bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of estrogens on boar sperm capacitation in vitro
Authors: Ded Lukas , Dostalova Pavla , Dorosh Andriy , Dvorakova-Hortova Katerina , Peknicova Jana
Published: July 2010

Background

Mammalian sperm must undergo a series of controlled molecular processes in the female reproductive tract called capacitation before they are capable of penetrating and fertilizing the egg. Capacitation, as a complex biological process, is influenced by many molecular factors, among which steroidal hormone estrogens play their role. Estrogens, present in a high concentration in the female reproductive tract are generally considered as primarily female hormones. However, there is increasing evidence of their important impact on male reproductive parameters. The purpose of this study is to investigate the effect of three natural estrogens such as estrone (E1), 17beta-estradiol (E2) and estriol (E3) as well as the synthetical one, 17alpha-ethynylestradiol (EE2) on boar sperm capacitation in vitro.

Methods

Boar sperm were capacitated in vitro in presence of estrogens. Capacitation progress in control and experimental samples was analyzed by flow cytometry with the anti-acrosin monoclonal antibody (ACR.2) at selected times of incubation. Sperm samples were analyzed at 120 min of capacitation by CTC (chlortetracycline) assay, immunocytochemistry and flow cytometry with anti-acrosin ACR.2 antibody. Furthermore, sperm samples and capacitating media were analyzed by immunocytochemistry, ELISA with the ACR.2 antibody, and the acrosin activity assay after induced acrosomal reaction (AR).

Results

Estrogens stimulate sperm capacitation of boar sperm collected from different individuals. The stimulatory effect depends on capacitation time and is highly influenced by differences in the response to estrogens such as E2 by individual animals. Individual estrogens have relatively same effect on capacitation progress. In the boar samples with high estrogen responsiveness, estrogens stimulate the capacitation progress in a concentration-dependent manner. Furthermore, estrogens significantly increase the number of acrosome-reacted sperm after zona pellucida- induced acrosomal reaction.

Conclusions

We demonstrate here the stimulatory effect of four different estrogens on boar sperm capacitation in vitro. According to our results, there is significant difference in the response to tested estrogens at different capacitation time and among individual animals. In animals with a high response to estrogens, there is a concentration-dependent stimulation of capacitation and individual estrogens have relatively the same effect. Effects of individual estrogens, differences in the response to them by individual animals, their time and concentration-dependent outcomes further contribute to our knowledge about steroidal action in sperm.
Ethnomedicine of the Kagera Region, north western Tanzania. Part 2: The medicinal plants used in Katoro Ward, Bukoba District
Authors: Moshi Mainen J , Otieno Donald F , Mbabazi Pamela K , Weisheit Anke
Published: July 2010

Background

The Kagera region of north western Tanzania has a rich culture of traditional medicine use and practices. The dynamic inter-ethnic interactions of different people from the surrounding countries constitute a rich reservoir of herbal based healing practices. This study, the second on an ongoing series, reports on the medicinal plant species used in Katoro ward, Bukoba District, and tries to use the literature to establish proof of the therapeutic claims.

Methodology

Ethnomedical information was collected using Semi-structured interviews in Kyamlaile and Kashaba villages of Katoro, and in roadside bushes on the way from Katoro to Bukoba through Kyaka. Data collected included the common/local names of the plants, parts used, the diseases treated, methods of preparation, dosage, frequency and duration of treatments. Information on toxicity and antidote were also collected. Literature was consulted to get corroborative information on similar ethnomedical claims and proven biological activities of the plants.

Results

Thirty three (33) plant species for treatement of 13 different disease categories were documented. The most frequently treated diseases were those categorized as specific diseases/conditions (23.8% of all remedies) while eye diseases were the least treated using medicinal plants (1.5% of all remedies). Literature reports support 47% of the claims including proven anti-malarial, anti-microbial and anti-inflammatory activity or similar ethnomedical uses. Leaves were the most frequently used plant part (20 species) followed by roots (13 species) while making of decoctions, pounding, squeezing, making infusions, burning and grinding to powder were the most common methods used to prepare a majority of the therapies.

Conclusion

Therapeutic claims made on plants used in traditional medicine in Katoro ward of Bukoba district are well supported by literature, with 47% of the claims having already been reported. This study further enhances the validity of plants used in traditional medicine in this region as resources that can be relied on to provide effective, accessible and affordable basic healthcare to the local communities. The plants documented also have the potential of being used in drug development and on farm domestication initiatives.
The function of communities in protein interaction networks at multiple scales
Authors: Lewis Anna CF , Jones Nick S , Porter Mason A , Deane Charlotte M
Published: July 2010

Background

If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network.

Results

Our results demonstrate that the functional homogeneity of communities depends on the scale selected, and that almost all proteins lie in a functionally homogeneous community at some scale. We judge functional homogeneity using a novel test and three independent characterizations of protein function, and find a high degree of overlap between these measures. We show that a high mean clustering coefficient of a community can be used to identify those that are functionally homogeneous. By tracing the community membership of a protein through multiple scales we demonstrate how our approach could be useful to biologists focusing on a particular protein.

