bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell Cycle Regulators Interact with Pathways That Modulate Microtubule Stability in Saccharomyces cerevisiae
Authors: Shohat-Tal Aya , Eshel Dan 
Published: October 2011

ABSTRACT

The integrity of mitosis is dependent upon strict regulation of microtubule stability and dynamics. Although much information has been accumulated on regulators of the microtubule cytoskeleton, our knowledge of the specific pathways involved is still limited. Here we designed genetic screens to identify regulators of microtubule stability that are dispensable in the wild type yet become essential under microtubule-disrupting conditions. We found that the transcriptional cofactor Swi6p and activator Swi4p, as well as the G
2
/M-specific cyclin Clb2p, are required in a microtubule-destabilizing environment. Swi6p and Swi4p can combine as a transcriptional complex, called the SBF complex (SBF for Swi4/6 cell cycle box [SCB]-binding factor) that is functionally homologous to the metazoan DP1/2-E2F complex and that controls the G
1
/S transition through the genes it regulates. We show that Swi6p's contribution to microtubule stability can be either dependent or independent of the SBF complex. The SBF-dependent pathway requires downregulation of SBF complex levels and may thereby reroute the transcriptional program in favor of greater microtubule stability. This pathway can be triggered by overexpression of Fcp1p, a phosphatase in the general transcription machinery, or by expression of an allele of
SWI6
that is associated with reduced transcription from SBF-controlled promoters. The SBF-independent pathway is activated by a constitutively nuclear allele of Swi6p. Our results introduce novel roles in microtubule stability for genes whose participation in the process may be masked under normal conditions yet nonetheless acquire a dominant role when microtubule stability is compromised.
PPE38 Modulates the Innate Immune Response and Is Required for Mycobacterium marinum Virulence
Authors: Dong Dandan , Wang Decheng , Li Ming , Wang Hui , Yu Jia , Wang Chuan , Liu Jun , Gao Qian 
Published: October 2011

ABSTRACTThe proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) family proteins are prevalent in pathogenic mycobacteria and play a diverse role in mycobacterial pathogenesis. While some members have been studied, the function of most PE/PPE proteins remains unknown. In this study, we isolated a transposon-inactivatedPPE38mutant ofMycobacterium marinumand characterized its phenotype. We found that the PPE38 protein is associated with the cell wall and exposed on the cell surface. The inactivation ofPPE38altered the bacterial cell surface properties and led to deficiencies in cord formation, sliding motility, and biofilm formation. ThePPE38mutant was defective in phagocytosis by macrophages and exhibited reduced virulence in adult zebrafish. We also found that PPE38 is involved in the induction of proinflammatory cytokines in infected macrophages. Together, our results indicate that PPE38, a previously uncharacterized protein, plays a role in mycobacterial virulence, presumably by modulating the host innate immune response.
Interleukin-4 (IL-4) and IL-13 Suppress Excessive Neutrophil Infiltration and Hepatocyte Damage during Acute Murine Schistosomiasis Japonica
Authors: Seki Takenori , Kumagai Takashi , Kwansa-Bentum Bethel , Furushima-Shimogawara Rieko , Anyan William K. , Miyazawa Yuuki , Iwakura Yoichiro , Ohta Nobuo 
Published: October 2011

