bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein
Authors: Piao Longzhen , Li Yuwen , Yang Keum-Jin , Park Kyeong Ah , Byun Hee Sun , Won Minho , Hong Janghee , Kim Jeong-Lan , Kweon Gi Ryang , Hur Gang Min , Seok Jeong Ho , Cho Jae Youl , Chun Taehoon , Hess Daniel , Sack Ragna , Maira Sauveur-Michel , Brazil Derek P , Hemmings Brian A , Park Jongsun 
Published: July 2009

AbstractBackgroundThe serine/threonine protein kinase B (PKB/Akt) is involved in insulin signaling, cellular survival, and transformation. Carboxyl-terminal modulator protein (CTMP) has been identified as a novel PKB binding partner in a yeast two-hybrid screen, and appears to be a negative PKB regulator with tumor suppressor-like properties. In the present study we investigate novel mechanisms by which CTMP plays a role in apoptosis process.ResultsCTMP is localized to mitochondria. Furthermore, CTMP becomes phosphorylated following the treatment of cells with pervanadate, an insulin-mimetic. Two serine residues (Ser37 and Ser38) were identified as novelin vivophosphorylation sites of CTMP. Association of CTMP and heat shock protein 70 (Hsp70) inhibits the formation of complexes containing apoptotic protease activating factor 1 and Hsp70. Overexpression of CTMP increased the sensitivity of cells to apoptosis, most likely due to the inhibition of Hsp70 function.ConclusionOur data suggest that phosphorylation on Ser37/Ser38 of CTMP is important for the prevention of mitochondrial localization of CTMP, eventually leading to cell death by binding to Hsp70. In addition to its role in PKB inhibition, CTMP may therefore play a key role in mitochondria-mediated apoptosis by localizing to mitochondria.
A method for identifying alternative or cryptic donor splice sites within gene and mRNA sequences. Comparisons among sequences from vertebrates, echinoderms and other groups
Authors: Buckley Katherine M , Florea Liliana D , Smith L Courtney 
Published: July 2009

Abstract

Background
As the amount of genome sequencing data grows, so does the problem of computational gene identification, and in particular, the splicing signals that flank exon borders. Traditional methods for identifying splicing signals have been created and optimized using sequences from model organisms, mostly vertebrate and yeast species. However, as genome sequencing extends across the animal kingdom and includes various invertebrate species, the need for mechanisms to recognize splice signals in these organisms increases as well. With that aim in mind, we generated a model for identifying donor and acceptor splice sites that was optimized using sequences from the purple sea urchin, Strongylocentrotus purpuratus. This model was then used to assess the possibility of alternative or cryptic splicing within the highly variable immune response gene family known as 185/333.

Results
A donor splice site model was generated from S. purpuratus sequences that incorporates non-adjacent dependences among positions within the 9 nt splice signal and uses position weight matrices to determine the probability that the site is used for splicing. The Purpuratus model was shown to predict splice signals better than a similar model created from vertebrate sequences. Although the Purpuratus model was able to correctly predict the true splice sites within the 185/333 genes, no evidence for alternative or trans-gene splicing was observed.

Conclusion
The data presented herein describe the first published analyses of echinoderm splice sites and suggest that the previous methods of identifying splice signals that are based largely on vertebrate sequences may be insufficient. Furthermore, alternative or trans-gene splicing does not appear to be acting as a diversification mechanism in the 185/333 gene family.
Gene expression patterns in heterozygous Plk4 murine embryonic fibroblasts
Authors: Morettin Alan , Ward Alejandra , Nantais Jordan , Hudson John W 
Published: July 2009

