bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Mitochondrial Proteomic Changes in Resistant Wheat Near‐Isogenic Line After Inoculation with Powdery Mildew
Authors: Liu Xiaoying , Gan Fu , Wang Zhenying , Gao Yue , Peng Yongkang , Dang Chen , Xie Chaojie , Liu Zhiyong , Yang Zuomin 
Published: November 2012

AbstractWheat powdery mildew resistance mechanisms have been studied extensively at genomic level, however, infection induced mitochondrial proteomic changes in resistant line have not been fully characterized. Being critical organelles of chemical energy metabolism, mitochondria have also been suggested to be involved in the environmental stress response. Using proteomic approaches, we did comparative analysis of mitochondrial proteome in resistant wheat near‐isogenic line (NIL) (Brock × Jing4117) and its recurrent parent Jing 411 after infection of Blumeria graminis f.sp. tritici (Bgt). More than 50 down‐regulated mitochondrial protein spots were identified in NIL after 24‐h pathogen inoculation, and their abundance recovered to the levels prior to infection after extended inoculation (72‐h). We further analyzed a subgroup of down‐regulated proteins using mass spectrometry. MS/MS data analysis revealed the identities of nine protein spots and assigned them into three functional classes: synthesis of protein, disease resistance response and energy metabolism. For the first time we demonstrated pathogen stress induced mitochondrial proteomic changes and provided evidences that wheat powdery mildew resistance involves multiple biochemical events. Moreover, our results indicate that wheat mitochondrial proteome analysis can serve as a powerful tool to identify potential regulators of fungal invasion resistance.
Cloning, Expression, Purification and Initial Analysis of a Novel Pectate Lyase Pcpel1 from Phytophthora capsici
Authors: Fu Li , Wang Hui Z. , Feng Bao Z. , Zhang Xiu G. 
Published: November 2012

AbstractPhytophthora capsici inflicts damage on numerous crop plants by secreting a series of pectinase including pectate lyase (PEL). Here, we report a pectate lyase gene (Pcpel1) from a genomic library of a highly virulent P. capsici strain SD33. Pcpel1 was identified as an open reading frame of 1233 bp encoding a protein of 410 amino acids with a predicted amino‐terminal signal sequence of 21 amino acids. The predicted protein of Pcpel1 has a calculated molecular mass of 43.8 kDa and a pI value of 6.8. Analysis of the amino acid sequence suggested that it was a member of the polysaccharide lyase family 1 that shows pectate lyase activity. Moreover, heterologous expression of Pcpel1 in Pichia pastoris produced proteins with molecular mass 66 kDa, very likely due to differential glycosylation by the yeast. By western blotting and northern blotting analysis, Pcpel1 was strongly expressed during interaction of P. capsici with the host plant, suggesting its involvement in the process of host infection. The role of Pcpel1 in cell wall disassembly and host/parasite interaction is discussed.
The association between periodontitis and obstructive sleep apnea: a preliminary study
Authors: Seo W. H. , Cho E. R. , Thomas R. J. , An S‐Y , Ryu J. J. , Kim H. , Shin C. 
Published: November 2012

Background and ObjectivePeriodontitis is becoming a highly prevalent disease worldwide. Obstructive sleep apnea (OSA) is a common disorder that is characterized by repeated disruptions in breathing during sleep, and mouth breathing is a common characteristic among patients with OSA. We aimed to assess the hypothesis that OSA is associated with the onset and progression of periodontal disease.Material and MethodsThis is a cross‐sectional study of a total of 687 participants (460 men and 227 women), 47–77 years of age, who were examined between August 2009 and September 2010 as part of the Korean Genome and Epidemiology Study. The participants underwent standard polysomnography, clinical periodontal examination and health‐screening examinations. Periodontitis was defined as clinical attachment level (CAL) ≥ 6 mm and probing pocket depth ≥ 4 mm. OSA was determined using the apnea–hypopnea index (AHI), and an AHI score of ≥ 5 was the cut‐off used to indicate the presence of OSA.ResultsThe results showed that 17.5% of the participants had periodontitis, 46.6% had OSA and 60.0% who were diagnosed with periodontitis had OSA. In our study, old age, male gender, current smoking status, mouth breathing during sleep and high AHI were identified as risk factors for periodontitis. OSA was positively associated with periodontitis [odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.18–2.87], probing pocket depth (OR = 2.22, 95% CI = 1.30–3.77) and CAL (OR = 1.86, 95% CI = 1.07–3.21) in a dose–response manner. Additionally, OSA was positively associated with periodontitis (OR = 2.51, 95% CI = 1.37–4.62) in subjects ≥ 55 years of age, but not in subjects < 55 years of age.ConclusionThere is a significant association between OSA and periodontal disease. Further research is needed to clarify the causal relationship between the two conditions.
Acetoacetyl‐CoA synthetase activity is controlled by a protein acetyltransferase with unique domain organization in Streptomyces lividans
Authors: Tucker Alex C. , Escalante‐Semerena Jorge C. 
Published: November 2012

