bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants
Authors: Sadakata Tetsushi , Washida Miwa , Furuichi Teiichi 
Published: May 2007

Abstract

Background
Ca2+-dependent activator protein 2 (CAPS2/CADPS2) is a secretory vesicle-associated protein involved in the release of neurotrophin. We recently reported that an aberrant, alternatively spliced CAPS2 mRNA that lacks exon 3 (CAPS2Δexon3) is detected in some patients with autism. Splicing variations in mouse CAPS2 and their expression and functions remain unclear.

Results
In this study, we defined 31 exons in the mouse CAPS2 gene and identified six alternative splicing variants, CAPS2a-f. CAPS2a is an isoform lacking exons 22 and 25, which encode part of the Munc13-1-homologous domain (MHD). CAPS2b lacks exon 25. CAPS2c lacks exons 11 and 22. CAPS2d, 2e, and 2f have C-terminal deletions from exon 14, exon 12, and exon 5, respectively. On the other hand, a mouse counterpart of CAPS2Δexon3 was not detected in the mouse tissues tested. CAPS2b was expressed exclusively in the brain, and the other isoforms were highly expressed in the brain, but also in some non-neural tissues. In the brain, all isoforms showed predominant expression patterns in the cerebellum. In the developing cerebellum, CAPS2b showed an up-regulated expression pattern, whereas the other isoforms exhibited transiently peaked expression patterns. CAPS2 proteins were mostly recovered in soluble fractions, but some were present in membrane fractions, except for CAPS2c and 2f, both of which lack the PH domain, suggesting that the PH domain is important for membrane association. In contrast to CAPS2a and 2b, CAPS2c showed slightly decreased BDNF-releasing activity, which is likely due to the C-terminal truncation of the PH domain in CAPS2c.

Conclusion
This study indicates that, in mouse, there are six splicing variants of CAPS2 (CAPS2a-f), and that these are subdivided into two groups: a long form containing the C-terminal MHD and a short form lacking the C-terminal MHD. These results demonstrate that the splicing variations correlate with their expression patterns and intracellular distribution, and affect BDNF release; however, whether or not the short forms possess activities other than BDNF release, for example as natural dominant-negative isoforms, remains to be determined.
Clofibrate treatment in pigs: Effects on parameters critical with respect to peroxisome proliferator-induced hepatocarcinogenesis in rodents
Authors: Luci Sebastian , Giemsa Beatrice , Hause Gerd , Kluge Holger , Eder Klaus 
Published: May 2007

Abstract

Background
In rodents treatment with fibrates causes hepatocarcinogenesis, probably as a result of oxidative stress and an impaired balance between apoptosis and cell proliferation in the liver. There is some debate whether fibrates could also induce liver cancer in species not responsive to peroxisome proliferation. In this study the effect of clofibrate treatment on peroxisome proliferation, production of oxidative stress, gene expression of pro- and anti-apoptotic genes and proto-oncogenes was investigated in the liver of pigs, a non-proliferating species.

Results
Pigs treated with clofibrate had heavier livers (+16%), higher peroxisome counts (+61%), higher mRNA concentration of acyl-CoA oxidase (+66%), a higher activity of catalase (+41%) but lower concentrations of hydrogen peroxide (-32%) in the liver than control pigs (P < 0.05); concentrations of lipid peroxidation products (thiobarbituric acid-reactive substances, conjugated dienes) and total and reduced glutathione in the liver did not differ between both groups. Clofibrate treated pigs also had higher hepatic mRNA concentrations of bax and the proto-oncogenes c-myc and c-jun and a lower mRNA concentration of bcl-XL than control pigs (P < 0.05).