Conclusions

We show that there is no one scale of interest in the community structure of the yeast protein interaction network, but we can identify the range of resolution parameters that yield the most functionally coherent communities, and predict which communities are most likely to be functionally homogeneous.
Ring chromosome 18 abnormality in acute myelogenous leukemia: the clinical dilemma
Authors: Sivendran Shanthi , Gruenstein Stephen , Malone Adriana K , Najfeld Vesna
Published: July 2010

The ring chromosome is a circular, structural abnormality composed of either multiple chromosomes or a single chromosome with loss of genetic material at one or both ends. This chromosomal rearrangement is often unstable with frequent recombinations and may be accompanied by either loss or amplification of genetic material[1]. Considering that ring chromosomes are rare in acute myelogenous leukemia (AML), it is difficult to risk stratify patient prognosis, particularly when the ring chromosome occurs as the sole abnormality. Here we report a case of a ring chromosome 18 abnormality in a patient with newly diagnosed AML with monocytic differentiation. Cytogenetic analysis demonstrated 46, XY, r(18)(p11q21) karyotype in 19 of 34 evaluated metaphase cells. The patient received induction chemotherapy and subsequent allogeneic cord blood transplant from a sex-matched donor, and remained in hematologic and cytogenetic remission for 120 days post transplant. Soon after, he developed post transplant lymphoproliferative disorder and died of multi-organ failure. Although r(18) chromosomal abnormalities were not classified in the recent updated evidence-and expert opinion-based recommendations for the diagnosis and management of AML (likely due to the small number of reported cases), the patient was treated as high risk with stem cell transplantation. This was based on the unstable nature of the ring chromosome and the poor outcomes described in the literature of patients with sole ring 18 abnormalities.
Characterization of monocyte/macrophage subsets in the skin and peripheral blood derived from patients with systemic sclerosis
Authors: Higashi-Kuwata Nobuyo , Jinnin Masatoshi , Makino Takamitsu , Fukushima Satoshi , Inoue Yuji , Muchemwa Faith C , Yonemura Yuji , Komohara Yoshihiro , Takeya Motohiro , Mitsuya Hiroaki , Ihn Hironobu
Published: July 2010

Introduction

Recent accumulating evidence indicates a crucial involvement of macrophage lineage in the pathogenesis of systemic sclerosis (SSc). To analyze the assembly of the monocyte/macrophage population, we evaluated the expression of CD163 and CD204 and various activated macrophage markers, in the inflammatory cells of the skin and in the peripheral blood mononuclear cells (PBMCs) derived from patients with SSc.

Methods

Skin biopsy specimens from 6 healthy controls and 10 SSc patients (7 limited cutaneous SSc and 3 diffuse cutaneous SSc) were analyzed by immunohistochemistry using monoclonal antibody against CD68 (pan-macrophage marker), CD163 and CD204. Surface and/or intracellular protein expression of CD14 (marker for monocyte lineage), CD163 and CD204 was analysed by flow cytometry in PBMCs from 16 healthy controls and 41 SSc patients (26 limited cutaneous SSc and 15 diffuse cutaneous SSc). Statistical analysis was carried out using Mann-Whitney U test for comparison of means.

Results

In the skin from SSc patients, the number of CD163+ cells or CD204+ cells between the collagen fibers was significantly larger than that in healthy controls. Flow cytometry showed that the population of CD14+ cells was significantly greater in PBMCs from SSc patients than that in healthy controls. Further analysis of CD14+ cells in SSc patients revealed higher expression of CD163 and the presence of two unique peaks in the CD204 histogram. Additionally, we found that the CD163+ cells belong to CD14brightCD204+ population.

Conclusions

This is the first report indicating CD163+ or CD204+ activated macrophages may be one of the potential fibrogenic regulators in the SSc skin. Furthermore, this study suggests a portion of PBMCs in SSc patients abnormally differentiates into CD14brightCD163+CD204+ subset. The subset specific to SSc may play an important role in the pathogenesis of this disease, as the source of CD163+ or CD204+ macrophages in the skin.
Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate
Authors: Fayed Nicolas , Garcia-Campayo Javier , Magallón Rosa , Andrés-Bergareche Helena , Luciano Juan V , Andres Eva , Beltrán Julián
Published: July 2010

Introduction

The purpose of this study was to investigate whether single-voxel (SV) proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) detected differences between fibromyalgia (FM) patients and healthy controls. We also searched for correlations between neuroimaging abnormalities and neuropsychological variables.

Methods

Ten patients with FM and 10 gender- and age-matched control subjects were studied. A neuropsychological examination, DWI, DTI, and proton MRS were performed on the brain areas known to be associated with pain processing.

Results

Compared with healthy controls, FM patients had significantly higher levels of glutamate + glutamine (Glx) (mean ± SD, 10.71 ± 0.50 arbitrary institutional units versus 9.89 ± 1.04; P = 0.049) and higher glutamate + glutamine/creatine (Glx/Cr) ratios (1.90 ± 0.12 versus 1.72 ± 0.23; P = 0.034) in the posterior gyrus. Myoinositol (Ins) levels of the right and left hippocampi were significantly lower in FM patients (4.49 ± 0.74 versus 5.17 ± 0.62; P = 0.008 and 4.91 ± 0.85 versus 6.09 ± 0.78; P = 0.004, respectively). In FM patients, decreased myoinositol/creatine (Ins/Cr) ratios were found in the left sensorimotor area (P = 0.05) and the left hippocampus (P = 0.002) and lower levels of choline (P = 0.019) and N-acetyl aspartate + N-acetyl aspartyl glutamate (NAA + NAG) (P = 0.034) in the left hippocampus. Significant correlations between depression, pain, and global function and the posterior gyrus Glx levels and Glx/Cr ratios were observed.

