bluuebunny/crossref_metadata_2025 huggingface dataset:
Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis
Authors: Gutiérrez Laura , Tsukamoto Saho , Suzuki Mikiko , Yamamoto-Mukai Harumi , Yamamoto Masayuki , Philipsen Sjaak , Ohneda Kinuko
Published: February 2008

The transcription factor Gata1 is expressed in several hematopoietic lineages and plays essential roles in normal hematopoietic development during embryonic stages. The lethality of Gata1-null embryos has precluded determination of its role in adult erythropoiesis. Here we have examined the effects of Gata1 loss in adult erythropoiesis using conditional Gata1 knockout mice expressing either interferon- or tamoxifen-inducible Cre recombinase (Mx-Cre and Tx-Cre, respectively). Mx-Cre–mediated Gata1 recombination, although incomplete, resulted in maturation arrest of Gata1-null erythroid cells at the proerythroblast stage, thrombocytopenia, and excessive proliferation of megakaryocytes in the spleen. Tx-Cre–mediated Gata1 recombination resulted in depletion of the erythroid compartment in bone marrow and spleen. Formation of the early and late erythroid progenitors in bone marrow was significantly reduced in the absence of Gata1. Furthermore, on treatment with a hemolytic agent, these mice failed to activate a stress erythropoietic response, despite the rising erythropoietin levels. These results indicate that, in addition to the requirement of Gata1 in adult megakaryopoiesis, Gata1 is necessary for steady-state erythropoiesis and for erythroid expansion in response to anemia. Thus, ablation of Gata1 in adult mice results in a condition resembling aplastic crisis in human.
Is tandem autotransplantation necessary in myeloma?
Authors: Jagannath Sundar
Published: February 2008

In this issue of Blood, Abdelkefi and coworkers use a randomized trial to show that the immunomodulatory agent thalidomide, applied after a single transplantation for 6 months, results in improved response rates and better progression-free and overall survival (OS) compared with tandem transplantation.
DAT ± AHA = bad CLL
Authors: Dyer Martin J. S.
Published: February 2008

Autoimmune complications arise commonly in chronic lymphocytic leukemia and may become life-threatening. Dearden and colleagues have analyzed the results of the UK Leukaemia Research CLL4 clinical trial and have come up with some interesting and unanticipated conclusions.
Dissecting “stress” in Fanconi anemia
Authors: Dokal Inderjeet
Published: February 2008

Briot and colleagues provide compelling evidence that aberrant activation of the MAPK stress-signaling cascade, which results in TNF-α oversecretion, plays an important role in the pathophysiology of Fanconi anemia.
Human glycolipid transfer protein (GLTP) genes: organization, transcriptional status and evolution
Authors: Zou Xianqiong , Chung Taeowan , Lin Xin , Malakhova Margarita L , Pike Helen M , Brown Rhoderick E
Published: February 2008

Background

Glycolipid transfer protein is the prototypical and founding member of the new GLTP superfamily distinguished by a novel conformational fold and glycolipid binding motif. The present investigation provides the first insights into the organization, transcriptional status, phylogenetic/evolutionary relationships of GLTP genes.

Results

In human cells, single-copy GLTP genes were found in chromosomes 11 and 12. The gene at locus 11p15.1 exhibited several features of a potentially active retrogene, including a highly homologous (~94%), full-length coding sequence containing all key amino acid residues involved in glycolipid liganding. To establish the transcriptional activity of each human GLTP gene, in silico EST evaluations, RT-PCR amplifications of GLTP transcript(s), and methylation analyses of regulator CpG islands were performed using various human cells. Active transcription was found for 12q24.11 GLTP but 11p15.1 GLTP was transcriptionally silent. Heterologous expression and purification of the GLTP paralogs showed glycolipid intermembrane transfer activity only for 12q24.11 GLTP. Phylogenetic/evolutionary analyses indicated that the 5-exon/4-intron organizational pattern and encoded sequence of 12q24.11 GLTP were highly conserved in therian mammals and other vertebrates. Orthologs of the intronless GLTP gene were observed in primates but not in rodentiates, carnivorates, cetartiodactylates, or didelphimorphiates, consistent with recent evolutionary development.

Conclusion

The results identify and characterize the gene responsible for GLTP expression in humans and provide the first evidence for the existence of a GLTP pseudogene, while demonstrating the rigorous approach needed to unequivocally distinguish transcriptionally-active retrogenes from silent pseudogenes. The results also rectify errors in the Ensembl database regarding the organizational structure of the actively transcribed GLTP gene in Pan troglodytes and establish the intronless GLTP as a primate-specific, processed pseudogene marker. A solid foundation has been established for future identification of hereditary defects in human GLTP genes.
Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection
Authors: Thiersch Markus , Raffelsberger Wolfgang , Frigg Rico , Samardzija Marijana , Wenzel Andreas , Poch Olivier , Grimm Christian
Published: February 2008

Background

Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. To address the molecular mechanisms of the protection, we analyzed the transcriptome of the hypoxic retina using microarrays and real-time PCR.