SummaryGCN5‐type N‐acetyltransferases (GNATs) are enzymes that catalyse the transfer of the acetyl group from acetyl‐CoA to a primary amine. GNATs are conserved in all domains of life. Some members of this family of enzymes acetylate the side‐chain of specific lysine residues in proteins of diverse function. In bacteria, GNAT‐catalysed protein acetylation regulates carbon metabolism, RNA metabolism and transcriptional regulation. Metabolic regulation in Streptomyces species is of interest due to the role of these organisms in natural product synthesis. Here we identify SlPatA, a GNAT in Streptomyces lividans with unique domain organization, and a new acetylation target, namely acetoacetyl‐CoA synthetase (SlAacS). The latter has homologues in all domains of life. In vitro and in vivo evidence show that SlAacS is a bona fide acetoacetyl‐CoA synthetase. SlPatA acetylates SlAacS more efficiently than it does acetyl‐CoA synthetase, an enzyme known to be under acetylation control. SlPatA acetylates SlAacS at the active‐site residue Lys617 and acetylation inactivates SlAacS. Acetylated SlAacS was deacetylated by a sirtuin‐type protein deacetylase. SlAacS acetylation/deacetylation may represent a conserved mechanism for regulation of acetoacetyl‐CoA synthetase activity in all domains of life.
Evaluating postintervention survival of free‐ranging odontocete cetaceans
Authors: Wells Randall S. , Fauquier Deborah A. , Gulland Frances M. D. , Townsend Forrest I. , DiGiovanni Robert A. 
Published: November 2012

AbstractUntil recently, few data were available for evaluating postintervention survival of free‐ranging cetaceans receiving aid from humans through: rescue from stranding, with rehabilitation and release; rescue, rehabilitation and release of debilitated or entangled individuals that had not beached; rescue of entangled animals with immediate release; and rescue, transport, and release of out‐of‐habitat animals. Advances in medical diagnosis, husbandry and therapy have improved survival of rehabilitation cases, and advances in radio‐telemetry have improved postrelease monitoring. In total, 69 cases (1986–2010) were evaluated, involving 10 species of odontocete cetaceans with release data. Findings suggested a success criterion of surviving at least six weeks postrelease is useful in evaluating intervention strategies. No species had better success than others. Stranded beached cetaceans were less successful than free‐swimming rescued animals. Rehabilitated animals were less successful than those released without rehabilitation. Mass stranded dolphins fared better than single stranded animals. Old age, diminished hearing ability, and lack of maternal care were factors in several unsuccessful cases. Success is not clearly related to rehabilitation duration. Retaining healthy individuals from mass strandings until all animals are ready for release may reduce success for some. Transport durations for unsuccessful cases were greater than for successful cases.
Pet keeping and tobacco exposure influence CD14 methylation in childhood
Authors: Munthe‐Kaas Monica Cheng , Bertelsen Randi J. , Torjussen Tale Mæhre , Hjorthaug Hanne Sagsveen , Undlien Dag E. , Lyle Robert , Gervin Kristina , Granum Berit , Mowinckel Petter , Carlsen Kai Håkon , Carlsen Karin C. Lødrup 
Published: November 2012

