bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep difficulties and alcohol use motives in female rape victims with posttraumatic stress disorder
Authors: Nishith Pallavi , Resick Patricia A. , Mueser Kim T.
Published: December 2002

The purpose of this study was to assess the relationship between sleep difficulties and drinking motives in female rape victims with posttraumatic stress disorder (PTSD). Seventy‐four participants were assessed for PTSD symptoms, depression, sleep difficulties, and drinking motives. Results demonstrated that neither PTSD symptoms nor depression were related to any motives for using alcohol. On the other hand, after controlling for education, sleep difficulties were significantly related to drinking motives for coping with negative affect, but not pleasure enhancement or socialization. The findings suggest that sleep difficulties may be an important factor contributing to alcohol use in rape victims with PTSD.
Genetic and environmental influences on the relationship among combat exposure, posttraumatic stress disorder symptoms, and alcohol use
Authors: McLeod D. Scott , Koenen Karestan C. , Meyer Joanne M. , Lyons Michael J. , Eisen Seth , True William , Goldberg Jack
Published: December 2002

The role of genetic and environmental influences on the relationship between combat exposure, posttraumatic stress disorder (PTSD) symptoms, and alcohol use were examined in 4072 male—male twin pairs who served in the United States military during the Vietnam era (1965–1975). Results indicate that the relationship between combat and alcohol use and between PTSD symptom factors and alcohol use were both substantially influenced by genetic factors. Findings are most consistent with a shared vulnerability model for the etiology of the association between PTSD symptoms and alcohol use. Specific unique environmental factors were more important than genetic factors for PTSD symptoms, and both factors were equally important for alcohol use. Further support is also found for the role of the unique environment in PTSD symptoms.
Sertraline, Paroxetine, and Venlafaxine in refugee posttraumatic stress disorder with depression symptoms
Authors: Smajkic Amer , Weine Stevan , Djuric‐Bijedic Zvezdana , Boskailo Esad , Lewis Jonathan , Pavkovic Ivan
Published: December 2002

Three new antidepressants were used in treating posttraumatic stress disorder (PTSD) and symptoms of depression in Bosnian refugees. Thirty‐two Bosnian refugees seeking treatment at a mental health clinic participated in a case series study. All received open trials of Sertraline (n = 15), Paroxetine (n = 12), or Venlafaxine (n = 5), with standard clinical doses. Overall, Sertraline and Paroxetine produced statistically significant improvement at 6 weeks in PTSD symptom severity, in depression, and in Global Assessment of Functioning. Venlafaxine produced improvement in PTSD symptom severity and in Global Assessment of Functioning did not yield improvement in symptoms of major depressive disorder, and had a high rate of side effects. Notwithstanding improvement of symptoms, all 32 refugees remained PTSD positive at the diagnostic level at the 6‐week follow‐up.
Enzyme replacement therapy in Fabry disease
Authors: Brady R. O. , Murray G. J. , Moore D. F. , Schiffmann R.
Published: December 2002

Recent clinical trials have demonstrated that enzyme replacement therapy with α‐galactosidase A (α‐Gal A) constitutes a major clinical advance in the treatment of patients with Fabry disease. This new therapeutic approach has been shown to be well tolerated and effective in reducing levels of the storage product globo‐triaosylceramide and in normalizing many of the debilitating manifestations of the disorder. A double‐blind placebo‐controlled trial in 26 hemizygous male patients showed that agalsidase alfa (human α‐Gal A) significantly reduced neuropathic pain (p= 0.02), increased creatinine clearance (p = 0.02), improved glomerular histology, reduced the QRS interval on electrocardiography and increased weight gain. Positron emission tomography also revealed normalization of cerebrovascular flow. After the 6‐month controlled period, all patients were given agalsidase alfa for a further12 months. At the end of this period, all patients had a decrease in neuropathic pain, and there was a significant improvement in their ability to sense heat and cold. In addition, renal function stabilized, even in patients with renal insufficiency at the onset of treatment, and patients reported a normalization of sweating and improvements in their level of energy and sense of well‐being. These findings show that enzyme replacement therapy offers promise as an effective management strategy for patients with Fabry disease.
Clinically relevant therapeutic endpoints in type I Gaucher disease
Authors: Hollak C. E. M. , Maas M. , Aerts J. M.
Published: December 2002

The introduction of enzyme supplementation therapy for Gaucherdisease has had a great impact on the lives of many patients. Organomegaly, cytopenia and bone disease have been shown to improve in response to treatment, resulting in an improvement in quality of life. However, the assessment of organ system involvement is not always done in such a way that the relationship with clinically relevant endpoints is clear. The lack of adequately validated methods of assessment, especially for bone disease, has hindered the establishment of treatment goals and guidelines for treatment optimization.
Multidimensional Profiles of Welfare and Work Dynamics: Development, Validation, and Associations with Child Cognitive and Mental Health Outcomes
Authors: Yoshikawa Hirokazu , Seidman Edward
Published: December 2002