Results

Hypoxic exposure induced a marked alteration in the retinal transcriptome with significantly different expression levels of 431 genes immediately after hypoxic exposure. The normal expression profile was restored within 16 hours of reoxygenation. Among the differentially regulated genes, several candidates for neuroprotection were identified like metallothionein-1 and -2, the HIF-1 target gene adrenomedullin and the gene encoding the antioxidative and cytoprotective enzyme paraoxonase 1 which was previously not known to be a hypoxia responsive gene in the retina. The strongly upregulated cyclin dependent kinase inhibitor p21 was excluded from being essential for neuroprotection.

Conclusion

Our data suggest that neuroprotection after hypoxic preconditioning is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult.
Asymmetric competitive suppression between strains of dengue virus
Authors: Pepin Kim M , Lambeth Kalli , Hanley Kathryn A
Published: February 2008

Background

Within-host competition between strains of a vector-borne pathogen can affect strain frequencies in both the host and vector, thereby affecting viral population dynamics. However little is known about inter-strain competition in one of the most genetically diverse and epidemiologically important mosquito-borne RNA virus: dengue virus (DENV). To assess the strength and symmetry of intra-host competition among different strains of DENV, the effect of mixed infection of two DENV serotypes, DENV2 and DENV4, on the replication of each in cultured mosquito cells was tested. The number of infectious particles produced by each DENV strain in mixed infections was compared to that in single infections to determine whether replication of each strain was decreased in the presence of the other strain (i.e., competition). The two DENV strains were added to cells either simultaneously (coinfection) or with a 1 or 6-hour time lag between first and second serotype (superinfection).

Results

DENV2 and DENV4 showed significantly reduced replication in mixed infection relative to single infection treatments. In superinfection treatments, replication was suppressed to a greater extent when the interval between addition of each strain was longer, and when a strain was added second. Additionally, competitive effects were asymmetric: although both strains replicated to similar peak population sizes in single infections, DENV2 was more suppressed than DENV4 in mixed infections. Superinfection treatments yielded significantly lower combined virus titers than coinfection or single infection treatments.

Conclusion

Competition between DENV strains in cultured mosquito cells can cause a significant decrease in peak viral population sizes, which could translate to decreased transmission by the vector. Effects of competition were asymmetric between DENV2 and DENV4, probably reflecting significant variation in the competitive ability of DENV strains in nature. Competition was strongest in superinfection treatments, suggesting that colonization of new DENV strains could be impeded in areas where numerous mosquitoes are infected with endemic DENV strains.
Structural analysis of inhibition of E. coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes
Authors: Ma Ze-Qiang , Xie Sheng-Xue , Huang Qing-Qing , Nan Fa-Jun , Hurley Thomas D , Ye Qi-Zhuang
Published: February 2008

Background

Methionine aminopeptidase is a potential target of future antibacterial and anticancer drugs. Structural analysis of complexes of the enzyme with its inhibitors provides valuable information for structure-based drug design efforts.

Results

Five new X-ray structures of such enzyme-inhibitor complexes were obtained. Analysis of these and other three similar structures reveals the adaptability of a surface-exposed loop bearing Y62, H63, G64 and Y65 (the YHGY loop) that is an integral part of the substrate and inhibitor binding pocket. This adaptability is important for accommodating inhibitors with variations in size. When compared with the human isozymes, this loop either becomes buried in the human type I enzyme due to an N-terminal extension that covers its position or is replaced by a unique insert in the human type II enzyme.

Conclusion

The adaptability of the YHGY loop in E. coli methionine aminopeptidase, and likely in other bacterial methionine aminopeptidases, enables the enzyme active pocket to accommodate inhibitors of differing size. The differences in this adaptable loop between the bacterial and human methionine aminopeptidases is a structural feature that can be exploited to design inhibitors of bacterial methionine aminopeptidases as therapeutic agents with minimal inhibition of the corresponding human enzymes.
Self-care and adherence to medication: a survey in the hypertension outpatient clinic
Authors: Gohar Faekah , Greenfield Sheila M , Beevers D Gareth , Lip Gregory YH , Jolly Kate
Published: February 2008

Background

Self-care practices for patients with hypertension include adherence to medication, use of blood pressure self-monitoring and use of complementary and alternative therapies (CAM) The prevalence of CAM use and blood pressure self-monitoring have not been described in a UK secondary care population of patients with hypertension and their impact on adherence to medication has not been described. Adherence to medication is important for blood pressure control, but poor adherence is common. The study aimed to determine the prevalence of self-care behaviours in patients attending a secondary care hypertension clinic.

Methods

Cross-sectional questionnaire survey. 196 patients attending a secondary care hypertension clinic in a teaching hospital serving a multiethnic population, Birmingham, UK. Main outcome measures: Prevalence of use of CAM, home monitors, adherence to anti-hypertensive medication.

Results

CAM use in previous 12 months was reported by 66 (43.1%) respondents. CAM users did not differ statistically from non-CAM users by age, gender, marital status or education. Vitamins, prayer a dietary supplements were the most commonly used CAM. Nine (12.7%) women reported using herbal CAM compared to one man (1.2%), (p = 0.006). Ten (6.7%) respondents reported ever being asked by a doctor about CAM use. Perfect adherence to anti-hypertensive medication was reported by 26 (44.8%) CAM-users and 46 (60.5%) non-CAM users (p = 0.07). Being female and a CAM user was significantly associated with imperfect adherence to anti-hypertensive medication. Older and white British respondents were significantly more likely to report perfect adherence. Blood pressure monitors were used by 67 (43.8%) respondents, which was not associated with gender, CAM use or adherence to medication.

