bluuebunny/crossref_metadata_2025 huggingface dataset:
Community‐based rapid HIV testing in homeless and marginally housed adults in San Francisco
Authors: Buchér JB , Thomas KM , Guzman D , Riley E , Dela Cruz N , Bangsberg DR
Published: January 2007

Background

Standard two‐step HIV testing is limited by poor return‐for‐results rates and misses high‐risk individuals who do not access conventional testing facilities.

Methods

We describe a community‐based rapid HIV testing programme in which homeless and marginally housed adults recruited from shelters, free meal programmes and single room occupancy hotels in San Francisco received OraQuick Rapid HIV‐1 Antibody testing (OraSure Technologies, Bethlehem, PA, USA).

Results

Over 8 months, 1614 adults were invited to participate and 1213 (75.2%) underwent testing. HIV seroprevalence was 15.4% (187 of 1213 individuals) overall and 3.5% (37 of 1063) amongst high‐risk individuals reporting no previous testing, a prior negative test, or previous testing without result disclosure. All 1213 participants received their results. Of 30 newly diagnosed persons who received confirmatory results, 26 (86.7%) reported at least one contact with a primary healthcare provider in the 6 months following diagnosis.

Conclusions

We conclude that community‐based rapid testing is feasible, acceptable and effective based on the numbers of high‐risk persons tested over a short period, the participation rate, the prevalence of new infection, the rate of result disclosure, and the proportion linked to care.
Once‐daily nevirapine dosing: a pharmacokinetics, efficacy and safety review
Authors: Cooper CL , Van Heeswijk RPG
Published: January 2007

In the context of attempts to simplify treatment regimens and enhance adherence, there is great interest in once‐daily dosing regimens for the treatment of HIV‐1 infection. Nevirapine has a long half‐life and achieves high steady‐state plasma concentrations relative to the concentration required to inhibit 50% viral replication in vitro (IC50) in patients. For this reason, it has been considered as a once‐daily antiretroviral. Pharmacokinetic and efficacy data support the use of this dosing approach, but excess rash and lingering concerns over liver toxicity preclude use of once‐daily dosed nevirapine at this time. Tolerance to high nevirapine concentrations may develop when dose escalation is used during initiation of therapy. It is theoretically possible that the benefits of once‐daily dosing may be achieved without excess toxicity by switching to once‐daily nevirapine following several months of twice‐daily administration. This dosing strategy is currently under evaluation.
Treatment outcomes amongst previously antiretroviral‐naïve HIV‐infected patients starting lopinavir/ritonavir‐containing antiretroviral regimens at the Royal Free Hospital*
Authors: Smith CJ , Phillips AN , Youle MS , Sabin CA , Lampe FC , Tsintas R , Tyrer M , Johnson MA
Published: January 2007

Objective

To describe outcomes in patients starting first‐line antiretroviral regimens including lopinavir/ritonavir (LPV/r) in a routine clinic setting.

Methods

Previously naïve patients starting LPV/r‐containing antiretroviral therapy were included in the study. Virological failure was defined as the first of two viral loads >500 HIV‐1 RNA copies/mL more than 6 months after starting LPV/r. Cumulative percentages experiencing virological failure were calculated using Kaplan–Meier methods.

Results

A total of 195 individuals had a median follow‐up time of 1.7 years. At 48 weeks, 87.9, 77.4 and 71.6% of patients with pretreatment CD4 counts of <50, 50–200 and >200 cells/μL, respectively, remained on LPV/r. By 48, 72 and 96 weeks, 2.2, 3.0 and 5.0% of patients, respectively, had experienced virological failure, ignoring treatment changes but censoring follow‐up at discontinuation of all antiretrovirals; these percentages became 24.0, 33.7 and 42.3% when LPV/r discontinuation was considered as virological failure. Censoring those who stopped LPV/r with a viral load <50 copies/mL and considering as virological failures those who stopped LPV/r with a viral load >50 copies/mL gave 12.1, 14.6 and 17.0% virological failure at 48, 72 and 96 weeks, respectively. Median CD4 count increases at 24, 48 and 72 weeks were 167, 230 and 253 cells/μL, respectively.

Conclusions

Few patients experienced virological failure whilst on a LPV/r‐based regimen, although it was not uncommon for patients in our clinic with higher baseline CD4 counts to discontinue LPV/r.
Safety of nevirapine in pregnancy
Authors: Natarajan U , Pym A , McDonald C , Velisetty P , Edwards SG , Hay P , Welch J , De Ruiter A , Taylor GP , Anderson J
Published: January 2007

Background

Nevirapine has been widely used in pregnancy for its efficacy, low pill burden, bioavailability and rapid transplacental transfer. Concern about nevirapine toxicity during pregnancy has emerged over recent years.

Objectives

The aims of the study were to document the frequency of cutaneous and hepatic toxicity secondary to nevirapine use during pregnancy and to compare rates in women starting nevirapine during the current pregnancy with those in women who had commenced nevirapine prior to the current pregnancy.

Design

This was a retrospective, comparative, five‐centre study carried out in London, UK, in 1997–2003.

Methods

All HIV‐1‐infected women who received nevirapine as part of combination antiretroviral therapy (ART) during pregnancy were included in the study. Data on demographics, HIV infection risk, Centers for Disease Control and Prevention (CDC) status, surrogate markers at initiation of therapy, other medications hepatitis B and C virus coinfection and clinical data relating to potential toxicity were collated and analysed.