This prospective longitudinal study addresses the research gap in the literature regarding multidimensional variation in welfare use and employment patterns, and relationships of such variation with parent earnings and child development outcomes. This study also aims to address the limitations of welfare dynamics studies that do not examine how multiple dimensions of welfare receipt and employment co‐occur. Cluster analysis was utilized, using monthly welfare and employment data from the National Longitudinal Survey of Youth, to examine variation within the welfare population in their welfare and work patterns across the first 5 years of children's lives. Six cluster profiles of welfare and work dynamics were found: Short‐Term, Short‐Term Work Exit, Working Cyclers, Nonworking Cyclers, Cycle to Long‐Term Exit, and Long‐Term. The clusters were validated using mother's 6th‐year earnings as the criterion. The clusters' associations with child development outcomes in the cognitive and mental health domains (at ages 6 and 7) were then explored. Work following short‐term welfare use was associated with higher child reading scores than that following long‐term use (a moderate‐size effect). Cycling on and off welfare in the context of high levels of employment was associated with higher child internalizing symptoms than cycling accompanied by low levels of employment (a moderate‐size effect). Implications for evaluation of TANF welfare‐to‐work policies are discussed.
Mouse Beta-Mannosidase: cDNA Cloning, Expression, and Chromosomal Localization
Authors: Beccari Tommaso , Bibi Lucia , Stinchi Sofia , Stirling John Laing , Orlacchio Aldo
Published: December 2002

β-mannosidase is an exoglycosidase involved in the degradation of N-linked oligosacharides moieties of glycoproteins. Lack of β-mannosidase activity leads to the lysosomal disorder β-mannosidosis (MIM 248510). We have isolated and sequenced the gene encoding the mouse β-mannosidase. Comparison of the deduced amino acid sequence of mouse, human, bovine, and goat β-mannosidase showed 64% identity, reflecting a high degree of evolutionary conservation. Analysis of a multiple tissue northern blotting revealed a major transcript of about 3.7 kb in all tissues examined. The northern analysis also demonstrates that there is differential tissue mRNA expression. The mouse β-mannosidase gene (Bmn) was mapped to the distal end of Chromosome (Chr) 3, in a region that is homologous with a segment of human Chr 4 containing the orthologous human gene.
Heat Production During Anesthetic-Induced Malignant Hyperthermia
Authors: Nelson Thomas E.
Published: December 2002

Malignant hyperthermia (MH) is a pharmacogenetic disease which predisposes to the trigger of a life-threatening, hypermetabolic syndrome by potent inhaled anesthetics and by depolarizing skeletal muscle relaxants. Heat production in the anesthetized MH can be profound with 5-fold increases in oxygen consumption. The trigger anesthetics cause an abnormal, sustained rise in myoplasmic calcium levels. Possible mechanisms by which continuous release of calcium from skeletal muscle sarcoplasmic reticulum stores can produce the profound hyperthermia are discussed. Mutations in the gene coding the ryanodine receptor calcium release channel have been found in MH families and these mutant channels may be the functionsl basis for MH.
Differential modulation of synaptic transmission by neuropeptide Y in rat neocortical neurons
Authors: Bacci Alberto , Huguenard John R. , Prince David A.
Published: December 2002

Neuropeptide Y (NPY) is widely expressed throughout the nervous system and is known to reduce excitatory (but also inhibitory) synaptic transmission in many CNS areas, leading to the proposal that it is an endogenous antiepileptic agent. In the neocortex, where NPY is present in γ-aminobutyric acid (GABA)ergic interneurons, its effects on inhibitory and excitatory synaptic activities have not been completely explored. Here we report that NPY application elicits a long-lasting
decrease
in evoked excitatory postsynaptic current amplitude and a delayed, long-lasting
increase
in the amplitude of evoked monosynaptic inhibitory postsynaptic current (IPSC) in layer V pyramidal neurons of rat neocortex. The novel, late, NPY-mediated increase of inhibitory synaptic transmission is caused by modulation of Ca
2+
-dependent GABA release onto pyramidal neurons, as it was accompanied by an increase in Ca
2+
-dependent miniature IPSC frequency. NPY
decreased
evoked monosynaptic IPSCs in GABAergic interneurons, indicating that this neuropeptide has differential effects on different neuronal subtypes in the neocortex. Each of these NPY actions would decrease excitability in cortical circuits, a result that has important implications for both physiological neocortical operations as well as pathophysiological epileptiform activities.
Distribution of nitric oxide synthase in normal and cirrhotic human liver
Authors: McNaughton Lance , Puttagunta Lakshmi , Martinez-Cuesta Maria Angeles , Kneteman Norm , Mayers Irvin , Moqbel Redwan , Hamid Qutayba , Radomski Marek W.
Published: December 2002

Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000–10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (
n
= 42) and control livers (
n
= 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including α
1
-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and
in situ
hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca
2+
-dependent and –independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by
in situ
hybridization. In diseased livers, there was a significant increase in Ca
2+
-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders.
Dicer is required for chromosome segregation and gene silencing in fission yeast cells
Authors: Provost Patrick , Silverstein Rebecca A. , Dishart David , Walfridsson Julian , Djupedal Ingela , Kniola Barbara , Wright Anthony , Samuelsson Bengt , Rådmark Olof , Ekwall Karl
Published: December 2002