ABSTRACTDue to the importance of neutrophils and proinflammatory cytokines in schistosomal liver damage, we analyzed the mechanisms underlying neutrophil and proinflammatory responses in murine schistosomiasis japonica. We found that granulomatous inflammation around parasite eggs in the liver was greater inSchistosoma japonicum-infected IL-4−/−IL-13−/−(double-knockout [DKO]) mice than in infected wild-type (WT) mice at 6 weeks, but not at 8 weeks, postinfection, suggesting the importance of Th2 responses in these typical hepatic lesions. Infected DKO mice also showed increased neutrophil infiltration accompanying more severe pathology, as shown by the enhanced necrosis of hepatocytes. This was not likely due to a Th1/Th2 imbalance, because there was no detectable increase in gamma interferon (IFN-γ) production in these DKO mice. mRNA expression of interleukin-17A (IL-17A), proinflammatory cytokines, and the neutrophil chemoattractant CXCL2 in liver was higher in infected DKO mice than in WT mice. However, in IL-4−/−IL-13−/−IL-17A−/−(triple-knockout [TKO]) mice, the absence of IL-17A was associated with only marginal differences in schistosomal liver damage, suggesting that IL-17A is only partially responsible for neutrophil-driven hepatic damage. Furthermore, the expression of mRNAs encoding proinflammatory cytokines was not under the control of IL-17A in TKO mice. These findings indicate that IL-4 and IL-13 suppress excessive neutrophil recruitment, proinflammatory cytokine production, and hepatic damage during the acute stage ofS. japonicuminfection, suggesting that neutrophils and proinflammatory cytokines are mainly responsible for hepatocyte damage during acute murine schistosomiasis japonica. However, neutrophil induction and the production of proinflammatory cytokines were not due solely to IL-17A.
Dectin-1-Dependent Interleukin-22 Contributes to Early Innate Lung Defense against Aspergillus fumigatus
Authors: Gessner Melissa A. , Werner Jessica L. , Lilly Lauren M. , Nelson Michael P. , Metz Allison E. , Dunaway Chad W. , Chan Yvonne R. , Ouyang Wenjun , Brown Gordon D. , Weaver Casey T. , Steele Chad 
Published: October 2011

ABSTRACTWe have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility toAspergillus fumigatuslung infection in the presence of lower interleukin 23 (IL-23) and IL-17A production in the lungs and have reported a role for IL-17A in lung defense. As IL-23 is also thought to control the production of IL-22, we examined the role of Dectin-1 in IL-22 production, as well as the role of IL-22 in innate host defense againstA. fumigatus. Here, we show that Dectin-1-deficient mice demonstrated significantly reduced levels of IL-22 in the lungs early afterA. fumigatuschallenge. Culturing cells from enzymatic lung digestsex vivofurther demonstrated Dectin-1-dependent IL-22 production. IL-22 production was additionally found to be independent of IL-1β, IL-6, or IL-18 but required IL-23. The addition of recombinant IL-23 augmented IL-22 production in wild-type (WT) lung cells and rescued IL-22 production by lung cells from Dectin-1-deficient mice.In vivoneutralization of IL-22 in the lungs of WT mice resulted in impairedA. fumigatuslung clearance. Moreover, mice deficient in IL-22 also demonstrated a higher lung fungal burden afterA. fumigatuschallenge in the presence of impaired IL-1α, tumor necrosis factor alpha (TNF-α), CCL3/MIP-1α, and CCL4/MIP-1β production and lower neutrophil recruitment, yet intact IL-17A production. We further show that lung lavage fluid collected from bothA. fumigatus-challenged Dectin-1-deficient and IL-22-deficient mice had compromised anti-fungal activity againstA. fumigatus in vitro. Although lipocalin 2 production was observed to be Dectin-1 and IL-22 dependent, lipocalin 2-deficient mice did not demonstrate impairedA. fumigatusclearance. Moreover, lungS100a8,S100a9, andReg3gmRNA expression was not lower in either Dectin-1-deficient or IL-22-deficient mice. Collectively, our results indicate that early innate lung defense againstA. fumigatusis mediated by Dectin-1-dependent IL-22 production.
Draft Genome Sequence of Escherichia coli XH001, a Producer of
l
-Threonine in Industry
Authors: Yang Huilin , Liao Yuling , Wang Bin , Lin Ying , Pan Li 
Published: October 2011