Conclusion
The data of this study show that clofibrate treatment induces moderate peroxisome proliferation but does not cause oxidative stress in the liver of pigs. Gene expression analysis indicates that clofibrate treatment did not inhibit but rather stimulated apoptosis in the liver of these animals. It is also shown that clofibrate increases the expression of the proto-oncogenes c-myc and c-jun in the liver, an event which could be critical with respect to carcinogenesis. As the extent of peroxisome proliferation by clofibrate was similar to that observed in humans, the pig can be regarded as a useful model for investigating the effects of peroxisome proliferators on liver function and hepatocarcinogenesis.
Isolation and functional characterization of a cDNA coding a hydroxycinnamoyltransferase involved in phenylpropanoid biosynthesis in Cynara cardunculus L
Authors: Comino Cinzia , Lanteri Sergio , Portis Ezio , Acquadro Alberto , Romani Annalisa , Hehn Alain , Larbat Romain , Bourgaud Frédéric 
Published: May 2007

Abstract

Background

Cynara cardunculus L. is an edible plant of pharmaceutical interest, in particular with respect to the polyphenolic content of its leaves. It includes three taxa: globe artichoke, cultivated cardoon, and wild cardoon. The dominating phenolics are the di-caffeoylquinic acids (such as cynarin), which are largely restricted to Cynara species, along with their precursor, chlorogenic acid (CGA). The scope of this study is to better understand CGA synthesis in this plant.

Results
A gene sequence encoding a hydroxycinnamoyltransferase (HCT) involved in the synthesis of CGA, was identified. Isolation of the gene sequence was achieved by using a PCR strategy with degenerated primers targeted to conserved regions of orthologous HCT sequences available. We have isolated a 717 bp cDNA which shares 84% aminoacid identity and 92% similarity with a tobacco gene responsible for the biosynthesis of CGA from p-coumaroyl-CoA and quinic acid. In silico studies revealed the globe artichoke HCT sequence clustering with one of the main acyltransferase groups (i.e. anthranilate N-hydroxycinnamoyl/benzoyltransferase). Heterologous expression of the full length HCT (GenBank accession DQ104740) cDNA in E. coli demonstrated that the recombinant enzyme efficiently synthesizes both chlorogenic acid and p-coumaroyl quinate from quinic acid and caffeoyl-CoA or p-coumaroyl-CoA, respectively, confirming its identity as a hydroxycinnamoyl-CoA: quinate HCT. Variable levels of HCT expression were shown among wild and cultivated forms of C. cardunculus subspecies. The level of expression was correlated with CGA content.

Conclusion
The data support the predicted involvement of the Cynara cardunculus HCT in the biosynthesis of CGA before and/or after the hydroxylation step of hydroxycinnamoyl esters.
Conifer R2R3-MYB transcription factors: sequence analyses and gene expression in wood-forming tissues of white spruce (Picea glauca)
Authors: Bedon Frank , Grima-Pettenati Jacqueline , Mackay John 
Published: May 2007

Abstract

Background
Several members of the R2R3-MYB family of transcription factors act as regulators of lignin and phenylpropanoid metabolism during wood formation in angiosperm and gymnosperm plants. The angiosperm Arabidopsis has over one hundred R2R3-MYBs genes; however, only a few members of this family have been discovered in gymnosperms.

Results
We isolated and characterised full-length cDNAs encoding R2R3-MYB genes from the gymnosperms white spruce, Picea glauca (13 sequences), and loblolly pine, Pinus taeda L. (five sequences). Sequence similarities and phylogenetic analyses placed the spruce and pine sequences in diverse subgroups of the large R2R3-MYB family, although several of the sequences clustered closely together. We searched the highly variable C-terminal region of diverse plant MYBs for conserved amino acid sequences and identified 20 motifs in the spruce MYBs, nine of which have not previously been reported and three of which are specific to conifers. The number and length of the introns in spruce MYB genes varied significantly, but their positions were well conserved relative to angiosperm MYB genes. Quantitative RTPCR of MYB genes transcript abundance in root and stem tissues revealed diverse expression patterns; three MYB genes were preferentially expressed in secondary xylem, whereas others were preferentially expressed in phloem or were ubiquitous. The MYB genes expressed in xylem, and three others, were up-regulated in the compression wood of leaning trees within 76 hours of induction.