RNA interference is a form of gene silencing in which the nuclease Dicer cleaves double-stranded RNA into small interfering RNAs. Here we report a role for Dicer in chromosome segregation of fission yeast. Deletion of the Dicer (
dcr1
+
) gene caused slow growth, sensitivity to thiabendazole, lagging chromosomes during anaphase, and abrogated silencing of centromeric repeats. As Dicer in other species, Dcr1p degraded double-stranded RNA into ≈23 nucleotide fragments
in vitro
, and
dcr1
Δ cells were partially rescued by expression of human Dicer, indicating evolutionarily conserved functions. Expression profiling demonstrated that
dcr1
+
was required for silencing of two genes containing a conserved motif.
Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblasts
Authors: Falet Hervé , Hoffmeister Karin M. , Neujahr Ralph , Italiano Joseph E. , Stossel Thomas P. , Southwick Frederick S. , Hartwig John H.
Published: December 2002

We investigated the effect of actin filament barbed end uncapping on Arp2/3 complex function both
in vivo
and
in vitro
. Arp2/3 complex redistributes rapidly and uniformly to the lamellar edge of activated wild-type platelets and fibroblasts but clusters in marginal actin filament clumps in gelsolin-null cells. Treatment of gelsolin-null platelets with the negative dominant N-WASp C-terminal CA domain has no effect on their residual actin nucleation activity, placing gelsolin actin filament severing, capping, and uncapping function upstream of Arp2/3 complex nucleation. Actin filaments capped by gelsolin or the gelsolin homolog CapG fail to enhance Arp2/3 complex nucleation
in vitro
, but uncapping of the barbed ends of these actin filaments restores their ability to potentiate Arp2/3 complex nucleation. We conclude that Arp2/3 complex contribution to actin filament nucleation in platelets and fibroblasts importantly requires free barbed ends generated by severing and uncapping.
Lévy laws in free probability
Authors: Barndorff-Nielsen Ole E. , Thorbjørnsen Steen
Published: December 2002

This article and its sequel outline recent developments in the theory of infinite divisibility and Lévy processes in free probability, a subject area belonging to noncommutative (or quantum) probability. The present paper discusses the classes of infinitely divisible probability measures in classical and free probability, respectively, via a study of the Bercovici–Pata bijection between these classes.
Sensitization of regulated exocytosis by protein kinase C
Authors: Zhu Hongliang , Hille Bertil , Xu Tao
Published: December 2002

Activation of protein kinase C (PKC) increases vesicular secretion in many cell types. We determined the calcium dependence of secretion and the size of the readily releasable pool of secretory granules in pituitary gonadotropes by photorelease of caged-calcium. The calcium affinity for exocytosis was roughly doubled by activation of PKC by a phorbol ester, whereas the size of the readily releasable pool was not greatly increased. The effect was due to activation of PKC, because it was blocked by a PKC inhibitor and was not mimicked by an inactive phorbol ester analogue. A similar increase in calcium sensitivity was induced by preincubation with gonadotropin-releasing hormone, the physiological releasing hormone. These findings provide direct evidence for physiological regulation of secretion by enhancement of Ca
2+
-sensing steps. Because exocytosis depends on the third- to fourth-power of intracellular free Ca
2+
concentration, this mechanism ensures a powerful up-regulation of hormone release and may explain how PKC can stimulate exocytosis without an increase of Ca
2+
above the resting level.
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences
Authors:   Mammalian Gene Collection (MGC) Program Team*
Published: December 2002

The National Institutes of Health Mammalian Gene Collection (MGC) Program is a multiinstitutional effort to identify and sequence a cDNA clone containing a complete ORF for each human and mouse gene. ESTs were generated from libraries enriched for full-length cDNAs and analyzed to identify candidate full-ORF clones, which then were sequenced to high accuracy. The MGC has currently sequenced and verified the full ORF for a nonredundant set of >9,000 human and >6,000 mouse genes. Candidate full-ORF clones for an additional 7,800 human and 3,500 mouse genes also have been identified. All MGC sequences and clones are available without restriction through public databases and clone distribution networks (see
http://mgc.nci.nih.gov
).
NOSTRIN: A protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase
Authors: Zimmermann Kirstin , Opitz Nils , Dedio Jürgen , Renné Christoph , Müller-Esterl Werner , Oess Stefanie
Published: December 2002

