bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization, gene expression and dependence on thyroid hormones of two type I keratin genes (sseKer1 and sseKer2) in the flatfish Senegalese sole (Solea senegalensisKaup)
Authors: Infante Carlos , Manchado Manuel , Asensio Esther , Cañavate José Pedro 
Published: October 2007

Abstract
Background
Keratins make up the largest subgroup of intermediate filaments, and, in chordates, represent the most abundant proteins in epithelial cells. They have been associated with a wide range of functions in the cell, but little information is still available about their expression profile and regulation during flatfish metamorphosis. Senegalese sole (Solea senegalensis) is a commercially important flatfish in which no keratin gene has been described yet.

Results
The development of large-scale genomics of Senegalese sole has facilitated the identification of two different type I keratin genes referred to as sseKer1 and sseKer2. Main characteristics and sequence identities with other fish and mammal keratins are described. Phylogenetic analyses grouped sseKer1 and sseKer2 in a significant clade with other teleost epidermal type I keratins, and have allowed for the identification of sseKer2 as a novel keratin. The expression profile of both genes was studied during larval development and in tissues using a real-time approach. sseKer1 and sseKer2 mRNA levels were significantly higher in skin than in other tissues examined. During metamorphosis, sseKer1 transcripts increased significantly at first stages, and reduced thereafter. In contrast, sseKer2 mRNA levels did not change during early metamorphosis although a significant drop at metamorphosis climax and late metamorphosis was also detected. To study the possible regulation of sseKer gene expressions by thyroid hormones (THs), larvae were exposed to the goitrogen thiourea (TU). TU-treated larvae exhibited higher sseKer1 and sseKer2 mRNA levels than untreated control at both 11 and 15 days after treatment. Moreover, addition of exogenous T4 hormone to TU-treated larvae restored or even reduced the steady-state levels with respect to the untreated control, demonstrating that expression of both genes is negatively regulated by THs.

Conclusion
We have identified two keratin genes, referred to as sseKer1 and sseKer2, in Senegalese sole. Phylogenetic analyses revealed sseKer2 as a novel keratin. Although they exhibit different expression patterns during larval development, both of them are negatively regulated by THs. The co-regulation by THs could explain the reduction of both keratin transcripts after the metamorphosis climax, suggesting their role in the tissue remodelling processes that occur during metamorphosis.
Genes involved in TGFβ1-driven epithelial-mesenchymal transition of renal epithelial cells are topologically related in the human interactome map
Authors: Campanaro Stefano , Picelli Simone , Torregrossa Rossella , Colluto Laura , Ceol Monica , Del Prete Dorella , D'Angelo Angela , Valle Giorgio , Anglani Franca 
Published: October 2007

Abstract

Background
Understanding how mesenchymal cells arise from epithelial cells could have a strong impact in unveiling mechanisms of epithelial cell plasticity underlying kidney regeneration and repair.
In primary human tubular epithelial cells (HUTEC) under different TGFβ1 concentrations we had observed epithelial-to-mesenchymal transition (EMT) but not epithelial-myofibroblast transdifferentiation. We hypothesized that the process triggered by TGFβ1 could be a dedifferentiation event. The purpose of this study is to comprehensively delineate genetic programs associated with TGFβ1-driven EMT in our in vitro model using gene expression profile on large-scale oligonucleotide microarrays.

Results
In HUTEC under TGFβ1 stimulus, 977 genes were found differentially expressed. Thirty genes were identified whose expression depended directly on TGFβ1 concentration. By mapping the differentially expressed genes in the Human Interactome Map using Cytoscape software, we identified a single scale-free network consisting of 2630 interacting proteins and containing 449 differentially expressed proteins. We identified 27 hub proteins in the interactome with more than 29 edges incident on them and encoded by differentially expressed genes. The Gene Ontology analysis showed an excess of up-regulated proteins involved in biological processes, such as "morphogenesis", "cell fate determination" and "regulation of development", and the most up-regulated genes belonged to these categories. In addition, 267 genes were mapped to the KEGG pathways and 14 pathways with more than nine differentially expressed genes were identified. In our model, Smad signaling was not the TGFβ1 action effector; instead, the engagement of RAS/MAPK signaling pathway seems mainly to regulate genes involved in the cell cycle and proliferation/apoptosis.

