bluuebunny/crossref_metadata_2025 huggingface dataset:
Competition between recombination and epistasis can cause a transition from allele to genotype selection
Authors: Neher Richard A. , Shraiman Boris I.
Published: April 2009

Biochemical and regulatory interactions central to biological networks are expected to cause extensive genetic interactions or epistasis affecting the heritability of complex traits and the distribution of genotypes in populations. However, the inference of epistasis from the observed phenotype–genotype correlation is impeded by statistical difficulties, while the theoretical understanding of the effects of epistasis remains limited, in turn limiting our ability to interpret data. Of particular interest is the biologically relevant situation of numerous interacting genetic loci with small individual contributions to fitness. Here, we present a computational model of selection dynamics involving many epistatic loci in a recombining population. We demonstrate that a large number of polymorphic interacting loci can, despite frequent recombination, exhibit cooperative behavior that locks alleles into favorable genotypes leading to a population consisting of a set of competing clones. When the recombination rate exceeds a certain critical value that depends on the strength of epistasis, this “genotype selection” regime disappears in an abrupt transition, giving way to “allele selection”—the regime where different loci are only weakly correlated as expected in sexually reproducing populations. We show that large populations attain highest fitness at a recombination rate just below critical. Clustering of interacting sets of genes on a chromosome leads to the emergence of an intermediate regime, where blocks of cooperating alleles lock into genetic modules. These haplotype blocks disappear in a second transition to pure allele selection. Our results demonstrate that the collective effect of many weak epistatic interactions can have dramatic effects on the population structure.
A randomized trial of the effect of estrogen and testosterone on economic behavior
Authors: Zethraeus Niklas , Kocoska-Maras Ljiljana , Ellingsen Tore , von Schoultz Bo , Hirschberg Angelica Lindén , Johannesson Magnus
Published: April 2009

Existing correlative evidence suggests that sex hormones may affect economic behavior such as risk taking and reciprocal fairness. To test this hypothesis we conducted a double-blind randomized study. Two-hundred healthy postmenopausal women aged 50–65 years were randomly allocated to 4 weeks of treatment with estrogen, testosterone, or placebo. At the end of the treatment period, the subjects participated in a series of economic experiments that measure altruism, reciprocal fairness, trust, trustworthiness, and risk attitudes. There was no significant effect of estrogen or testosterone on any of the studied behaviors.
Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity
Authors: Wilhelm Jennifer C. , Rich Mark M. , Wenner Peter
Published: April 2009

When neuronal activity is reduced over a period of days, compensatory changes in synaptic strength and/or cellular excitability are triggered, which are thought to act in a manner to homeostatically recover normal activity levels. The time course over which changes in homeostatic synaptic strength and cellular excitability occur are not clear. Although many studies show that 1–2 days of activity block are necessary to trigger increases in excitatory quantal strength, few studies have been able to examine whether these mechanisms actually underlie recovery of network activity. Here, we examine the mechanisms underlying recovery of embryonic motor activity following block of either excitatory GABAergic or glutamatergic inputs in vivo. We find that GABA
A
receptor blockade triggers fast changes in cellular excitability that occur during the recovery of activity but before changes in synaptic scaling. This increase in cellular excitability is mediated in part by an increase in sodium currents and a reduction in the fast-inactivating and calcium-activated potassium currents. These findings suggest that compensatory changes in cellular excitability, rather than synaptic scaling, contribute to activity recovery. Further, we find a special role for the GABA
A
receptor in triggering several homeostatic mechanisms after activity perturbations, including changes in cellular excitability and GABAergic and AMPAergic synaptic strength. The temporal difference in expression of homeostatic changes in cellular excitability and synaptic strength suggests that there are multiple mechanisms and pathways engaged to regulate network activity, and that each may have temporally distinct functions.
VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis
Authors: Zhang Fan , Tang Zhongshu , Hou Xu , Lennartsson Johan , Li Yang , Koch Alexander W. , Scotney Pierre , Lee Chunsik , Arjunan Pachiappan , Dong Lijin , Kumar Anil , Rissanen Tuomas T. , Wang Bin , Nagai Nobuo , Fons Pierre , Fariss Robert , Zhang Yongqing , Wawrousek Eric , Tansey Ginger , Raber James , Fong Guo-Hua , Ding Hao , Greenberg David A. , Becker Kevin G. , Herbert Jean-Marc , Nash Andrew , Yla-Herttuala Seppo , Cao Yihai , Watts Ryan J. , Li Xuri
Published: April 2009

VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a “survival,” rather than an “angiogenic” factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
Leishmania amazonensispromastigotes induce and are killed by neutrophil extracellular traps
Authors: Guimarães-Costa Anderson B. , Nascimento Michelle T. C. , Froment Giselle S. , Soares Rodrigo P. P. , Morgado Fernanda N. , Conceição-Silva Fátima , Saraiva Elvira M.
Published: April 2009