Results

Fifteen of 235 eligible women (6.4%) developed rash and eight (3.4%) developed hepatotoxicity, including four with coexistent rash, giving a combined incidence of 19 potential cases of nevirapine toxicity during pregnancy (8.1%). Alternative causes of rash/hepatotoxicity were suspected in seven cases and only 10 mothers (5.8%) discontinued nevirapine. Of the 170 women who commenced nevirapine during this pregnancy, 13 (7.6%) developed rash and eight (4.7%) hepatotoxicity, a combined incidence of 10%. Only two of 65 women with nevirapine exposure prior to this pregnancy developed rash (3.1%).

Conclusions

Nevirapine‐containing ART was well tolerated in this cohort of pregnant women. Although pregnancy did not appear to increase the risk of nevirapine‐associated toxicity compared to published adult data, CD4 count may be less predictive of toxicity in pregnancy.
Haemoglobin and albumin as markers of HIV disease progression in the highly active antiretrovial therapy era: relationships with gender*
Authors: Shah S , Smith CJ , Lampe F , Youle M , Johnson MA , Phillips AN , Sabin CA
Published: January 2007

Objectives

The aims of the study were to describe gender differences in haemoglobin and albumin and to investigate the prognostic value of these measurements in relation to highly active antiretroviral therapy (HAART).

Methods

Anaemia was defined as haemoglobin <13.5 g/dL for men and <11.5 g/dL for women. Albumin <35 g/L was defined as hypoalbuminaemia. Proportional hazards models were used to describe relationships between these markers and HIV progression and death.

Results

A total of 291 patients had pre‐HAART and 1‐year measurements. Mean haemoglobin and albumin levels pre‐HAART were lower in women than in men (haemoglobin: 11.2 vs 13.2 g/dL, respectively, P<0.0001; albumin: 37.4 vs 40.2 g/L, respectively, P<0.0001), and a higher proportion of women were anaemic and hypoalbuminaemic compared with men. Despite a rise in both markers in the first year on HAART, mean haemoglobin levels remained lower by 2.08 g/dL (P<0.0001) and albumin by 2.88 g/L (P<0.0001) in women. In the 495 patients included in this analysis, haemoglobin and albumin levels were both significantly related to short‐term risk of AIDS and death independently of CD4 count [hazards ratio (HR)=0.73/g/dL higher haemoglobin, 95% confidence interval (CI) 0.55–0.82, P<0.0001 and HR=0.87/g/L higher albumin, 95% CI 0.83–0.91, P<0.0001]. The prognostic value did not differ by gender.

Conclusions

Women were more likely to be anaemic and/or hypoalbuminaemic pre‐HAART, but post‐HAART increases were similar to those in men. Both haemoglobin and albumin were strong independent prognostic factors for risk of AIDS and death, regardless of gender.
Identification and characterization of eight microsatellite loci in Aster amellus L. (Asteraceae)
Authors: MAYOR R. , NACIRI Y.
Published: January 2007

Eight polymorphic microsatellites were developed in the perennial herbaceous Aster amellus L. (Asteraceae) and characterized on three populations from France and Switzerland. The number of alleles ranged between four and 30 depending on the locus, and the mean number of effective alleles was 5.8. The average gene diversity equalled 0.744 (range: 0.419–0.957) and the overall differentiation was found significant (θ = 0.092, P < 0.01). Three loci displayed significant heterozygote deficiencies, which might indicate the presence of null alleles. Amplifications were detected on eight loci in Aster alpinus L.
Importance of Well‐Designed Monitoring Programs for the Conservation of Endangered Species: Case Study of the Snail Kite
Authors: MARTIN JULIEN , KITCHENS WILEY M. , HINES JAMES E.
Published: January 2007

Abstract:  Monitoring natural populations is often a necessary step to establish the conservation status of species and to help improve management decisions. Nevertheless, many monitoring programs do not effectively address primary sources of variability in monitoring data, which ultimately may limit the utility of monitoring in identifying declines and improving management. To illustrate the importance of taking into account detectability and spatial variation, we used a recently proposed estimator of abundance (superpopulation estimator) to estimate population size of and number of young produced by the Snail Kite (Rostrhamus sociabilis plumbeus) in Florida. During the last decade, primary recovery targets set by the U.S. Fish and Wildlife Service for the Snail Kite that were based on deficient monitoring programs (i.e., uncorrected counts) were close to being met (by simply increasing search effort during count surveys). During that same period, the Snail Kite population declined dramatically (by 55% from 1997 to 2005) and the number of young decreased by 70% between 1992–1998 and 1999–2005. Our results provide a strong practical case in favor of the argument that investing a sufficient amount of time and resources into designing and implementing monitoring programs that carefully address detectability and spatial variation is critical for the conservation of endangered species.
The doctrine of the two depressions in historical perspective
Authors: Shorter E.
Published: January 2007

Objective:  To determine if the concept of two separate depressions – melancholia and non‐melancholia – has existed in writings of the main previous thinkers about mood disorders.

Method:  Representative contributions to writing on mood disorders over the past hundred years have been systematically evaluated.

Results:  The concept of two separate depressions does indeed emerge in the psychiatric literature from the very beginning of modern writing about the concept of ‘melancholia’. For the principal nosologists of psychiatry, melancholic depression has always meant something quite different from non‐melancholic depression. Exceptions to this include Aubrey Lewis and Karl Leonhard. Yet the balance of opinion among the chief theorists overwhelmingly favors the existence of two quite different illnesses.