Conclusions

Glx within the posterior gyrus could be a pathologic factor in FM. Hippocampal dysfunction may be partially responsible for the depressive symptoms of FM. Additional studies with larger samples are required to confirm these preliminary data.
Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesis
Authors: Letouzé Eric , Allory Yves , Bollet Marc A , Radvanyi François , Guyon Frédéric
Published: July 2010

We present a computational method, TuMult, for reconstructing the sequence of copy number changes driving carcinogenesis, based on the analysis of several tumor samples from the same patient. We demonstrate the reliability of the method with simulated data, and describe applications to three different cancers, showing that TuMult is a valuable tool for the establishment of clonal relationships between tumor samples and the identification of chromosome aberrations occurring at crucial steps in cancer progression.
Increased Male Offspring’s Risk of Metabolic-Neuroendocrine Dysfunction and Overweight after Fructose-Rich Diet Intake by the Lactating Mother
Authors: Alzamendi Ana , Castrogiovanni Daniel , Gaillard Rolf C. , Spinedi Eduardo , Giovambattista Andrés
Published: July 2010

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49–60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.
Ovarian Steroids, Mitogen-Activated Protein Kinases, and/or Aspartic Proteinases Cooperate to Control Endometrial Remodeling by Regulating Gene Expression in the Stroma and Glands
Authors: Gaide Chevronnay Héloïse P. , Lemoine Pascale , Courtoy Pierre J. , Marbaix Etienne , Henriet Patrick
Published: July 2010

Explants from nonmenstrual endometria cultured in the absence of ovarian hormones undergo tissue breakdown. Addition of estradiol and progesterone (EP) prevents proteolysis. Explants include stromal and epithelial compartments which play different but complementary roles in endometrial physiology, including tissue remodeling and hormonal response. In order to characterize the cell type-specific contribution to regulation of tissue breakdown, we characterized the transcriptomes of microdissected stromal and glandular areas from endometrial explants cultured with or without EP. The datasets were also compared to other published endometrial transcriptomes. Finally, the contribution of proteolysis, hypoxia, and MAPKs to the regulation of selected genes was further investigated in explant culture. This analysis identified distinct gene expression profiles in stroma and glands, with differential response to EP, but functional clustering underlined convergence in biological processes, further indicating that endometrial remodeling requires cooperation between the two compartments through expression of cell type-specific genes. Only partial overlaps were observed between lists of genes involved in different occurrences of endometrial breakdown, pointing to a limited number of potentially crucial regulators but also to the requirement for additional mechanisms controlling tissue remodeling. We identified a group of genes differentially regulated by EP in stroma and glands among which some were sensitive to MAPKs and/or aspartic proteinases and were not induced by hypoxia. In conclusion, MAPKs and/or aspartic proteinases likely act in concert with EP to locally and specifically control differential expression of genes between degrading and preserved areas of the human endometrium.
Identification of Early Response Genes and Pathway Activated by Androgens in the Initial Segment and Caput Regions of the Regressed Rat Epididymis
Authors: Hamzeh Mahsa , Robaire Bernard
Published: July 2010

To identify the initial response to androgens and estrogens in the orchidectomized, regressed epididymis, we determined the gene expression changes triggered by the administration of either of two metabolites of testosterone, 5α-dihydrotestosterone (DHT) or 17β-estradiol (E2), in the regressed rat epididymis. Adult rats were orchidectomized and 8 d later implanted with either empty implants (control), DHT-filled-, or E2-filled-polydioxanone implants. Rats were euthanized 12 h, 1 d, and 7 d later, and RNA was extracted and probed on Rat230–2.0 Affymetrix arrays. Probe sets that respond to DHT or E2 were identified at early time points; although the expression of some was repressed, the expression of many others was either transiently or chronically elevated. Nerve growth factor receptor (Ngfr) and S100 calcium binding protein G (S100g) were two E2 up-regulated genes detected at 12 h. Among the genes that showed a dramatic early response to DHT were endothelin 1 (Edn1), bone morphogenetic protein 4 (Bmp4), and IGF binding protein 3 (Igfbp3), which were suppressed, and IGF-I (Igf1), which was induced. Genes that were up- or down-regulated by DHT were classified based on biological function. Using PathwayStudio 4.0, we identified genes that were linked and directly influenced either the expression or regulation of one another. Epidermal growth factor and IGF-I play an important role in the pathway due to their function in regulation and expression of many other genes. These results provide novel insights into the impact of androgen action on the expression of genes that are important for epididymal function.
Deletion of the Isg15 Gene Results in Up-Regulation of Decidual Cell Survival Genes and Down-Regulation of Adhesion Genes: Implication for Regulation by IL-1β
Authors: Ashley Ryan L. , Henkes Luiz E. , Bouma Gerrit J. , Pru James K. , Hansen Thomas R.
Published: July 2010