Neutrophils are short-lived leukocytes that die by apoptosis, necrosis, and NETosis. Upon death by NETosis, neutrophils release fibrous traps of DNA, histones, and granule proteins named neutrophil extracellular traps (NETs), which can kill bacteria and fungi. Inoculation of the protozoanLeishmaniainto the mammalian skin causes local inflammation with neutrophil recruitment. Here, we investigated the release of NETs by human neutrophils upon their interaction withLeishmaniaparasites and NETs' ability to kill this protozoan. The NET constituents DNA, elastase, and histones were detected in traps associated to promastigotes by immunofluorescence. Electron microscopy revealed thatLeishmaniawas ensnared by NETs released by neutrophils. Moreover,Leishmaniaand its surface lipophosphoglycan induced NET release by neutrophils in a parasite number- and dose-dependent manner. Disruption of NETs by DNase treatment duringLeishmania–neutrophil interaction increased parasite survival, evidencing NETs' leishmanicidal effect.Leishmaniakilling was also elicited by NET-rich supernatants from phorbol 12-myristate 13-acetate-activated neutrophils. Immunoneutralization of histone duringLeishmania–neutrophil interaction partially revertedLeishmaniakilling, and purified histone killed the parasites. Meshes composed of DNA and elastase were evidenced in biopsies of human cutaneous leishmaniasis. NET is an innate response that might contribute to diminish parasite burden in theLeishmaniainoculation site.
Synthesis, characterization, and immunogenicity in mice of
Shigella sonnei
O-specific oligosaccharide-core-protein conjugates
Authors: Robbins John B. , Kubler-Kielb Joanna , Vinogradov Evguenii , Mocca Christopher , Pozsgay Vince , Shiloach Joseph , Schneerson Rachel
Published: April 2009

Shigellosis, an enteric disease, is on the World Health Organization's priority prevention list. In one study, the
Shigella sonnei
O-specific polysaccharide (O-SP)-protein conjugate showed 72% protection against disease in Israeli army recruits exposed to high rates (8–14%) of infection. The protection was related to vaccine-induced IgG anti-O-SP levels. Synthetic oligosaccharides of
Shigella dysenteriae
type 1, bound by their reducing ends to a carrier protein (“sun”-type configuration), induced significantly higher antibody levels than the native O-SP bound to protein by multiple-point attachments (“lattice”-type configuration). Attempts to synthesize the
S. sonnei
O-SP based oligosaccharides were not successful. Here, we describe the isolation, characterization, and conjugation of low-molecular-mass O-SP-core (O-SPC) fragments. The O-SPC fragments were bound by their reducing ends similar to the preparation of the synthetic
S. dysenteriae
type 1 conjugates. The O-SPC conjugates used oxime linkages between the terminal Kdo residues at the reducing ends of the
S. sonnei
saccharides and aminooxy linkers bound to BSA or a recombinant diphtheria toxin. The coupling reaction was carried out at a neutral pH and room temperature. IgG antibody levels induced in young outbred mice by the
S. sonnei
O-SPC conjugates were significantly higher then those elicited by the O-SP conjugates. Accordingly, we propose to evaluate clinically these conjugates.
Antigen storage compartments in mature dendritic cells facilitate prolonged cytotoxic T lymphocyte cross-priming capacity
Authors: van Montfoort Nadine , Camps Marcel G. , Khan Selina , Filippov Dmitri V. , Weterings Jimmy J. , Griffith Janice M. , Geuze Hans J. , van Hall Thorbald , Verbeek J. Sjef , Melief Cornelis J. , Ossendorp Ferry
Published: April 2009

Dendritic cells (DCs) are crucial for priming of naive CD8
+
T lymphocytes to exogenous antigens, so-called “cross-priming.” We report that exogenous protein antigen can be conserved for several days in mature DCs, coinciding with strong cytotoxic T lymphocyte cross-priming potency in vivo. After MHC class I peptide elution, protein antigen-derived peptide presentation is efficiently restored, indicating the presence of an intracellular antigen depot. We characterized this depot as a lysosome-like organelle, distinct from MHC class II compartments and recently described early endosomal compartments that allow acute antigen presentation in MHC class I. The storage compartments we report here facilitate continuous supply of MHC class I ligands. This mechanism ensures sustained cross-presentation by DCs, despite the short-lived expression of MHC class I–peptide complexes at the cell surface.
Transience of MHC Class I-restricted antigen presentation after influenza A virus infection
Authors: Mintern Justine D. , Bedoui Sammy , Davey Gayle M. , Moffat Jessica M. , Doherty Peter C. , Turner Stephen J.
Published: April 2009

Antigen expressed as MHC Class I glycoprotein (pMHCI) complexes on dendritic cells is the primary driver of CD8
+
T cell clonal expansion and differentiation. As we seek to define the molecular differences between acutely stimulated cytotoxic T lymphocyte (CTL) effectors and long-lived memory T cells, it is essential that we understand the duration of
in vivo
pMHCI persistence. Although infectious influenza A virus is readily cleared by mammalian hosts, that does not necessarily mean that all influenza antigen is totally eliminated. An exhaustive series of carefully controlled adoptive transfer experiments using 3 different carboxy fluorescein diacetate succinimidyl ester–labeled T cell receptor–transgenic CTL populations and a spectrum of genetically engineered and wild-type influenza A viruses provided no evidence for pMHCI persistence over the 30–60-d interval after virus challenge. Molecular profiles identified in antigen-specific T cells at this time may thus be considered to reflect established immunologic memory and not recent CTL activation from a persistent pMHCI pool.
Initial formation of an indigenous crop complex in eastern North America at 3800 B.P
Authors: Smith Bruce D. , Yarnell Richard A.
Published: April 2009