ABSTRACT

l
-Threonine has been widely used as a supplement in the food, pharmaceutical, and cosmetic industries. Here, we present a high-quality draft annotated genome sequence of
Escherichia coli
XH001, a producer of
l
-threonine in industry. Its genome and plasmid sequence will provide clues about the molecular mechanisms underlying its beneficial properties.
Genome Sequence of Serinicoccus profundi, a Novel Actinomycete Isolated from Deep-Sea Sediment
Authors: Xiao Jing , Luo Yingxue , Xu Jun 
Published: October 2011

ABSTRACT

Serinicoccus profundi
MCCC 1A05965
T
was isolated from deep-sea sediment collected from the Indian Ocean. It was a Gram-positive, moderately halophilic, aerobic bacterium. Here, we describe the 3.4-Mbp draft genome sequence of
S. profundi
MCCC 1A05965
T
.
Remote specialist assessment for intravenous thrombolysis of acute ischaemic stroke by telephone
Authors: Rudd Matthew , Rodgers Helen , Curless Richard , Sudlow Mark , Huntley Stuart , Madhava Badanahatti , Garside Mark , Price Christopher I 
Published: October 2011

ObjectiveTo describe the process, efficacy and safety of intravenous thrombolysis for acute ischaemic stroke in an emergency department (ED) setting with remote specialist support through structured telephone consultation.DesignRetrospective case series.SettingThree EDs within a single stroke service in northern England.ParticipantsPatients with acute stroke given intravenous thrombolytic therapy between 6 September 2007 and 1 October 2010.Outcome measuresCombined death and dependency at 90 days (0–2 on the modified Rankin Scale for a good outcome vs 3–6 for a poor outcome), door-to-needle time, neurological impairment and presence of treatment related haemorrhage.Results192 patients received intravenous thrombolysis. 94/178 (53%) were treated after remote specialist assessment. Data available from 178 patients showed similar proportions with a good outcome after each mode of assessment (56% in person and 48% by telephone). The median door-to-needle time was 8 min faster in the group assessed in person (65 vs 73 min by telephone) but there was no difference in neurological outcome or symptomatic haemorrhage. After review in person, the stroke specialist tended to treat patients with a higher median modified Rankin Scale (1 vs 0 by telephone).ConclusionIn a single stroke service the clinical outcomes of treatment with intravenous thrombolysis were similar whether assessment was performed after specialist review in person or via a telemedicine service consisting of ED staff training, telephone consultation and remote review of brain imaging by a stroke specialist.
Attitudes of ED staff to the presence of family during cardiopulmonary resuscitation: a Trinidad and Tobago perspective
Authors: Mahabir Dhiyan , Sammy Ian 
Published: October 2011

IntroductionPatients' relatives have been allowed in the resuscitation room during active resuscitation in the UK since at least 1994. Several studies have indicated that relatives value the opportunity to observe the care provided, and this has been shown to help the grieving process. However, this enthusiasm has not always been shared by emergency department staff. In Trinidad and Tobago the concept of family presence in the resuscitation room is still a novel one. This study seeks to identify the attitudes of staff towards relatives in the resuscitation room in this setting.MethodsA cross-sectional survey of attitudes of staff towards family presence in the resuscitation room was undertaken. All full-time doctors and nurses practising in emergency departments in the public sector in Trinidad and Tobago were surveyed, and the responses of doctors and nurses were compared.Results214 individuals responded to the questionnaire (108 nurses and 106 doctors). 81.4% of respondents felt that relatives would be traumatised by witnessing resuscitation. 64% felt that staff performance would be inhibited by the presence of a family member during resuscitation. 71.1% believed that allowing a family member to witness resuscitation would prolong the resuscitation. 72% believed that witnessed resuscitation would increase the stress for the staff.ConclusionStrong feelings against the presence of family members in the resuscitation room were expressed by physicians and nurses. Implementation of such a policy will require careful preparation and education of staff as to the benefits of this intervention.
Genome-Wide High-Density SNP Linkage Search for Glioma Susceptibility Loci: Results from the Gliogene Consortium
Authors: Shete Sanjay , Lau Ching C. , Houlston Richard S. , Claus Elizabeth B. , Barnholtz-Sloan Jill , Lai Rose , Il'yasova Dora , Schildkraut Joellen , Sadetzki Siegal , Johansen Christoffer , Bernstein Jonine L. , Olson Sara H. , Jenkins Robert B. , Yang Ping , Vick Nicholas A. , Wrensch Margaret , Davis Faith G. , McCarthy Bridget J. , Leung Eastwood Hon-chiu , Davis Caleb , Cheng Rita , Hosking Fay J. , Armstrong Georgina N. , Liu Yanhong , Yu Robert K. , Henriksson Roger ,   The Gliogene Consortium, Melin Beatrice S. , Bondy Melissa L. 
Published: October 2011

