherichia coli by binding directly to a stem‐loop in the rne 5′ untranslated region
Authors: Schuck Alyssa , Diwa Alexis , Belasco Joel G. 
Published: March 2009

SummaryRNase E autoregulates its production in Escherichia coli by governing the decay rate of rne (RNase E) mRNA. It does so by a mechanism that is dependent in part on hp2, a cis‐acting stem‐loop within the rne 5′ untranslated region. In principle, hp2 could function either as a cleavage site for RNase E or as a binding site for that protein or an ancillary factor. Here we show that the effector region at the top of hp2 is cleaved poorly by RNase E yet binds the catalytic domain of that ribonuclease with a sequence specificity reflecting its efficacy in feedback regulation. These findings suggest that hp2 controls RNase E synthesis by binding to RNase E and expediting cleavage elsewhere within the rne transcript.
PRECLINICAL STUDY: Corticotropin‐releasing factor‐1 receptor antagonists decrease heroin self‐administration in long‐ but not short‐access rats
Authors: Greenwell Thomas N. , Funk Cindy K. , Cottone Pietro , Richardson Heather N. , Chen Scott A. , Rice Kenner C. , Zorrilla Eric P. , Koob George F. 
Published: March 2009

ABSTRACTDysregulation of the stress‐related corticotropin‐releasing factor (CRF) system has been implicated in the development of drug dependence. The present study examined the effects of administering CRF type 1 (CRF1) receptor antagonists on heroin self‐administration in animals allowed short (1 hour) or long (8–12 hours) access to intravenous heroin self‐administration sessions. The nonpeptide CRF1antagonists MJL‐1‐109‐2 (1 hour versus 8 hours access) or R121919 (1 hour versus 12 hours access) were systemically injected in both short‐ and long‐access rats. MJL‐1‐109‐2 (10 mg/kg) and R121919 (10 and 20 mg/kg) reduced heroin self‐administration in long‐access animals without altering heroin intake in short‐access animals. Both MJL‐1‐109‐2 and R121919 decreased first‐hour intravenous heroin self‐administration selectively in long‐access rats, with R121919 decreasing cumulative heroin intake across the 12‐hour session. The results demonstrate that blockade of the CRF–CRF1receptor system attenuates the increased heroin intake of rats with extended access to the drug.
PRECLINICAL STUDY: The effect of naltrexone on amphetamine‐induced conditioned place preference and locomotor behaviour in the rat
Authors: Häggkvist Jenny , Lindholm Sara , Franck Johan 
Published: March 2009

ABSTRACTWhereas amphetamine and other psychostimulants primarily act on the dopamine system, there is also evidence that other neurotransmitter systems, such as the endogenous opioid system, modulate psychostimulant‐induced effects. Several studies have investigated the role of opioid antagonists on cocaine‐induced conditioned place preference (CPP), but there is limited information about the interaction with amphetamines. The aim of the present study was to investigate the effect of the opioid receptor antagonist, naltrexone (NTX) on the conditioning, expression and reinstatement of amphetamine‐induced place preference. In addition, the effect of NTX on locomotor behaviour was measured during all sessions. During training, animals were conditioned with amphetamine (2 mg/kg) to induce place preference. In order to extinguish the conditioned behaviour, animals received saline for 12 days. Reinstatement of CPP was induced by a priming dose of amphetamine (0.5 mg/kg). The interaction of NTX and amphetamine was evaluated using three paradigms of CPP: with NTX (vehicle, 0.3, 1.0 and 3.0 mg/kg) administered either 30 minutes prior to amphetamine conditioning, or 30 minutes before the expression, or 30 minutes before the amphetamine priming to induce reinstatement. Naltrexone had no effect on the conditioning, the expression or the reinstatement induced by a priming dose of amphetamine. Further, NTX by itself did not induce place preference or place aversion. In contrast, NTX significantly attenuated the locomotor response to a priming dose of amphetamine without affecting general locomotor behaviour. The results suggest differences in opioid modulation of amphetamine‐induced behaviours in the rat.
No differential effect of age on brain matter volume and cognition in bipolar patients and healthy individuals
Authors: Sarnicola Antonio , Kempton Matthew , Germanà Cristina , Haldane Morgan , Hadjulis Michael , Christodoulou Tessa , Koukopoulos Athanasios , Girardi Paolo , Tatarelli Roberto , Frangou Sophia 
Published: March 2009

Background:  Bipolar disorder (BD) is associated with brain structural and cognitive abnormalities. There is a paucity of evidence regarding the evolution of these deficits over time. This study examined the relationship between age and brain morphology and cognition in patients with BD type I.Methods:  Brain structural magnetic resonance imaging data were acquired using a 1.5T scanner from 71 BD patients and 82 age‐ and gender‐matched controls and analysed using Statistical Parametric Mapping. In addition, participants were evaluated using the Wechsler Adult Intelligence Scale, Revised; the Wechsler Memory Scale, third edition; the Hayling Sentence Completion Task, a measure of response inhibition; and the Wisconsin Card Sorting Test, which reflects rule discovery and perseveration.Results:  We found a significant effect of age but not of diagnosis and no age‐by‐diagnosis interaction in global gray and white matter and cerebrospinal fluid volumes. There was no differential effect of age on the two diagnostic groups with respect to cognitive task performance.Conclusions:  Our findings do not support differential age‐related changes in brain structure and cognition in patients with bipolar disorder compared to healthy individuals. Cross‐sectional studies are, however, limited and longitudinal data will be required to further explore this issue.
“Albumin” Auto‐Agglutinating Property in Three Sera. “A Pitfall for the Unwary”
Authors: WEINER W. , TOVEY G. H. , GILLESPIE E. M. , LEWIS H. B. M. , HOLLIDAY T. D. S. 
Published: March 2009

SummaryThree unusual sera are described which showed non‐specific auto‐agglutination of red cells suspended in bovine albumin but in no other commonly used suspending medium. The property found is most unlikely to be due to an auto‐antibody but no satisfactory explanation regarding its origin has yet been found.RésuméTrois sérums ont été trouvés, doués de la curieuse propriété d'autoagglutination des érythrocytes suspendus dans de l'albumine bovine mais pas dans d'autres milieux de suspension couramment employés. Cette propriété n'est très probablement pas due à un auto‐anti‐corps, mais les auteurs n'ont pu lui trouver aucune autre explication.ZusammenfassungDrei Seren zeigten eine ungewohnte Eigenschaft, indem sie unspe‐zifische Autoagglutination der in Rinderabumin suspendierten Erythrozyten bewirkten. Es ist unwahrscheinlich, daß dieses Phänomen durch Autoantikörper verursacht wird, doch können die Autoren dafür keine befriedigende Erklärung geben.