AbstractBackgroundThe polo-like kinases (Plks) are a group of serine/threonine kinases which have roles in many aspects of cellular function including the regulation of mitotic activity and cellular stress responses. This study focuses on Plk4, the most divergent member of the Plk family, which is necessary for proper cellular proliferation. More specifically, alterations in Plk4 levels cause significantly adverse mitotic defects including abnormal centrosome duplication and aberrant mitotic spindle formation. We sought to clarify the effect of reduced Plk4 levels on the cell by examining transcript profiles ofPlk4wild-type and heterozygous mouse embryonic fibroblasts (MEFs). Subsequently, the levels of several key proteins involved in the DNA damage response were examined.Results143 genes were found to be significantly up-regulated in the heterozygous MEFs compared to their wild-type counterparts, while conversely, 9 genes were down-regulated. Numerous genes with increased transcript levels in heterozygous MEFs were identified to be involved in p53-dependent pathways. Furthermore, examination of the promoter regions of all up- and down-regulated genes revealed that the majority contained putative p53 responsive elements.An analysis of transcript levels in MEFs after exposure to either ionizing or ultraviolet radiation revealed a significant change between wild type and heterozygous MEFS for Plk4 transcript levels upon only UV exposure. Furthermore, changes in protein levels of several important cell check-point and apoptosis regulators were examined, including p53, Chk1, Chk2, Cdc25C and p21. In heterozygous MEFs, p53, p21 and Chk2 protein levels were at significantly higher levels. Furthermore, p53 activity was increased 5 fold in thePlk4heterozygous MEFs.ConclusionGlobal transcript profiles and levels of key proteins involved in cellular proliferation and DNA damage pathways were examined in wild-type andPlk4heterozygous MEFs. It was determined that Plk4 haploinsufficiency leads to changes in the levels of RNA accumulation for a number of key cellular genes as well as changes in protein levels for several important cell cycle/DNA damage proteins. We propose a model in which reduced Plk4 levels invoke an increase in p53 levels that leads to the aforementioned changes in global transcription profiles.
The protist Trichomonas vaginalis harbors multiple lineages of transcriptionally active Mutator-like elements
Authors: Lopes Fabrício R , Silva Joana C , Benchimol Marlene , Costa Gustavo GL , Pereira Gonçalo AG , Carareto Claudia MA 
Published: July 2009

Abstract

Background
For three decades the Mutator system was thought to be exclusive of plants, until the first homolog representatives were characterized in fungi and in early-diverging amoebas earlier in this decade.

Results
Here, we describe and characterize four families of Mutator-like elements in a new eukaryotic group, the Parabasalids. These
T

richomonas

v

aginalis

Mu

tator-

l

ike

e

lements, or TvMULEs, are active in T. vaginalis and patchily distributed among 12 trichomonad species and isolates. Despite their relatively distinctive amino acid composition, the inclusion of the repeats TvMULE1, TvMULE2, TvMULE3 and TvMULE4 into the Mutator superfamily is justified by sequence, structural and phylogenetic analyses. In addition, we identified three new TvMULE-related sequences in the genome sequence of Candida albicans. While TvMULE1 is a member of the MuDR clade, predominantly from plants, the other three TvMULEs, together with the C. albicans elements, represent a new and quite distinct Mutator lineage, which we named TvCaMULEs. The finding of TvMULE1 sequence inserted into other putative repeat suggests the occurrence a novel TE family not yet described.

Conclusion
These findings expand the taxonomic distribution and the range of functional motif of MULEs among eukaryotes. The characterization of the dynamics of TvMULEs and other transposons in this organism is of particular interest because it is atypical for an asexual species to have such an extreme level of TE activity; this genetic landscape makes an interesting case study for causes and consequences of such activity. Finally, the extreme repetitiveness of the T. vaginalis genome and the remarkable degree of sequence identity within its repeat families highlights this species as an ideal system to characterize new transposable elements.
The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells
Authors: Wang Li-Chieh , Lin Yu-Li , Liang Yu-Chih , Yang Yao-Hsu , Lee Jyh-Hong , Yu Hsin-Hui , Wu Wen-Mein , Chiang Bor-Luen 
Published: July 2009

AbstractBackgroundPropolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE), the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs) was investigated.ResultsCAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IκBα phosphorylation and NF-κB activation but not mitogen-activated protein kinase (MAPK) family phosphorylation in human MoDCs.ConclusionThese results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-κB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.
Interrelationship between TP53gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma
Authors: Khayat André S , Guimarães Adriana C , Calcagno Danielle Q , Seabra Aline D , Lima Eleonidas M , Leal Mariana F , Faria Mário HG , Rabenhorst Silvia HB , Assumpção Paulo P , Demachki Samia , Smith Marília AC , Burbano Rommel R 
Published: July 2009

Abstract

Background
This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics.

Methods
Dual-color fluorescence in situ hybridization and immunostaining were performed in twenty gastric cancer samples of individuals from Northern Brazil.

