bluuebunny/crossref_metadata_2025 huggingface dataset:
Video Gaming in Children Improves Performance on a Virtual Reality Trainer but Does Not yet Make a Laparoscopic Surgeon
Authors: Rosenthal Rachel , Geuss Steffen , Dell-Kuster Salome , Schäfer Juliane , Hahnloser Dieter , Demartines Nicolas
Published: January 2011

Background: In children, video game experience improves spatial performance, a predictor of surgical performance. This study aims at comparing laparoscopic virtual reality (VR) task performance of children with different levels of experience in video games and residents. Participants and methods: A total of 32 children (8.4 to 12.1 years), 20 residents, and 14 board-certified surgeons (total n = 66) performed several VR and 2 conventional tasks (cube/spatial and pegboard/fine motor). Performance between the groups was compared (primary outcome). VR performance was correlated with conventional task performance (secondary outcome). Results: Lowest VR performance was found in children with low video game experience, followed by those with high video game experience, residents, and board-certified surgeons. VR performance correlated well with the spatial test and moderately with the fine motor test. Conclusions: The use of computer games can be considered not only as pure entertainment but may also contribute to the development of skills relevant for adequate performance in VR laparoscopic tasks. Spatial skills are relevant for VR laparoscopic task performance.
Quality of Life and Functional Results of Submucosal Injection Therapy Using Dextranomer Hyaluronic Acid for Fecal Incontinence
Authors: Schwandner Oliver , Brunner Marion , Dietl Otto
Published: January 2011

Background and aim: The aim of this prospective study was to analyze safety and functional outcome of transanal submucosal injection of dextranomer hyaluronic acid (“bulking agents therapy”) in patients with passive fecal incontinence. Methods: All patients who underwent transanal injection therapy were prospectively enrolled in this study. Inclusion criteria included fecal incontinence (internal anal sphincter dysfunction) after failed conservative treatment. The procedure was performed in a standardized technique, including submucosal injection of 4 × 1 mL dextranomer hyaluronic acid 5 mm above the dentate line. The primary endpoint focused on symptom improvement provided as the change in incontinence status and quality of life using validated scores (Wexner incontinence score, symptom-specific Fecal Incontinence Quality of Life [FIQoL] scale, and generic EQ-5D-Visual Analogue Scale [EQ-5D-VAS]). Results: Within the observation period (July 2007 to May 2009), a total of 21 patients (17 women) with passive fecal incontinence were treated. Neither morbidity nor adverse events were documented. Three months postoperatively, 61.1% (11/18) showed significant improvement of symptoms (reduction of incontinence episodes and soiling), which was sustained after 20 months in 55.6% (10/18). Wexner incontinence score decreased from 16.8 to 12.3 ( P > .05). Significant improvement was documented for FIQoL and EQ-5D-VAS ( P < .05). Conclusion: The current results indicate that injection therapy using hyaluronic acid is an innovative and minimally invasive procedure with no morbidity. Although Wexner incontinence score is not significantly influenced, a significant improvement in quality of life was observed in more than 50% of patients.
Endoscopic Treatment of Postgastrectomy Duodenal Fistula With an Over-the-Scope Clip
Authors: Bini Roberto , Coppola Franco , Recchia Serafino , Fusca Marcella , Gaia Silvia , Leli Renzo
Published: January 2011

Bleeding peptic ulcer is a life threatening condition with high mortality rate but often treatable by endoscopy. Surgical indications in case of gastroduodenal ulcers are confined to endoscopic and radiological failures in bleeding control. Duodenal fistula (DF) is a rare complication of gastric resection and even if a rare event it may be a life threatening condition. Surgical and medical options could not solve the DF. Herein we report a case of an old patient underwent emergency gastrectomy for ulcer’s bleeding who developed DF associated to sepsis, malnutrition and, hydro-electrolyte disorders not responding to surgical and medical attempts. We demonstrated, for the first time, the efficacy of over the scope clips (OTSC®) in the treatment of postoperative duodenal fistulas not responding to surgical and medical treatment in high risk patient.
Differential requirements for CD45 in NK-cell function reveal distinct roles for Syk-family kinases
Authors: Hesslein David G. T. , Palacios Emil H. , Sun Joseph C. , Beilke Joshua N. , Watson Susan R. , Weiss Arthur , Lanier Lewis L.
Published: January 2011