Conclusion
Our survey of 18 conifer R2R3-MYB genes clearly showed a gene family structure similar to that of Arabidopsis. Three of the sequences are likely to play a role in lignin metabolism and/or wood formation in gymnosperm trees, including a close homolog of the loblolly pine PtMYB4, shown to regulate lignin biosynthesis in transgenic tobacco.
Impact of AtNHX1, a vacuolar Na+/H+ antiporter, upon gene expression during short- and long-term salt stress in Arabidopsis thaliana
Authors: Sottosanto Jordan B , Saranga Yehoshua , Blumwald Eduardo 
Published: May 2007

Abstract

Background
AtNHX1, the most abundant vacuolar Na+/H+ antiporter in Arabidopsis thaliana, mediates the transport of Na+ and K+ into the vacuole, influencing plant development and contributing to salt tolerance. In this report, microarray expression profiles of wild type plants, a T-DNA insertion knockout mutant of AtNHX1 (nhx1), and a 'rescued' line (NHX1::nhx1) were exposed to both short (12 h and 48 h) and long (one and two weeks) durations of a non-lethal salt stress to identify key gene transcripts associated with the salt response that are influenced by AtNHX1.

Results
147 transcripts showed both salt responsiveness and a significant influence of AtNHX1. Fifty-seven of these genes showed an influence of the antiporter across all salt treatments, while the remaining genes were influenced as a result of a particular duration of salt stress. Most (69%) of the genes were up-regulated in the absence of AtNHX1, with the exception of transcripts encoding proteins involved with metabolic and energy processes that were mostly down-regulated.

Conclusion
While part of the AtNHX1-influenced transcripts were unclassified, other transcripts with known or putative roles showed the importance of AtNHX1 to key cellular processes that were not necessarily limited to the salt stress response; namely calcium signaling, sulfur metabolism, cell structure and cell growth, as well as vesicular trafficking and protein processing. Only a small number of other salt-responsive membrane transporter transcripts appeared significantly influenced by AtNHX1.
Discovery of chemically induced mutations in rice by TILLING
Authors: Till Bradley J , Cooper Jennifer , Tai Thomas H , Colowit Peter , Greene Elizabeth A , Henikoff Steven , Comai Luca 
Published: May 2007

Abstract

Background
Rice is both a food source for a majority of the world's population and an important model system. Available functional genomics resources include targeted insertion mutagenesis and transgenic tools. While these can be powerful, a non-transgenic, unbiased targeted mutagenesis method that can generate a range of allele types would add considerably to the analysis of the rice genome. TILLING (Targeting Induced Local Lesions in Genomes), a general reverse genetic technique that combines traditional mutagenesis with high throughput methods for mutation discovery, is such a method.

Results
To apply TILLING to rice, we developed two mutagenized rice populations. One population was developed by treatment with the chemical mutagen ethyl methanesulphonate (EMS), and the other with a combination of sodium azide plus methyl-nitrosourea (Az-MNU). To find induced mutations, target regions of 0.7–1.5 kilobases were PCR amplified using gene specific primers labeled with fluorescent dyes. Heteroduplexes were formed through denaturation and annealing of PCR products, mismatches digested with a crude preparation of CEL I nuclease and cleaved fragments visualized using denaturing polyacrylamide gel electrophoresis. In 10 target genes screened, we identified 27 nucleotide changes in the EMS-treated population and 30 in the Az-MNU population.

Conclusion
We estimate that the density of induced mutations is two- to threefold higher than previously reported rice populations (about 1/300 kb). By comparison to other plants used in public TILLING services, we conclude that the populations described here would be suitable for use in a large scale TILLING project.
Chinese and white Canadian satisfaction and compliance with physicians
Authors: Liu Richard , So Lawrence , Quan Hude 
Published: May 2007

Abstract

Background
Patient satisfaction has become an important indicator of primary care and healthcare system performance. Ethnic disparities in patient satisfaction and compliance with physician care have been studied in several countries. However, this issue has not received significant attention in Canada. The unique characteristics of the Canadian healthcare system and ethnic population make it worthwhile to examine this issue in this population. Therefore, we conducted a survey among Chinese and Whites in a Canadian city to determine their reported satisfaction, and perceptions of physicians.