Conclusion:  The concept of ‘major depression’ popularized in DSM‐III in 1980 is a historical anomaly. It mixes together psychopathologic entities that previous generations of experienced clinicians and thoughtful nosologists had been at pains to keep separate. Recently, there has been a tendency to return to the concept of two depressions: melancholic and non‐melancholic illness. ‘Major depression’ is coming into increasing disfavor. In the next edition of DSM (DSM‐V), major depression should be abolished; melancholic mood disorder (MMD) and non‐melancholic mood disorder (NMMD) should become two of the principle entities in the mood disorder section.
The facets of melancholia
Authors: Coryell W.
Published: January 2007

Objective:  To clarify the role of ‘melancholia’ in psychiatric nomenclature.

Most clinicians and researchers are convinced that the syndrome currently termed major depressive disorder encompasses multiple subgroups that differ meaningfully in phenomenology, natural history, treatment response, and pathophysiology. Delusional depression and melancholia have attracted the most empirical work, but efforts to define the latter condition have declined in recent years following a number of failures to show the validity of the melancholic/nonmelancholic distinction.

Method:  Review of experience.

Results:  Beyond the DSM‐IV symptom profile, melancholia has been associated with greater overall severity, a low likelihood of placebo response, an episodic course, a family history of depression without alcoholism, a relatively healthy personality, and hypothalamic‐pituitary‐adrenal axis hyperactivity. Evidence for the validity of the melancholia concept lies in the fact that the presence of each of these characteristics has been shown to increase the likelihood of one or more of the others.

Conclusion:  A diagnosis of melancholia may eventually prove valuable in treatment selection, but the necessary evidence will not be forthcoming until a widely accepted definition exists that is both inherently valid and that can be applied consistently across research sites.
The incidence and prevalence of manic‐melancholic syndromes in North West Wales: 1875–2005
Authors: Farquhar F. , Le Noury J. , Tschinkel S. , Harris M. , Kurien R. , Healy D.
Published: January 2007

Objective:  Against a background of recent interest in the concept of melancholia, we report data on the incidence and prevalence of manic, melancholic and postpartum syndromes from North West Wales.

Method:  We have utilized a database of the complete records of all admission to the North Wales Asylum from 1875 to 1924, and compared the findings for mania, melancholia, and postpartum psychoses from this sample, with admissions for these disorders to the North West Wales mental health services between 1995 and 2005.

Results:  The incidence of bipolar disorder, as well as melancholia with and without psychotic features appears stable from 1875 to 2005 but there has been a dramatic decline in the incidence of de novo onset psychoses in the postpartum period. The prevalence of admissions for bipolar disorder, and for severe depressive disorders has increased dramatically during this period.

Conclusion:  There are some grounds for revisiting the concept of manic‐melancholic disorder put forward by Rafaelsen. The changes in the incidence of postpartum psychoses may have a wider significance for the affective disorders in general.
A mixed state core for melancholia: an exploration in history, art and clinical science
Authors: Akiskal H. S. , Akiskal K. K.
Published: January 2007

Objective:  We argue for a mixed state core for melancholia comparing concepts of melancholia across centuries using examples from art, history and scientific literature.

Method:  Literature reviews focusing on studies from Kraepelin onward, DSM‐IV classification and view‐points from clinical experience highlighting phenomenologic and biologic features as predictors of bipolar outcome in prospective studies of depression.

Results:  Despite the implied chemical pathology in the term endogenous/melancholic depression, frequently reported glucocortical and sleep neurophysiologic abnormalities, there is little evidence that melancholia is inherited independently from more broadly defined depressions. Prospective follow‐up of ‘neurotic’ depressions have shown melancholic outcomes in as many as a third; hypomania has also been observed in such follow‐up.

Conclusion:  These findings and considerations overall do suggest that melancholia as defined today is more closely aligned with the depressive and/or mixed phase of bipolar disorder. Given the high suicidality from many of these patients the practice of treating them with antidepressant monotherapy needs re‐evaluation.
Atypical depression: current status and relevance to melancholia
Authors: Stewart J. W. , McGrath P. J. , Quitkin F. M. , Klein D. F.
Published: January 2007

Objective:  The Diagnostic and Statistical Manual, Fourth Edition (DSM‐IV, 1994) included atypical features as an illness specifier for major depression and dysthymia. We asked whether subsequent literature supported its validity and addressed the relationship between depression with atypical features and melancholia.

Method:  Literature review focusing on studies addressing the validity of atypical depression, supplemented by the authors’ previously unpublished data.

Results:  Most studies support the discriminant validity of depression with atypical features relative to melancholia and depression having neither melancholic nor atypical features. However, studies addressing illness course suggest that criteria for depression with atypical features define a heterogeneous patient population.

Conclusion:  DSM‐IV criteria for depression with atypical features define a valid, but heterogeneous disorder. Criteria including age of onset and chronicity may define a more homogeneous group that is distinct from both melancholia and other depressed patients.
Melancholia and atypical depression in the Zurich study: epidemiology, clinical characteristics, course, comorbidity and personality
Authors: Angst J. , Gamma A. , Benazzi F. , Ajdacic V. , Rössler W.
Published: January 2007

Objective:  A comparison of psychiatric, psychological and somatic characteristics in specified subgroups of major depressive episodes (MDE).