Conclusion

Hypertensive patients use a variety of self-care methods, including CAM, home blood pressure monitors, and adherence to prescribed medication. This study found the prevalence of CAM use in hypertensive patients was higher than in the UK population. It is important to acknowledge the self-care behaviour of hypertensive patients, in order to assess potential harm, and encourage effective methods of self-care.
Host erythrocyte polymorphisms and exposure to Plasmodium falciparum in Papua New Guinea
Authors: Fowkes Freya JI , Michon Pascal , Pilling Lynn , Ripley Ruth M , Tavul Livingstone , Imrie Heather J , Woods Caira M , Mgone Charles S , Luty Adrian JF , Day Karen P
Published: February 2008

Background

The protection afforded by human erythrocyte polymorphisms against the malaria parasite, Plasmodium falciparum, has been proposed to be due to reduced ability of the parasite to invade or develop in erythrocytes. If this were the case, variable levels of parasitaemia and rates of seroconversion to infected-erythrocyte variant surface antigens (VSA) should be seen in different host genotypes.

Methods

To test this hypothesis, P. falciparum parasitaemia and anti-VSA antibody levels were measured in a cohort of 555 asymptomatic children from an area of intense malaria transmission in Papua New Guinea. Linear mixed models were used to investigate the effect of α+-thalassaemia, complement receptor-1 and south-east Asian ovalocytosis, as well as glucose-6-phosphate dehydrogenase deficiency and ABO blood group on parasitaemia and age-specific seroconversion to VSA.

Results

No host polymorphism showed a significant association with both parasite prevalence/density and age-specific seroconversion to VSA.

Conclusion

Host erythrocyte polymorphisms commonly found in Papua New Guinea do not effect exposure to blood stage P. falciparum infection. This contrasts with data for sickle cell trait and highlights that the above-mentioned polymorphisms may confer protection against malaria via distinct mechanisms.
Topical anti-inflammatory activity of Polygonum cuspidatum extract in the TPA model of mouse ear inflammation
Authors: Bralley Eve E , Greenspan Phillip , Hargrove James L , Wicker Louise , Hartle Diane K
Published: February 2008

Background

This study tested the ability of a characterized extract ofPolygonum cuspidatum(PCE) to inhibit mouse ear inflammation in response to topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA).

Methods

A 50% (wt:vol) ethanolic solution of commercial 200:1 PCE was applied to both ears of female Swiss mice (n = 8) at 0.075, 0.15, 0.3, 1.25 and 2.5 mg/ear 30 min after TPA administration (2 μg/ear). For comparison, 3 other groups were treated with TPA and either 1) the vehicle (50% ethanol) alone, 2) indomethacin (0.5 mg/ear), or 3)trans-resveratrol (0.62 mg/ear). Ear thickness was measured before TPA and at 4 and 24 h post-TPA administration to assess ear edema. Ear punch biopsies were collected at 24 h and weighed as a second index of edema. Myeloperoxidase activity was measured in each ear punch biopsy to assess neutrophil infiltration.

Results

PCE treatment at all doses significantly reduced ear edema compared to the TPA control. The PCE response was dose-dependent and 2.5 mg PCE significantly inhibited all markers of inflammation to a greater extent than indomethacin (0.5 mg). MPO activity was inhibited at PCE doses ≥ 1.25 mg/ear.Trans-resveratrol inhibited inflammation at comparable doses.

Conclusion

PCE inhibits development of edema and neutrophil infiltration in the TPA-treated mouse ear model of topical inflammation.
Organ distribution of transgene expression following intranasal mucosal delivery of recombinant replication-defective adenovirus gene transfer vector
Authors: Damjanovic Daniela , Zhang Xizhong , Mu Jingyu , Fe Medina Maria , Xing Zhou
Published: February 2008

It is believed that respiratory mucosal immunization triggers more effective immune protection than parenteral immunization against respiratory infection caused by viruses and intracellular bacteria. Such understanding has led to the successful implementation of intranasal immunization in humans with a live cold-adapted flu virus vaccine. Furthermore there has been an interest in developing effective mucosal-deliverable genetic vaccines against other infectious diseases. However, there is a concern that intranasally delivered recombinant viral-based vaccines may disseminate to the CNS via the olfactory tissue. Initial experimental evidence suggests that intranasally delivered recombinant adenoviral gene transfer vector may transport to the olfactory bulb. However, there is a lack of quantitative studies to compare the relative amounts of transgene products in the respiratory tract, lung, olfactory bulb and brain after intranasal mucosal delivery of viral gene transfer vector. To address this issue, we have used fluorescence macroscopic imaging, luciferase quantification and PCR approaches to compare the relative distribution of transgene products or adenoviral gene sequences in the respiratory tract, lung, draining lymph nodes, olfactory bulb, brain and spleen. Intranasal mucosal delivery of replication-defective recombinant adenoviral vector results in gene transfer predominantly in the respiratory system including the lung while it does lead to a moderate level of gene transfer in the olfactory bulb. However, intranasal inoculation of adenoviral vector leads to little or no viral dissemination to the major region of the CNS, the brain. These experimental findings support the efficaciousness of intranasal adenoviral-mediated gene transfer for the purpose of mucosal immunization and suggest that it may not be of significant safety concern.
Autotaxin, a Synthetic Enzyme of Lysophosphatidic Acid (LPA), Mediates the Induction of Nerve-Injured Neuropathic Pain
Authors: Inoue Makoto , Ma Lin , Aoki Junken , Chun Jerold , Ueda Hiroshi
Published: February 2008