Abstract
Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32
and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. Cancer Res; 71(24); 7568–75. ©2011 AACR.
PAX3-FOXO1 Induces Cannabinoid Receptor 1 to Enhance Cell Invasion and Metastasis
Authors: Marshall Amy D. , Lagutina Irina , Grosveld Gerard C. 
Published: October 2011

Abstract
Alveolar rhabdomyosarcoma (ARMS) is a muscle-derived childhood tumor characterized by production of oncogenic PAX3/7-FOXO1 chimeric transcription factors. While downstream targets of the PAX3-FOXO1 oncoprotein in ARMS have been defined, the functional relevance of these targets is unclear. Here, we show that upregulation of the cannabinoid receptor 1 (Cnr1/Cb1) by PAX3-FOXO1 in mouse primary myoblasts and ARMS cell lines, contributes to PAX3-FOXO1 phenotypes, both in vivo and in vitro. In primary myoblasts, Cnr1 was dispensable for PAX3-FOXO1 to mediate cell proliferation, differentiation, or transformation; however, Cnr1 function was essential to increase the invasive capacity conferred by PAX3-FOXO1 overexpression in these cells. Genetic or pharmacologic abrogation of Cnr1 inhibited the enhanced basement membrane invasion induced by PAX3-FOXO1. Cnr1 loss by either route also dramatically reduced lung metastasis formation. Taken together, our findings strongly implicate Cnr1 as a novel tractable target to inhibit ARMS invasion and metastasis. Cancer Res; 71(24); 7471–80. ©2011 AACR.
Lysosomal Transmembrane Protein LAPTM4B Promotes Autophagy and Tolerance to Metabolic Stress in Cancer Cells
Authors: Li Yang , Zhang Qing , Tian Ruiyang , Wang Qi , Zhao Jean J. , Iglehart J. Dirk , Wang Zhigang Charles , Richardson Andrea L. 
Published: October 2011

Abstract
Amplification of chromosome 8q22, which includes the gene for lysosomal associated transmembrane protein LAPTM4B, has been linked to de novo anthracycline resistance in primary breast cancers with poor prognosis. LAPTM4B overexpression can induce cytosolic retention of anthracyclines and decrease drug-induced DNA damage. In this study, we tested the hypothesis that LAPTM4B may contribute to tumor cell growth or survival in the absence of a chemotherapeutic exposure. In mammary cells, LAPTM4B protein was localized in lysosomes where its depletion increased membrane permeability, pH, cathepsin release, and cellular apoptosis. Loss of LAPTM4B also inhibited later stages of autophagy by blocking maturation of the autophagosome, thereby rendering cells more sensitive to nutrient deprivation or hypoxia. Conversely, enforced overexpression of LAPTM4B promoted autophagic flux and cell survival during in vitro starvation and stimulated more rapid tumor growth in vivo. Together, our results indicate that LAPTM4B is required for lysosome homeostasis, acidification, and function, and that LAPTM4B renders tumor cells resistant to lysosome-mediated cell death triggered by environmental and genotoxic stresses. Cancer Res; 71(24); 7481–9. ©2011 AACR.
Egfl7 Promotes Tumor Escape from Immunity by Repressing Endothelial Cell Activation
Authors: Delfortrie Suzanne , Pinte Sébastien , Mattot Virginie , Samson Chantal , Villain Gaëlle , Caetano Bertrand , Lauridant-Philippin Géraldine , Baranzelli Marie-Christine , Bonneterre Jacques , Trottein François , Faveeuw Christelle , Soncin Fabrice 
Published: October 2011

AbstractDownregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines [IFN-γ, interleukin-12 (IL-12)] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-γ. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control. Cancer Res; 71(23); 7176–86. ©2011 AACR.
Variations in HSPA1B at 6p21.3 Are Associated with Lung Cancer Risk and Prognosis in Chinese Populations
Authors: Guo Huan , Deng Qifei , Wu Chen , Hu Lingmin , Wei Sheng , Xu Ping , Kuang Dan , Liu Li , Hu Zhibin , Miao Xiaoping , Shen Hongbing , Lin Dongxin , Wu Tangchun 
Published: October 2011

Abstract
The heat shock protein Hsp70 is crucial for regulating cellular homeostasis in stressed cells. Although the tumorigenic potential and prognostic applications of Hsp70 have been widely investigated, it remains unclear whether genetic variations of the human isoforms HSPA1L, HSPA1A, and HSPA1B are associated with cancer risk and prognosis. In this study, we genotyped six tagSNPs in these genes in 1,152 paired patients with lung cancer and controls, and then validated the results in additional cohorts of 1,781 patients with lung cancer and 1,038 controls. In addition, we evaluated the associations of these tagSNPs with survival in 330 patients with advanced non–small cell lung cancer (NSCLC) with additional validation in another 331 patients with advanced NSCLC. Functions of the risk variants identified were investigated using cell-based reporter assays. We found that the HSPA1B rs6457452T allele was associated with increased lung cancer risk compared with the rs6457452C allele in both data sets and also pooled analysis (adjusted OR = 1.41; P = 2.8 × 10−5). The HSPA1B rs2763979TT genotype conferred poor survival outcomes for patients with advanced NSCLC in two independent cohorts and pooled analysis [adjusted hazard ratio (HR) = 1.80, 1.61, and 1.66; P = 0.013, 0.036, and 0.002, respectively]. Lastly, we also found that the rs2763979T and rs6457452T alleles were each sufficient to reduce expression of transcriptional reporter constructs, when compared with the rs2763979C and rs6457452C alleles, respectively. Taken together, our findings define that functional HSPA1B variants are associated with lung cancer risk and survival. These Hsp70 genetic variants may offer useful biomarkers to predict lung cancer risk and prognosis. Cancer Res; 71(24); 7576–86. ©2011 AACR.
Autophagy Enhanced by Microtubule- and Mitochondrion-Associated MAP1S Suppresses Genome Instability and Hepatocarcinogenesis
Authors: Xie Rui , Wang Fen , McKeehan Wallace L. , Liu Leyuan 
Published: October 2011

Abstract
Dysfunctional autophagy is associated with tumorigenesis; however, the relationship between the two processes remains unclear. In the present study, we showed that MAP1S levels immediately become elevated in response to diethylnitrosamine-induced or genome instability-driven metabolic stress in a murine model of hepatocarcinoma. Upregulation of MAP1S enhanced autophagy to remove aggresomes and dysfunctional organelles that trigger DNA double-strand breaks and genome instability. The early accumulation of an unstable genome before signs of tumorigenesis indicated that genome instability caused tumorigenesis. After tumorigenesis, tumor development triggered the activation of autophagy to reduce genome instability in tumor foci. We, therefore, conclude that an increase in MAP1S levels triggers autophagy to suppress genome instability such that both the incidence of diethylnitrosamine-induced hepatocarcinogenesis and malignant progression are suppressed. Taken together, the data establish a link between MAP1S-enhanced autophagy and suppression of genomic instability and tumorigenesis. Cancer Res; 71(24); 7537–46. ©2011 AACR.