AbstractBackgroundSeveral CD14 gene–environment interactions in relation to the development of allergic diseases have been reported, but the underlying biological mechanisms are unclear. We recently showed that CD14 methylation increased during childhood, parallelling a decreased impact of CD14 polymorphisms on soluble CD14 levels. Here, we aim to explore whether environmental stimuli during childhood affects CD14 methylation, thereby providing a biological mechanism through which environment may modulate genetic effect.MethodsCD14 methylation levels were quantified in 157 children from the prospective Environment and Childhood Asthma birth cohort at ages 2 and 10. Associations between CD14 methylation levels and house dust levels of endotoxin, β(1,3)‐glucans (at 2 yr only), allergens (dog, cat, and house dust mite), pet keeping and tobacco smoke exposure (TSE; questionnaire data) at 2 and 10 yr were explored.ResultsChildren in homes without pets had larger increases in CD14 methylation through childhood (2–10 yr) compared with children with pets (2.1% increase (p = 0.003) vs. 0.4% decrease (n.s.), global p = 0.04). At 10 yr of age, lower CD14 methylation values were found in children with pets compared with children without pets at both 2 and 10 yr (5.4% vs. 7.5% [p = 0.02]). A similar trend was detected for TSE; children not exposed show larger increases in CD14 methylation, most pronounced in school‐age girls exposed vs. not exposed to tobacco (5.5% vs. 7.5% methylation, p = 0.037).ConclusionPet keeping and TSE appears to limit increase in CD14 methylation from 2 to 10 yr of age. This may partly explain the diverging CD14 allele associations with allergic diseases detected in different environments.
CTCF Regulates Kaposi's Sarcoma-Associated Herpesvirus Latency Transcription by Nucleosome Displacement and RNA Polymerase Programming
Authors: Kang Hyojeung , Cho Hyosun , Sung Gi-Ho , Lieberman Paul M. 
Published: November 2012

ABSTRACTCCCTC-binding factor (CTCF) has been implicated in various aspects of viral and host chromatin organization and transcriptional control. We showed previously that CTCF binds to a cluster of three sites in the first intron of the Kaposi's sarcoma-associated herpesvirus (KSHV) multicistronic latency-associated transcript that encodes latency-associated nuclear antigen (LANA), viral cyclin (vCyclin), vFLIP, viral microRNAs, and kaposin. We show here that these CTCF binding sites regulate mRNA production, RNA polymerase II (RNAPII) programming, and nucleosome organization of the KSHV latency transcript control region. We also show that KSHV bacmids lacking these CTCF binding sites have elevated and altered ratios of spliced latency transcripts. CTCF binding site mutations altered RNAPII and RNAPII-accessory factor interactions with the latency control region. CTCF binding sites were required for thein vitrorecruitment of RNAPII to the latency control region, suggesting that direct interactions between CTCF and RNAPII contribute to transcription regulation. Histone modifications in the latency control region were also altered by mutations in the CTCF binding sites. Finally, we show that CTCF binding alters the regular phasing of nucleosomes in the latency gene transcript and intron, suggesting that nucleosome positioning can be an underlying biochemical mechanism of CTCF function. We propose that RNAPII interactions and nucleosome displacement serve as a biochemical basis for programming RNAPII in the KSHV transcriptional control region.
Varicella-Zoster Virus ORF12 Protein Activates the Phosphatidylinositol 3-Kinase/Akt Pathway To Regulate Cell Cycle Progression
Authors: Liu XueQiao , Cohen Jeffrey I. 
Published: November 2012