Conclusion
Our present findings support the hypothesis that context-dependent EMT generated in our model by TGFβ1 might be the outcome of a dedifferentiation. In fact: 1) the principal biological categories involved in the process concern morphogenesis and development; 2) the most up-regulated genes belong to these categories; and, finally, 3) some intracellular pathways are involved, whose engagement during kidney development and nephrogenesis is well known. These long-term effects of TGFβ1 in HUTEC involve genes that are highly interconnected, thereby generating a scale-free network that we named the "TGFβ1 interactome", whose hubs represent proteins that may have a crucial role for HUTEC in response to TGFβ1.
A systems-biology analysis of isogenic megakaryocytic and granulocytic cultures identifies new molecular components of megakaryocytic apoptosis
Authors: Chen Chi , Fuhrken Peter G , Huang Li Ting , Apostolidis Pani , Wang Min , Paredes Carlos J , Miller William M , Papoutsakis Eleftherios T 
Published: October 2007

Abstract

Background
The differentiation of hematopoietic stem cells into platelet-forming megakaryocytes is of fundamental importance to hemostasis. Constitutive apoptosis is an integral, yet poorly understood, facet of megakaryocytic (Mk) differentiation. Understanding Mk apoptosis could lead to advances in the treatment of Mk and platelet disorders.

Results
We used a Gene-ontology-driven microarray-based transcriptional analysis coupled with protein-level and activity assays to identify genes and pathways involved in Mk apoptosis. Peripheral blood CD34+ hematopoietic progenitor cells were induced to either Mk differentiation or, as a negative control without observable apoptosis, granulocytic differentiation. Temporal gene-expression data were analyzed by a combination of intra- and inter-culture comparisons in order to identify Mk-associated genes. This novel approach was first applied to a curated set of general Mk-related genes in order to assess their dynamic transcriptional regulation. When applied to all apoptosis associated genes, it revealed a decrease in NF-κB signaling, which was explored using phosphorylation assays for IκBα and p65 (RELA). Up-regulation was noted among several pro-apoptotic genes not previously associated with Mk apoptosis such as components of the p53 regulon and TNF signaling. Protein-level analyses probed the involvement of the p53-regulated GADD45A, and the apoptosis signal-regulating kinase 1 (ASK1). Down-regulation of anti-apoptotic genes, including several of the Bcl-2 family, was also detected.

Conclusion
Our comparative approach to analyzing dynamic large-scale transcriptional data, which was validated using a known set of Mk genes, robustly identified candidate Mk apoptosis genes. This led to novel insights into the molecular mechanisms regulating apoptosis in Mk cells.
Ecological study of Paracoccidioides brasiliensis in soil: growth ability, conidia production and molecular detection
Authors: Terçarioli Gisela Ramos , Bagagli Eduardo , Reis Gabriela Martins , Theodoro Raquel Cordeiro , Bosco Sandra De Moraes Gimenes , Macoris Severino Assis da Graça , Richini-Pereira Virgínia Bodelão 
Published: October 2007

Abstract

Background

Paracoccidioides brasiliensis ecology is not completely understood, although several pieces of evidence point to the soil as its most probable habitat. The present study aimed to investigate the fungal growth, conidia production and molecular pathogen detection in different soil conditions.

Methods
Soils samples of clayey, sandy and medium textures were collected from ground surface and the interior of armadillo burrows in a hyperendemic area of Paracoccidioidomycosis. P. brasiliensis was inoculated in soil with controlled humidity and in culture medium containing soil extracts. The molecular detection was carried out by Nested PCR, using panfungal and species specific primers from the ITS-5.8S rDNA region.

Results
The soil texture does not affect fungus development and the growth is more abundant on/in soil saturated with water. Some soil samples inhibited the development of P. brasiliensis, especially those that contain high values of Exchangeable Aluminum (H+Al) in their composition. Some isolates produced a large number of conidia, mainly in soil-extract agar medium. The molecular detection was positive only in samples collected from armadillo burrows, both in sandy and clayey soil.