Recently, we reported that lysophosphatidic acid (LPA) induces long-lasting mechanical allodynia and thermal hyperalgesia as well as demyelination and upregulation of pain-related proteins through one of its cognate receptors, LPA1. In addition, mice lacking the LPA1 receptor gene ( lpa 1-/- mice) lost these nerve injury-induced neuropathic pain behaviors and phenomena. However, since lpa 1-/- mice did not exhibit any effects on the basal nociceptive threshold, it is possible that nerve injury-induced neuropathic pain and its machineries are initiated by LPA via defined biosynthetic pathways that involve multiple enzymes. Here, we attempted to clarify the involvement of a single synthetic enzyme of LPA known as autotaxin (ATX) in nerve injury-induced neuropathic pain. Wild-type mice with partial sciatic nerve injury showed robust mechanical allodynia starting from day 3 after the nerve injury and persisting for at least 14 days, along with thermal hyperalgesia. On the other hand, heterozygous mutant mice for the autotaxin gene ( atx+/-), which have 50% ATX protein and 50% lysophospholipase D activity compared with wild-type mice, showed approximately 50% recovery of nerve injury-induced neuropathic pain. In addition, hypersensitization of myelinated A[Formula: see text] - or Aδ-fiber function following nerve injury was observed in electrical stimuli-induced paw withdrawal tests using a Neurometer®. The hyperalgesia was completely abolished in lpa 1-/- mice, and reduced by 50% in atx+/- mice. Taken together, these findings suggest that LPA biosynthesis through ATX is the source of LPA for LPA1 receptor-mediated neuropathic pain. Therefore, targeted inhibition of ATX-mediated LPA biosynthesis as well as LPA1 receptor and its downstream pathways may represent a novel way to prevent nerve injury-induced neuropathic pain.
Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks
Authors: Oliveira Ana Paula , Patil Kiran Raosaheb , Nielsen Jens
Published: February 2008

Background

Uncovering the operating principles underlying cellular processes by using 'omics' data is often a difficult task due to the high-dimensionality of the solution space that spans all interactions among the bio-molecules under consideration. A rational way to overcome this problem is to use the topology of bio-molecular interaction networks in order to constrain the solution space. Such approaches systematically integrate the existing biological knowledge with the 'omics' data.

Results

Here we introduce a hypothesis-driven method that integrates bio-molecular network topology with transcriptome data, thereby allowing the identification of key biological features (Reporter Features) around which transcriptional changes are significantly concentrated. We have combined transcriptome data with different biological networks in order to identify Reporter Gene Ontologies, Reporter Transcription Factors, Reporter Proteins and Reporter Complexes, and use this to decipher the logic of regulatory circuits playing a key role in yeast glucose repression and human diabetes.

Conclusion

Reporter Features offer the opportunity to identify regulatory hot-spots in bio-molecular interaction networks that are significantly affected between or across conditions. Results of the Reporter Feature analysis not only provide a snapshot of the transcriptional regulatory program but also are biologically easy to interpret and provide a powerful way to generate new hypotheses. Our Reporter Features analyses of yeast glucose repression and human diabetes data brings hints towards the understanding of the principles of transcriptional regulation controlling these two important and potentially closely related systems.
Moisturizing body milk as a reservoir of Burkholderia cepacia: outbreak of nosocomial infection in a multidisciplinary intensive care unit
Authors: Álvarez-Lerma Francisco , Maull Elena , Terradas Roser , Segura Concepción , Planells Irene , Coll Pere , Knobel Hernando , Vázquez Antonia
Published: February 2008

Background

An outbreak of severe nosocomial Burkholderia cepacia infections in patients admitted to intensive care unit (ICU), including investigation of the reservoir, is described.

Methods

Over a period of 18 days, isolates of Burkholderia cepacia were recovered from different biological samples from five patients who were admitted to a multidisciplinary 18-bed intensive care unit. Isolation of B. cepacia was associated with bacteraemia in three cases, lower respiratory tract infection in one and urinary tract infection in one. Contact isolation measures were instituted; new samples from the index patients and adjacent patients were collected; and samples of antiseptics, eau de Cologne and moisturizing body milk available in treatment carts at that time were collected and cultured.