ABSTRACT

Varicella-zoster virus (VZV) activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and alters cell cycle progression, but the viral protein(s) responsible for these activities is unknown. We previously reported that the VZV open reading frame 12 (ORF12) protein triggers phosphorylation of ERK. Here, we demonstrate that the VZV ORF12 protein also activates the PI3K/Akt pathway to regulate cell cycle progression. Transfection of cells with a plasmid expressing the ORF12 protein induced phosphorylation of Akt, which was dependent on PI3K. Infection of cells with wild-type VZV triggered phosphorylation of Akt, while infection with an ORF12 deletion mutant induced less phosphorylated Akt. The activation of Akt by ORF12 protein was associated with its binding to the p85 subunit of PI3K. Infection of cells with wild-type VZV resulted in increased levels of cyclin B1, cyclin D3, and phosphorylated glycogen synthase kinase 3β (GSK-3β), while infection with the ORF12 deletion mutant induced lower levels of these proteins. Wild-type VZV infection reduced the G
1
phase cell population and increased the M phase cell population, while infection with the ORF12 deletion mutant had a reduced effect on the G
1
and M phase populations. Inhibition of Akt activity with LY294002 reduced the G
1
and M phase differences observed in cells infected with wild-type and ORF12 mutant viruses. In conclusion, we have found that the VZV ORF12 protein activates the PI3K/Akt pathway to regulate cell cycle progression. Since VZV replicates in both dividing (e.g., keratinocytes) and nondividing (neurons) cells, the ability of the VZV ORF12 protein to regulate the cell cycle is likely important for VZV replication in various cell types in the body.
Hypomethylating Therapy in an Aggressive Stroma-Rich Model of Pancreatic Carcinoma
Authors: Shakya Reena , Gonda Tamas , Quante Michael , Salas Martha , Kim Samuel , Brooks Jenna , Hirsch Steffen , Davies Justine , Cullo Angelica , Olive Kenneth , Wang Timothy C. , Szabolcs Matthias , Tycko Benjamin , Ludwig Thomas 
Published: November 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer, we used the DNA demethylating drug 5-aza-2′-deoxycytidine (DAC) in an aggressive mouse model of stromal rich PDAC (KPC-Brca1 mice). In untreated tumors, we found globally decreased 5-methyl-cytosine (5-mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAF), along with increased amounts of 5-hydroxymethyl-cytosine (5-HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early-treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the CAFs. Expression profiling and immunohistochemistry highlighted DAC induction of STAT1 in the tumors, and DAC plus IFN-γ produced an additive antiproliferative effect on PDAC cells. DAC induced strong expression of the testis antigen deleted in azoospermia-like (DAZL) in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy. Cancer Res; 73(2); 885–96. ©2012 AACR.
Trastuzumab-Resistant Cells Rely on a HER2-PI3K-FoxO-Survivin Axis and Are Sensitive to PI3K Inhibitors
Authors: Chakrabarty Anindita , Bhola Neil E. , Sutton Cammie , Ghosh Ritwik , Kuba María Gabriela , Dave Bhuvanesh , Chang Jenny C. , Arteaga Carlos L. 
Published: November 2012

Abstract
The antibody trastuzumab is approved for treatment of patients with HER2 (ERBB2)-overexpressing breast cancer. A significant fraction of these tumors are either intrinsically resistant or acquire resistance rendering the drug ineffective. The development of resistance has been attributed to failure of the antibody to inhibit phosphoinositide 3-kinase (PI3K), which is activated by the HER2 network. Herein, we examined the effects of PI3K blockade in trastuzumab-resistant breast cancer cell lines. Treatment with the pan-PI3K inhibitor XL147 and trastuzumab reduced proliferation and pAKT levels, triggering apoptosis of trastuzumab-resistant cells. Compared with XL147 alone, the combination exhibited a superior antitumor effect against trastuzumab-resistant tumor xenografts. Furthermore, treatment with XL147 and trastuzumab reduced the cancer stem-cell (CSC) fraction within trastuzumab-resistant cells both in vitro and in vivo. These effects were associated with FoxO-mediated inhibition of transcription of the antiapoptosis gene survivin (BIRC5) and the CSC-associated cytokine interleukin-8. RNA interference–mediated or pharmacologic inhibition of survivin restored sensitivity to trastuzumab in resistant cells. In a cohort of patients with HER2-overexpressing breast cancer treated with trastuzumab, higher pretreatment tumor levels of survivin RNA correlated with poor response to therapy. Together, our results suggest that survivin blockade is required for therapeutic responses to trastuzumab and that by combining trastuzumab and PI3K inhibitors, CSCs can be reduced within HER2+ tumors, potentially preventing acquired resistance to anti-HER2 therapy. Cancer Res; 73(3); 1190–200. ©2012 AACR.
miR-186 Downregulation Correlates with Poor Survival in Lung Adenocarcinoma, Where It Interferes with Cell-Cycle Regulation
Authors: Cai Junchao , Wu Jueheng , Zhang Huizhong , Fang Lishan , Huang Yongbo , Yang Yi , Zhu Xun , Li Rong , Li Mengfeng 
Published: November 2012