Although geneticists and archaeologists continue to make progress world-wide in documenting the time and place of the initial domestication of a growing number of plants and animals, far less is known regarding the critically important context of coalescence of various species into distinctive sets or complexes of domesticates in each of the world's 10 or more independent centers of agricultural origin. In this article, the initial emergence of a crop complex is described for one of the best-documented of these independent centers, eastern North America (ENA). Before 4000 B.P. there is no indication of a crop complex in ENA, only isolated evidence for single indigenous domesticate species. By 3800 B.P., however, at least 5 domesticated seed-bearing plants formed a coherent complex in the river valley corridors of ENA. Accelerator mass spectrometer radiocarbon dates and reanalysis of archaeobotanical assemblages from a short occupation of the Riverton Site in Illinois documents the contemporary cultivation at 3800 B.P. of domesticated bottle gourd (
Lagenaria siceraria
), marshelder (
Iva annua
var.
macrocarpa
), sunflower (
Helianthus annuus
var.
macrocarpus
), and 2 cultivated varieties of chenopod (
Chenopodium berlandieri
), as well as the possible cultivation of
Cucurbita pepo
squash and little barley (
Hordeum pusillum
). Rather than marking either an abrupt developmental break or a necessary response to population-packing or compressed resource catchments, the coalescence of an initial crop complex in ENA appears to reflect an integrated expansion and enhancement of preexisting hunting and gathering economies that took place within a context of stable long-term adaptation to resource-rich river valley settings.
Anomalous optical and electronic properties of dense sodium
Authors: Lazicki A. , Goncharov A. F. , Struzhkin V. V. , Cohen R. E. , Liu Z. , Gregoryanz E. , Guillaume C. , Mao H.-K. , Hemley Russell J.
Published: April 2009

Synchrotron infrared spectroscopy on sodium shows a transition from a high reflectivity, nearly free-electron metal to a low-reflectivity, poor metal in an orthorhombic phase at 118 GPa. Optical spectra calculated within density functional theory (DFT) agree with the experimental measurements and predict a gap opening in the orthorhombic phase at compression beyond its stability field, a state that would be experimentally attainable by appropriate choice of pressure-temperature path. We show that a transition to an incommensurate phase at 125 GPa results in a partial recovery of good metallic character up to 180 GPa, demonstrating the strong relationship between structure and electronic properties in sodium.
Daily rhythms of food-anticipatory behavioral activity do not require the known circadian clock
Authors: Storch Kai-Florian , Weitz Charles J.
Published: April 2009

When food availability is restricted to a particular time each day, mammals exhibit food-anticipatory activity (FAA), a daily increase in locomotor activity preceding the presentation of food. Considerable historical evidence suggests that FAA is driven by a food-entrainable circadian clock distinct from the master clock of the suprachiasmatic nucleus. Multiple food-entrainable circadian clocks have been discovered in the brain and periphery, raising strong expectations that one or more underlie FAA. We report here that mutant mice lacking known circadian clock function in all tissues exhibit normal FAA both in a light–dark cycle and in constant darkness, regardless of whether the mutation disables the positive or negative limb of the clock feedback mechanism. FAA is thus independent of the known circadian clock. Our results indicate either that FAA is not the output of an oscillator or that it is the output of a circadian oscillator different from known circadian clocks.
Geometric and electronic structure differences between the type 3 copper sites of the multicopper oxidases and hemocyanin/tyrosinase
Authors: Yoon Jungjoo , Fujii Satoshi , Solomon Edward I.
Published: April 2009

The coupled binuclear “type 3” Cu sites are found in hemocyanin (Hc), tyrosinase (Tyr), and the multicopper oxidases (MCOs), such as laccase (Lc), and play vital roles in O
2
respiration. Although all type 3 Cu sites share the same ground state features, those of Hc/Tyr have very different ligand-binding properties relative to those of the MCOs. In particular, the type 3 Cu site in the MCOs (Lc
T3
) is a part of the trinuclear Cu cluster, and if the third (i.e., type 2) Cu is removed, the Lc
T3
site does not react with O
2
. Density functional theory calculations indicate that O
2
binding in Hc is ≈9 kcal mol
−1
more favorable than for Lc
T3
. The difference is mostly found in the total energy difference of the deoxy states (≈7 kcal mol
−1
), where the stabilization of deoxy Lc
T3
derives from its long equilibrium Cu–Cu distance of ≈5.5–6.5 Å, relative to ≈4.2 Å in deoxy Hc/Tyr. The O
2
binding in Hc is driven by the electrostatic destabilization of the deoxy Hc site, in which the two Cu(I) centers are kept close together by the protein for facile 2-electron reduction of O
2
. Alternatively, the lack of O
2
reactivity in Lc
T3
reflects the flexibility of the active site, capable of minimizing the electrostatic repulsion of the 2 Cu(I)s. Thus, the O
2
reactivity of the MCOs is intrinsic to the trinuclear Cu cluster, leading to different O
2
intermediates as required by its function of irreversible reduction of O
2
to H
2
O.
G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models
Authors: Shojaei Farbod , Wu Xiumin , Qu Xueping , Kowanetz Marcin , Yu Lanlan , Tan Martha , Meng Y. Gloria , Ferrara Napoleone
Published: April 2009