Results

B. cepacia was isolated from three samples of the moisturizing body milk that had been applied to the patients. Three new hermetically closed units, from three different batches, were sent for culture; two of these were positive as well. All strains recovered from environmental and biological samples were identified as belonging to the same clone by pulsed-field gel electrophoresis. The cream was withdrawn from all hospitalization units and no new cases of B. cepacia infection developed.

Conclusion

Moisturizing body milk is a potential source of infection. In severely ill patients, the presence of bacteria in cosmetic products, even within accepted limits, may lead to severe life-threatening infections.
Selective Loss of Leptin Receptors in the Ventromedial Hypothalamic Nucleus Results in Increased Adiposity and a Metabolic Syndrome
Authors: Bingham Nathan C. , Anderson Kimberly K. , Reuter Anne L. , Stallings Nancy R. , Parker Keith L.
Published: February 2008

Leptin, an adipocyte-derived hormone, has emerged as a critical regulator of energy homeostasis. The leptin receptor (Lepr) is expressed in discrete regions of the brain; among the sites of highest expression are several mediobasal hypothalamic nuclei known to play a role in energy homeostasis, including the arcuate nucleus, the ventromedial hypothalamic nucleus (VMH), and the dorsomedial hypothalamic nucleus. Although most studies have focused on leptin’s actions in the arcuate nucleus, the role of Lepr in these other sites has received less attention. To explore the role of leptin signaling in the VMH, we used bacterial artificial chromosome transgenesis to target Cre recombinase to VMH neurons expressing steroidogenic factor 1, thereby inactivating a conditional Lepr allele specifically in steroidogenic factor 1 neurons of the VMH. These knockout (KO) mice, designated Lepr KOVMH, exhibited obesity, particularly when challenged with a high-fat diet. On a low-fat diet, Lepr KOVMH mice exhibited significantly increased adipose mass even when their weights were comparable to wild-type littermates. Furthermore, these mice exhibited a metabolic syndrome including hepatic steatosis, dyslipidemia, and hyperleptinemia. Lepr KOVMH mice were hyperinsulinemic from the age of weaning and eventually developed overt glucose intolerance. These data define nonredundant roles of the Lepr in VMH neurons in energy homeostasis and provide a model system for studying other actions of leptin in the VMH.
The Murine Stanniocalcin 2 Gene Is a Negative Regulator of Postnatal Growth
Authors: Chang Andy C.-M. , Hook Jeff , Lemckert Frances A. , McDonald Michelle M. , Nguyen Mai-Anh T. , Hardeman Edna C. , Little David G. , Gunning Peter W. , Reddel Roger R.
Published: February 2008

Stanniocalcin (STC), a secreted glycoprotein, was first studied in fish as a classical hormone with a role in regulating serum calcium levels. There are two closely related proteins in mammals, STC1 and STC2, with functions that are currently unclear. Both proteins are expressed in numerous mammalian tissues rather than being secreted from a specific endocrine gland. No phenotype has been detected yet in Stc1-null mice, and to investigate whether Stc2 could have compensated for the loss of Stc1, we have now generated Stc2−/− and Stc1−/−Stc2−/− mice. Although Stc1 is expressed in the ovary and lactating mouse mammary glands, like the Stc1−/− mice, the Stc1−/−Stc2−/− mice had no detected decrease in fertility, fecundity, or weight gain up until weaning. Serum calcium and phosphate levels were normal in Stc1−/−Stc2−/− mice, indicating it is unlikely that the mammalian stanniocalcins have a major physiological role in mineral homeostasis. Mice with Stc2 deleted were 10–15% larger and grew at a faster rate than wild-type mice from 4 wk onward, and the Stc1−/−Stc2−/− mice had a similar growth phenotype. This effect was not mediated through the GH/IGF-I axis. The results are consistent with STC2 being a negative regulator of postnatal growth.
DEAD-Box Protein-103 (DP103, Ddx20) Is Essential for Early Embryonic Development and Modulates Ovarian Morphology and Function
Authors: Mouillet Jean-François , Yan Xiaomei , Ou Qinglin , Jin Lingling , Muglia Louis J. , Crawford Peter A. , Sadovsky Yoel
Published: February 2008

The DEAD-box helicase DP103 (Ddx20, Gemin3) is a multifunctional protein that interacts with Epstein-Barr virus nuclear proteins (EBNA2/EBNA3) and is a part of the spliceosomal small nuclear ribonucleoproteins complex. DP103 also aggregates with the micro-RNA machinery complex. We have previously shown that DP103 interacts with the nuclear receptor steroidogenic factor-1 (SF-1, NR5A1), a key regulator of reproductive development, and represses its transcriptional activity. To further explore the physiological function of DP103, we disrupted the corresponding gene in mice. Homozygous Dp103-null mice die early in embryonic development before a four-cell stage. Although heterozygous mice are healthy and fertile, analysis of steroidogenic tissues revealed minor abnormalities in mutant females, including larger ovaries, altered estrous cycle, and reduced basal secretion of ACTH. Our data point to diverse functions of murine DP103, with an obligatory role during early embryonic development and also in modulation of steroidogenesis.
Wnt signaling: an essential regulator of cardiovascular differentiation,morphogenesis and progenitor self-renewal
Authors: Cohen Ethan David , Tian Ying , Morrisey Edward E.
Published: February 2008