The protein tyrosine phosphatase CD45 is an important regulator of Src-family kinase activity. We found that in the absence of CD45, natural killer (NK) cells are defective in protecting the host from mouse cytomegalovirus infection. We show that although CD45 is necessary for all immunoreceptor tyrosine–based activation motif (ITAM)–specific NK-cell functions and processes such as degranulation, cytokine production, and expansion during viral infection, the impact of CD45 deficiency on ITAM signaling differs depending on the downstream function. CD45-deficient NK cells are normal in their response to inflammatory cytokines when administered ex vivo and in the context of viral infection. Syk and ζ chain–associated protein kinase 70 (Zap70) are thought to play redundant roles in transmitting ITAM signals in NK cells. We show that Syk, but not Zap70, controls the remaining CD45-independent, ITAM-specific NK-cell functions, demonstrating a functional difference between these 2 Syk-kinase family members in primary NK cells.
Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes
Authors: Piccaluga Pier Paolo , De Falco Giulia , Kustagi Manjunath , Gazzola Anna , Agostinelli Claudio , Tripodo Claudio , Leucci Eleonora , Onnis Anna , Astolfi Annalisa , Sapienza Maria Rosaria , Bellan Cristiana , Lazzi Stefano , Tumwine Lynnette , Mawanda Michael , Ogwang Martin , Calbi Valeria , Formica Serena , Califano Andrea , Pileri Stefano A. , Leoncini Lorenzo
Published: January 2011

Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.
High interferon type I responses in the lung, plasma and spleen during highly pathogenic H5N1 infection of chicken
Authors: Moulin Hervé R , Liniger Matthias , Python Sylvie , Guzylack-Piriou Laurence , Ocaña-Macchi Manuela , Ruggli Nicolas , Summerfield Artur
Published: January 2011

This study shows that high pathogenic H5N1 influenza virus infection of chicken induced high levels of bioactive interferon type I in the lung (4.3 × 105 U/mg tissue), plasma (1.1 × 105 U/mL), and spleen (9.1 × 105 U/mg tissue). In contrast, a low pathogenic attenuated H5N1 vaccine strain only induced approximately 24 times less IFN in the lung, 441 times less in the spleen and 649 less in the plasma. This was in the same range as a reassortant carrying the HA from the vaccine strain and the remaining genes from the high pathogenic virus. On the other hand, a reassortant virus with the HA from the high pathogenic H5N1 with the remaining genes from the vaccine strain had intermediate levels of IFN. The level of interferon responses related to the viral load, and those in the spleen and blood to the spread of virus to lymphoid tissue, as well as disease severity. In vitro, the viruses did not induce interferon in chicken embryonic fibroblasts, but high levels in splenocytes, with not clear relationship to pathogenicity and virulence. This, and the responses also with inactivated viruses imply the presence of plasmacytoid dendritic cell-like leukocytes within the chicken immune system, possibly responsible for the high interferon responses during H5N1 infection. Our data also indicate that the viral load as well as the cleavability of the HA enabling systemic spread of the virus are two major factors controlling systemic IFN responses in chicken.
Enhanced glutamate, IP3 and cAMP activity in the cerebral cortex of Unilateral 6-hydroxydopamine induced Parkinson's rats: Effect of 5-HT, GABA and bone marrow cell supplementation
Authors: Nandhu MS , Paul Jes , Kuruvilla Korah P , Malat Anitha , Romeo Chinthu , Paulose CS
Published: January 2011

Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in Bmax (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B, mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's disease is of prominence.
Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model
Authors: Chang Han-Hsin , Chen Bo-Yie , Wu Chia-Yung , Tsao Zih-Jay , Chen Ying-Yu , Chang Chin-Pao , Yang Chi-Rei , Lin David Pei-Cheng
Published: January 2011

Background

Hedgehog signalling has been implicated in prostate tumorigenesis in human subjects and mouse models, but its effects on transforming normal basal/stem cells toward malignant cancer stem cells remain poorly understood.

Methods

We produced pCX-shh-IG mice that overexpress Hedgehog protein persistently in adult prostates, allowing for elucidation of the mechanism during prostate cancer initiation and progression. Various markers were used to characterize and confirm the transformation of normal prostate basal/stem cells into malignant cancer stem cells under the influence of Hedgehog overexpression.