The ubiquitin homolog interferon stimulated gene 15 (ISG15) is up-regulated in the endometrium in response to pregnancy in primates, ruminants, pigs, and mice. ISG15 covalently attaches to intracellular proteins (isgylation) and regulates numerous intracellular responses. We hypothesized that ISG15 depletion (Isg15−/−) alters decidual tissue gene expression and that IL-1β induces ISG15 expression and isgylation in cultured murine decidual explants and human uterine fibroblasts (HuFs). After studying the reproductive phenotype, contrary to earlier reports, up to 50% of the fetuses die between 7.5 and 12.5 d post coitum (dpc) in Isg15−/− mothers when mated to Isg15−/− fathers. Using microarray analysis, over 500 genes are differentially regulated in 7.5 dpc deciduas from Isg15−/− compared with Isg15+/+ mice. The gene for interferon-inducible protein 202b, which functions in cell-survival mechanisms, was up-regulated (mRNA and protein) in deciduas from Isg15−/− mice. Culture of Isg15+/+ mouse decidual explants (7.5 dpc) with IL-1β decreased Isg15 mRNA but increased free and conjugated ISG15. In predecidual HuF cells, IL-1β treatment increased ISG15 mRNA and isgylation. Additionally, IL-1β up-regulated expression of enzymes (HERC5, UBCH8) that coordinate the covalent conjugation of ISG15 to target proteins, as well as the gene that encodes the deisglyation enzyme UBP43 in HuF cells. In conclusion, deletion of Isg15 gene results in 50% fetal loss after 7.5 dpc, which can be explained through differential decidual gene expression that is functionally tied to cell survival and adhesion pathways. This fetal death also might relate to impaired IL-1β signaling, because ISG15 and isgylation are induced by IL-1β in human and murine endometrial stromal cells.
Interleukin-1β May Mediate Insulin Resistance in Liver-Derived Cells in Response to Adipocyte Inflammation
Authors: Nov Ori , Kohl Ayelet , Lewis Eli C. , Bashan Nava , Dvir Irit , Ben-Shlomo Shani , Fishman Sigal , Wueest Stephan , Konrad Daniel , Rudich Assaf
Published: July 2010

Central obesity is frequently associated with adipose tissue inflammation and hepatic insulin resistance. To identify potential individual mediators in this process, we used in vitro systems and assessed if insulin resistance in liver cells could be induced by secreted products from adipocytes preexposed to an inflammatory stimulus. Conditioned medium from 3T3-L1 adipocytes pretreated without (CM) or with TNFα (CM-TNFα) was used to treat Fao hepatoma cells. ELISAs were used to assess the concentration of several inflammatory mediators in CM-TNFα. CM-TNFα-treated Fao cells exhibited about 45% diminution in insulin-stimulated phosphorylation of insulin receptor, insulin receptor substrate proteins, protein kinase B, and glycogen synthase kinase-3 as compared with CM-treated cells, without changes in the total abundance of these protein. Insulin increased glycogenesis by 2-fold in CM-treated Fao cells but not in cells exposed to CM-TNFα. Expression of IL-1β mRNA was elevated 3-fold in TNFα-treated adipocytes, and CM-TNFα had 10-fold higher concentrations of IL-1β but not TNFα or IL-1α. IL-1β directly induced insulin resistance in Fao, HepG2, and in primary rat hepatocytes. Moreover, when TNFα-induced secretion/production of IL-1β from adipocytes was inhibited by the IL-1 converting enzyme (ICE-1) inhibitor II (Ac-YVAD-CMK), insulin resistance was prevented. Furthermore, liver-derived cells treated with IL-1 receptor antagonist were protected against insulin resistance induced by CM-TNFα. Finally, IL-1β secretion from human omental fat explants correlated with body mass index (R2 = 0.639, P < 0.01), and the resulting CM induced insulin resistance in HepG2 cells, inhibitable by IL-1 receptor antagonist. Our results suggest that adipocyte-derived IL-1β may constitute a mediator in the perturbed cross talk between adipocytes and liver cells in response to adipose tissue inflammation.
Minireview: A Skeleton in Serotonin’s Closet?
Authors: Kawai Masanobu , Rosen Clifford J.
Published: July 2010

The serotonin molecule plays a multifunctional role in mammalian homeostasis serving as a neurotransmitter in the central nervous system, a gut-derived mediator of peristalsis, and a circulating hormone that regulates appetite, cardiovascular function, and hemostasis. Recent evidence from the clinic and the bench highlight an unexpected target for serotonin action, the skeleton. Clinically, two classes of drugs, the second generation antipsychotic drugs (SGAs) and selective serotonin reuptake inhibitors (SSRIs), which modulate central and peripheral serotonin signaling, have been shown to alter bone remodeling although the mechanism is not clear. In contrast, genetically engineered mouse models have demonstrated a bimodal control system whereby gut-derived serotonin under the control of the Wnt/Lrp/β-catenin system acts systemically to suppress bone formation, whereas CNS serotonin activated by leptin modulates sympathetic outflow to the skeleton. In this brief review, we will summarize recent findings linking serotonin to the skeleton and discuss future directions for this new but challenging aspect of this multidimensional molecule.
Female Gonadal Function before and after Treatment of Acromegaly
Authors: Grynberg Michaël , Salenave Sylvie , Young Jacques , Chanson Philippe
Published: July 2010

Context: The menstrual cycle is often abnormal in women with acromegaly. Gonadotropin deficiency may be due to a tumor mass effect (macroadenomas) and/or hyperprolactinemia and/or GH excess.