Recent studies suggest that tumor-associated CD11b
+
Gr1
+
myeloid cells contribute to refractoriness to antiangiogenic therapy with an anti-VEGF-A antibody. However, the mechanisms of peripheral mobilization and tumor-homing of CD11b
+
Gr1
+
cells are unclear. Here, we show that, compared with other cytokines [granulocyte-macrophage colony stimulating factor (GM-CSF), stromal derived factor 1α, and placenta growth factor], G-CSF and the G-CSF-induced Bv8 protein have preferential expression in refractory tumors. Treatment of refractory tumors with the combination of anti-VEGF and anti-G-CSF (or anti-Bv8) reduced tumor growth compared with anti-VEGF-A monotherapy. Anti-G-CSF treatment dramatically suppressed circulating or tumor-associated CD11b
+
Gr1
+
cells, reduced Bv8 levels, and affected the tumor vasculature. Conversely, G-CSF delivery to animals bearing anti-VEGF sensitive tumors resulted in reduced responsiveness to anti-VEGF-A treatment through induction of Bv8-dependent angiogenesis. We conclude that, at least in the models examined, G-CSF expression by tumor or stromal cells is a determinant of refractoriness to anti-VEGF-A treatment.
Large spinose microfossils in Ediacaran rocks as resting stages of early animals
Authors: Cohen Phoebe A. , Knoll Andrew H. , Kodner Robin B.
Published: April 2009

Large (>100 μm), profusely ornamented microfossils comprise a distinctive paleontological component of sedimentary rocks deposited during the Ediacaran Period (635–542 million years ago). Smaller spinose fossils in Paleozoic rocks have commonly been interpreted as algal cysts or phycomata, but the Ediacaran populations differ from modern algal analogs in size, shape, ultrastructure, and internal contents. In contrast, cysts formed during the diapause egg-resting stages of many metazoans share features of size, ornamentation, and internal contents with large ornamented Ediacaran microfossils (LOEMs). Moreover, transmission electron microscopic observations of animal-resting cysts reveal a 3-layer wall ultrastructure comparable to that of LOEM taxa. Interpretation of these distinctive Ediacaran microfossils as resting stages in early metazoan life cycles offers additional perspectives on their functional morphology and stratigraphic distribution. Based on comparisons with modern marine invertebrates, the recalcitrant life stage represented by LOEMs is interpreted as an evolutionary response to prolonged episodes of bottom water anoxia in Ediacaran shelf and platform environments. As predicted by this hypothesis, the later Ediacaran disappearance of LOEM taxa coincides with geochemical evidence for a marked decline in the extent of oxygen-depleted waters impinging on continental shelves and platforms. Thus, the form, diversity, and stratigraphic range of LOEMs illuminate life cycle evolution in early animals as influenced by the evolving redox state of the oceans.
Gendered patterns of high violence exposure among Swedish youth
Authors: DANIELSSON INGELA , BLOM HELENA , NILSES CARIN , HEIMER GUN , HÖGBERG ULF
Published: April 2009

Objective. The WHO describes violence as a global public health problem. In contrast to domestic violence, violence against youth has been little explored. Our aims were to investigate the prevalence and gender differences in relation to emotional, physical and sexual abuse among young men and women attending youth health centers in Sweden, the current adverse effects of the abuse and the perpetrators of the abuse. Design. Cross‐sectional study. Setting. Nationally representative youth health centers in Sweden. Population and methods. In total, 2,250 women and 920 men aged 15–23 years answered a validated questionnaire about emotional, physical and sexual abuse. Results. A total of 33% (CI: 31–35) of the young women and 18% (CI: 16–21) of the young men had been exposed to emotional abuse during the past year. For physical abuse, 18% (CI: 17–20) of the women and 27% (CI: 24–30) of the men stated that they had been abused during the past year. The gender differences for sexual abuse were pronounced, with 14% (CI: 12–15) of the young women and 4.7% (CI: 3.3–6.0) of the men stating that they had been abused during the past 12 months. The young women reported more severe adverse effects from all types of abuse and were more often abused by a person close to them. Conclusions. The exposure to violence among young people is alarming and presents prominent gender differences, and should be taken into serious consideration as it is a matter of health, democracy and human rights.
Reduced bone mineral density in adult women diagnosed with menstrual disorders during adolescence
Authors: WIKSTEN‐ALMSTRÖMER MARIANNE , HIRSCHBERG ANGELICA LINDÉN , HAGENFELDT KERSTIN
Published: April 2009

Objective. To evaluate the long‐term effects on bone mineral density (BMD) in women diagnosed with menstrual disorders in their adolescence. Design. Prospective follow‐up study six years after the initial investigation. Setting. A youth clinic that is part of the school health system in Stockholm. Population. Eighty‐seven women diagnosed with secondary amenorrhea or oligomenorrhea in adolescence. Methods. Subjects underwent gynecological examination, evaluation of eating behavior and physical activity. Whole body Dual Energy X‐ray Absorptiometry was used for measurement of BMD. Main outcome measures. BMD. Results. The overall frequency of osteopenia/osteoporosis was 52%, and three girls had osteoporosis. Women with previous secondary amenorrhea had significantly lower BMD in the pelvis and lumbar spine than those with previous oligomenorrhea. The strongest predictor of low BMD was a restrictive eating disorder in adolescence and the most important counteraction was high physical activity at follow‐up and a body mass index (BMI) ≥ 22. Persistent menstrual dysfunction at follow‐up was associated with polycystic ovary syndrome and lower frequency of osteopenia. Conclusions. This clinical follow‐up study has demonstrated a high frequency of osteopenia in women diagnosed with menstrual disorders in adolescence. Previous anorectic behavior was the strongest negative predictor of BMD. It is important to pay attention to an underlying eating disorder in young women with menstrual dysfunction in order to promote bone health.
Laparoscopic sacrocolpopexy: A comparison of Prolene® and Tutoplast® mesh
Authors: LOFFELD CORA J.W. , THIJS SUSANNE , MOL BEN W. , BONGERS MARLIES Y. , ROOVERS JAN‐PAUL W.R.
Published: April 2009