Method:  In a stratified community sample of young adults investigated prospectively from age 20/21 to 40/41, we defined four MDE subgroups: i) DSM‐IV melancholia or atypical depression (the ‘combined group’), ii) pure melancholia, iii) pure atypical depression, and iv) unspecified MDE.

Results:  The cumulative incidence rates of the four groups were 4.1%, 7.1%, 3.5% and 8.2% respectively. Women were over‐represented in the combined and atypically depressed group. In 56 of 117 (47.9%) cases, melancholia was longitudinally associated with atypical MDE (n = 84) (OR = 11.9).

Conclusion:  Melancholic MDE was more severe than atypical MDE although the two groups shared many characteristics. The longitudinal overlap of melancholia with atypical depression in almost half of all cases calls for comparative analyses of combined, pure and unspecified MDE.
Pathophysiology of hypercortisolism in depression
Authors: Carroll B. J. , Cassidy F. , Naftolowitz D. , Tatham N. E. , Wilson W. H. , Iranmanesh A. , Liu P. Y. , Veldhuis J. D.
Published: January 2007

Objective:  The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non‐hypercortisolemic depressed in‐patients, and in normal volunteers.

Method:  Deconvolution analysis of 24‐h pulsatile secretion, approximate entropy (ApEn) estimation of secretory regularity, cross‐ApEn quantitation of forward and reverse ACTH–cortisol synchrony, and cosine regression of 24‐h rhythmicity.

Results:  Hypercortisolemia was strongly associated with melancholic and psychotic depressive subtypes. Hypercortisolemic patients had elevated ACTH and cortisol secretion, mediated chiefly by increased burst masses. Basal ACTH secretion was increased, ACTH half‐life was reduced, and mean 24‐h ACTH concentration was normal. Cortisol secretion was increased in a highly irregular pattern (high ApEn), with high ACTH → cortisol cross‐ApEn (impaired feedforward coupling). Cortisol‐mediated feedback on the secretory pattern of ACTH was normal. Hypercortisolemic depressed patients had normal programming of the central hypothalamo–pituitary–adrenal (HPA) axis pulse generator: ACTH pulse frequency, cortisol pulse frequency, circadian acrophases, and ApEn of ACTH secretion were normal. Responsiveness of the adrenal cortex to endogenous ACTH was normal. Non‐hypercortisolemic patients resembled hypercortisolemic patients on ACTH regulatory parameters but had low total cortisol secretion.

Conclusion:  Increased ACTH secretion occurs in depressed in‐patients regardless of cortisolemic status, confirming central HPA axis overdrive in severe depression. Depressive hypercortisolemia results from an additional change in the adrenal cortex that causes ACTH‐independent, disorderly basal cortisol release, a sign of physiological stress in melancholic/psychotic depression.
Sleep and circadian rhythms in mood disorders
Authors: Armitage R.
Published: January 2007

Objective:  Self‐reported sleep disturbances are present in over 80% of patients with depression. However, sleep electroencephalography (EEG) findings, based on overnight polysomnography have not always differentiated depressed patients from healthy individuals.

Method:  The present paper will review the findings on sleep EEG studies in depression highlighting how recent technological and methodological advances have impacted on study outcomes.

Results:  The majority of studies, including our own work, do indicate that sleep homeostasis and sleep EEG rhythms are abnormal in depression, but the sleep disturbances were strongly moderated by gender and age. Melancholic features of depression correlated significantly with low slow‐wave activity in depressed men, but not in depressed women. Women with depression showed low temporal coherence of sleep EEG rhythms but the presence or absence of melancholic features did not influence correlations.

Conclusion:  Diagnostic classification schemas and clinical features of depression may influence sleep EEG findings, but gender may be a more important consideration.
Electroconvulsive therapy in melancholia: the role of hippocampal neurogenesis
Authors: Bolwig T. G. , Madsen T. M.
Published: January 2007

Objective:  To elucidate the relationship between the effects of electroconvulsive therapy (ECT) on hippocampal anatomy and function in the therapy of melancholic depression and preclinical observations of increased neurogenesis in the hippocampus of experimental animals receiving electroconvulsive seizures (ECS). We emphasize the role of hypercortisolaemia in melancholic depression and in experimental hippocampal neurogenesis.

Method:  Our statements are based on a variety of studies pointing to i) ECT being superior to all other treatment modalities in the therapy of melancholia, ii) melancholia being associated with hypercortisolaemia and iii) evidence of hippocampal neurogenesis being relevant for understanding both melancholia and ECT.

Results:  The increased neurogenesis found in animal studies shows stronger effect of seizures than of antidepressant drugs. The onset of effect is not only faster but is also sustained. Newborn cells are found to be functional. Suppression of neurogenesis by chronic treatment with corticosterone is associated with depression‐like biology and behaviour making comparison with human depression and its response to ECT relevant.

Conclusion:  We hypothesize that the superior antimelancholic effect of induced seizures may be understood in the light of the powerful control of neural plasticity exerted by the regulation of the hypothalamic–pituitary–adrenal axis and, perhaps, other regulatory factors.
Cyclooxygenase‐2 inhibitor reduces simvastatin‐induced bone morphogenetic protein‐2 and bone formation in vivo
Authors: Bradley J. D. , Cleverly D. G. , Burns A. M. , Helm N. B. , Schmid M. J. , Marx D. B. , Cullen D. M. , Reinhardt R. A.
Published: January 2007

Background and Objective:  Simvastatin, a cholesterol‐lowering drug, also stimulates oral bone growth when applied topically, without systemic side‐effects. However, the mechanisms involved in vivo are not known. We hypothesized that bone morphogenetic protein‐2, nitric oxide synthase, and cyclooxygenase‐2 are involved, based on prior in vitro evidence.