Results

The pCX-shh-IG mice developed prostatic intraepithelial neoplasia (PIN) that led to invasive and metastatic prostate cancers within 90 days. The prostate cancer was initiated through activation of P63+ basal/stem cells along with simultaneous activation of Hedgehog signalling members, suggesting that P63+/Patch1+ and P63+/Smo+ cells may serve as cancer-initiating cells and progress into malignant prostate cancer stem cells (PCSCs). In the hyperplastic lesions and tumors, the progeny of PCSCs differentiated into cells of basal-intermediate and intermediate-luminal characteristics, whereas rare ChgA+ neuroendocrine differentiation was seen. Furthermore, in the metastatic loci within lymph nodes, kidneys, and lungs, the P63+ PCSCs formed prostate-like glandular structures, characteristic of the primitive structures during early prostate development. Besides, androgen receptor (AR) expression was detected heterogeneously during tumor progression. The existence of P63+/AR-, CK14+/AR- and CD44+/AR- progeny indicates direct procurement of AR- malignant cancer trait.

Conclusions

These data support a cancer stem cell scenario in which Hedgehog signalling plays important roles in transforming normal prostate basal/stem cells into PCSCs and in the progression of PCSCs into metastatic tumor cells.
Pathway-based analysis using reduced gene subsets in genome-wide association studies
Authors: Zhao Jingyuan , Gupta Simone , Seielstad Mark , Liu Jianjun , Thalamuthu Anbupalam
Published: January 2011

Background

Single Nucleotide Polymorphism (SNP) analysis only captures a small proportion of associated genetic variants in Genome-Wide Association Studies (GWAS) partly due to small marginal effects. Pathway level analysis incorporating prior biological information offers another way to analyze GWAS's of complex diseases, and promises to reveal the mechanisms leading to complex diseases. Biologically defined pathways are typically comprised of numerous genes. If only a subset of genes in the pathways is associated with disease then a joint analysis including all individual genes would result in a loss of power. To address this issue, we propose a pathway-based method that allows us to test for joint effects by using a pre-selected gene subset. In the proposed approach, each gene is considered as the basic unit, which reduces the number of genetic variants considered and hence reduces the degrees of freedom in the joint analysis. The proposed approach also can be used to investigate the joint effect of several genes in a candidate gene study.

Results

We applied this new method to a published GWAS of psoriasis and identified 6 biologically plausible pathways, after adjustment for multiple testing. The pathways identified in our analysis overlap with those reported in previous studies. Further, using simulations across a range of gene numbers and effect sizes, we demonstrate that the proposed approach enjoys higher power than several other approaches to detect associated pathways.

Conclusions

The proposed method could increase the power to discover susceptibility pathways and to identify associated genes using GWAS. In our analysis of genome-wide psoriasis data, we have identified a number of relevant pathways for psoriasis.
easyDAS: Automatic creation of DAS servers
Authors: Moreno Bernat Gel , Jenkinson Andrew M , Jimenez Rafael C , Peypoch Xavier Messeguer , Hermjakob Henning
Published: January 2011

Background

The Distributed Annotation System (DAS) has proven to be a successful way to publish and share biological data. Although there are more than 750 active registered servers from around 50 organizations, setting up a DAS server comprises a fair amount of work, making it difficult for many research groups to share their biological annotations. Given the clear advantage that the generalized sharing of relevant biological data is for the research community it would be desirable to facilitate the sharing process.

Results

Here we present easyDAS, a web-based system enabling anyone to publish biological annotations with just some clicks. The system, available at http://www.ebi.ac.uk/panda-srv/easydas is capable of reading different standard data file formats, process the data and create a new publicly available DAS source in a completely automated way. The created sources are hosted on the EBI systems and can take advantage of its high storage capacity and network connection, freeing the data provider from any network management work. easyDAS is an open source project under the GNU LGPL license.

Conclusions

easyDAS is an automated DAS source creation system which can help many researchers in sharing their biological data, potentially increasing the amount of relevant biological data available to the scientific community.
Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation
Authors: Sandahl Melissa , Hunter Debra M , Strunk Karen E , Earp H Shelton , Cook Rebecca S
Published: January 2011

Background

Mammary glands harbor a profound burden of apoptotic cells (ACs) during post-lactational involution, but little is known regarding mechanisms by which ACs are cleared from the mammary gland, or consequences if this process is interrupted. We investigated AC clearance, also termed efferocytosis, during post-lactational remodeling, using mice deficient for MerTK, Axl, and Tyro3, three related receptor tyrosine kinases (RTKs) regulating macrophage-mediated efferocytosis in monocytes. MerTK expression, apoptosis and the accumulation of apoptotic debris were examined in histological sections of MerTK-deficient, Axl/Tyro3-deficient, and wild-type mammary glands harvested at specific time points during lactation and synchronized involution. The ability of primary mammary epithelial cells (MECs) to engulf ACs was assessed in culture. Transplant of MerTK-deficient mammary epithelium into cleared WT mammary fat pads was used to assess the contribution of WT mammary macrophages to post-lactational efferocytosis.