A retrospective study was carried out to evaluate which mesh (cadaveric fascia lata (Tutoplast®) or Prolene® mesh) is associated with the best outcome of laparoscopic sacrocolpopexy for vaginal vault prolapse. Nineteen women who had surgery with Tutoplast® and 20 who underwent surgery with Prolene® were followed and asked to complete the Urogenital Distress Inventory and Defecation Distress Inventory to measure disease‐specific quality of life. The women were invited for a follow‐up visit for pelvic examination at a mean time of 45 months. There were no significant differences in operating time, blood loss or hospital stay between the groups. The risk of re‐intervention because of recurrent prolapse was higher in the Tutoplast® group than in the Prolene® group (relative risk 2.9 (95% Confidence interval 0.9–9.5)). Women in the Prolene® group were significantly more satisfied with the operative result.
The incidence of neural tube defects in Norway and the Arkhangelskaja Oblast in Russia and the association with maternal age
Authors: PETROVA JELENA G. , VAKTSKJOLD ARILD
Published: April 2009

Objective. To determine the incidence of isolated anencephaly and spina bifida in the Arkhangelskaja Oblast (AO) in Russia and in Norway, and to study the maternal age distribution of these congenital defects. Design. A register‐based incidence study. Setting. Two different populations in Northern Europe. Population. All registered fetuses and newborns with at least 12 weeks’ gestation in the populations of AO (1995–2004) and Norway (1999–2003) were included. A total of 141,159 in AO and 293,708 in Norway. Methods. Data were obtained from the malformation register in AO and the Medical Birth Registry of Norway. Main outcome measures. Total and maternal age‐group specific incidence of anencephaly and spina bifida. Results. A total of 298 newborns and abortuses had one of the defects in AO (21.1/10,000 (95% confidence interval:±3.4)) and 317 (10.8/10,000 (±1.2)) in Norway. The incidence of anencephaly was 10.7/10,000 in AO and 5.5 in Norway, and of spina bifida 10.4 and 5.3, respectively. An inverse association between the age of the pregnant women and the incidence of neural tube defects was observed in both populations; for both anencephaly and spina bifida in AO; but only for anencephaly (age < 30 years) in Norway. Conclusions. The incidence of both anencephaly and spina bifida was higher in a northern population of Russia than in Norway. The burden of anencephaly was highest in the youngest maternal age group in both populations. The relatively high incidence of both anencephaly and spina bifida in the Russian population warrants further studies.
Comparison of radiation therapy alone and concurrent chemoradiation therapy in stage III cervical cancer: A multicenter retrospective study
Authors: LEE JONG‐MIN , TONG SEO‐YUN , LEE KWANG‐BEOM , KIM YOUNG‐TAE , KIM YOUNG‐JAE , KIM JAE WEON , KIM SEOK‐MO , CHO CHI‐HEUM , KIM KI‐TAE , CHO YOUNG‐LAE , LEE KYU‐CHAN
Published: April 2009

Objective. To evaluate whether concurrent chemoradiation therapy (CRT) improves overall survival as compared to radiation therapy (RT) alone in stage III cervical cancers. Design. A multicenter retrospective review. Setting. Nine tertiary medical centers in Korea. Population. A total of 277 patients treated for stage III cervical cancer without para‐aortic lymph node (PALN) metastasis based on clinical staging workup from 1996 to 2003. Methods. Medical and histopathological record review. Main outcome measures. Disease‐specific overall survival. Results. CRT and RT alone were performed in 172 and 105 patients, respectively. There was no significant difference in disease‐specific overall survival between the CRT and RT alone arms based on clinical staging workup, even though the CRT arm was characterized by younger age, more favorable performance status and lower pretreatment blood urea nitrogen level as compared to the RT alone arm. In the CRT arm, three patients succumbed to treatment‐related death. Conclusion. CRT does not improve the overall survival rate in stage III cervical cancer as compared to RT alone based on clinical staging workup for PALN status. Special care needs to be taken regarding optimal dose and duration of RT, use of brachytherapy, anemia control and accurate pretreatment staging workup to improve survival outcome in patients with stage III cervical cancer.
Abnormal expression of MMP‐9 and imbalance of MMP‐9/TIMP‐1 is associated with prolonged uterine bleeding after a medical abortion with mifepristone and misoprostol
Authors: LI LI , ZHOU ZANHUA , HUANG LILI
Published: April 2009