Material and Methods:  A rat bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was placed on one side and gel alone on the other, was used to quantify nitric oxide, cyclooxygenase‐2 and bone morphogenetic protein‐2 (via tissue extraction, enzyme activity or immunoassay), and to analyze the bone formation rate (via undecalcified histomorphometry). Cyclooxygenase‐2 and nitric oxide synthase inhibitors (NS‐398 and L‐NAME, respectively) were administered intraperitoneally.

Results:  Simvastatin was found to stimulate local bone morphogenetic protein‐2, nitric oxide and the regional bone formation rate (p < 0.05), whereas NS‐398 inhibited bone morphogenetic protein‐2 and reduced the bone formation rate (p < 0.05).

Conclusion:  These data suggest an association between simvastatin‐induced bone morphogenetic protein‐2 and bone formation in the mandibular microenvironment, and the negative effect of cyclooxygenase‐2 inhibitors on bone growth.
Sensory Cilia and Integration of Signal Transduction in Human Health and Disease
Authors: Christensen Søren T. , Pedersen Lotte B. , Schneider Linda , Satir Peter
Published: January 2007

The primary cilium is a hallmark of mammalian tissue cells. Recent research has shown that these organelles display unique sets of selected signal transduction modules including receptors, ion channels, effector proteins and transcription factors that relay chemical and physical stimuli from the extracellular environment in order to control basic cellular processes during embryonic and postnatal development, as well as in tissue homeostasis in adulthood. Consequently, defects in building of the cilium or in transport or function of ciliary signal proteins are associated with a series of pathologies, including developmental disorders and cancer. In this review, we highlight recent examples of the mechanisms by which signal components are selectively targeted and transported to the ciliary membrane and we present an overview of the signal transduction pathways associated with primary and motile cilia in vertebrate cells, including platelet‐derived growth factor receptor‐alpha (PDGFRα), hedgehog and Wnt signaling pathways. Finally, we discuss the functions of these cilia‐associated signal transduction pathways and their role in human health and development.
Location‐Specific Depletion of a Dual‐Localized Protein
Authors: Shlevin Lee , Regev‐Rudzki Neta , Karniely Sharon , Pines Ophry
Published: January 2007

In recent years, a growing number of proteins have been shown to be localized in more than one subcellular location, although encoded from a single gene. Fundamental aspects in the research of such dual‐distributed proteins involve determination of their subcellular localization and their location‐specific functions. The lack of sensitive and suitable tools to address these issues has led us to develop a novel tool for functional detection of cytosolic/nuclear isoproteins in the cell, which we term location‐specific depletion or subcellular knockout. The depletion of the protein occurs post‐translationally via degradation by the ubiquitin–proteasome system, which operates only in the cytosol and the nucleus. As an example, we fused the yeast tricarboxylic acid (TCA) cycle enzyme aconitase to a degron sequence (SL17) recognizable by the ubiquitin–proteasome system. This fusion resulted in the degradation of the cytosolic enzyme, specifically eliminating its activity within the cytosolic glyoxylate shunt without disrupting the protein's activity within the mitochondrial TCA cycle. We show that the degradation of the fusion protein can be attributed specifically to the ubiquitin–proteasome system and that inhibition of this degradation restores its cytosolic activity. This novel tool can be used to detect small subpopulations of dual‐targeted proteins, thereby revealing isoproteins that were considered to be confined to a single compartment. The particular advantage of this specific subcellular depletion is that it can reveal the functions of the cytosolic/nuclear isoproteins.
Traffic of Botulinum Toxins A and E in Excitatory and Inhibitory Neurons
Authors: Verderio Claudia , Grumelli Carlotta , Raiteri Luca , Coco Silvia , Paluzzi Silvio , Caccin Paola , Rossetto Ornella , Bonanno Giambattista , Montecucco Cesare , Matteoli Michela
Published: January 2007

Botulinum neurotoxins (BoNTs), proteases specific for the SNARE proteins, are used to study the molecular machinery supporting exocytosis and are used to treat human diseases characterized by cholinergic hyperactivity. The recent extension of the use of BoNTs to central nervous system (CNS) pathologies prompted the study of their traffic in central neurons. We used fluorescent BoNT/A and BoNT/E to study the penetration, the translocation and the catalytic action of these toxins in excitatory and inhibitory neurons. We show that BoNT/A and BoNT/E, besides preferentially inhibiting synaptic vesicle recycling at glutamatergic relative to Gamma‐aminobutyric acid (GABA)‐ergic neurons, are more efficient in impairing the release of excitatory than inhibitory neurotransmitter from brain synaptosomes. This differential effect does not result from a defective penetration of the toxin in line with the presence of the BoNT/A receptor, synaptic vesicle protein 2 (SV2), in both types of neurons. Interestingly, exogenous expression of SNAP‐25 in GABAergic neurons confers sensitivity to BoNT/A. These results indicate that the expression of the toxin substrate, and not the toxin penetration, most likely accounts for the distinct effects of the two neurotoxins at the two types of terminals and support the use of BoNTs for the therapy of CNS diseases caused by the altered activity of selected neuronal populations.
PKC Anchoring to GluR4 AMPA Receptor Subunit Modulates PKC‐Driven Receptor Phosphorylation and Surface Expression
Authors: Gomes André R. , Correia Susana S. , Esteban José A. , Duarte Carlos B. , Carvalho Ana Luísa
Published: January 2007