Results

ACs induced MerTK expression in MECs, resulting in elevated MerTK levels at the earliest stages of involution. Loss of MerTK resulted in AC accumulation in post-lactational MerTK-deficient mammary glands, but not in Axl and Tyro3-deficient mammary glands. Increased vascularization, fibrosis, and epithelial hyperproliferation were observed in MerTK-deficient mammary glands through at least 60 days post-weaning, due to failed efferocytosis after lactation, but did not manifest in nulliparous mice. WT host-derived macrophages failed to rescue efferocytosis in transplanted MerTK-deficient mammary epithelium.

Conclusion

Efferocytosis by MECs through MerTK is crucial for mammary gland homeostasis and function during the post-lactational period. Efferocytosis by MECs thus limits pathologic consequences associated with the apoptotic load following lactation.
Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome
Authors: Allensworth Melody , Saha Anand , Reiter Lawrence T , Heck Detlef H
Published: January 2011

Background

Angelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with mental retardation, a generally happy disposition, ataxia and characteristic behaviors such as inappropriate laughter, social-seeking behavior and hyperactivity. The majority of AS cases are due to loss of the maternal copy of the UBE3A gene. Maternal Ube3a deficiency (Ube3a
m-/p+), as well as complete loss of Ube3a expression (Ube3a
m-/p-), have been reproduced in the mouse model used here.

Results

Here we asked if two characteristic AS phenotypes - social-seeking behavior and hyperactivity - are reproduced in the Ube3a deficient mouse model of AS. We quantified social-seeking behavior as time spent in close proximity to a stranger mouse and activity as total time spent moving during exploration, movement speed and total length of the exploratory path. Mice of all three genotypes (Ube3am+/p+, Ube3a
m-/p+, Ube3a
m-/p-) were tested and found to spend the same amount of time in close proximity to the stranger, indicating that Ube3a deficiency in mice does not result in increased social seeking behavior or social dis-inhibition. Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range.

Conclusions

Although hyperactivity and social-seeking behavior are characteristic phenotypes of Angelman Syndrome in humans, the Ube3a deficient mouse model does not reproduce these phenotypes in comparison to their wild-type littermates. These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.
The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis
Authors: Fang Xuefeng , Yoon Jae-Geun , Li Lisha , Yu Wei , Shao Jiaofang , Hua Dasong , Zheng Shu , Hood Leroy , Goodlett David R , Foltz Gregory , Lin Biaoyang
Published: January 2011

Background

SOX2 is a key gene implicated in maintaining the stemness of embryonic and adult stem cells. SOX2 appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of SOX2 in GBM has not yet been defined.

Results

We show that knockdown of the SOX2 gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the SOX2 response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883 SOX2 binding regions in the GBM cancer genome. SOX2 binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312 SOX2 binding regions. Microarray analysis identified 489 genes whose expression altered in response to SOX2 knockdown. Interesting findings include that SOX2 regulates the expression of SOX family proteins SOX1 and SOX18, and that SOX2 down regulates BEX1 (brain expressed X-linked 1) and BEX2 (brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by SOX2, including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and SOX2 form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.

Conclusions

We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the SOX2 response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of SOX2 in carcinogenesis and serves as a useful resource for the research community.
Erratum to: Identification and analysis of the germin-like gene family in soybean
Authors: Lu Mo , Han Ying-Peng , Gao Ji-Guo , Wang Xiang-Jing , Li Wen-Bin
Published: January 2011

In line 12 of page 1, replace "GmGER 9" with "GmGER 15".
Global gene expression profile progression in Gaucher disease mouse models
Authors: Xu You-Hai , Jia Li , Quinn Brian , Zamzow Matthew , Stringer Keith , Aronow Bruce , Sun Ying , Zhang Wujuan , Setchell Kenneth DR , Grabowski Gregory A
Published: January 2011

Background

Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells) in visceral organs and their abnormal functions are obscure.