Emerging evidence indicates that Wnt signaling regulates crucial aspects of cardiovascular biology (including cardiac morphogenesis, and the self-renewal and differentiation of cardiac progenitor cells). The ability of Wnt signaling to regulate such diverse aspects of cardiovascular development rests on the multifarious downstream and tangential targets affected by this pathway. Here,we discuss the roles for Wnt signaling in cardiac and vascular development,and focus on the emerging role of Wnt signaling in cardiovascular morphogenesis and progenitor cell self-renewal.
General, rapid, and transcription-dependent fragmentation of nucleolar antigens in S. cerevisiae mRNA export mutants
Authors: Thomsen Rune , Saguez Cyril , Nasser Tommy , Jensen Torben Heick
Published: February 2008

In the yeast Saccharomyces cerevisiae, mutation of some effectors of mRNA nuclear export leads to the rapid accumulation of HSP104 RNA in transcription site-associated foci. We have screened the S. cerevisiae complement of viable gene deletion mutants for their inability to export HSP104 RNA. The 15 strains identified comprise deletions of components of the THO, Thp1p/Sac3p, and nuclear pore complexes. In all three mutant classes, retained RNA overlaps the HSP104 transcription site. Thus, an early block to HSP104 RNA export is general. Incubation of the identified deletion strains, as well as seven additional mutants, under conditions where mRNA export is blocked results in rapid dissipation of nucleolar protein and RNA constituents. Time course experiments show that dissipation of nucleolar antigens succeeds mRNA retention and is reversed when the load of nuclear mRNA ceases. Consistent with a causal role of excess nuclear mRNA, nucleolar morphology in an mRNA export mutant environment remains intact when transcription by RNA polymerase II is inhibited.
Improved Fisherzestimators for univariate random‐effects meta‐analysis of correlations
Authors: Hafdahl Adam R.
Published: February 2008

Several authors have studied or used the following estimation strategy for meta‐analysing correlations: obtain a point estimate or confidence interval for the mean Fisherzcorrelation, and transform this estimate to the Pearsonrmetric. Using the relationship between Fisherzand Pearsonrrandom variables, I demonstrate the potential discrepancy induced by directlyz‐to‐rtransforming a mean correlation parameter. Point and interval estimators based on an alternative integralz‐to‐rtransformation are proposed. Analytic expressions for the expectation and variance of certain meta‐analytic point estimators are also provided, as are selected moments of correlation parameters; numerical examples are included. In an application of these analytic results, the proposed point estimator outperformed its usual directz‐to‐rcounterpart and compared favourably with an estimator based on Pearsonrcorrelations. Practical implications, extensions of the proposed estimators, and uses for the analytic results are discussed.
Spatial ability in secondary school students: Intra‐sex differences based on self‐selection for physical education
Authors: Tlauka Michael , Williams Jennifer , Williamson Paul
Published: February 2008

Past research has demonstrated consistent sex differences with men typically outperforming women on tests of spatial ability. However, less is known about intra‐sex effects. In the present study, two groups of female students (physical education and non‐physical education secondary students) and two corresponding groups of male students explored a large‐scale virtual shopping centre. In a battery of tasks, spatial knowledge of the shopping centre as well as mental rotation ability were tested. Additional variables considered were circulating testosterone levels, the ratio of 2D:4D digit length, and computer experience. The results revealed both sex and intra‐sex differences in spatial ability. Variables related to virtual navigation and computer ability and experience were found to be the most powerful predictors of group membership. Our results suggest that in female and male secondary students, participation in physical education and spatial skill are related.
Parental communication style and family relationships in children of bipolar parents
Authors: Vance Yvonne H. , Huntley Steven Jones , Espie Jonathan , Bentall Richard , Tai Sara
Published: February 2008

Objectives

To examine relationships between parental communication styles and family environment in parents with bipolar disorder (BD) and their children (CBP).

Methods

On measures of parental communication styles and family environment, 20 BD parents and their 23 children (CBP) were compared to controls. Children completed a current mood measure.

Results

BD parents endorsed more negative communication styles and were less expressive than controls. CBP presented with more current or lifetime mood disorder diagnoses than control children (CC). Current depressive mood was associated with different perceptions of family environment for both CBP and CC.

Conclusions

This familial high risk design indicated differences in family environment, parenting style, and in children of bipolar parents' perception of their family environment as it relates to their current mood.
‘Tolling for the luckless, the abandoned and forsaked’: Therapeutic jurisprudence and international human rights law as applied to prisoners and detainees by forensic psychologists
Authors: Birgden Astrid , Perlin Michael L.
Published: February 2008

Objectives. There has been an explosion of interest in therapeutic jurisprudence as both a filter and lens for viewing the extent to which the legal system serves therapeutic or anti‐therapeutic consequences. However, little attention has been paid to the impact of therapeutic jurisprudence on questions of international human rights law and the role of forensic psychologists. The paper aims to provide an intersection between human rights, therapeutic jurisprudence, and forensic psychology.

Method. Human rights are based on legal, social, and moral rules. Human rights literature generally considers legal rights but such policy statements do not provide principles to guide forensic psychologists in addressing moral or social rights. Therefore, a framework to guide forensic psychologists is required.