Abstract
Deeper mechanistic understanding of lung adenocarcinoma (non–small cell lung carcinoma, or NSCLC), a leading cause of cancer-related deaths overall, may lead to more effective therapeutic strategies. In analyzing NSCLC clinical specimens and cell lines, we discovered a uniform decrease in miR-186 (MIR186) expression in comparison with normal lung tissue or epithelial cell lines. miR-186 expression correlated with patient survival, with median overall survival time of 63.0 or 21.5 months in cases exhibiting high or low levels of miR-186, respectively. Enforced overexpression of miR-186 in NSCLC cells inhibited proliferation by inducing G1–S checkpoint arrest. Conversely, RNA interference–mediated silencing miR-186 expression promoted cell-cycle progression and accelerated the proliferation of NSCLC cells. Cyclin D1 (CCND1), cyclin-dependent kinase (CDK)2, and CDK6 were each directly targeted for inhibition by miR-186 and restoring their expression reversed miR-186–mediated inhibition of cell-cycle progression. The inverse relationship between expression of miR-186 and its targets was confirmed in NSCLC tumor xenografts and clinical specimens. Taken together, our findings established a tumor-suppressive role for miR-186 in the progression of NSCLC. Cancer Res; 73(2); 756–66. ©2012 AACR.
Expression of CD137 on Hodgkin and Reed–Sternberg Cells Inhibits T-cell Activation by Eliminating CD137 Ligand Expression
Authors: Ho Weng Tong , Pang Wan Lu , Chong Siew Meng , Castella Antonio , Al-Salam Suhail , Tan Teng Ee , Moh Mei Chung , Koh Liang Kai , Gan Shu Uin , Cheng Cheong Kin , Schwarz Herbert 
Published: November 2012

AbstractHodgkin lymphoma is caused by a minority population of malignant Hodgkin and Reed–Sternberg (HRS) cells that recruit an abundance of inflammatory cells. The long-term survival of HRS cells among the vast majority of immune cells indicates that they have developed potent immune escape mechanisms. We report that the TNF receptor family member CD137 (TNFRSF9) is expressed on HRS cells, while normal B cells, from which HRS cells are most often derived, do not express CD137. In 48 of 53 cases of classical Hodgkin lymphoma, CD137 was detected on HRS cells. Ectopically expressed CD137 transferred by trogocytosis from HRS cells to neighboring HRS and antigen-presenting cells, which constitutively express the CD137 ligand (CD137L and TNFSF9), became associated with CD137L and the CD137–CD137L complex was internalized. Disappearance of CD137L from the surface of HRS and antigen-presenting cells led to reduced costimulation of T cells through CD137, reducing IFN-γ release and proliferation. Our results reveal a new regulatory mechanism for CD137L expression that mediates immune escape by HRS cells, and they identify CD137 as a candidate target for immunotherapy of Hodgkin lymphoma. Cancer Res; 73(2); 652–61. ©2012 AACR.
A Single-Nucleotide Substitution Mutator Phenotype Revealed by Exome Sequencing of Human Colon Adenomas
Authors: Nikolaev Sergey I. , Sotiriou Sotirios K. , Pateras Ioannis S. , Santoni Federico , Sougioultzis Stavros , Edgren Henrik , Almusa Henrikki , Robyr Daniel , Guipponi Michel , Saarela Janna , Gorgoulis Vassilis G. , Antonarakis Stylianos E. , Halazonetis Thanos D. 
Published: November 2012

Abstract
Oncogene-induced DNA replication stress is thought to drive genomic instability in cancer. In particular, replication stress can explain the high prevalence of focal genomic deletions mapping within very large genes in human tumors. However, the origin of single-nucleotide substitutions (SNS) in nonfamilial cancers is strongly debated. Some argue that cancers have a mutator phenotype, whereas others argue that the normal DNA replication error rates are sufficient to explain the number of observed SNSs. Here, we sequenced the exomes of 24, mostly precancerous, colon polyps. Analysis of the sequences revealed mutations in the APC, CTNNB1, and BRAF genes as the presumptive cancer-initiating events and many passenger SNSs. We used the number of SNSs in the various lesions to calculate mutation rates for normal colon and adenomas and found that colon adenomas exhibit a mutator phenotype. Interestingly, the SNSs in the adenomas mapped more often than expected within very large genes, where focal deletions in response to DNA replication stress also map. We propose that single-stranded DNA generated in response to oncogene-induced replication stress compromises the repair of deaminated cytosines and other damaged bases, leading to the observed SNS mutator phenotype. Cancer Res; 72(23); 6279–89. ©2012 AACR.