Aim of the Study: The aim of the study was to analyze the causes of ovarian dysfunction in a large series of patients with acromegaly followed up in a single center.

Patients and Methods: Gonadal function was assessed on the basis of menstrual status and hormone assays before and after treatment of acromegaly, between 1985 and 2005, in 55 patients aged from 17 to less than 45 yr.

Results: Seventeen women (31%) were considered to be eugonadal because they had regular menstrual cycles and/or conceived spontaneously. The remaining 38 women had anovulatory cycles. Of these, 11 had hyperprolactinemia and six had hypogonadism due to a mass effect. The cause of the menstrual disturbances was mixed or unclassifiable in 14 cases. In the seven remaining cases, the gonadal dysfunction was likely related to the GH/IGF-I excess, which exerts a direct effect on the gonadotropic axis. Two had polycystic ovary syndrome, which disappeared after normalization of serum GH/IGF-I levels, suggesting that GH/IGF-I excess may also have a direct effect on the ovary. Thirty-eight women became pregnant, and all had healthy children, despite active acromegaly in 12 cases (31%).

Conclusion: Gonadal dysfunction is very common in premenopausal women with acromegaly. The potential causes include the lactogenic effect of prolactin, GH, or both on gonadotropic axis. Tumor mass effect or direct effect of GH or IGF-I on the ovary may also participate in ovarian dysfunction.
Cooperation between Cyclin E and p27Kip1 in Pituitary Tumorigenesis
Authors: Roussel-Gervais Audrey , Bilodeau Steve , Vallette Sophie , Berthelet France , Lacroix André , Figarella-Branger Dominique , Brue Thierry , Drouin Jacques
Published: July 2010

Cushing’s disease is caused by glucocorticoid-resistant pituitary corticotroph adenomas. We have previously identified the loss of nuclear Brg1 as one mechanism that may lead to partial glucocorticoid resistance: this loss is observed in about 33% of human corticotroph adenomas. We now show that Brg1 loss of function correlates with cyclin E expression in corticotroph adenomas and with loss of the cell cycle inhibitor p27Kip1 expression. Because Brg1 is thought to have tumor suppressor activity, the present study was undertaken to understand the putative contribution of cyclin E derepression produced by loss of Brg1 expression on adenoma development. Overexpression of cyclin E in pituitary proopiomelanocortin cells leads to abnormal reentry into cell cycle of differentiated proopiomelanocortin cells and to centrosome instability. These alterations are consistent with the intermediate lobe hyperplasia and anterior lobe adenomas that were observed in these pituitaries. When combined with the p27Kip1 knockout, overexpression of cyclin E increased the incidence of pituitary tumors, their size, and their proliferation index. These results suggest that cyclin E up-regulation and p27Kip1 loss-of-function act cooperatively on pituitary adenoma development.
Structural and biochemical characterization of CRN-5 and Rrp46: An exosome component participating in apoptotic DNA degradation
Authors: Yang Che-Chuan , Wang Yi-Ting , Hsiao Yu-Yuan , Doudeva Lyudmila G. , Kuo Pan-Hsien , Chow Sih Yao , Yuan Hanna S.
Published: July 2010

Rrp46 was first identified as a protein component of the eukaryotic exosome, a protein complex involved in 3′ processing of RNA during RNA turnover and surveillance. The Rrp46 homolog, CRN-5, was subsequently characterized as a cell death-related nuclease, participating in DNA fragmentation during apoptosis in Caenorhabditis elegans. Here we report the crystal structures of CRN-5 and rice Rrp46 (oRrp46) at a resolution of 3.9 Å and 2.0 Å, respectively. We found that recombinant human Rrp46 (hRrp46), oRrp46, and CRN-5 are homodimers, and that endogenous hRrp46 and oRrp46 also form homodimers in a cellular environment, in addition to their association with a protein complex. Dimeric oRrp46 had both phosphorolytic RNase and hydrolytic DNase activities, whereas hRrp46 and CRN-5 bound to DNA without detectable nuclease activity. Site-directed mutagenesis in oRrp46 abolished either its DNase (E160Q) or RNase (K75E/Q76E) activities, confirming the critical importance of these residues in catalysis or substrate binding. Moreover, CRN-5 directly interacted with the apoptotic nuclease CRN-4 and enhanced the DNase activity of CRN-4, suggesting that CRN-5 cooperates with CRN-4 in apoptotic DNA degradation. Taken together all these results strongly suggest that Rrp46 forms a homodimer separately from exosome complexes and, depending on species, is either a structural or catalytic component of the machinery that cleaves DNA during apoptosis.
Improving New-Product Forecasting at Intel Corporation
Authors: Wu S. David , Kempf Karl G. , Atan Mehmet O. , Aytac Berrin , Shirodkar Shamin A. , Mishra Asima
Published: July 2010