Activity and localization of endothelial nitric oxide synthase (eNOS) is regulated in a remarkably complex fashion, yet the complex molecular machinery mastering stimulus-induced eNOS translocation and trafficking is poorly understood. In a search by the yeast two-hybrid system using the eNOS oxygenase domain as bait, we have identified a previously uncharacterized eNOS-interacting protein, dubbed NOSTRIN (for eNOS traffic inducer). NOSTRIN contains a single polypeptide chain of 506-aa residues of 58 kDa with an N-terminal cdc15 domain and a C-terminal SH3 domain. NOSTRIN mRNA is abundant in highly vascularized tissues such as placenta, kidney, lung, and heart, and NOSTRIN protein is expressed in vascular endothelial cells. Coimmunoprecipitation experiments demonstrated the eNOS–NOSTRIN interaction
in vitro
and
in vivo
, and NOSTRIN's SH3 domain was essential and sufficient for eNOS binding. NOSTRIN colocalized extensively with eNOS at the plasma membrane of confluent human umbilical venous endothelial cells and in punctate cytosolic structures of CHO-eNOS cells. NOSTRIN overexpression induced a profound redistribution of eNOS from the plasma membrane to vesicle-like structures matching the NOSTRIN pattern and at the same time led to a significant inhibition of NO release. We conclude that NOSTRIN contributes to the intricate protein network controlling activity, trafficking, and targeting of eNOS.
Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics
Authors: Goh Ee-Been , Yim Grace , Tsui Wayne , McClure JoAnn , Surette Michael G. , Davies Julian
Published: December 2002

Antibiotics such as erythromycin and rifampicin, at low concentrations, alter global bacterial transcription patterns as measured by the stimulation or inhibition of a variety of promoter–
lux
reporter constructs in a
Salmonella typhimurium
library. Analysis of a 6,500-clone library indicated that as many as 5% of the promoters may be affected, comprising genes for a variety of functions, as well as a significant fraction of genes with no known function. Studies of a selection of the reporter clones showed that stimulation varied depending on the nature of the antibiotic, the promoter, and what culture medium was used; the response differed on solid as compared with liquid media. Transcription was markedly reduced in antibiotic-resistant hosts, but the presence of mutations deficient in stress responses such as SOS or universal stress did not prevent antibiotic-induced modulation. The results show that small molecules may have contrasting effects on bacteria depending on their concentration: either the modulation of bacterial metabolism by altering transcription patterns or the inhibition of growth by the inhibition of specific target functions. Both activities could play important roles in the regulation of microbial communities. These studies indicate that the detection of pharmaceutically useful natural product inhibitors could be effectively achieved by measuring activation of transcription at low concentrations in high-throughput assays using appropriate bacterial promoter–reporter constructs.
A systematic approach to reconstructing transcription networks in
Saccharomyces
cerevisiae
Authors: Wang Wei , Cherry J. Michael , Botstein David , Li Hao
Published: December 2002

Decomposing regulatory networks into functional modules is a first step toward deciphering the logical structure of complex networks. We propose a systematic approach to reconstructing transcription modules (defined by a transcription factor and its target genes) and identifying conditions/perturbations under which a particular transcription module is activated/deactivated. Our approach integrates information from regulatory sequences, genome-wide mRNA expression data, and functional annotation. We systematically analyzed gene expression profiling experiments in which the yeast cell was subjected to various environmental or genetic perturbations. We were able to construct transcription modules with high specificity and sensitivity for many transcription factors, and predict the activation of these modules under anticipated as well as unexpected conditions. These findings generate testable hypotheses when combined with existing knowledge on signaling pathways and protein–protein interactions. Correlating the activation of a module to a specific perturbation predicts links in the cell's regulatory networks, and examining coactivated modules suggests specific instances of crosstalk between regulatory pathways.
Identification and cloning of human polynucleotide phosphorylase,
hPNPase

old-35

, in the context of terminal differentiation and cellular senescence
Authors: Leszczyniecka Magdalena , Kang Dong-chul , Sarkar Devanand , Su Zao-zhong , Holmes Matthew , Valerie Kristoffer , Fisher Paul B.
Published: December 2002

Terminal differentiation and cellular senescence display common properties including irreversible growth arrest. To define the molecular and ultimately the biochemical basis of the complex physiological changes associated with terminal differentiation and senescence, an overlapping-pathway screen was used to identify genes displaying coordinated expression as a consequence of both processes. This approach involved screening of a subtracted cDNA library prepared from human melanoma cells induced to terminally differentiate by treatment with fibroblast IFN and mezerein with mRNA derived from senescent human progeria cells. This strategy identified
old-35
, which encodes an evolutionary conserved gene, human polynucleotide phosphorylase (

hPNPase
old-35

), that is regulated predominantly by type I IFNs. The hPNPase
OLD-35
protein localizes in the cytoplasm of human cells and induces RNA degradation
in vitro
, as does its purified bacterial protein homologue. Ectopic expression of

hPNPase
old-35

in human melanoma cells reduces colony formation, confirming inhibitory activity of this RNA-degradation enzyme. Identification of

hPNPase
old-35

, an IFN-inducible 3′-5′ RNA exonuclease, provides additional support for a relationship between IFN action and RNA processing and suggests an important role for this gene in growth control associated with terminal differentiation and cellular senescence.
An Ethiopian pattern of human adaptation to high-altitude hypoxia
Authors: Beall Cynthia M. , Decker Michael J. , Brittenham Gary M. , Kushner Irving , Gebremedhin Amha , Strohl Kingman P.
Published: December 2002

