bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional Transgenic Expression of Fibroblast Growth Factor 9 in the Adult Mouse Heart Reduces Heart Failure Mortality After Myocardial Infarction
Authors: Korf-Klingebiel Mortimer , Kempf Tibor , Schlüter Klaus-Dieter , Willenbockel Christian , Brod Torben , Heineke Jörg , Schmidt Volker J. , Jantzen Franziska , Brandes Ralf P. , Sugden Peter H. , Drexler Helmut , Molkentin Jeffery D. , Wollert Kai C. 
Published: January 2011

Background—
Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart.

Methods and Results—
We used a tetracycline-responsive binary transgene system based on the α-myosin heavy chain promoter to test whether conditional expression of FGF9 in the adult myocardium supports adaptation after MI. In sham-operated mice, transgenic FGF9 stimulated left ventricular hypertrophy with microvessel expansion and preserved systolic and diastolic function. After coronary artery ligation, transgenic FGF9 enhanced hypertrophy of the noninfarcted left ventricular myocardium with increased microvessel density, reduced interstitial fibrosis, attenuated fetal gene expression, and improved systolic function. Heart failure mortality after MI was markedly reduced by transgenic FGF9, whereas rupture rates were not affected. Adenoviral FGF9 gene transfer after MI similarly promoted left ventricular hypertrophy with improved systolic function and reduced heart failure mortality. Mechanistically, FGF9 stimulated proliferation and network formation of endothelial cells but induced no direct hypertrophic effects in neonatal or adult rat cardiomyocytes in vitro. FGF9-stimulated endothelial cell supernatants, however, induced cardiomyocyte hypertrophy via paracrine release of bone morphogenetic protein 6. In accord with this observation, expression of bone morphogenetic protein 6 and phosphorylation of its downstream targets SMAD1/5 were increased in the myocardium of FGF9 transgenic mice.

Conclusions—
Conditional expression of FGF9 promotes myocardial vascularization and hypertrophy with enhanced systolic function and reduced heart failure mortality after MI. These observations suggest a previously unrecognized therapeutic potential for FGF9 after MI.
Functional Connectivity and Coactivation of the Nucleus Accumbens: A Combined Functional Connectivity and Structure-Based Meta-analysis
Authors: Cauda Franco , Cavanna Andrea E. , D'agata Federico , Sacco Katiuscia , Duca Sergio , Geminiani Giuliano C. 
Published: January 2011

AbstractThis article investigates the functional connectivity patterns of the nucleus accumbens (NAcc) in 18 healthy participants using a resting state functional connectivity (rsFC) protocol. Also, a meta-analytic connectivity modeling (MACM) was used to characterize patterns of functional coactivations involving NAcc: The results of a structure-based meta-analyses of 57 fMRI and PET studies were submitted to activation likelihood estimation analysis to estimate consistent activation patterns across the different imaging studies. The results of the combined rsFC and MACM analyses show that spontaneous activity in NAcc predicts activity in regions implicated in reward circuitries, including orbitomedial prefrontal cortex, globus pallidus, thalamus, midbrain, amygdala, and insula. This confirms the key role of NAcc in the mesocorticolimbic system, which integrates inputs from limbic and cortical regions. We also detected activity in brain regions having few or no direct anatomical connections with NAcc, such as sensorimotor cortex, cerebellum, medial and posterior parietal cortex, and medial/inferior temporal cortex, supporting the view that not all functional connections can be explained by anatomical connections but can also result from connections mediated by third areas. Our rsFC findings are in line with the results of the structure-based meta-analysis: MACM maps are superimposable with NAcc rsFC results, and the reward paradigm class is the one that most frequently generates activation in NAcc. Our results overlap considerably with recently proposed schemata of the main neuron systems in the limbic forebrain and in the anterior part of the limbic midbrain in rodents and nonhuman primates.
Tonal Expectations Influence Early Pitch Processing
Authors: Marmel Frédéric , Perrin Fabien , Tillmann Barbara 
Published: January 2011