Changes in the synaptic content of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)–type glutamate receptors lead to synaptic efficacy modifications, involved in synaptic plasticity mechanisms believed to underlie learning and memory formation. Early in development, GluR4 is highly expressed in the hippocampus, and GluR4‐containing AMPA receptors are inserted into synapses. During synapse maturation, the number of AMPA receptors at the synapse is dynamically regulated, and both addition and removal of receptors from postsynaptic sites occur through regulated mechanisms. GluR4 delivery to synapses in rat hippocampal slices was shown to require protein kinase A (PKA)–mediated phosphorylation of GluR4 at serine 842 (Ser842). Protein kinase C (PKC) can also phosphorylate Ser842, and we have shown that PKCγ can associate with GluR4. Here we show that activation of PKC in retina neurons, or in human embryonic kidney 293 cells cotransfected with GluR4 and PKCγ, increases GluR4 surface expression and Ser842 phosphorylation. Moreover, mutation of amino acids R821A, K825A and R826A at the GluR4 C‐terminal, within the interacting region of GluR4 with PKCγ, abolishes the interaction between PKCγ and GluR4 and prevents the stimulatory effect of PKCγ on GluR4 Ser842 phosphorylation and surface expression. These data argue for a role of anchored PKCγ in Ser842 phosphorylation and targeting to the plasma membrane. The triple GluR4 mutant is, however, phosphorylated by PKA, and it is targeted to the synapse in CA1 hippocampal neurons in organotypic rat hippocampal slices. The present findings show that the interaction between PKCγ and GluR4 is specifically required to assure PKC‐driven phosphorylation and surface membrane expression of GluR4.
Oligomerization Is a Specific Requirement for Apical Sorting of Glycosyl‐Phosphatidylinositol‐Anchored Proteins but Not for Non‐Raft‐Associated Apical Proteins
Authors: Paladino Simona , Sarnataro Daniela , Tivodar Simona , Zurzolo Chiara
Published: January 2007

Protein apical sorting in polarized epithelial cells is mediated by two different mechanisms, raft dependent and raft independent. In Madin–Darby canine kidney (MDCK) cells, an essential step for apical sorting of glycosyl‐phosphatidylinositol (GPI)‐anchored proteins (GPI‐APs) is their coalescence into high‐molecular‐weight (HMW) oligomers. Here we show that this mechanism is also functional in Fischer rat thyroid cells, which possess a different sorting phenotype compared with MDCK cells. We demonstrate that, as in MDCK cells, both apical and basolateral GPI‐APs associate with detergent‐resistant microdomains, but that only the apical proteins are able to oligomerize into HMW complexes during their passage through the medial Golgi. We also show that oligomerization is a specific requirement for apical sorting of GPI‐APs and is not used by transmembrane, non‐raft‐associated apical proteins.
Host ABCE1 is at Plasma Membrane HIV Assembly Sites and Its Dissociation from Gag is Linked to Subsequent Events of Virus Production
Authors: Dooher Julia E. , Schneider Bobbie L. , Reed Jonathan C. , Lingappa Jaisri R.
Published: January 2007

In primate cells, assembly of a single HIV‐1 capsid involves multimerization of thousands of Gag polypeptides, typically at the plasma membrane. Although studies support a model in which HIV‐1 assembly proceeds through complexes containing Gag and the cellular adenosine triphosphatase ABCE1 (also termed HP68 or ribonuclease L inhibitor), whether these complexes constitute true assembly intermediates remains controversial. Here we demonstrate by pulse labeling in primate cells that a population of Gag associates with endogenous ABCE1 within minutes of translation. In the next ∼2 h, Gag–ABCE1 complexes increase in size to approximately that of immature capsids. Dissociation of ABCE1 from Gag correlates closely with Gag processing during virion maturation and occurs much less efficiently when the HIV‐1 protease is inactivated. Finally, quantitative double‐label immunogold electron microscopy reveals that ABCE1 is recruited to sites of assembling wild‐type Gag at the plasma membrane but not to sites of an assembly‐defective Gag mutant at the plasma membrane. Together these findings demonstrate that a population of Gag present at plasma membrane sites of assembly associates with ABCE1 throughout capsid formation until the onset of virus maturation, which is then followed by virus release. Moreover, the data suggest a linkage between Gag–ABCE1 dissociation and subsequent events of virion production.
Sherlock Holmes and the proteome − a detective story
Authors: Righetti Pier Giorgio , Boschetti Egisto
Published: January 2007

The performance of a hexapeptide ligand library in capturing the ‘hidden proteome’ is illustrated and evaluated. This library, insolubilized on an organic polymer and available under the trade name ‘Equalizer Bead Technology’, acts by capturing all components of a given proteome, by concentrating rare and very rare proteins, and simultaneously diluting the abundant ones. This results in a proteome of ‘normalized’ relative abundances, amenable to analysis by MS and any other analytical tool. Examples are given of analysis of human urine and serum, as well as cell and tissue lysates, such as Escherichia coli and Saccharomyces cerevisiae extracts. Another important application is impurity tracking and polishing of recombinant DNA products, especially biopharmaceuticals meant for human consumption.
Field performance of Solanum sisymbriifolium, a trap crop for potato cyst nematodes. I. Dry matter accumulation in relation to sowing time, location, season and plant density
Authors: Timmermans B.G.H. , Vos J. , Van Nieuwburg J. , Stomph T.J. , Van der Putten P.E.L. , Molendijk P.G.
Published: January 2007