We describe, in Ethiopia, a third successful pattern of human adaptation to high-altitude hypoxia that contrasts with both the Andean “classic” (erythrocytosis with arterial hypoxemia) and the more recently identified Tibetan (normal venous hemoglobin concentration with arterial hypoxemia) patterns. A field survey of 236 Ethiopian native residents at 3,530 m (11,650 feet), 14–86 years of age, without evidence of iron deficiency, hemoglobinopathy, or chronic inflammation, found an average hemoglobin concentration of 15.9 and 15.0 g/dl for males and females, respectively, and an average oxygen saturation of hemoglobin of 95.3%. Thus, Ethiopian highlanders maintain venous hemoglobin concentrations and arterial oxygen saturation within the ranges of sea level populations, despite the unavoidable, universal decrease in the ambient oxygen tension at high altitude.
Crop pollination from native bees at risk from agricultural intensification
Authors: Kremen Claire , Williams Neal M. , Thorp Robbin W.
Published: December 2002

Ecosystem services are critical to human survival; in selected cases, maintaining these services provides a powerful argument for conserving biodiversity. Yet, the ecological and economic underpinnings of most services are poorly understood, impeding their conservation and management. For centuries, farmers have imported colonies of European honey bees (
Apis mellifera
) to fields and orchards for pollination services. These colonies are becoming increasingly scarce, however, because of diseases, pesticides, and other impacts. Native bee communities also provide pollination services, but the amount they provide and how this varies with land management practices are unknown. Here, we document the individual species and aggregate community contributions of native bees to crop pollination, on farms that varied both in their proximity to natural habitat and management type (organic versus conventional). On organic farms near natural habitat, we found that native bee communities could provide full pollination services even for a crop with heavy pollination requirements (e.g., watermelon,
Citrullus lanatus
), without the intervention of managed honey bees. All other farms, however, experienced greatly reduced diversity and abundance of native bees, resulting in insufficient pollination services from native bees alone. We found that diversity was essential for sustaining the service, because of year-to-year variation in community composition. Continued degradation of the agro-natural landscape will destroy this “free” service, but conservation and restoration of bee habitat are potentially viable economic alternatives for reducing dependence on managed honey bees.
Chemical complementation: A reaction-independent genetic assay for enzyme catalysis
Authors: Baker Kathleen , Bleczinski Colleen , Lin Hening , Salazar-Jimenez Gilda , Sengupta Debleena , Krane Sonja , Cornish Virginia W.
Published: December 2002

A high-throughput assay for enzyme activity has been developed that is reaction independent. In this assay, a small-molecule yeast three-hybrid system is used to link enzyme catalysis to transcription of a reporter gene
in vivo
. Here we demonstrate the feasibility of this approach by using a well-studied enzyme-catalyzed reaction, cephalosporin hydrolysis by the
Enterobacter cloacae
P99 cephalosporinase (β-lactam hydrolase, EC

). We show that the three-hybrid system can be used to read out cephalosporinase activity
in vivo
as a change in the level of transcription of a
lacZ
reporter gene and that the wild-type cephalosporinase can be isolated from a pool of inactive mutants by using a
lacZ
screen. The assay has been designed so that it can be applied to different chemical reactions without changing the components of the three-hybrid system. A reaction-independent high-throughput assay for protein function should be a powerful tool for protein engineering and enzymology, drug discovery, and proteomics.
Photoresponsive polymer–enzyme switches
Authors: Shimoboji Tsuyoshi , Larenas Edmund , Fowler Tim , Kulkarni Samarth , Hoffman Allan S. , Stayton Patrick S.
Published: December 2002

The ability to photoregulate enzyme activities could provide important new opportunities for development of diagnostic assays, sequential bioprocessing, and lab assays in both traditional and microfluidic formats. We show here that the photoinduced changes in the size and hydration of a “smart” polymer chain coil can be used to regulate substrate access and enzyme activity when conjugated to the enzyme at a specific point just outside the active site. The photoresponsive polymers thus serve jointly as antennae and actuators that reversibly respond to distinct optical signals to switch the polymer–enzyme conjugates on and off, and work when the conjugate is free in solution or when immobilized on magnetic beads.
Direct imaging of nanoscale magnetic interactions in minerals
Authors: Harrison Richard J. , Dunin-Borkowski Rafal E. , Putnis Andrew
Published: December 2002

The magnetic microstructure of a natural, finely exsolved intergrowth of submicron magnetite blocks in an ulvöspinel matrix is characterized by using off-axis electron holography in the transmission electron microscope. Single-domain and vortex states in individual blocks, as well as magnetostatic interaction fields between them, are imaged at a spatial resolution approaching the nanometer scale. The images reveal an extremely complicated magnetic structure dominated by the shapes of the blocks and magnetostatic interactions. Magnetic superstates, in which clusters of magnetite blocks act collectively to form vortex and multidomain states that have zero net magnetization, are observed directly.
Polyphosphate kinase (PPK2), a potent, polyphosphate-driven generator of GTP
Authors: Ishige Kazuya , Zhang Haiyu , Kornberg Arthur
Published: December 2002