Conclusion. As duty‐bearers, forensic psychologists need to address the core values of freedom and well‐being in rights holders (in this instance, prisoners and detainees with a mental illness). The paper proposes that human rights principles can add to the normative base of a therapeutic jurisprudence framework, and in‐turn, therapeutic jurisprudence can assist forensic psychologists to actively address human rights.
Dangerous decisions: A theoretical framework for understanding how judges assess credibility in the courtroom
Authors: Porter Stephen , ten Brinke Leanne
Published: February 2008

Purpose.Numerous wrongful convictions have brought into question the ability of judges and juries to accurately evaluate the credibility of witnesses, including defendants. Dangerous decisions theory (DDT) offers a theoretical framework to build our understanding of the decision‐making process that can culminate in such injustices.

Arguments.According to DDT, the reading of a defendant's face and emotional expressions play a major role in initiating a series of ‘dangerous’ decisions concerning his/her credibility. Specifically, potent judgments of trustworthiness occur rapidly upon seeing a defendant's face, subjectively experienced as intuition. Originally evolved to reduce the danger to the observer, the initial judgment – which may be unreliable – will be enduring and have a powerful influence on the interpretation and assimilation of incoming evidence concerning the defendant. Ensuing inferences will be irrational, but rationalized by the decision maker through his/her subjective schemas about trustworthiness and heuristics for identifying deceptive behaviour. Facilitated by a high level of motivation, a non‐critical, tunnel vision assimilation of potentially disconfirming or ambiguous target information can culminate in a mistaken evaluation of guilt or innocence.

Conclusions.Empirically based education and responsible expert testimony could serve to reduce such biases and improve legal decision‐making.
Memory profiling in mild cognitive impairment: Can we determine risk for Alzheimer's disease?
Authors: Pike Kerryn E. , Savage Greg.
Published: February 2008

Mild cognitive impairment (MCI) is considered a transitional stage between normal ageing and Alzheimer's disease (AD), but not all MCI cases progress to AD and there has been limited focus on how to identify who will progress. Given claims for a characteristic kind of memory impairment in AD involving deficits in encoding and consolidation of information, we propose that ‘memory profiling’ of individuals with MCI may help identify which individuals will progress. We initially set out to establish whether the same characteristic memory profile was present prior to the onset of AD (preAD). Very few studies provided data that allowed us to examine this, but results tentatively supported an encoding/consolidation profile in preAD. A single study tested the clinically important contrast of preAD versus non‐preAD MCI cases and found no difference under any condition or in memory profiles, but interpretation of the findings is limited by short duration of follow‐up, ceiling effects, and task limitations in assessing more complex and qualitative aspects of memory. Although existing data lead to equivocal conclusions, we believe that memory profiling is an endeavour worth pursuing, particularly given the increasing number of people with MCI presenting for clinical assessment. We propose that tests designed specifically to measure memory processes should be sensitive to preAD and are required in prospective longitudinal designs to identify these clinically crucial MCI cases.
Social problem‐solving skills as a mediator between executive function and long‐term social outcome following paediatric traumatic brain injury
Authors: Muscara Frank. , Catroppa Cathy. , Anderson Vicki.
Published: February 2008

There is debate regarding the relationship between executive function and social outcome following paediatric traumatic brain injury (TBI), due to inconsistent findings in the literature. It has been suggested that these contradictory results may reflect the absence of an established mechanism to explain this relationship. Yeates and colleagues (2004) proposed a possible model in which the maturity of social problem‐solving skills mediates the relationship between executive function and social outcome. The current study aimed to explore this model and determine whether social problem solving mediates the relationship between executive function and social outcome in a TBI population. The sample consisted of 36 adolescents and young adults who sustained a TBI between 8 and 12 years of age. They ranged between 16 and 22 years of age and were 7–10 years post‐injury. Findings indicated that a higher level of executive dysfunction was associated with less sophisticated social problem‐solving skills and poorer social outcome. Further, the maturity of social problem‐solving skills was found to mediate the relationship between executive function and social outcome in this group.
Array-Based Resequencing Assay for Mutations Causing Hypertrophic Cardiomyopathy
Authors: Waldmüller Stephan , Müller Melanie , Rackebrandt Kirsten , Binner Priska , Poths Sven , Bonin Michael , Scheffold Thomas
Published: February 2008

Background: Dissecting the complex genetic basis of hypertrophic cardiomyopathy (HCM) may be key to both better understanding and optimally managing this most prevalent genetic cardiovascular disease. An array-based resequencing (ABR) assay was developed to facilitate genetic testing in HCM.

Methods: An Affymetrix resequencing array and a single long-range PCR protocol were developed to cover the 3 most commonly affected genes in HCM, MYH7 (myosin, heavy chain 7, cardiac muscle, beta), MYBPC3 (myosin binding protein C, cardiac), and TNNT2 [troponin T type 2 (cardiac)].

Results: The assay detected the underlying point mutation in 23 of 24 reference samples and provided pointers toward identifying a G insertion and a 3-bp deletion. The comparability of array-based assay results to conventional capillary sequencing was ≥99.9%. Both techniques detected 1 heterozygous variant that was missed by the other method.