Objective. To investigate the expression of matrix metalloproteinase‐9 (MMP‐9) and tissue inhibitory of metalloproteinase‐1 (TIMP‐1) in women who had undergone a medical abortion and explore their possible role in the mechanism of prolonged uterine bleeding after a mifepristone‐misoprostol abortion. Design. Cross‐sectional study. Setting. Tertiary referral university hospital. Sample. Forty women were recruited following a medical abortion with mifepristone and misoprostol, 20 with duration of bleeding >14 days and 20 with duration of bleeding ≤ 14 days. Methods. Endometrial specimens were stained with hematoxylin and eosin for histological examination. The expression of MMP‐9 and TIMP‐1 was evaluated by immunohistochemistry. Main outcome measures. Histology was analyzed by light microscope and expression of MMP‐9 and TIMP‐1 was semi‐quantitatively evaluated. Results. Histological examination showed residual villi and trophoblasts with inflammatory cell infiltration in women with duration of bleeding >14 days after a medical abortion (bleeding group), whereas each sample of women with duration of bleeding ≤ 14 days after a medical abortion (control group) showed normal endometrial changes. Immunohistochemistry and semi‐quantitative scoring showed a significantly decreased expression level of MMP‐9 in the bleeding group, compared with the control group. There was no significant difference of TIMP‐1 expression between the bleeding group and the control group. The MMP‐9/TIMP‐1 ratio value was significantly lower in the bleeding group than in the control group. Conclusion. This study documents that prolonged bleeding after a medical abortion with mifepristone and misoprostol is associated with retained products of conception with inflammatory cell infiltration, abnormal expression of MMP‐9 and imbalance of MMP‐9/TIMP‐1.
Human and peoples' rights: Social representations among Cameroonian students
Authors: Pirttilä‐Backman Anna‐Maija , Kassea Raul , Sakki Inari
Published: April 2009

Social representations of human and peoples' rights were studied among Cameroonian university students (N = 666) with a questionnaire based on the UN Declaration of Human Rights and the African Charter on Human and Peoples' Rights and Duties. The respondents were asked how important and how well realized they regarded the 39 human and peoples' rights to be. A 13‐factor model provided the best fit with Cameroonian students' perceptions of human and peoples' rights. Taken as a whole, our results are in line with previous quantitative studies on human rights, confirming structural similarity but also country‐specific variation in the aggregation of specific rights. Moreover, our data showed that Cameroonian students value human and peoples' rights highly (M = 6.18), whereas their fulfillment is not regarded as highly (M = 5.09). Same law for all, equality and freedom, and right to work and living were highly appreciated but lowly realized rights. Higher than average in importance and realization were right to education and self‐fulfillment, right to marriage and property, peoples' social and political basic rights and right to life and safety. Low in importance and realization were peoples' right to their country's natural resources and independence, right to meetings, and right to express opinion. Women appreciated the rights more than men and thought of their rights as better realized compared to men. We suggest that when women say that their rights are better fulfilled than men do, it is in comparison with the older generation, who are still very dependent on men. Nowadays, thanks to education and urbanization, young women have wider choices or opportunities for marriage and jobs. Men may feel frustrated in the context of political liberalization because the freedoms are more theoretical than fulfilled; the economic crises and cultural changes have hindered their economic domination and their prerogatives.
Calvarial lesions: A radiological approach to diagnosis
Authors: Lloret I. , Server A. , Taksdal I.
Published: April 2009

Calvarial lesions are frequently identified in radiological studies. A wide variety of neoplasms and non-neoplastic lesions can involve the calvarium, and their imaging appearances vary according to their pathologic features. These lesions are usually asymptomatic but may manifest as a lump with or without associated pain. Clinical information, including the age of patient, is an important factor in the diagnostic process. In this paper, we illustrate the value of cross-sectional imaging techniques by computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating these lesions. We also review the literature and discuss the specific imaging characteristics of the most common calvarial lesions in order to provide information that can guide radiological diagnosis or limit differential diagnosis.
Reactive Oxygen Species Are Necessary for High Flow (Shear Stress)‐induced Diameter Enlargement of Rat Resistance Arteries
Authors: BELIN DE CHANTEMÈLE ERIC J. , VESSIÈRES EMILIE , DUMONT ODILE , GUIHOT ANNE‐LAURE , TOUTAIN BERTRAND , LOUFRANI LAURENT , HENRION DANIEL
Published: April 2009

Objectives: Chronic increases in blood flow induce remodeling associated with increases in diameter and endothelium‐mediated dilation. Remodeling requires cell growth and migration, which may involve reactive oxygen species (ROS). Nevertheless, the role of ROS in flow‐mediated remodeling in resistance arteries is not known. Materials and Methods: Rat mesenteric resistance arteries (MRAs) were exposed to high flow (HF) by sequentially ligating second‐order MRAs in vivo. After three weeks, arteries were collected for structural, pharmacological, and biochemical analysis. Results: In HF arteries, luminal diameter (431±12 to 553±14 μm; n=10), endothelium (acetylcholine)‐mediated vasodilatation (61±6 to 77±6% relaxation) and NAD(P)H subunit (gp91phox and p67phox) expression levels, and ROS (dihydroethydine microphotography) and peroxynitrite (3‐nitro‐tyrosine) production were higher than in normal flow arteries. Acute ROS scavenging with tempol improved acetylcholine‐dependent relaxation (92±4% relaxation), confirming that ROS are produced in HF arteries. Chronic treatment with tempol prevented the increase in diameter, reduced ROS and peroxynitrite production, and improved endothelium‐mediated relaxation in HF arteries. Thus, ROS and NO were involved in HF‐induced diameter enlargement, possibly through the formation of peroxynitrite, while ROS reduced the increase in endothelium‐dependent relaxation. Conclusions: ROS production is necessary for flow‐mediated diameter enlargement of resistance arteries. However, ROS counteract, in part, the associated improvement in endothelium‐mediated relaxation.
Effects of Estrogen on Postischemic Pial Artery Reactivity to ADP
Authors: LI MIN , ZEYNALOV EMIL , LI XIAOLING , MIYAZAKI CHIKAO , KOEHLER RAYMOND C. , LITTLETON‐KEARNEY MARGUERITE T.
Published: April 2009