Forecasting demand for new products is becoming increasingly difficult as the technology treadmill continually drives product life cycles shorter. The task is even more challenging for electronic goods; these products have life cycles measured in quarters, manufacturing processes measured in months, and market volatility that takes place on a day-to-day basis. We present a model that perpetually reduces forecast variance as new market information is acquired over time. Our model extends Bass' original idea of product diffusion [Bass, F. M. 1969. A new product growth for model consumer durables. Management Sci. 15(5) 215–227] to a more comprehensive theoretical setting. We first describe how forecast variances can be reduced when combining predictive information from multiple diffusion models. We then introduce the notion of demand-leading indicators in a Bayesian framework that reduces forecast variance by incorporating a wide variety of information emerging during the product life cycle. We describe a successful implementation of this model at Intel, where we tested one-third of the microprocessor products. When compared with the current forecasting method, our model reduced forecasting time from three days to two hours and decreased forecasting errors by 33 percent, leading to $11.8 million in cost savings over four months of demand realization.
Doing Good with Good OR: Supporting Cost-Effective Hepatitis B Interventions
Authors: Hutton David W. , Brandeau Margaret L. , So Samuel K.
Published: July 2010

In an era of limited health-care budgets, mathematical models can be useful tools to identify cost-effective programs and support policy makers in making informed decisions. This paper reports the results of our work, which we carried out over several years with the Asian Liver Center at Stanford University. Hepatitis B is a vaccine-preventable viral disease that, if untreated, can lead to death from cirrhosis and liver cancer. It is a major public health problem, particularly in Asian populations. We used new combinations of decision analysis and Markov models to analyze the cost effectiveness of several interventions to combat the disease in the United States and China. The results of our operations research (OR)-based analyses have helped change US public health policy on hepatitis B screening for millions of people, and have helped encourage policy makers in China to enact legislation to provide free catch-up vaccination for hundreds of millions of children. These policies are an important step in eliminating health disparities, reducing discrimination, and ensuring that millions of people can now receive the hepatitis B vaccination or life-saving treatment that they need.
Timing of Effort and Reward: Three-Sided Moral Hazard in a Continuous-Time Model
Authors: Yang Jun
Published: July 2010

This paper studies a three-sided moral hazard problem with one agent exerting up-front effort and two agents exerting ongoing effort in a continuous-time model. The agents' efforts jointly affect the probability of survival and thus the expected cash flow of the project. In the optimal contract, the timing of payments reflects the timing of effort: payments for up-front effort precede payments for ongoing effort. Several patterns are possible for the cash allocation between the two agents with ongoing effort. In one case, where the two agents face equally severe moral hazard, they share the cash flow equally at each point of time. In another case, where the two agents have different severities of moral hazard, their payments are sequential. In a more general case, the two agents with ongoing effort first receive the cash flow alternately with an increasing frequency of switches and then divide the cash flow at each point of time. This study provides a framework for understanding a broad set of business-contracting issues. The characteristics suggested in the optimal contract help us analyze the causes of business failure such as the recent debacle of mortgage-backed securities.
The new politics of community cohesion: making use of human rights policy and legislation
Authors: Gavrielides Theo
Published: July 2010

Although community cohesion and human rights are currently two of the most discussed political discourses in the UK, their links for policy are underplayed. This article presents the findings of a nine-month research project that included interviews with a selected expert sample, and which aimed to explore whether human rights values and legislation can be used as tools for community cohesion. Available levers within human rights and the 1998 Human Rights Act are identified, and evidence-based policy recommendations are posited. The article aims to start a new and more inclusive dialogue on community cohesion policy.
Antecedents and trajectories of achievement goals: A self‐determination theory perspective
Authors: Ciani Keith D. , Sheldon Kennon M. , Hilpert Jonathan C. , Easter Matthew A.
Published: July 2010

Background. Research has shown that both achievement goal theory and self‐determination theory (SDT) are quite useful in explaining student motivation and success in academic contexts. However, little is known about how the two theories relate to each other.

Aim. The current research used SDT as a framework to understand why students enter classes with particular achievement goal profiles, and also, how those profiles may change over time.

Sample. One hundred and eighty‐four undergraduate preservice teachers in a required domain course agreed to participate in the study.

Method. Data were collected at three time points during the semester, and both path modelling and multi‐level longitudinal modelling techniques were used.

Results. Path modelling techniques with 169 students, results indicated that students' autonomy and relatedness need satisfaction in life predict their initial self‐determined class motivation, which in turn predicts initial mastery‐approach and ‐avoidance goals. Multi‐level longitudinal modelling with 108 students found that perceived teacher autonomy support buffered against the general decline in students' mastery‐approach goals over the course of the semester.