Results

To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinctGba1point-mutated mice (V394L/V394L and D409 V/null). About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change), representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk) of INFγ-regulated pro-inflammatory (13) and IL-4-regulated anti-inflammatory (11) cytokine/mediator networks showed tissue differential profiles in the lung and liver of theGba1mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with theGba1mutation.

Conclusions

Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.
Full mitochondrial genome sequences of two endemic Philippine hornbill species (Aves: Bucerotidae) provide evidence for pervasive mitochondrial DNA recombination
Authors: Sammler Svenja , Bleidorn Christoph , Tiedemann Ralph
Published: January 2011

Background

Although nowaday it is broadly accepted that mitochondrial DNA (mtDNA) may undergo recombination, the frequency of such recombination remains controversial. Its estimation is not straightforward, as recombination under homoplasmy (i.e., among identical mt genomes) is likely to be overlooked. In species with tandem duplications of large mtDNA fragments the detection of recombination can be facilitated, as it can lead to gene conversion among duplicates. Although the mechanisms for concerted evolution in mtDNA are not fully understood yet, recombination rates have been estimated from "one per speciation event" down to 850 years or even "during every replication cycle".

Results

Here we present the first complete mt genome of the avian family Bucerotidae, i.e., that of two Philippine hornbills, Aceros waldeni and Penelopides panini. The mt genomes are characterized by a tandemly duplicated region encompassing part of cytochrome b, 3 tRNAs, NADH6, and the control region. The duplicated fragments are identical to each other except for a short section in domain I and for the length of repeat motifs in domain III of the control region. Due to the heteroplasmy with regard to the number of these repeat motifs, there is some size variation in both genomes; with around 21,657 bp (A. waldeni) and 22,737 bp (P. panini), they significantly exceed the hitherto longest known avian mt genomes, that of the albatrosses. We discovered concerted evolution between the duplicated fragments within individuals. The existence of differences between individuals in coding genes as well as in the control region, which are maintained between duplicates, indicates that recombination apparently occurs frequently, i.e., in every generation.

Conclusions

The homogenised duplicates are interspersed by a short fragment which shows no sign of recombination. We hypothesize that this region corresponds to the so-called Replication Fork Barrier (RFB), which has been described from the chicken mitochondrial genome. As this RFB is supposed to halt replication, it offers a potential mechanistic explanation for frequent recombination in mitochondrial genomes.
Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation
Authors: Grober Oli MV , Mutarelli Margherita , Giurato Giorgio , Ravo Maria , Cicatiello Luigi , De Filippo Maria Rosaria , Ferraro Lorenzo , Nassa Giovanni , Papa Maria Francesca , Paris Ornella , Tarallo Roberta , Luo Shujun , Schroth Gary P , Benes Vladimir , Weisz Alessandro
Published: January 2011

Background

Estrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype of breast cancer (BC). The two receptors can be found co-expressed and play specific, often opposite, roles, with ERβ being able to modulate the effects of ERα on gene transcription and cell proliferation. ERβ is frequently lost in BC, where its presence generally correlates with a better prognosis of the disease. The identification of the genomic targets of ERβ in hormone-responsive BC cells is thus a critical step to elucidate the roles of this receptor in estrogen signaling and tumor cell biology.

Results

Expression of full-length ERβ in hormone-responsive, ERα-positive MCF-7 cells resulted in a marked reduction in cell proliferation in response to estrogen and marked effects on the cell transcriptome. By ChIP-Seq we identified 9702 ERβ and 6024 ERα binding sites in estrogen-stimulated cells, comprising sites occupied by either ERβ, ERα or both ER subtypes. A search for TF binding matrices revealed that the majority of the binding sites identified comprise one or more Estrogen Response Element and the remaining show binding matrixes for other TFs known to mediate ER interaction with chromatin by tethering, including AP2, E2F and SP1. Of 921 genes differentially regulated by estrogen in ERβ+ vs ERβ- cells, 424 showed one or more ERβ site within 10 kb. These putative primary ERβ target genes control cell proliferation, death, differentiation, motility and adhesion, signal transduction and transcription, key cellular processes that might explain the biological and clinical phenotype of tumors expressing this ER subtype. ERβ binding in close proximity of several miRNA genes and in the mitochondrial genome, suggests the possible involvement of this receptor in small non-coding RNA biogenesis and mitochondrial genome functions.