AbstractThe present study investigated the ERP correlates of the influence of tonal expectations on pitch processing. Participants performed a pitch discrimination task between penultimate and final tones of melodies. These last two tones were a repetition of the same musical note, but penultimate tones were always in tune whereas final tones were slightly out of tune in half of the trials. The pitch discrimination task allowed us to investigate the influence of tonal expectations in attentive listening and, for penultimate tones, without being confounded by decisional processes (occurring on final tones). Tonal expectations were manipulated by a tone change in the first half of the melodies that changed their tonality, hence changing the tonal expectedness of penultimate and final tones without modifying them acoustically. Manipulating tonal expectations with minimal acoustic changes allowed us to focus on the cognitive expectations based on listeners' knowledge of tonal structures. For penultimate tones, tonal expectations modulated processing within the first 100 msec after onset resulting in an Nb/P1 complex that differed in amplitude between tonally related and less related conditions. For final tones, out-of-tune tones elicited an N2/P3 complex and, on in-tune tones only, tonal manipulation elicited an ERAN/RATN-like negativity overlapping with the N2. Our results suggest that cognitive tonal expectations can influence pitch perception at several steps of processing, starting with early attentional selection of pitch.
Cooperative and Opposing Effects of Strategic and Involuntary Attention
Authors: Mazza Veronica , Dallabona Monica , Chelazzi Leonardo , Turatto Massimo 
Published: January 2011

Abstract
To assess whether working memory contents can effectively bias visual selection even when they do not represent the current target in the attention task, we recorded the ERP activity from participants performing both a memory task and, in the retention period, a visual search task. In this task, a distracter matching the memory content could be presented on the same side (congruent trials) or on the opposite side (incongruent trials) relative to the target location (Experiment 1 and Experiment 2). On some trials, only the matching distracter (but no target) was presented (catch trials, Experiment 2). Results showed that the N2pc component was modulated by the presence and location of a matching distracter. We interpret these results as evidence that the involuntary control exerted by the irrelevant memory contents coexists with the strategic mechanism related to the search target, influencing attention selection with roughly equal power. In Experiment 3, we found that the modulation of the N2pc is not strictly related to the active maintenance of the memory-target features but can also be elicited by repetition priming. Overall, these findings suggest that, together with the physical properties of the stimuli presented in the visual field, irrelevant memory contents represent a powerful class of factors that lead to involuntary attentional control.
An In Situ Study of the Habits of Users That Affect Office Chair Design and Testing
Authors: Benden Mark E. , Fink Rainer , Congleton Jerome 
Published: January 2011

Objective: The purpose of this study was to perform an in situ assessment of office seating habits that influence chair testing and design. Background: Many chair testing parameters were derived decades ago when the average weight of people within the United States was dramatically lower and the office work tasks less computer based. Method: For the study, 51 participants were randomly selected from Brazos Valley, Texas, businesses to participate in 8-hr assessments of office seating habits. Overall results were compared with current chair testing and design assumptions. Data were collected through written survey and through data logging of seat and back contact pressure and duration with the use of the X-SENSOR™ pressure mapping device and software. Additionally, 1 day per participant of caster roll distance was recorded with the use of a caster mounted digital encoder. Participants were grouped by body mass index (BMI) and weight (BMI <35 and weight <102 kg or BMI >35 and weight >102 kg). Results: It was determined that a significant difference did exist between the groups in mean seat time per shift ( p < .001), back cycles per shift ( p < .002), seat cycles per shift ( p < .01), and caster distance rolled per shift ( p < .001). Conclusion: Several key parameters and assumptions of current chair test methods and design specifications may no longer be valid for the upper quartile of weight range of the current U.S. population. Application: The data collected in this study will enable engineers to determine whether revision of design standards for testing office seating for both normal weight and extremely obese workers is indicated.
Sox6 enhances erythroid differentiation in human erythroid progenitors
Authors: Cantù Claudio , Ierardi Rossella , Alborelli Ilaria , Fugazza Cristina , Cassinelli Letizia , Piconese Silvia , Bosè Francesca , Ottolenghi Sergio , Ferrari Giuliana , Ronchi Antonella 
Published: January 2011