An enzyme that uses inorganic polyphosphate (poly P) as a donor to convert GDP to GTP has been purified 1,300-fold to homogeneity from lysates of
Pseudomonas aeruginosa
PAOM5. Poly P chains of 30–50 residues are optimal; those of 15–700 residues can also serve. GDP is preferred over ADP among nucleoside diphosphate acceptors. This nucleoside diphosphate kinase (NDK) activity resides in the same protein isolated for its synthesis of poly P from GTP and designated PPK2 in an accompanying report. The reaction that synthesizes poly P and the reaction that utilizes poly P differ in their kinetic features. Especially notable is the catalytic potency of the NDK activity, which is 75-fold greater than that of poly P synthesis. PPK2 appears in the stationary phase of growth and reaches NDK levels of 5–10% that of the classic NDK; both kinase activities may figure in the generation of the guanosine precursors in the synthesis of alginate, an exopolysaccharide essential for the virulence of
P. aeruginosa
.
The promoter of IL-18 binding protein: Activation by an IFN-γ-induced complex of IFN regulatory factor 1 and CCAAT/enhancer binding protein β
Authors: Hurgin Vladimir , Novick Daniela , Rubinstein Menachem
Published: December 2002

The IL-18 binding protein (IL-18BP) is a circulating inhibitor of the proinflammatory cytokine IL-18. It is constitutively expressed in mononuclear cells, and elevated expression is induced by IFN-γ. In this study, we characterized the IL-18BP promoter. We first showed that induction is at the transcriptional level and requiresde novoprotein synthesis. The IL-18BP promoter resides within 1.6 kb DNA upstream of the first exon and includes at least six regulatory elements. We identified in the basal promoter a gamma-activated sequence (GAS) proximal to the transcription start site (base 1), followed by an IFN regulatory factor 1 response element (IRF-E) and two CCAAT/enhancer binding protein β (C/EBPβ) sites, all of which are essential for basal promoter activity. Furthermore, GAS and IRF-E were essential for IFN-γ-induced transcription. Indeed, sera of IRF-1-deficient mice lacked basal and IFN-γ-induced IL-18BP. We found that after induction of IRF-1 by IFN-γ, it formed a complex with C/EBPβ, which bound to the IRF-E and GAS-containing proximal DNA. In contrast, the IFN-γ-induced signal transducer and activator of transcription 1 dimer did not associate with this GAS. In addition, we identified a silencer element and a distal enhancer at bases −1081 to −1272, which was also physically associated with IRF-1. The IRF-1–C/EBPβ complex described here probably plays a fundamental role in regulating additional IFN-γ-responsive genes.
Functional reorganization and stability of somatosensory-motor cortical topography in a tetraplegic subject with late recovery
Authors: Corbetta Maurizio , Burton Harold , Sinclair Robert J. , Conturo Thomas E. , Akbudak Erbil , McDonald John W.
Published: December 2002

The functional organization of somatosensory and motor cortex was investigated in an individual with a high cervical spinal cord injury, a 5-year absence of nearly all sensory/motor function at and below the shoulders, and rare recovery of some function in years 6–8 after intense and sustained rehabilitation therapies. We used functional magnetic resonance imaging to study brain activity to vibratory stimulation and voluntary movements of body parts above and below the lesion. No response to vibratory stimulation of the hand was observed in the primary somatosensory cortex (SI) hand area, which was conversely recruited during tongue movements that normally evoke responses only in the more lateral face area. This result suggests SI reorganization analogous to previously reported neuroplasticity changes after peripheral lesions in animals and humans. In striking contradistinction, vibratory stimulation of the foot evoked topographically appropriate responses in SI and second somatosensory cortex (SII). Motor cortex responses, tied to a visuomotor tracking task, displayed a near-typical topography, although they were more widespread in premotor regions. These findings suggest possible preservation of motor and some somatosensory cortical representations in the absence of overt movements or conscious sensations for several years after spinal cord injury and have implications for future rehabilitation and neural-repair therapies.
Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli
Authors: Arnoult Damien , Parone Philippe , Martinou Jean-Claude , Antonsson Bruno , Estaquier Jérôme , Ameisen Jean Claude
Published: December 2002

Mitochondrial outer membrane permeabilization by proapoptotic Bcl-2 family proteins, such as Bax, plays a crucial role in apoptosis induction. However, whether this only causes the intracytosolic release of inducers of caspase-dependent death, such as cytochrome c, or also of caspase-independent death, such as apoptosis-inducing factor (AIF) remains unknown. Here, we show that on isolated mitochondria, Bax causes the release of cytochrome c, but not of AIF, and the association of AIF with the mitochondrial inner membrane provides a simple explanation for its lack of release upon Bax-mediated outer membrane permeabilization. In cells overexpressing Bax or treated either with the Bax- or Bak-dependent proapoptotic drugs staurosporine or actinomycin D, or with hydrogen peroxide, caspase inhibitors did not affect the intracytosolic translocation of cytochrome c, but prevented that of AIF. These results provide a paradigm for mitochondria-dependent death pathways in which AIF cannot substitute for caspase executioners because its intracytosolic release occurs downstream of that of cytochrome c.
Search for structural similarity in proteins
Authors: Leluk Jacek , Konieczny Leszek , Roterman Irena
Published: December 2002