Conclusions

Results indicate that the vast majority of the genomic targets of ERβ can bind also ERα, suggesting that the overall action of ERβ on the genome of hormone-responsive BC cells depends mainly on the relative concentration of both ERs in the cell.
Next-generation sequencing for HLA typing of class I loci
Authors: Erlich Rachel L , Jia Xiaoming , Anderson Scott , Banks Eric , Gao Xiaojiang , Carrington Mary , Gupta Namrata , DePristo Mark A , Henn Matthew R , Lennon Niall J , de Bakker Paul IW
Published: January 2011

Background

Comprehensive sequence characterization across the MHC is important for successful organ transplantation and genetic association studies. To this end, we have developed an automated sample preparation, molecular barcoding and multiplexing protocol for the amplification and sequence-determination of class I HLA loci. We have coupled this process to a novel HLA calling algorithm to determine the most likely pair of alleles at each locus.

Results

We have benchmarked our protocol with 270 HapMap individuals from four worldwide populations with 96.4% accuracy at 4-digit resolution. A variation of this initial protocol, more suitable for large sample sizes, in which molecular barcodes are added during PCR rather than library construction, was tested on 95 HapMap individuals with 98.6% accuracy at 4-digit resolution.

Conclusions

Next-generation sequencing on the 454 FLX Titanium platform is a reliable, efficient, and scalable technology for HLA typing.
Salmonella Typhimurium ST213 is associated with two types of IncA/C plasmids carrying multiple resistance determinants
Authors: Wiesner Magdalena , Calva Edmundo , Fernández-Mora Marcos , Cevallos Miguel A , Campos Freddy , Zaidi Mussaret B , Silva Claudia
Published: January 2011

Background

Salmonella Typhimurium ST213 was first detected in the Mexican Typhimurium population in 2001. It is associated with a multi-drug resistance phenotype and a plasmid-borne bla
CMY-2 gene conferring resistance to extended-spectrum cephalosporins. The objective of the current study was to examine the association between the ST213 genotype and bla
CMY-2 plasmids.

Results

The bla
CMY-2 gene was carried by an IncA/C plasmid. ST213 strains lacking the bla
CMY-2 gene carried a different IncA/C plasmid. PCR analysis of seven DNA regions distributed throughout the plasmids showed that these IncA/C plasmids were related, but the presence and absence of DNA stretches produced two divergent types I and II. A class 1 integron (dfrA12, orfF and aadA2) was detected in most of the type I plasmids. Type I contained all the plasmids carrying the bla
CMY-2 gene and a subset of plasmids lacking bla
CMY-2. Type II included all of the remaining bla
CMY-2-negative plasmids. A sequence comparison of the seven DNA regions showed that both types were closely related to IncA/C plasmids found in Escherichia, Salmonella, Yersinia, Photobacterium, Vibrio and Aeromonas. Analysis of our Typhimurium strains showed that the region containing the bla
CMY-2 gene is inserted between traA and traC as a single copy, like in the E. coli plasmid pAR060302. The floR allele was identical to that of Newport pSN254, suggesting a mosaic pattern of ancestry with plasmids from other Salmonella serovars and E. coli. Only one of the tested strains was able to conjugate the IncA/C plasmid at very low frequencies (10-7 to 10-9). The lack of conjugation ability of our IncA/C plasmids agrees with the clonal dissemination trend suggested by the chromosomal backgrounds and plasmid pattern associations.

Conclusions

The ecological success of the newly emerging Typhimurium ST213 genotype in Mexico may be related to the carriage of IncA/C plasmids. We conclude that types I and II of IncA/C plasmids originated from a common ancestor and that the insertion and deletion of DNA stretches have shaped their evolutionary histories.
Bottom-up driven involuntary attention modulates auditory signal in noise processing
Authors: Lagemann Lothar , Okamoto Hidehiko , Teismann Henning , Pantev Christo
Published: January 2011

Background

Auditory evoked responses can be modulated by both the sequencing and the signal-to-noise ratio of auditory stimuli. Constant sequencing as well as intense masking sounds basically lead to N1m response amplitude reduction. However, the interaction between these two factors has not been investigated so far. Here, we presented subjects tone stimuli of different frequencies, which were either concatenated in blocks of constant frequency or in blocks of randomly changing frequencies. The tones were presented either in silence or together with broad-band noises of varying levels.