Abstract
Sox6 belongs to the Sry (sex-determining region Y)–related high-mobility-group–box family of transcription factors, which control cell-fate specification of many cell types. Here, we explored the role of Sox6 in human erythropoiesis by its overexpression both in the erythroleukemic K562 cell line and in primary erythroid cultures from human cord blood CD34+ cells. Sox6 induced significant erythroid differentiation in both models. K562 cells underwent hemoglobinization and, despite their leukemic origin, died within 9 days after transduction; primary erythroid cultures accelerated their kinetics of erythroid maturation and increased the number of cells that reached the final enucleation step. Searching for direct Sox6 targets, we found SOCS3 (suppressor of cytokine signaling-3), a known mediator of cytokine response. Sox6 was bound in vitro and in vivo to an evolutionarily conserved regulatory SOCS3 element, which induced transcriptional activation. SOCS3 overexpression in K562 cells and in primary erythroid cells recapitulated the growth inhibition induced by Sox6, which demonstrates that SOCS3 is a relevant Sox6 effector.
Long-term clinical outcomes of patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study
Authors: Nørgaard Mette , Jensen Annette Ø. , Engebjerg Malene C. , Farkas Dóra K. , Thomsen Reimar W. , Cha Steven , Zhao Sean , Sørensen Henrik T. 
Published: January 2011

AbstractFew data exist on the long-term prognosis of patients with chronic primary chronic immune thrombocytopenia (ITP). We examined the risk of infections, hemorrhage resulting in hospitalization, hematologic malignancies, and total and cause-specific mortality among patients with ITP compared with the general population. We used population-based medical databases to identify 407 patients with primary chronic ITP diagnosed during 1996 to 2007 and 4069 general population members individually matched on age, sex, and comorbidity level. We used Cox regression analysis to estimate rate ratios (RRs) adjusted for age (≤ 60 or > 60 years), sex, calendar year, and level of comorbidity. The adjusted 1-year RR of infection was 4.5 (95% confidence interval [CI], 3.3-6.1) for patients with chronic ITP compared with the general population cohort. The adjusted RR decreased to 1.8 (95% CI, 1.3-2.5) for the second to fifth year of follow-up. The adjusted 5-year RR was 3.2 (95% CI, 1.2-9.0) for hospitalized intracranial hemorrhage, 4.4 (95% CI, 2.3-8.3) for other hospitalized hemorrhages, and 4.7 (95% CI, 1.7-12.7) for hematologic malignancy. The 5-year all-cause mortality RR was 2.3 (95% CI, 1.8-3.0). In summary, primary chronic ITP was associated with substantially increased long-term risk of infections, hemorrhagic episodes requiring hospitalization, hematologic malignancies, and mortality.
Changes in HSP gene and protein expression in natural scrapie with brain damage
Authors: Serrano Carmen , Bolea Rosa , Lyahyai Jaber , Filali Hicham , Varona Luis , Marcos-Carcavilla Ane , Acín Cristina , Calvo Jorge H , Serrano Magdalena , Badiola Juan J , Zaragoza Pilar , Martín-Burriel Inmaculada 
Published: January 2011