Results
Deletion of TP53 was found in all samples. TP53 was inactivated mainly by single allelic deletion, varying to 7–39% of cells/case. Aneusomy of chromosome 17 was observed in 85% of cases. Chromosome 17 monosomy and gain were both observed in about half of cases. Cells with gain of chromosome 17 frequently presented TP53 deletion. The frequency of cells with two chr17 and one TP53 signals observed was higher in diffuse than in intestinal-type GC. Immunoreactivity of p53 was found only in intestinal-type samples. The frequency of cells with two chr17 and two TP53 signals found was higher in samples with positive p53 expression than in negative cases in intestinal-type GC.

Conclusion
We suggest that TP53 deletion and chromosome 17 aneusomy is a common event in GC and other TP53 alterations, as mutation, may be implicated in the distinct carcinogenesis process of diffuse and intestinal types.
A role of BRCA1 and BRCA2germline mutations in breast cancer susceptibility within Sardinian population
Authors: Palomba Grazia , Loi Angela , Uras Antonella , Fancello Patrizia , Piras Giovanna , Gabbas Attilio , Cossu Antonio , Budroni Mario , Contu Antonio , Tanda Francesco , Farris Antonio , Orrù Sandra , Floris Carlo , Pisano Marina , Lovicu Mario , Santona Maria Cristina , Landriscina Gennaro , Crisponi Laura , Palmieri Giuseppe , Monne Maria 
Published: July 2009

Abstract

Background
In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated.

Methods
Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.

Results and Conclusion
Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.
Efficacy of sorafenib on metastatic renal cell carcinoma in Asian patients: Results from a multicenter study
Authors: Zhang Hailiang , Dong Baijun , Lu Jiade J , Yao Xudong , Zhang Shilin , Dai Bo , Shen Yijun , Zhu Yao , Ye Dingwei , Huang Yiran 
Published: July 2009

Abstract

Background
The effects of sorafenib in the treatment of advanced renal cell carcinoma (RCC) have been confirmed in an international collaborative phase III trial. This study aims to confirm similar efficacy and treatment-induced toxicities of sorafenib in the treatment of metastatic RCC in ethnic Chinese patients.

Methods
Ninety-eight consecutive and non-selected patients with pathologically confirmed metastatic RCC were treated according to an institutional treatment protocol. All patients were treated with 400 mg of sorafenib orally twice daily on a continuous basis until disease progression or intolerance to treatment occurred. Dose reduction to 400 mg once daily was required if grade 3 or 4 toxicities occurred. All patients except for 7 received nephrectomy in the course of their disease. All patients were assessed for tumor response, progression-free survival (PFS), overall survival (OS), and treatment-induced toxicities.

Results
The median follow-up time was 76 weeks (range 2–296 weeks) for the entire group of patients. Radiologically confirmed complete response (CR), partial response (PR), stable disease (SD) of more than 4 months, and disease progression as best objective responses were observed in 1 (1%), 23 (23.5%), 62 (63.3%), and 12 (12.2%) patients, respectively. The tumor control rate (CR+PR+SD of >4 months) was 87.8%. The 1-year estimated PFS and OS were 58.4% and 64.6%, respectively. The median progression-free survival (PFS) time was 60 weeks (95% CI 41–79); and the median overall survival (OS) time was not reached with a follow-up of 76 weeks. Reduction of sorafenib dose was required in 26 patients who developed grade 3 or 4 treatment-cause adverse-effects. An additional 9 patients discontinued sorafenib treatment due to severe adverse-effects. No grade 5 toxicity occurred.
Multivariate analysis revealed that independent predictive factors for tumor response to sorafenib treatment included ECOG status, presence of lymph node metastasis, and nephrectomy prior to the development of metastasis.

Conclusion
Sorafenib produced an 87.8% disease control rate for metastatic renal cell carcinoma in Chinese patients, with acceptable rates of toxicity. The medication dosed at 400 mg twice daily is both efficacious and safe in the treatment of metastatic renal cell carcinoma in Chinese patients.
Dietary restriction abrogates antibody production induced by a DNA vaccine encoding the mycobacterial 65 kDa heat shock protein
Authors: Ishikawa Larissa Lumi Watanabe , França Thaís Graziela Donegá , Chiuso-Minicucci Fernanda , Zorzella-Pezavento Sofia Fernanda Gonçalves , Marra Nelson Mendes , Pereira Paulo Câmara Marques , Silva Célio Lopes , Sartori Alexandrina 
Published: July 2009