Results

In silence, tones presented with random sequencing elicited a larger N1m response than tones presented with constant sequencing. With increasing noise level, this difference decreased and even vanished in the condition where noise intensity exceeded the tone intensity by 10 dB. Furthermore, under noisy conditions, the N1m latency was shorter in the constant sequencing condition compared to the random sequencing condition.

Conclusions

Besides the well-known neural habituation mechanisms, bottom-up driven attention plays an important role during auditory processing in noisy environments. This bottom-up driven attention would allow us to track a certain auditory signal in noisy situations without voluntarily paying attention to the auditory modality.
Rice Hypersensitive Induced Reaction Protein 1 (OsHIR1) associates with plasma membrane and triggers hypersensitive cell death
Authors: Zhou Liang , Cheung Ming-Yan , Li Man-Wah , Fu Yaping , Sun Zongxiu , Sun Sai-Ming , Lam Hon-Ming
Published: January 2011

Background

In plants, HIR (Hypersensitive Induced Reaction) proteins, members of the PID (Proliferation, Ion and Death) superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley. However, not much was known about the HIR proteins in rice. Since rice is an important cereal crop consumed by more than 50% of the populations in Asia and Africa, it is crucial to understand the mechanisms of disease responses in this plant. We previously identified the rice HIR1 (OsHIR1) as an interacting partner of the OsLRR1 (rice Leucine-Rich Repeat protein 1). Here we show that OsHIR1 triggers hypersensitive cell death and its localization to the plasma membrane is enhanced by OsLRR1.

Result

Through electron microscopy studies using wild type rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a minor portion localized to the tonoplast. Moreover, the plasma membrane localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the plasma membrane was confirmed by double-labeling electron microscopy. Pathogen inoculation studies using transgenic Arabidopsis thaliana expressing either OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However, OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive response lesions and contained lower titers of the invading pathogen, when compared to OsLRR1 transgenic plants.

Conclusion

The OsHIR1 protein is mainly localized to the plasma membrane, and its subcellular localization in that compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the plant so that it is more prone to HR and hence can react more promptly to limit the invading pathogens' spread from the infection sites.
A systems biology model of the regulatory network in Populusleaves reveals interacting regulators and conserved regulation
Authors: Street Nathaniel Robert , Jansson Stefan , Hvidsten Torgeir R
Published: January 2011

Background

Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species.

Results

We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis.

Conclusions

We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about the underlying cause of emergent properties and are needed if we are to identify target genes other than those constituting the "low hanging fruit" of genomic analysis.
Timing is everything: early degradation of abscission layer is associated with increased seed shattering in U.S. weedy rice
Authors: Thurber Carrie S , Hepler Peter K , Caicedo Ana L
Published: January 2011

Background

Seed shattering, or shedding, is an important fitness trait for wild and weedy grasses. U.S. weedy rice (Oryza sativa) is a highly shattering weed, thought to have evolved from non-shattering cultivated ancestors. All U.S. weedy rice individuals examined to date contain a mutation in the sh4 locus associated with loss of shattering during rice domestication. Weedy individuals also share the shattering trait with wild rice, but not the ancestral shattering mutation at sh4; thus, how weedy rice reacquired the shattering phenotype is unknown. To establish the morphological basis of the parallel evolution of seed shattering in weedy rice and wild, we examined the abscission layer at the flower-pedicel junction in weedy individuals in comparison with wild and cultivated relatives.

Results

Consistent with previous work, shattering wild rice individuals possess clear, defined abscission layers at flowering, whereas non-shattering cultivated rice individuals do not. Shattering weedy rice from two separately evolved populations in the U.S. (SH and BHA) show patterns of abscission layer formation and degradation distinct from wild rice. Prior to flowering, the abscission layer has formed in all weedy individuals and by flowering it is already degrading. In contrast, wild O. rufipogon abscission layers have been shown not to degrade until after flowering has occurred.