Motivation: The expanding protein sequence and structure databases await methods allowing rapid similarity search. Geometric parameters—dihedral angle between two sequential peptide bond planes (V) and radius of curvature (R) as they appear in pentapeptide fragments in polypeptide chains—are proposed for use in evaluating structural similarity in proteins (VeaR). The parabolic (empirical) function expressing the radius of curvature’s dependence on the V-angle in model polypeptides is altered in real proteins in a form characteristic for a particular protein. This can be used as a criterion for judging similarity.

Results: A structural comparison of proteins representing a wide spectrum of structures was assessed versus sequence similarity analysis based on the genetic semihomology algorithm. The term ‘consensus structure’, analogous to ‘consensus sequence’, was introduced for the serpine family.

Availability: Semihom—sequence comparison freely available on request from J. Leluk. VeaR—structural comparison freely available on request from I. Roterman.

Contact: lulu@bf.uni.wroc.pl for SEMIHOM program myroterm@cyf-kr.edu.pl for VeaR program.

* To whom correspondence should be addressed.
MAVG: locating non-overlapping maximum average segments
in a given sequence
Authors: Lin Yaw-Ling , Huang Xiaoqiu , Jiang Tao , Chao Kun-Mao
Published: December 2002

Summary: MAVG is a software tool for finding k non-overlapping maximum-average segments that are sufficiently long in a given sequence of real numbers, for any k > 0. It has applications in several areas of biomolecular sequence analysis including locating GC-rich regions and CpG islands in a genomic sequence, and annotating multiple sequence alignments.

Availability: http://iubio.bio.indiana.edu/soft/molbio/pattern/cpg_islands/

Contact: kmchao@csie.ntu.edu.tw

* To whom correspondence should be addressed.
Microarray data assembler
Authors: Anbazhagan Ramswamy
Published: December 2002

Summary: Large volumes of microarray data are generated and deposited in public databases. Most of this data is in the form of tab-delimited text files or Excel spreadsheets. Combining data from several of these files to reanalyze these data sets is time consuming. Microarray Data Assembler is specifically designed to simplify this task. The program can list files and data sources, convert selected text files into Excel files and assemble data across multiple Excel worksheets and workbooks. This program thus makes data assembling easy, saves time and helps avoid manual error.

Availability: The program is freely available for non-profit use, via email request from the author, after signing a Material Transfer Agreement with Johns Hopkins University.

Contact: anba@jhmi.edu

* To whom correspondence should be addressed.
Analysis of whole-genome microarray replicates using mixed models
Authors: Wernisch Lorenz , Kendall Sharon L. , Soneji Shamit , Wietzorrek Andreas , Parish Tanya , Hinds Jason , Butcher Philip D. , Stoker Neil G.
Published: December 2002

Motivation: Microarray experiments are inherently noisy. Replication is the key to estimating realistic fold-changes despite such noise. In the analysis of the various sources of noise the dependency structure of the replication needs to be taken into account.

Results: We analyzed replicate data sets from a Mycobacterium tuberculosis trcS mutant in order to identify differentially expressed genes and suggest new methods for filtering and normalizing raw array data and for imputing missing values. Mixed ANOVA models are applied to quantify the various sources of error. Such analysis also allows us to determine the optimal number of samples and arrays. Significance values for differential expression are obtained by a hierarchical bootstrapping scheme on scaled residuals. Four highly upregulated genes, including bfrB, were analyzed further. We observed an artefact, where transcriptional readthrough from these genes led to apparent upregulation of adjacent genes.

Availability: All methods and data discussed are available in the package YASMAhttp://www.cryst.bbk.ac.uk/wernisch/yasma.html for the statistical data analysis system R (http://www.R-project.org).

Contact: l.wernisch@bbk.ac.uk

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Prediction of biologically significant components from microarray data:
Independently Consistent Expression Discriminator (ICED)
Authors: Bijlani Rahul , Cheng Yinhe , Pearce David A. , Brooks Andrew I. , Ogihara Mitsunori
Published: December 2002

Motivation: Class distinction is a supervised learning approach that has been successfully employed in the analysis of high-throughput gene expression data. Identification of a set of genes that predicts differential biological states allows for the development of basic and clinical scientific approaches to the diagnosis of disease. The Independent Consistent Expression Discriminator (ICED) was designed to provide a more biologically relevant search criterion during predictor selection by embracing the inherent variability of gene expression in any biological state. The four components of ICED include (i) normalization of raw data; (ii) assignment of weights to genes from both classes; (iii) counting of votes to determine optimal number of predictor genes for class distinction; (iv) calculation of prediction strengths for classification results. The search criteria employed by ICED is designed to identify not only genes that are consistently expressed at one level in one class and at a consistently different level in another class but identify genes that are variable in one class and consistent in another. The result is a novel approach to accurately select biologically relevant predictors of differential disease states from a small number of microarray samples.