Abstract
Heat shock proteins (Hsp) perform cytoprotective functions such as apoptosis regulation and inflammatory response control. These proteins can also be secreted to the extracellular medium, acting as inflammatory mediators, and their chaperone activity permits correct folding of proteins and avoids the aggregation of anomalous isoforms. Several studies have proposed the implication of Hsp in prion diseases. We analysed the gene expression and protein distribution of different members of the Hsp27, Hsp70, and Hsp90 families in the central nervous system of sheep naturally infected with scrapie. Different expression profiles were observed in the areas analysed. Whereas changes in transcript levels were not observed in the cerebellum or medulla oblongata, a significant decrease in HSP27 and HSP90 was detected in the prefrontal cortex. In contrast, HSP73 was over-expressed in diencephalons of scrapie animals. Western blotting did not reveal significant differences in Hsp90 and Hsp70 protein expression between scrapie and control animals. Expression rates identified by real-time RT-PCR and western blotting were compared with the extent of classical scrapie lesions using stepwise regression. Changes in Hsp gene and protein expression were associated with prion protein deposition, gliosis and spongiosis rather than with apoptosis. Finally, immunohistochemistry revealed intense Hsp70 and Hsp90 immunolabelling in Purkinje cells of scrapie sheep. In contrast, controls displayed little or no staining in these cells. The observed differences in gene expression and protein distribution suggest that the heat shock proteins analysed play a role in the natural form of the disease.
Variation of inflammatory dynamics and mediators in primiparous cows after intramammary challenge with Escherichia coli
Authors: Pezeshki Adel , Stordeur Philippe , Wallemacq Hugues , Schynts Frédéric , Stevens Mieke , Boutet Philippe , Peelman Luc J , De Spiegeleer Bart , Duchateau Luc , Bureau Fabrice , Burvenich Christian 
Published: January 2011

Abstract
The objective of the current study was to investigate (i) the outcome of experimentally induced Escherichia coli mastitis in primiparous cows during early lactation in relation with production of eicosanoids and inflammatory indicators, and (ii) the validity of thermography to evaluate temperature changes on udder skin surface after experimentally induced E. coli mastitis. Nine primiparous Holstein Friesian cows were inoculated 24 ± 6 days (d) after parturition in both left quarters with E. coli P4 serotype O32:H37. Blood and milk samples were collected before and after challenge with E. coli. The infrared images were taken from the caudal view of the udder following challenge with E. coli. No relationship was detected between severity of mastitis and changes of thromboxane B2 (TXB2), leukotriene B4 (LTB4) and lipoxin A4 (LXA4). However, prostaglandin E2 (PGE2) was related to systemic disease severity during E. coli mastitis. Moreover, reduced somatic cell count (SCC), fewer circulating basophils, increased concentration of tumor necrosis factor-α (TNF-α) and higher milk sodium and lower milk potassium concentrations were related to systemic disease severity. The thermal camera was capable of detecting 2-3°C temperature changes on udder skin surface of cows inoculated with E. coli. Peak of udder skin temperature occurred after peak of rectal temperature and appearance of local signs of induced E. coli mastitis. Although infrared thermography was a successful method for detecting the changes in udder skin surface temperature following intramammary challenge with E. coli, it did not show to be a promising tool for early detection of mastitis.
SPI-1-encoded type III secretion system of Salmonella enterica is required for the suppression of porcine alveolar macrophage cytokine expression
Authors: Pavlova Barbora , Volf Jiri , Ondrackova Petra , Matiasovic Jan , Stepanova Hana , Crhanova Magdalena , Karasova Daniela , Faldyna Martin , Rychlik Ivan 
Published: January 2011

Abstract
Genes localized at Salmonella pathogenicity island-1 (SPI-1) are involved in Salmonella enterica invasion of host non-professional phagocytes. Interestingly, in macrophages, SPI-1-encoded proteins, in addition to invasion, induce cell death via activation of caspase-1 which also cleaves proIL-1β and proIL-18, precursors of 2 proinflammatory cytokines. In this study we were therefore interested in whether SPI-1-encoded type III secretion system (T3SS) may influence proinflammatory response of macrophages. To test this hypothesis, we infected primary porcine alveolar macrophages with wild-type S. Typhimurium and S. Enteritidis and their isogenic SPI-1 deletion mutants. ΔSPI1 mutants of both serovars invaded approx. 5 times less efficiently than the wild-type strains and despite this, macrophages responded to the infection with ΔSPI1 mutants by increased expression of proinflammatory cytokines IL-1β, IL-8, TNFα, IL-23α and GM-CSF. Identical macrophage responses to that induced by the ΔSPI1 mutants were also observed to the infection with sipB but not the sipA mutant. The hilA mutant exhibited an intermediate phenotype between the ΔSPI1 mutant and the wild-type S. Enteritidis. Our results showed that the SPI-1-encoded T3SS is required not only for cell invasion but in macrophages also for the suppression of early proinflammatory cytokine expression.
Macrophage colony-stimulating factor and its receptor signaling augment glycated albumin-induced retinal microglial inflammation in vitro
Authors: Liu Wei , Xu Ge Z , Jiang Chun H , Tian Jie 
Published: January 2011