Conclusions: The data provide evidence that ABR can substantially reduce the high workload previously associated with a genetic test for HCM. Therefore, the HCM array could facilitate large-scale studies aimed at broadening the understanding of the genetic and phenotypic diversity of HCM and related cardiomyopathies.
Use of Serum FSH to Identify Perimenopausal Women with Pituitary hCG
Authors: Gronowski Ann M , Fantz Corinne R , Parvin Curtis A , Sokoll Lori J , Wiley Carmen L , Wener Mark H , Grenache David G
Published: February 2008

Background: Human chorionic gonadotropin (hCG) tests are performed on many female patients before performing medical procedures or administering medications that may harm a fetus. hCG of pituitary origin has been shown to increase with age. Therefore, mild increases in serum hCG in an older patient can be of pituitary origin and does not necessarily indicate pregnancy. The inability to rule out pregnancy in perimenopausal women can create clinical confusion and may delay needed therapies. Our objective was to determine the diagnostic utility of serum follicle-stimulating hormone (FSH) concentrations to rule out hCG of placental origin in perimenopausal women with a low concentration of serum hCG (5.0–14.0 IU/L).

Methods: Seven testing centers performed 39 742 physician-ordered serum quantitative hCG tests over a 15-month period. From these, 100 samples from women 41–55 years of age with serum hCG concentrations 5–14 IU/L were identified. We performed FSH testing and patient chart review for each sample.

Results: Twenty-three patients were found to have hCG of placental origin (pregnancy, resolving abortion, or gestational trophoblastic disease), and in those cases serum FSH was 0.4–43.8 IU/L. An FSH cutoff of 45.0 IU/L identified hCG of placental origin with 100% sensitivity and 75% specificity. FSH >45 IU/L was never observed when hCG was of placental origin (negative predictive value).

Conclusions: These data indicate that quantitative serum FSH can be used to rule out pregnancy and hCG of placental origin in women 41–55 years of age with mild increase in serum hCG concentrations.
Population Concentration in Los Angeles, 1940–2000
Authors: Lotchin Roger W.
Published: February 2008

Scholars have long considered Los Angeles the paradigm of a low-density area, yet they have focused more on the effects of density than on density itself. This research note tests the idea that the Los Angeles metropolitan area is low-density—a decentralized metropolis without a pronounced population center. It finds that Los Angeles city is denser than most California cities and most eastern cities that in 1950 were of comparable size. In addition, Los Angeles suburbs are denser than those of Chicago and Philadelphia, two comparably sized cities in 2000. Finally, the Los Angeles area has a visible population center and does not have a polycentric population makeup; there may be several business centers, but only one pronounced population center.
The Religious and Racial Meanings ofThe Green Pastures
Authors: Evans Curtis J.
Published: February 2008

Marc Connelly'sThe Green Pasturesplay was one of the longest running dramas in Broadway history. Responses to the play by blacks and whites demonstrate its contested nature. Whites generally lauded the drama for its simplicity and its childlike depiction of black religion in the rural South. African Americans, though hopeful that its allblack cast would lead to more opportunities for blacks on stage, were divided between a general appreciation of the extraordinary display of talent by its actors and worries about the implications of a play that seemed to idealize the rural South as the natural environment of carefree overly religious blacks. Connelly's widely popular drama became a site of cultural debates about the significance of black migration to the urban North, the nature and importance of religion in black communities, and the place of blacks in the nation. Precisely when black social scientists were urging rural black Christians to abandon an otherworldly and emotional religion, white dramatists and literary artists were making more widely available what they saw as a picturesque and deeply rooted aspect of black folk culture.
Vaccinia Virus Infection Modulates the Hematopoietic Cell Compartments in the Bone Marrow
Authors: Singh Pratibha , Yao Yongxue , Weliver Abigail , Broxmeyer Hal E. , Hong Soon-Cheol , Chang Cheong-Hee
Published: February 2008

Successful proliferation and differentiation of hematopoietic progenitor cells in bone marrow (BM) is essential to generate all mature blood cell types, including those involved in the immune response. Although vaccinia virus (VV) is known to induce a strong immune response, the effect of VV infection on hematopoiesis remains largely unknown. Here, we showed that in vivo VV infection results in the expansion of c-KithiSca-1+Lin− (KSL) hematopoietic stem cells. The in vivo expansion of the KSL population requires MyD88 that is a critical adaptor for Toll-like receptor-mediated signaling. Moreover, in BM of VV-infected mice, common myeloid progenitors (CMP) was decreased because of the rapid differentiation of CMP to more mature cells. However, the CMP compartment was not affected by VV infection in the absence of MyD88. The common lymphoid progenitor (CLP) cell population was increased regardless of MyD88 status, suggesting the independent regulation of CMP and CLP compartments by VV infection. VV infection also enhanced the potential of progenitors that preferentially induce the programming of dendritic cell (DC) development toward plasmacytoid DC. Therefore, the host immune response is gearing toward antiviral responses as early as at the precursor level upon VV infection.

Disclosure of potential conflicts of interest is found at the end of this article.