Methods
The survey was conducted in English, Mandarin and Cantonese in 2005 among Chinese and White Canadians, 18 years of age or older, who had visited at least one physician in Canada.

Results
We analyzed 746 Chinese and 711 Whites in the general practitioner (GP) visit group and 485 Chinese and 637 Whites in the specialist visit group. A lower proportion of Chinese compared to Whites reported that they were very satisfied or satisfied with GP (73.7% vs. 92.8%) and specialist care (75.5% vs. 85.6%) and the differences between the two groups remained after adjustment for demographic variables and chronic conditions (risk adjusted OR: 0.70, 95%CI: 0.42–1.18 for the GP visit group and OR: 0.77, 95%CI: 0.48–1.23 for the specialist visit group). A similar proportion of Chinese and Whites reported that they always followed a physician's advice (59.4% vs. 59.6% for the GP visit group and 67.2% vs. 62.8% for the specialist visit group). Non-English speaking Chinese and recent arrivals in Canada were less likely to be satisfied with GPs than Chinese born in Canada [risk adjusted OR: 0.5, 95%CI: 0.3–0.9, 0.2 and 0.1–0.7, respectively].

Conclusion
Chinese Canadians reported lower satisfaction with physicians and perceived physicians slightly more negatively than White Canadians. Particularly, Chinese with limited English and short length of stay in Canada were less satisfied than Canadian born Chinese.
Sex- and age-dependent association of SLC11A1polymorphisms with tuberculosis in Chinese: a case control study
Authors: Leung Kim Hung , Yip Shea Ping , Wong Wa Sang , Yiu Lap San , Chan Kam Keung , Lai Wai Man , Chow Eudora YD , Lin Che Kit , Yam Wing Cheong , Chan Kin Sang 
Published: May 2007

AbstractBackgroundHost genetic factors are important determinants in tuberculosis (TB). TheSLC11A1(orNRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship betweenSLC11A1polymorphisms and TB.MethodsA case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers fromSLC11A1and one from the nearbyIL8RBlocus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products.ResultsStatistically significant differences in allele (P= 0.0165, OR = 1.51) and genotype (P= 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of theSLC11A1locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P= 0.0049, OR = 2.54) and genotype (P= 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P= 0.0047, OR = 2.52) and genotype (P= 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (oneSLC11A1marker and oneIL8RBmarker) either.ConclusionThis study confirmed the association betweenSLC11A1and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.
Empirical use of antibiotics and adjustment of empirical antibiotic therapies in a university hospital: a prospective observational study
Authors: Mettler Julian , Simcock Mathew , Sendi Pedram , Widmer Andreas F , Bingisser Roland , Battegay Manuel , Fluckiger Ursula , Bassetti Stefano 
Published: May 2007

Abstract

Background
Several strategies to optimise the use of antibiotics have been developed. Most of these interventions can be classified as educational or restrictive. Restrictive measures are considered to be more effective, but the enforcement of these measures may be difficult and lead to conflicts with prescribers. Any intervention should be aimed at targets with the highest impact on antibiotic prescribing. The aim of the present study was to assess the adequacy of empirical and adjusted antibiotic therapies in a Swiss university hospital where no antibiotic use restrictions are enforced, and to identify risk factors for inadequate treatment and targets for intervention.

Methods
A prospective observational study was performed during 9 months. All patients admitted through the emergency department who received an antibiotic therapy within 24 hours of admission were included. Data on demographic characteristics, diagnoses, comorbidities, systemic inflammatory response syndrome (SIRS) parameters, microbiological tests, and administered antibiotics were collected prospectively. Antibiotic therapy was considered adequate if spectrum, dose, application modus, and duration of therapy were appropriate according to local recommendations or published guidelines.