Solanum sisymbriifolium is an interesting trap crop to control potato cyst nematodes. A series of field experiments was carried out in the Netherlands between 2001 and 2003 to test its performance under field conditions. Experimental factors included sowing time, sowing density and site. Rate of germination, plant establishment and change over time in light interception were monitored. Growth analysis was performed at 7 and 14 weeks after emergence, and dry weight of component plant parts was determined. Time to 50% emergence was 36–38 days for planting at early April and declined to minimum values of ca 8–11 days when planting took place in June, July or the first week of August. When planted later, time to 50% germination increased again. Time to 50% light interception showed a similar trend with sowing time; minimum time was 35–40 days for planting between June and half of July. Planting before May did not advance crop growth. Crop performance was very variable across years and sites when planted later than the end of July to beginning of August. Dry matter accumulation up to 400 g m−2 was found at 7 weeks after emergence and up to 1040 g m−2 after 14 weeks. At 7 weeks after emergence, dry matter production increased with planting density (range 50–400 m−2), but no statistically significant differences were found after 14 weeks. A seed rate of 100 m−2 seems generally sufficient. Radiation use efficiency was 1.69 g MJ−1 PAR (SE = 0.0208). Dry matter accumulation (2002–2003) was somewhat higher in Wageningen (51°58’N) on light sandy soil than in Flevoland (52°31′N) on clay soil and in Drenthe (52°51′N) on reclaimed peat soil. It is concluded that above‐ground growth of S. sisymbriifolium in the Netherlands is adequate if planted between early May and the end of July.
X-ray flares and the duration of engine activity in gamma-ray bursts
Authors: Lazzati Davide , Perna Rosalba
Published: January 2007

The detection of bright X-ray flares superimposed on the regular afterglow decay in Swift gamma-ray bursts has triggered theoretical speculations on their origin. We study the temporal properties of flares due to internal dissipation and external shock mechanisms. We first show that at least a sizable fraction of the flares cannot be related to external shock mechanisms, as external shock flares evolve on much longer time-scales than observed. We then study flares from internal dissipation, showing that the temporal properties allow us to distinguish the emission of slow early shells from that of late faster shells. We show that, due to the rapid evolution of the detected flares, it is most likely that the flares are produced by relatively fast shells ejected by the central engine shortly before they are observed. This implies that the central engine must be active for, in some cases, as long as one day. We finally discuss the constraints and implications that this observation has on the properties and physics of the inner engine, and we elaborate on possible future observational tests on the flare sample to further understand their origin and physics.
MRF-ICA MIXTURE MODEL FOR HYPERSPECTRAL IMAGERY UNMIXING
Authors: JIA SEN , QIAN YUNTAO
Published: January 2007

Recently, independent component analysis (ICA) has been used in hyperspectral imagery (HSI) unmixing. It considers the hyperspectral signal from a given pixel as a linear mixture of the constituent spectra (endmember spectra) weighted by the correspondent abundance fractions (sources). This subpixel-based ICA model has two disadvantages. One is that it is difficult to choose the "mixed" pixels automatically, and the other is that the sources are not statistically independent. As the spatial resolution of HSI data grows higher, we introduce a new substance-based ICA model; that is, distinct substances are regarded as the original sources, and every band image is a linear mixture of them. However, ICA is a very general-purpose statistical technique — it does not take the spatial information into account while unmixing HSI. In this paper, the Markov random field (MRF) model is adopted to incorporate the spatial information into ICA. It is thought of as a powerful tool to model the joint probability distribution of the image pixels based on local spatial interactions. The experimental results demonstrate that the proposed MRF-ICA mixture model provides an effective approach for HSI unmixing.
ROBUST ADAPTIVE FUZZY TRACKING CONTROL FOR A CLASS OF PERTURBED UNCERTAIN NONLINEAR SYSTEMS WITH UVCGF
Authors: LI TIESHAN , YANG YANSHENG , HU JIANGQIANG , YANG LINJIA
Published: January 2007

In this paper, a robust adaptive fuzzy controller is presented for a wide class of perturbed uncertain nonlinear system with unknown virtual control gain function (UVCGF). The Mamdani fuzzy system is used to approximate unstructured uncertain functions in the system. The proposed algorithm, which incorporated Nussbaum-type gain into the decoupled backstepping approach, does not require a priori knowledge of the sign of UVCGF, and circumvents the controller-singularity problem gracefully in some existing literatures. It proved that the tracking error can be driven to a small residual set while keeping all signals in the closed-loop system semi-globally uniformly ultimately bounded (SGUUB). Simulation results are presented to validate the effectiveness of the proposed controller.
MODELING OF CHAOTIC SYSTEMS WITH MULTIWAVELET TRANSFORM COMBINED WITH RECURRENT LEAST SQUARES SUPPORT VECTOR MACHINES
Authors: XIANG ZHENG , ZHANG TAIYI , SUN JIANCHENG
Published: January 2007