Conclusion

P. brasiliensis may grow and produce the infectious conidia in sandy and clayey soil, containing high water content, mainly in wild animal burrows, but without high values of H+Al.
luxRI homologs are universally present in the genus Aeromonas
Authors: Jangid Kamlesh , Kong Richard , Patole Milind S , Shouche Yogesh S 
Published: October 2007

Abstract

Background

Aeromonas spp. have been regarded as "emerging pathogens". Aeromonads possess multifactorial virulence and the production of many of these virulence determinants is associated with high cell density, a phenomenon that might be regulated by quorum sensing. However, only two species of the genus are reported to possess the luxRI quorum sensing gene homologs. The purpose of this study was to investigate if the luxRI homologs are universally present in the Aeromonas strains collected from various culture collections, clinical laboratories and field studies.

Results
Of all the 73 Aeromonas strains used in the study, seventy-one strains elicited acyl-homoserine lactone-mediated response in multiple biosensor strains. However, dot blot hybridization revealed that the luxRI homologs are present in all the strains. PCR amplification and sequencing revealed that the luxRI homologs shared a very high percentage sequence similarity. No evidence for lateral gene transfer of the luxRI homologs between aeromonads and other genera was noted.

Conclusion
We propose that the luxRI quorum sensing gene homologs are universally present in the genus Aeromonas independently from their origin. This study is the first genus-wide report of the taxonomic distribution of the luxRI homologs.
Factors associated with good self-rated health of non-disabled elderly living alone in Japan: a cross-sectional study
Authors: Sun Wei , Watanabe Misuzu , Tanimoto Yoshimi , Shibutani Takahiro , Kono Rei , Saito Masahisa , Usuda Kan , Kono Koichi 
Published: October 2007

AbstractBackgroundSelf-rated health (SRH) is reported as a reliable predictor of disability and mortality in the aged population and has been studied worldwide to enhance the quality of life of the elderly. Nowadays, the elderly living alone, a particular population at great risk of suffering physical and mental health problems, is increasing rapidly in Japan and could potentially make up the majority of the aged population. However, few data are available pertaining to SRH of this population. Given the fact that sufficient healthcare is provided to the disabled elderly whereas there is little support for non-disabled elderly, we designed this population-based survey to investigate SRH of non-disabled elderly living alone and to identify the factors associated with good SRH with the purpose of aiding health promotion for the elderly.MethodsA cross-sectional study was conducted in a metropolitan suburb in Japan. Questionnaires pertaining to SRH and physical conditions, lifestyle factors, psychological status, and social activities, were distributed in October 2005 to individuals aged ≥ 65 years and living alone. Response rate was 75.1%. Among these respondents, a total of 600 male and 2587 female respondents were identified as non-disabled elderly living alone and became our subjects. Multivariate logistic regression was used to identify the factors associated with good SRH and sex-specific effect was tested by stepwise logistic regression.ResultsGood SRH was reported by 69.8% of men and 73.8% of women. Multivariate logistic regression analysis showed that good SRH correlated with, in odds ratio sequence, "can go out alone to distant places", no depression, no weight loss, absence of self-rated chronic disease, good chewing ability, and good visual ability in men; whereas with "can go out alone to distant places", absence of self-rated chronic disease, no weight loss, no depression, no risk of falling, independent IADL, good chewing ability, good visual ability, and social integration (attend) in women.ConclusionFor the non-disabled elderly living alone, sex-appropriate support should be considered by health promotion systems from the view point of SRH. Overall, the ability to go out alone to distant places is crucial to SRH of both men and women.
The structure of Mycobacteria 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery
Authors: Buetow Lori , Brown Amanda C , Parish Tanya , Hunter William N 
Published: October 2007

Abstract

Background
The prevalence of tuberculosis, the prolonged and expensive treatment that this disease requires and an increase in drug resistance indicate an urgent need for new treatments. The 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid precursor biosynthesis is an attractive chemotherapeutic target because it occurs in many pathogens, including Mycobacterium tuberculosis, and is absent from humans. To underpin future drug development it is important to assess which enzymes in this biosynthetic pathway are essential in the actual pathogens and to characterize them.