Results: The data described herein utilized ICED to analyze the large AML/ALL training and test data set (Golub et al., 1999, Science, 286, 531–537) in addition to a smaller data set consisting of an animal model of the childhood neurodegenerative disorder, Batten disease, generated for this study. Both of the analyses presented herein have correctly predicted biologically relevant perturbations that can be used for disease classification, irrespective of sample size. Furthermore, the results have provided candidate proteins for future study in understanding the disease process and the identification of potential targets for therapeutic intervention.

Contact: andrew_brooks@urmc.rochester.edu

* To whom correspondence should be addressed.

† The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
Gene selection: a Bayesian variable selection approach
Authors: Lee Kyeong Eun , Sha Naijun , Dougherty Edward R. , Vannucci Marina , Mallick Bani K.
Published: December 2002

Selection of significant genes via expression patterns is an important problem in microarray experiments. Owing to small sample size and the large number of variables (genes), the selection process can be unstable. This paper proposes a hierarchical Bayesian model for gene (variable) selection. We employ latent variables to specialize the model to a regression setting and uses a Bayesian mixture prior to perform the variable selection. We control the size of the model by assigning a prior distribution over the dimension (number of significant genes) of the model. The posterior distributions of the parameters are not in explicit form and we need to use a combination of truncated sampling and Markov Chain Monte Carlo (MCMC) based computation techniques to simulate the parameters from the posteriors. The Bayesian model is flexible enough to identify significant genes as well as to perform future predictions. The method is applied to cancer classification via cDNA microarrays where the genes BRCA1 and BRCA2 are associated with a hereditary disposition to breast cancer, and the method is used to identify a set of significant genes. The method is also applied successfully to the leukemia data.

Supplementary information: http://stat.tamu.edu/people/faculty/bmallick.html

Contact: bmallick@stat.tanu.edu

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The Psychology of Religion
Authors: Emmons Robert A. , Paloutzian Raymond F.
Published: December 2002

This chapter discusses progress in the psychology of religion by highlighting its rapid growth during the past 25 years. Recent conceptual and empirical developments are described, with an emphasis on the cognitive and affective basis of religious experience within personality and social psychology. Religion and spirituality as domains of study, as well as being common and important process variables that touch a large portion of human experience, are highlighted. Movement away from the previously dominant measurement paradigm is noted, and particularly promising directions suggestive of an emerging interdisciplinary paradigm are described.
Human-Computer Interaction: Psychological Aspects of the Human Use of Computing
Authors: Olson Gary M. , Olson Judith S.
Published: December 2002

Human-computer interaction (HCI) is a multidisciplinary field in which psychology and other social sciences unite with computer science and related technical fields with the goal of making computing systems that are both useful and usable. It is a blend of applied and basic research, both drawing from psychological research and contributing new ideas to it. New technologies continuously challenge HCI researchers with new options, as do the demands of new audiences and uses. A variety of usability methods have been developed that draw upon psychological principles. HCI research has expanded beyond its roots in the cognitive processes of individual users to include social and organizational processes involved in computer usage in real environments as well as the use of computers in collaboration. HCI researchers need to be mindful of the longer-term changes brought about by the use of computing in a variety of venues.
Personality, Culture, and Subjective Well-Being: Emotional and Cognitive Evaluations of Life
Authors: Diener Ed , Oishi Shigehiro , Lucas Richard E.
Published: December 2002

Subjective well-being (SWB), people's emotional and cognitive evaluations of their lives, includes what lay people call happiness, peace, fulfillment, and life satisfaction. Personality dispositions such as extraversion, neuroticism, and self-esteem can markedly influence levels of SWB. Although personality can explain a significant amount of the variability in SWB, life circumstances also influence long-term levels. Cultural variables explain differences in mean levels of SWB and appear to be due to objective factors such as wealth, to norms dictating appropriate feelings and how important SWB is considered to be, and to the relative approach versus avoidance tendencies of societies. Culture can also moderate which variables most influence SWB. Although it is challenging to assess SWB across societies, the measures have some degree of cross-cultural validity. Although nations can be evaluated by their levels of SWB, there are still many open questions in this area.
Progress and Controversy in the Study of Posttraumatic Stress Disorder
Authors: McNally Richard J.
Published: December 2002

Research on posttraumatic stress disorder (PTSD) has been notable for controversy as well as progress. This article concerns the evidence bearing on the most contentious issues in the field of traumatic stress: broadening of the definition of trauma, problems with the dose-response model of PTSD, distortion in the recollection of trauma, concerns about “phony combat vets,” psychologically toxic guilt as a traumatic stressor, risk factors for PTSD, possible brain-damaging effects of stress hormones, recovered memories of childhood sexual abuse, and the politics of trauma.