Conclusions. Data provide a promising integration of SDT and achievement goal theory, posing a host of potentially fruitful future research questions regarding goal adoption and trajectories.
In‐group identification mediates the effects of subjective in‐group status on mental health
Authors: Sani Fabio. , Elena Maria Magrin , Scrignaro Marta , McCollum Rachel
Published: July 2010

We present two studies exploring the effects of the relative standing of one's in‐group in the social hierarchy, which we conceptualize as ‘subjective in‐group status’, on mental health and well‐being. Study 1 focuses on the subjective status of a professional in‐group (prison guards) while Study 2 concerns the subjective status of the family in‐group. Results show that higher subjective in‐group status predicts better mental health (e.g., less depression) and greater well‐being (e.g., higher satisfaction with life). Also, results demonstrate that the effects of subjective in‐group status on mental health are mediated by the extent to which one subjectively identifies with the in‐group.
Navigating Multiple Modernities: Soon Hyun and the Envisioning of Korean/American Modernities
Authors: Yamamoto Genzo , Kim Daniel
Published: July 2010

Reflecting on the life of a Korean American statesman and pastor who played prominent roles in the Korean Independence Movement, Soon Hyun (1879-1968), this article argues that the "multiple modernities" framework suggested by postcolonial scholars and others offers a useful framework for approaching the experience, ideas, and role of immigrants coming to the United States. Immigrants bring the experience of, and evaluations of, the multiple modernities that make up our world, and so bring with them critical experiences and voices that are increasingly valuable and necessary as the United States seeks to navigate the multi-ethnic and multi-cultural globalizing world.
Cognitive Enhancement, Cheating, and Accomplishment
Authors: Goodman Rob
Published: July 2010

An ethics of enhancement should not rest on blanket judgments; it should ask us to distinguish between the kinds of activities we want to enhance. Both students and academics have turned to cognition-enhancing drugs in significant numbers—but is their enhancement a form of cheating? The answer should hinge on whether the activity subject to enhancement is zero-sum or non-zero-sum, and whether one is more concerned with excellence in process or excellence in outcome. Cognitive enhancement should be especially tolerated when the activities at stake are non-zero-sum and when the importance of process is outweighed by the importance of outcome. The use of cognition-enhancing drugs does not unnaturally cheapen accomplishments achieved under their influence; instead, cognitive enhancement is in line with well-established conceptions of collaborative authorship, which shift the locus of praise and blame from individual creators to the ultimate products of their efforts.
The New Woman of the Tenements: Anzia Yezierska’s Salome
Authors: Botshon Lisa
Published: July 2010

This essay focuses on twentieth-century Jewish immigrant author Anzia Yezierska’s proto-feminism and how she employed the genre of the romance novel in order to promote new ideas about ethnic identity and female independence. A focal point is her relationship to the trope of the New Woman, especially through her 1923 novel Salome of the Tenements , a work that simultaneously incorporates fresh perspectives concerning popular genres, feminism, and sexuality.
Passing Into Diplomacy: U.S. Consul James Weldon Johnson and The Autobiography of an Ex-Colored Man
Authors: Roberts Brian Russell
Published: July 2010

This essay focuses on James Weldon Johnson’s overlapping literary and diplomatic careers. Johnson’s novel The Autobiography of an Ex-Colored Man , written while he worked as a US consul in Latin America, draws upon tropes of international representation to weigh in upon questions of aesthetic and racial representation. Tracing Johnson’s transition from a US representative abroad to a race representative within the US, the essay argues that Johnson’s case illustrates the importance of permitting the significant tradition of black work in the US’s diplomatic program to inform the ways we approach African America’s expressive and geopolitical engagements with the international world.
Negotiating the “Negro Problem”: Stew’s Passing (Made) Strange
Authors: Woolf Brandon
Published: July 2010

“Black folks passing for black folks. That’s a trip!” A trip is just what we get in Passing Strange , Stew’s Tony Award–winning piece of “genre-defying rock-pop-funk-punk-cabaret.” Stew and his band, The Negro Problem, serve as tour guides on a semi-autobiographical “pilgrimage” beyond the tightly patrolled borders of the North American continent, the traditions of black musical theatre performance, and the “chains” of a rooted, African American authenticity. Passing Strange renders a musical critique of any traditional or idealist rendering of “double consciousness” and explores the negative—and hybridized—nature of black identity formation. In turn, this essay employs a dialectical and diasporic vocabulary to situate Stew in problematic yet productive relation to critical interlocutors like W. E. B. Du Bois and Paul Gilroy among others in order to articulate the complex relations between racial and national identity that Passing Strange performs. It maps the varied problems of problematization for which Passing Strange is arguing by charting the piece’s often contradictory trajectories. Finally, the essay works to understand Stew where he is most at home, “between the clicks of a metronome”: between black and white, between music and theatre, between the United States and Europe, between past and present, between fictional representation and lived experience.
Tau and neurodegenerative disorders
Authors: Motoi Yumiko , Sahara Naruhiko , Kambe Taiki , Hattori Nobutaka
Published: July 2010

The mechanisms that render tau a toxic agent are still unclear, although increasing evidence supports the assertion that alterations of tau can directly cause neuronal degeneration. In addition, it is unclear whether neurodegeneration in various tauopathies occurs via a common mechanism or that specific differences exist. The aim of this review is to provide an overview of tauopathies from bench to bedside. The review begins with clinicopathological findings of familial and sporadic tauopathies. It includes a discussion of the similarities and differences between these two conditions. The second part concentrates on biochemical alterations of tau such as phosphorylation, truncation and acetylation. Although pathological phosphorylation of tau has been studied for many years, recently researchers have focused on the physiological role of tau during development. Finally, the review contains a summary of the significance of tauopathy model mice for research on neurofibrillary tangles, axonopathies, and synaptic alteration.
Leitlinien-Update 061/017 In-vitro-Allergiediagnostik1, 2 / In-vitro allergy diagnostics Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Ärzteverband deutscher Allergologen (ÄDA), Gesellschaft für pädiatrische Allergologie (GPA), Deutsche Dermatologische Gesellschaft (DDG)
Authors: Renz Harald , Biedermann Thomas , Bufe Albrecht , Eberlein Bernadette , Jappe Uta , Ollert Markus , Petersen Arnd , Kleine-Tebbe Jörg , Raulf-Heimsoth Monika , Saloga Joachim , Werfel Thomas , Worm Margitta , In-vitro-Allergiediagnostik (Arbeitsgruppe „In-vitro-Allergi
Published: July 2010