AbstractBackgroundProtein-calorie malnutrition (PCM) is the most common type of malnutrition. PCM leads to immunodeficiency and consequent increased susceptibility to infectious agents. In addition, responses to prophylactic vaccines depend on nutritional status. This study aims to evaluate the ability of undernourished mice to mount an immune response to a genetic vaccine (pVAXhsp65) against tuberculosis, containing the gene coding for the heat shock protein 65 from mycobacteria.MethodsYoung adult female BALB/c mice were fedad libitumor with 80% of the amount of food consumed by a normal diet group. We initially characterized a mice model of dietary restriction by determining body and spleen weights, hematological parameters and histopathological changes in lymphoid organs. The ability of splenic cells to produce IFN-gamma and IL-4 uponin vitrostimulation with LPS orS. aureusand the serum titer of specific IgG1 and IgG2a anti-hsp65 antibodies after intramuscular immunization with pVAXhsp65 was then tested.ResultsDietary restriction significantly decreased body and spleen weights and also the total lymphocyte count in blood. This restriction also determined a striking atrophy in lymphoid organs as spleen, thymus and lymphoid tissue associated with the small intestine. Specific antibodies were not detected in mice submitted to dietary restriction whereas the well nourished animals produced significant levels of both, IgG1 and IgG2a anti-hsp65.Conclusion20% restriction in food intake deeply compromised humoral immunity induced by a genetic vaccine, alerting, therefore, for the relevance of the nutritional condition in vaccination programs based on these kinds of constructs.
Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures
Authors: Jazedje Tatiana , Perin Paulo M , Czeresnia Carlos E , Maluf Mariangela , Halpern Silvio , Secco Mariane , Bueno Daniela F , Vieira Natassia M , Zucconi Eder , Zatz Mayana 
Published: July 2009

Abstract

Background
The possibility of using stem cells for regenerative medicine has opened a new field of investigation. The search for sources to obtain multipotent stem cells from discarded tissues or through non-invasive procedures is of great interest. It has been shown that mesenchymal stem cells (MSCs) obtained from umbilical cords, dental pulp and adipose tissue, which are all biological discards, are able to differentiate into muscle, fat, bone and cartilage cell lineages. The aim of this study was to isolate, expand, characterize and assess the differentiation potential of MSCs from human fallopian tubes (hFTs).

Methods
Lineages of hFTs were expanded, had their karyotype analyzed, were characterized by flow cytometry and underwent in vitro adipogenic, chondrogenic, osteogenic, and myogenic differentiation.

Results
Here we show for the first time that hFTs, which are discarded after some gynecological procedures, are a rich additional source of MSCs, which we designated as human tube MSCs (htMSCs).

Conclusion
Human tube MSCs can be easily isolated, expanded in vitro, present a mesenchymal profile and are able to differentiate into muscle, fat, cartilage and bone in vitro.
Experimental evidence indicating that mastreviruses probably did not co-diverge with their hosts
Authors: Harkins Gordon W , Delport Wayne , Duffy Siobain , Wood Natasha , Monjane Adérito L , Owor Betty E , Donaldson Lara , Saumtally Salem , Triton Guy , Briddon Rob W , Shepherd Dionne N , Rybicki Edward P , Martin Darren P , Varsani Arvind 
Published: July 2009

Abstract

Background
Despite the demonstration that geminiviruses, like many other single stranded DNA viruses, are evolving at rates similar to those of RNA viruses, a recent study has suggested that grass-infecting species in the genus Mastrevirus may have co-diverged with their hosts over millions of years. This "co-divergence hypothesis" requires that long-term mastrevirus substitution rates be at least 100,000-fold lower than their basal mutation rates and 10,000-fold lower than their observable short-term substitution rates. The credibility of this hypothesis, therefore, hinges on the testable claim that negative selection during mastrevirus evolution is so potent that it effectively purges 99.999% of all mutations that occur.

Results
We have conducted long-term evolution experiments lasting between 6 and 32 years, where we have determined substitution rates of between 2 and 3 × 10-4 substitutions/site/year for the mastreviruses Maize streak virus (MSV) and Sugarcane streak Réunion virus (SSRV). We further show that mutation biases are similar for different geminivirus genera, suggesting that mutational processes that drive high basal mutation rates are conserved across the family. Rather than displaying signs of extremely severe negative selection as implied by the co-divergence hypothesis, our evolution experiments indicate that MSV and SSRV are predominantly evolving under neutral genetic drift.

Conclusion
The absence of strong negative selection signals within our evolution experiments and the uniformly high geminivirus substitution rates that we and others have reported suggest that mastreviruses cannot have co-diverged with their hosts.