A new algorithm for modeling of chaotic systems is presented in this paper. First, more information is acquired utilizing the reconstructed embedding phase space, and the multiwavelets transform provides a sensible decomposition of the data so that the underlying temporal structures of the original time series become more tractable. Second, based on the Recurrent Least Squares Support Vector Machines (RLS-SVM), modeling of the chaotic system is realized. To demonstrate the effectiveness of our algorithm, we use the power spectrum and dynamic invariants involving the Lyapunov exponents and the correlation dimension as criterions, and then apply our method to Chua's circuit time series. The similarity of dynamic invariants between the original and generated time series shows that the proposed method can capture the dynamics of the chaotic time series more effectively.
AN ANTI-NOISE ALGORITHM FOR ENHANCING GLOBAL AND LOCAL CONTRAST FOR INFRARED IMAGE
Authors: ZHANG CHANGJIANG , WANG XIAODONG , ZHANG HAORAN , DUANMU CHUNJIANG
Published: January 2007

Having performed discrete stationary wavelet transform (DSWT) to an infrared image and employing generalized cross validation (GCV), noise is reduced in high frequency sub-bands. These sub-bands are at finer resolution levels and the local contrast is enhanced by combining the de-noising method with non-linear operator in these sub-bands which are at coarser resolutionn levels. In order to enhance global contrast for an infrared image, the low frequency sub-band image is also enhanced employing non-incomplete Beta transform (IBT), simulated annealing algorithm (SA) and wavelet neural network (WNN). IBT is used to obtain non-linear gray transform curve. Transform parameters are determined by SA so as to obtain optimal non-linear gray transform parameters. Contrast type of an original image is determined by a new criterion. Gray transform parameters space is determined respectively according to different contrast types. A kind of WNN is proposed to approximate the IBT in the whole low frequency sub-band image. The quality of enhanced image is evaluated by an overall cost criterion. Experimental results show that the new algorithm can greatly improve the global and local contrast for an infrared image while efficiently reducing the correlative noise (CN), gauss white noise (GWN) and multiplicative noise (MN) in the infrared image.
NEURAL NETWORKS AS A TOOL FOR NONLINEAR PREDICTIVE CONTROL: APPLICATION TO SOME BENCHMARK SYSTEMS
Authors: JALILI MAHDI , ATASHBARI SAEID , MOMENBELLAH SAMAD , ROUDSARI FARZAD HABIBIPOUR
Published: January 2007

This paper deals with the application of neural networks to design intelligent nonlinear predictive controllers. Predictive controllers are now widely used in many industrial applications. They have been used for linear systems in early applications and then some methods based on predictive control theory were proposed to govern the dynamics of nonlinear systems. In this paper, we will make use of multi-layer perceptron neurofuzzy models with Locally Linear Model Tree (LoLiMoT) learning algorithm as a part of intelligent predictive control system, which has shown excellent performance in identifying of nonlinear systems. The nonlinear dynamics of the system is identified using the neural network based method and then the identified model is used as a part of predictive control algorithm. The proposed method is used to solve the control problems in some benchmark systems. As a first study, the viscosity control in a Continuous Stirred Tank Reactor (CSTR) plant is considered. The mathematical model of the plant is used to generate the input output data set and then the dynamic behavior of the system is identified using a proper multi-layer perceptron neural network, which is used in the predictive control loop. Also, the predictive control based on the locally linear neurofuzzy model is applied to temperature control of an electrically heated micro heat exchanger. The dynamic behavior of the heat exchanger is identified based on some experimental data of the real plant. Comparing the identification results obtained by the neurofuzzy model with those of some linear models such as ARX and BJ, confirms the superior performance for the locally linear neurofuzzy model. Then, the predictive control is applied to the identified model to obtain a satisfactory performance in the output temperature that should track a desired reference signal. As another application, the algorithm is applied to temperature control of a solution polymerization methyl methacrylate in a batch reactor. The results show also somehow satisfactory performance for this highly nonlinear system. All the simulation results reveal the effectiveness of the proposed intelligent control strategy.
DIFFERENTIAL SHAPE STATISTICAL ANALYSIS
Authors: CHEN YUFENG , ZHANG MANDUN , LU PENG , WANG YANGSHENG
Published: January 2007

A novel statistical approach that involves differential shape is proposed to analyze contour segments. First, a moment-based algorithm to represent the differential contour segment in an efficient way is introduced. Then, a curvature mean-shift method is adopted to search for the salient features. An optimized function is also developed to segment a contour into parts based on its structural properties. Compared with some other methods used in CSS (Curvature Scale Space) and shock graphs, our method is more powerful for shape contour analysis, especially for the incomplete or occluded contours. Experiments show that our method can track salient parts in real-time and give a judgment of the basic shape properties such as symmetry.
ROBUST IMAGE RETRIEVAL APPROACH BASED ON CLUSTERING ANALYSIS OF RE-QUANTIZED COLOR IMAGE
Authors: JI YA-LI , CHENG XIAO-PING , FENG NAI-QIN
Published: January 2007

In this paper, we propose a robust approach about color image retrieval. It can realize fast matching in CBIR (Content-Based Image Retrieval) when we search in large image databases. Indexes root in object features of Z image which is the result of re-quantization in HSV color space, matching with a non-geometrical distance is based on objects, so time consumption pixel by pixel can be avoided. Because Z image is made up of many color clustering regions and invariant moments are used for feature representation, our approach is robust to translation, scale and rotation.