Objective: The aims of this work were to determine if 1) ischemia alters pial artery responsiveness to the partially nitric oxide (NO)‐dependent dilator, ADP, 2) the alteration depends on 17β‐estradial (E2), and 3) NO contributes to E2 protective effects. Materials and Methods: Response to ADP and the non‐NO‐dependent dilator, PGE2, were examined through closed cranial windows. Ovariectomized (OVX) and E2‐replaced (E25, 0.025 mg; or E50, 0.05 mg) rats were subjected to 15‐minute forebrain ischemia and one‐hour reperfusion. Endothelial NO synthase (eNOS) expression was determined in pre‐ and postischemic isolated cortical microvessels. Results: In OVX rats, ischemia depressed pial responses to ADP, but not to PGE2. Both doses of E2 maintained responses to ADP and had no effect on the response to PGE2. eNOS inhibition decreased the ADP response by 60% in the E25 rats and 50% in the E50 rats, but had no effect in the OVX rats. Compared to the OVX group, microvessel expression of eNOS was increased by E2, but postischemic eNOS was unchanged in both groups. Conclusions: The nearly complete loss of postischemic dilation to ADP suggests that normal non‐NO‐mediated dilatory mechanisms may be acutely impaired after ischemic injury. Estrogen's protective action on ADP dilation may involve both NO‐ and non‐NO‐mediated mechanisms.
Identification of ribosomal RNA genes in metagenomic fragments
Authors: Huang Ying , Gilna Paul , Li Weizhong
Published: April 2009

Motivation: Identification of genes coding for ribosomal RNA (rRNA) is considered an important goal in the analysis of data from metagenomics projects. Here, we report the development of a software program designed for the identification of rRNA genes from metagenomic fragments based on hidden Markov models (HMMs). This program provides rRNA gene predictions with high sensitivity and specificity on artificially fragmented genomic DNAs.

Availability: Supplementary files, scripts and sample data are available at http://tools.camera.calit2.net/camera/meta_rna.

Contact:  liwz@sdsc.edu

Supplementary information:  Supplementary Data are available at Bioinformatics online.
Data structures and algorithms for analysis of genetics of gene expression with Bioconductor: GGtools 3.x
Authors: Carey Vincent J. , Davis Adam R. , Lawrence Michael F. , Gentleman Robert , Raby Benjamin A.
Published: April 2009

Summary: Associations between DNA polymorphisms and mRNA abundance are a natural target of genetic investigations, and microarrays facilitate genome-wide and transcriptome-wide surveys of these associations. This work is motivated by emerging requirements for data architectures and algorithm interfaces to allow flexible exploration of public and private archives of genotyping and expression arrays. Using R/Bioconductor facilities, Phase II HapMap genotypes and Illumina 47K expression assay results archived on multiple populations may be interactively explored and analyzed using commodity hardware.

Availability and Implementation: Open Source. Bioconductor 2.3 packages GGtools, GGBase, GGdata, hmyriB36. Freely available on the web at http://www.bioconductor.org

Contact:  stvjc@channing.harvard.edu
IGG3: a tool to rapidly integrate large genotype datasets for whole-genome imputation and individual-level meta-analysis
Authors: Li Miao-Xin , Jiang Lin , Kao Patrick Yu-Ping , Sham Pak-C. , Song You-Qiang
Published: April 2009

Summary: There is an urgent and increasing demand for integrating large genotype datasets across genome-wide association studies and HapMap project for whole-genome imputation and individual-level meta-analysis. A new algorithm was developed to efficiently merge raw genotypes across large datasets and implemented in the latest version of IGG, IGG3. In addition, IGG3 can integrate the latest phased and unphased HapMap genotypes and can flexibly generate complete sets of input files for six popular genotype imputation tools. We demonstrated the efficiency of IGG3 by simulation tests, which could rapidly merge genotypes in tens of thousands of large genotype chips (e.g. Affymetrix Genome-Wide Human SNP Array 6.0 and Illumina Human1m-duo) and in HapMap III project on an ordinary desktop computer.

Availability:  http://bioinfo.hku.hk/iggweb (version 3.0).

Contacts:  songy@hkucc.hku.hk; limx54@yahoo.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Globally optimal stitching of tiled 3D microscopic image acquisitions
Authors: Preibisch Stephan , Saalfeld Stephan , Tomancak Pavel
Published: April 2009

Motivation: Modern anatomical and developmental studies often require high-resolution imaging of large specimens in three dimensions (3D). Confocal microscopy produces high-resolution 3D images, but is limited by a relatively small field of view compared with the size of large biological specimens. Therefore, motorized stages that move the sample are used to create a tiled scan of the whole specimen. The physical coordinates provided by the microscope stage are not precise enough to allow direct reconstruction (Stitching) of the whole image from individual image stacks.

Results: To optimally stitch a large collection of 3D confocal images, we developed a method that, based on the Fourier Shift Theorem, computes all possible translations between pairs of 3D images, yielding the best overlap in terms of the cross-correlation measure and subsequently finds the globally optimal configuration of the whole group of 3D images. This method avoids the propagation of errors by consecutive registration steps. Additionally, to compensate the brightness differences between tiles, we apply a smooth, non-linear intensity transition between the overlapping images. Our stitching approach is fast, works on 2D and 3D images, and for small image sets does not require prior knowledge about the tile configuration.