Results
The fifth enzyme of this pathway, encoded by ispF, is 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase (IspF). A two-step recombination strategy was used to construct ispF deletion mutants in M. tuberculosis but only wild-type double crossover strains were isolated. The chromosomal copy could be deleted when a second functional copy was provided on an integrating plasmid, demonstrating that ispF is an essential gene under the conditions tested thereby confirming its potential as a drug target. We attempted structure determination of the M. tuberculosis enzyme (Mt IspF), but failed to obtain crystals. We instead analyzed the orthologue M. smegmatis IspF (Ms IspF), sharing 73% amino acid sequence identity, at 2.2 Å resolution. The high level of sequence conservation is particularly pronounced in and around the active site. Ms IspF is a trimer with a hydrophobic cavity at its center that contains density consistent with diphosphate-containing isoprenoids. The active site, created by two subunits, comprises a rigid CDP-Zn2+ binding pocket with a flexible loop to position the 2C-methyl-D-erythritol moiety of substrate. Sequence-structure comparisons indicate that the active site and interactions with ligands are highly conserved.

Conclusion
Our study genetically validates Mt IspF as a therapeutic target and provides a model system for structure-based ligand design.
AhR transcriptional activity in serum of Inuits across Greenlandic districts
Authors: Long Manhai , Deutch Bente , Bonefeld-Jorgensen Eva C 
Published: October 2007

Abstract

Background
Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors.

Methods
The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors.

Results
In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk ≥ Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food.

Conclusion
i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.
Warning: Anti-tobacco activism may be hazardous to epidemiologic science
Authors: Phillips Carl V 
Published: October 2007

AbstractThis commentary accompanies two articles submitted to Epidemiologic Perspectives & Innovations in response to a call for papers about threats to epidemiology or epidemiologists from organized political interests. Contrary to our expectations, we received no submissions that described threats from industry or government; all were about threats from anti-tobacco activists. The two we published, by James E. Enstrom and Michael Siegel, both deal with the issue of environmental tobacco smoke. This commentary adds a third story of attacks on legitimate science by anti-tobacco activists, the author's own experience. These stories suggest a willingness of influential anti-tobacco activists, including academics, to hurt legitimate scientists and turn epidemiology into junk science in order to further their agendas. The willingness of epidemiologists to embrace such anti-scientific influences bodes ill for the field's reputation as a legitimate science.
Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors
Authors: Collins Brian T , Erickson Kelly , Reichner Cristina A , Collins Sean P , Gagnon Gregory J , Dieterich Sonja , McRae Don A , Zhang Ying , Yousefi Shadi , Levy Elliot , Chang Thomas , Jamis-Dow Carlos , Banovac Filip , Anderson Eric D 
Published: October 2007

Abstract
Background
Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors.

Methods
Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3–5) were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45–60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months.

Results
Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease.

Conclusion
Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.
Traumatic pulmonary pseuodocysts: two case reports
Authors: Kocer Bulent , Gulbahar Gultekin , Gunal Nesimi , Dural Koray , Sakinci Unal 
Published: October 2007

Abstract
Traumatic pulmonary pseudocyst (TPP) is a rare complication, sometimes encountered after blunt thoracic trauma and even more rarely following penetrating injuries. It is more common among pediatric and young adult patients. Although TPP is usually benign in nature, complications associated with hemoptysis and secondary infection may develop. The treatment is conservative. In this report, we present two rare cases of TPP occuring after a high-speed accident and a stab wound injury, where conservative treatment provided good outcomes.
Pseudo-transient computational fluid dynamics analysis of an underbonnet compartment during thermal soak
Authors: Franchetta M , Suen K O , Bancroft T G 
Published: October 2007

Underbonnet simulations are proving to be crucially important within a vehicle development programme, reducing test work and time-to-market. While computational fluid dynamics (CFD) simulations of steady forced flows have been demonstrated to be reliable, studies of transient convective flows in engine compartments are not yet carried out owing to high computing demands and lack of validated work. The present work assesses the practical feasibility of applying the CFD tool at the initial stage of a vehicle development programme for investigating the thermally driven flow in an engine bay under thermal soak. A computation procedure that enables pseudo time-marching CFD simulations to be performed with significantly reduced central processing unit (CPU) time usage is proposed. The methodology was initially tested on simple geometries and then implemented for investigating a simplified half-scale underbonnet compartment. The numerical results are compared with experimental data taken with thermocouples and with particle image velocimetry (PIV). The novel computation methodology is successful in efficiently providing detailed and time-accurate time-dependent thermal and flow predictions. Its application will extend the use of the CFD tool for transient investigations, enabling improvements to the component packaging of engine bays and the refinement of thermal management strategies with reduced need for in-territory testing.