Abstract

Background
Microglial activation and the proinflammatory response are controlled by a complex regulatory network. Among the various candidates, macrophage colony-stimulating factor (M-CSF) is considered an important cytokine. The up-regulation of M-CSF and its receptor CSF-1R has been reported in brain disease, as well as in diabetic complications; however, the mechanism is unclear. An elevated level of glycated albumin (GA) is a characteristic of diabetes; thus, it may be involved in monocyte/macrophage-associated diabetic complications.

Results
The basal level of expression of M-CSF/CSF-1R was examined in retinal microglial cells in vitro. Immunofluorescence, real-time PCR, immunoprecipitation, and Western blot analyses revealed the up-regulation of CSF-1R in GA-treated microglial cells. We also detected increased expression and release of M-CSF, suggesting that the cytokine is produced by activated microglia via autocrine signaling. Using an enzyme-linked immunosorbent assay, we found that GA affects microglial activation by stimulating the release of tumor necrosis factor-α and interleukin-1β. Furthermore, the neutralization of M-CSF or CSF-1R with antibodies suppressed the proinflammatory response. Conversely, this proinflammatory response was augmented by the administration of M-CSF.

Conclusions
We conclude that GA induces microglial activation via the release of proinflammatory cytokines, which may contribute to the inflammatory pathogenesis of diabetic retinopathy. The increased microglial expression of M-CSF/CSF-1R not only is a response to microglial activation in diabetic retinopathy but also augments the microglial inflammation responsible for the diabetic microenvironment.
Lineage-specific evolution of the vertebrate Otopetringene family revealed by comparative genomic analyses
Authors: Hurle Belen , Marques-Bonet Tomas , Antonacci Francesca , Hughes Inna , Ryan Joseph F ,   NISC Comparative Sequencing Program, Eichler Evan E , Ornitz David M , Green Eric D 
Published: January 2011

Abstract

Background
Mutations in the Otopetrin 1 gene (Otop1) in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP) family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence- and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH) subtype 1G (Ush1g), both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes.

Results
We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF), a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq) data in mouse and human embryonic stem (ES) cells combined with detection of CTCF-binding motifs.

Conclusions
The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s) of Ush1g and Otop in developmental pathways.
Comprehensive prediction of chromosome dimer resolution sites in bacterial genomes
Authors: Kono Nobuaki , Arakawa Kazuharu , Tomita Masaru 
Published: January 2011

Abstract

Background
During the replication process of bacteria with circular chromosomes, an odd number of homologous recombination events results in concatenated dimer chromosomes that cannot be partitioned into daughter cells. However, many bacteria harbor a conserved dimer resolution machinery consisting of one or two tyrosine recombinases, XerC and XerD, and their 28-bp target site, dif.

Results
To study the evolution of the dif/ XerCD system and its relationship with replication termination, we report the comprehensive prediction of dif sequences in silico using a phylogenetic prediction approach based on iterated hidden Markov modeling. Using this method, dif sites were identified in 641 organisms among 16 phyla, with a 97.64% identification rate for single-chromosome strains. The dif sequence positions were shown to be strongly correlated with the GC skew shift-point that is induced by replicational mutation/selection pressures, but the difference in the positions of the predicted dif sites and the GC skew shift-points did not correlate with the degree of replicational mutation/selection pressures.

Conclusions
The sequence of dif sites is widely conserved among many bacterial phyla, and they can be computationally identified using our method. The lack of correlation between dif position and the degree of GC skew suggests that replication termination does not occur strictly at dif sites.