Availability: The implementation of this method is available as an ImageJ plugin distributed as a part of the Fiji project (FijiisjustImageJ: http://pacific.mpi-cbg.de/).

Contact:  tomancak@mpi-cbg.de
Analgesic Effects and the Mechanisms of Anti‐Inflammation of Hispolon in Mice
Authors: Chang Heng-Yuan , Sheu Ming-Jyh , Yang Chun-Hung , Lu Tsung-Chun , Chang Yuan Shiun , Peng Wen-Huang , Huang Shyh-Shyun , Huang Guan-Jhong
Published: April 2009

Hispolon, an active ingredient in the fungi Phellinus linteus was evaluated with analgesic and anti‐inflammatory effects. Treatment of male ICR mice with hispolon (10 and 20 mg/kg) significantly inhibited the numbers of acetic acid‐induced writhing response. Also, our result showed that hispolon (20 mg/kg) significantly inhibited the formalin‐induced pain in the later phase (P<.01). In the anti‐inflammatory test, hispolon (20 mg/kg) decreased the paw edema at the fourth and fifth hour after λ‐carrageenin (Carr) administration, and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver tissue. We also demonstrated that hispolon significantly attenuated the malondialdehyde (MDA) level in the edema paw at the fifth hour after Carr injection. Hispolon (10 and 20 mg/kg) decreased the nitric oxide (NO) levels on both the edema paw and serum level at the fifth hour after Carr injection. Also, hispolon (10 and 20 mg/kg) diminished the serum TNF‐α at the fifth hour after Carr injection. The anti‐inflammatory mechanisms of hispolon might be related to the decrease in the level of MDA in the edema paw by increasing the activities of SOD, GPx and GRx in the liver. It probably exerts anti‐inflammatory effects through the suppression of TNF‐α and NO.
Simulating the effects of side-aspect fish orientation on acoustic biomass estimates
Authors: Boswell Kevin M. , Roth Brian M. , Cowan James H.
Published: April 2009

Boswell, K. M., Roth, B. M., and Cowan, Jr J. H. 2009. Simulating the effects of side-aspect fish orientation on acoustic biomass estimates. – ICES Journal of Marine Science, 66: 1398–1403. Simulation methods were used to investigate the effect of side-aspect fish orientation on estimates of fish biomass derived from acoustic data. Three population-level length distributions (n = 1000 individuals) were simulated (identical, uniform, and age class) and applied to a target strength (TS) function of fish length previously derived for Gulf menhaden (Brevoortia patronus). Systematic manipulation of the TS–length coefficients strongly affected the biomass estimates. Based on simulations, biomass estimates decreased markedly from the true side-aspect to head- or tail-on orientation, with estimates of population biomass decreasing by 80% when orientation deviated by as little as 30° from true side-aspect. Simulated data indicate that biomass estimates generated from surveys may be grossly inaccurate if fish orientation is not taken into account.
The Microfoundations of Mass Polarization
Authors: Levendusky Matthew S.
Published: April 2009

Although there has been considerable attention to the question ofhow muchpolarization there is in the mass electorate, there has been much less attention paid to themechanismthat causes polarization. I provide evidence demonstrating the occurrence of individual-level conversion—individual Democrats and Republicans becoming more liberal and conservative. Although over the short term most of the observed changes are quite small and cannot be distinguished from measurement error, over time and many respondents, these movements aggregate to generate polarization. Small individual-level preference shifts provide an important foundation for aggregate polarization.
Cultivation of ‘Candidatus Liberibacter asiaticus’, ‘Ca. L. africanus’, and ‘Ca. L. americanus’ Associated with Huanglongbing
Authors: Sechler A. , Schuenzel E. L. , Cooke P. , Donnua S. , Thaveechai N. , Postnikova E. , Stone A. L. , Schneider W. L. , Damsteegt V. D. , Schaad N. W.
Published: April 2009

A new medium designated Liber A has been designed and used to successfully cultivate all three ‘Candidatus Liberibacter spp.,’ the suspect causative agents of huanglongbing (HLB) in citrus. The medium containing citrus vein extract and a growth factor sustained growth of ‘Ca. Liberibacter spp.’ for four or five single-colony transfers before viability declined. Colonies, positive for ‘Ca. L. asiaticus’ by a 16s-based rDNA real-time polymerase chain reaction (RT-PCR) assay and sequencing, were irregular-shaped, convex, and 0.1 to 0.3 mm after 3 to 4 days. Suspect ‘Ca. L. asiaticus’ and ‘Ca. L. americanus’ cells were observed in infected tissue and on agar culture by scanning electron microscopy. The cells were ovoid to rod shaped, 0.3 to 0.4 by 0.5 to 2.0 μm, often with fimbriae-like appendages. Two strains of ‘Ca. L. asiaticus’ and one of ‘Ca. L. americanus’ grown on Liber A medium were pathogenic on citrus and could be isolated from noninoculated tissues of inoculated trees and seedlings 9 and 2 months later, respectively. The identity was confirmed by RT-PCR and 16s rDNA sequencing. This is the first report of the cultivation and pathogenicity of ‘Ca. L. asiaticus’ and ‘Ca. L. americanus’ associated with symptoms of HLB.