Conclusions

Seed shattering in weedy rice involves the formation and degradation of an abscission layer in the flower-pedicel junction, as in wild Oryza, but is a developmentally different process from shattering in wild rice. Weedy rice abscission layers appear to break down earlier than wild abscission layers. The timing of weedy abscission layer degradation suggests that unidentified regulatory genes may play a critical role in the reacquisition of shattering in weedy rice, and sheds light on the morphological basis of parallel evolution for shattering in weedy and wild rice.
Construction of a potato consensus map and QTL meta-analysis offer new insights into the genetic architecture of late blight resistance and plant maturity traits
Authors: Danan Sarah , Veyrieras Jean-Baptiste , Lefebvre Véronique
Published: January 2011

Background

Integrating QTL results from independent experiments performed on related species helps to survey the genetic diversity of loci/alleles underlying complex traits, and to highlight potential targets for breeding or QTL cloning. Potato (Solanum tuberosum L.) late blight resistance has been thoroughly studied, generating mapping data for many Rpi-genes (R-genes to Phytophthora infestans) and QTLs (quantitative trait loci). Moreover, late blight resistance was often associated with plant maturity. To get insight into the genomic organization of late blight resistance loci as compared to maturity QTLs, a QTL meta-analysis was performed for both traits.

Results

Nineteen QTL publications for late blight resistance were considered, seven of them reported maturity QTLs. Twenty-one QTL maps and eight reference maps were compiled to construct a 2,141-marker consensus map on which QTLs were projected and clustered into meta-QTLs. The whole-genome QTL meta-analysis reduced by six-fold late blight resistance QTLs (by clustering 144 QTLs into 24 meta-QTLs), by ca. five-fold maturity QTLs (by clustering 42 QTLs into eight meta-QTLs), and by ca. two-fold QTL confidence interval mean. Late blight resistance meta-QTLs were observed on every chromosome and maturity meta-QTLs on only six chromosomes.

Conclusions

Meta-analysis helped to refine the genomic regions of interest frequently described, and provided the closest flanking markers. Meta-QTLs of late blight resistance and maturity juxtaposed along chromosomes IV, V and VIII, and overlapped on chromosomes VI and XI. The distribution of late blight resistance meta-QTLs is significantly independent from those of Rpi-genes, resistance gene analogs and defence-related loci. The anchorage of meta-QTLs to the potato genome sequence, recently publicly released, will especially improve the candidate gene selection to determine the genes underlying meta-QTLs. All mapping data are available from the Sol Genomics Network (SGN) database.
Antibody dynamics and spontaneous viral clearance in patients with acute hepatitis C infection in Rio de Janeiro, Brazil
Authors: Strasak Alexander M , Kim Arthur Y , Lauer Georg M , de Sousa Paulo S , Ginuino Cleber F , Fernandes Carlos A , Velloso Carlos E , de Almeida Adilson J , de Oliveira Jaqueline M , Yoshida Clara F , zur Wiesch Julian Schulze , Paranhos-Baccalá Gláucia , Lang Stefan , Brant Larry J , Ulmer Hanno , Strohmaier Susanne , Kaltenbach Lalit , Lampe Elisabeth , Lewis-Ximenez Lia L
Published: January 2011

Background

The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period.

Methods

We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up.

Results

Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8-111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001].

Conclusion

Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection.
Is public transport a risk factor for acute respiratory infection?
Authors: Troko Joy , Myles Puja , Gibson Jack , Hashim Ahmed , Enstone Joanne , Kingdon Susan , Packham Christopher , Amin Shahid , Hayward Andrew , Van-Tam Jonathan Nguyen
Published: January 2011

Background

The relationship between public transport use and acquisition of acute respiratory infection (ARI) is not well understood but potentially important during epidemics and pandemics.

Methods

A case-control study performed during the 2008/09 influenza season. Cases (n = 72) consulted a General Practitioner with ARI, and controls with another non-respiratory acute condition (n = 66). Data were obtained on bus or tram usage in the five days preceding illness onset (cases) or the five days before consultation (controls) alongside demographic details. Multiple logistic regression modelling was used to investigate the association between bus or tram use and ARI, adjusting for potential confounders.

Results

Recent bus or tram use within five days of symptom onset was associated with an almost six-fold increased risk of consulting for ARI (adjusted OR = 5.94 95% CI 1.33-26.5). The risk of ARI appeared to be modified according to the degree of habitual bus and tram use, but this was not statistically significant (1-3 times/week: adjusted OR = 0.54 (95% CI 0.15-1.95; >3 times/week: 0.37 (95% CI 0.13-1.06).

Conclusions

We found a statistically significant association between ARI and bus or tram use in the five days before symptom onset. The risk appeared greatest among occasional bus or tram users, but this trend was not statistically significant. However, these data are plausible in relation to the greater likelihood of developing protective antibodies to common respiratory viruses if repeatedly exposed. The findings have differing implications for the control of seasonal acute respiratory infections and for pandemic influenza.