Diese S1 Leitlinie befasst sich mit allen aktuellen Aspekten der In-vitro-Allergiediagnostik, einschließlich der internen und externen Qualitätskontrolle und deren nationalen Richtlinien, der Messung von Gesamt- und allergenspezifischen IgE- und IgG-Antikörpern, den zellulären Testsystemen für Mastzellen, basophile und eosinophile Granulozyten, den zellulären Testsystemen für T-Zellen sowie der Bestimmung von Entzündungsmediatoren wie ECP (eosinophiles catio-nisches Protein), Tryptase, Histamin und deren Metaboliten. Diese Leitlinie ist zwischenzeitlich von mehreren nationalen medizinisch-wissenschaftlichen Fachgesellschaften adoptiert worden.
Kryptopyrrol, ein vergessener, aber wichtiger Laborparameter? / Kryptopyrrole: a forgotten but important diagnostic parameter?
Authors: Kinkeldei Jürgen
Published: July 2010

In den 1960er- und 1970er-Jahren wurde über eine Substanz im Urin spekuliert, die zunächst Malven-Faktor genannt, dann falsch als Kryptopyrrol und schließlich korrekt als Hydroxyhämopyrrollaktam identifiziert wurde. Man wollte sie als Marker für die Schizophrenie verwenden und auch bei bestimmten Porphyrien sollte sie vermehrt im Urin ausgeschieden werden. Jedoch konnte man diese Vermutungen bis Ende der 1970er-Jahre eindeutig widerlegen. Jetzt taucht diese Substanz wieder als Hämopyrrollaktam auf und soll einen ausgeprägten Vitamin B6- und Zink-Mangel bewirken, der zu unterschiedlichen Krankheitsbildern führt. Dafür werden unnötige und teure Laboruntersuchen sowie zur Korrektur der Mangelzustände Nahrungsergänzungsmittel angeboten.
ESBL, AmpC und Carbapenemasen: Vorkommen, Verbreitung und Diagnostik β-Lactamase-bildender Gram-negativer Krankheitserreger / ESBL, AmpC and carbapenemases: emergence, dissemination and diagnostics of β-lactamase-producing Gram-negative pathogens
Authors: Pfeifer Yvonne
Published: July 2010

Die Zunahme der β-Lactamresistenz bei Gram-negativen Erregern von Krankenhausinfektionen ist überwiegend auf die Bildung von β-Lactamasen zurückzuführen. An neuentwickelte β-Lactame passen sich die Bakterien durch Modifizierung dieser Enzyme oder Erwerb neuer β-Lactamasen schnell an. Heute ist eine Vielzahl verschiedener β-Lactamasen mit vielfältigen Wirkspektren bekannt, wobei einige in der Lage sind selbst moderne β-Lactame, wie die Carbapeneme, zu hydrolysieren. Die Lokalisation der β-Lactamase-Gene innerhalb mobiler genetischer Elemente ermöglicht die schnelle Weiterverbreitung der Resistenz sowohl innerhalb einer Spezies als auch zwischen den verschiedenen Gram-negativen Spezies. Das wiederum begünstigt die Entstehung multiresistenter Erreger (MRE), deren Resistenzspektrum die Grenzen der therapeutischen Möglichkeiten erreicht. Am Robert Koch Institut in Wernigerode wird im Rahmen des ARS-Projektes (Antibiotikaresistenz Surveillance Deutschland) die β-Lactamase-Bildung Cephalosporin- und Carbapenem-resistenter Enterobacteriaceae und Nonfermenter mittels molekularer Methoden untersucht. Ziel ist die Beschreibung der Häufigkeit und der Verbreitungswege relevanter β-Lactamasen sowie die frühzeitige Erkennung und Überwachung neuer Resistenzdeterminanten und multiresistenter nosokomialer Erreger.
Spezifische Immuntherapie und Vakzination als Störfaktoren in der serologischen Diagnostik / Immunotherapy and vaccination: interfering factors in serological diagnostics
Authors: Reinheimer Claudia , Doerr Hans Wilhelm
Published: July 2010

Qualitative und quantitative serologische Verfahren können durch Interferenzen gestört sein. Wir konnten in einem exemplarischen Fall anhand des Influenza A/H1N1v-Hämagglutinationshemmtests (H1N1-HHT) zeigen, dass auch Hyposensibilisierungstherapie und Vakzination zu Interaktionen in der serologischen Diagnostik führen und die Aussagekraft des H1N1-HHT massiv beeinträchtigen. Vor dem Hintergrund, dass Hyposensibilisierung und Vakzination im Klinik- und Praxisalltag häufig erbrachte Leistungen darstellen, erscheint dieser Umstand berichtenswert.