Results
2943 admitted patients were evaluated. Of these, 572 (19.4%) received antibiotics within 24 hours and 539 (94%) were analysed in detail. Empirical antibiotic therapy was inadequate in 121 patients (22%). Initial therapy was adjusted in 168 patients (31%). This adjusted antibiotic therapy was inadequate in 46 patients (27%). The main reason for inadequacy was the use of antibiotics with unnecessarily broad spectrum (24% of inadequate empirical, and 52% of inadequate adjusted therapies). In 26% of patients with inadequate adjusted therapy, antibiotics used were either ineffective against isolated pathogenic bacteria or antibiotic therapy was continued despite negative results of microbiological investigations.

Conclusion
The rate of inadequate antibiotic therapies was similar to the rates reported from other institutions despite the absence of a restrictive antibiotic policy. Surprisingly, adjusted antibiotic therapies were more frequently inappropriate than empirical therapies. Interventions aiming at improving antibiotic prescribing should focus on both initial empirical therapy and streamlining and adjustment of therapy once microbiological results become available.
Trends of Hepatitis A hospitalization and risk factors in Quebec, Canada, between 1990 and 2003
Authors: Canuel Magalie , De Serres Gaston , Duval Bernard , Gilca Rodica , De Wals Philippe , Gilca Vladimir 
Published: May 2007

Abstract

Background
In Canada, targeted vaccination of at risk groups for hepatitis A (HA) is done since the mid 1990s resulting in declining incidence. This study estimated the year and age specific hospitalization rates and distribution of risk factors for HA in Quebec, Canada, between 1990 and 2003.

Methods
Records of patients hospitalized with HA-related diagnostic codes were retrieved from the provincial database. Hospital charts of all deceased cases and a random sample of all other records were reviewed.

Results
From 1503 hospitalization records, 573 charts were reviewed including 49 (91%) of the 54 deceased patients. Confirmed acute HA was present in 79% of records where HA was the primary diagnosis, and in 3%–8% of records where HA was a secondary diagnosis. From the total estimated number of hospitalizations, 96% had HA as the primary diagnosis. The hospitalization rate decreased from 1.06 per 100 000 person-years between 1990 and 1997 to 0.36 between 1998 and 2003. During the study period, 54% HA hospitalizations were in 20–39 year-olds. The overall case fatality ratio among hospitalized patients was 1.4%, increasing from 0.4% in those < 40 years old to 12.5% in those ≥60 years. By decreasing order, reported risk factors were travel to HA endemic countries (30%), MSM (18%) and household contacts (11%).

Conclusion
HA hospitalization rates have been low since 1998 but the cause of this is unclear given the cyclical pattern of HA. Travel to endemic countries remains the most important risk factor and improved control of HA will require better strategies to vaccinate travelers.
Analysis of meiotic recombination in 22q11.2, a region that frequently undergoes deletions and duplications
Authors: Torres-Juan Laura , Rosell Jordi , Sánchez-de-la-Torre Manuel , Fibla Joan , Heine-Suñer Damià 
Published: May 2007

Abstract

Background
The 22q11.2 deletion syndrome is the most frequent genomic disorder with an estimated frequency of 1/4000 live births. The majority of patients (90%) have the same deletion of 3 Mb (Typically Deleted Region, TDR) that results from aberrant recombination at meiosis between region specific low-copy repeats (LCRs).

Methods
As a first step towards the characterization of recombination rates and breakpoints within the 22q11.2 region we have constructed a high resolution recombination breakpoint map based on pedigree analysis and a population-based historical recombination map based on LD analysis.

Results
Our pedigree map allows the location of recombination breakpoints with a high resolution (potential recombination hotspots), and this approach has led to the identification of 5 breakpoint segments of 50 kb or less (8.6 kb the smallest), that coincide with historical hotspots. It has been suggested that aberrant recombination leading to deletion (and duplication) is caused by low rates of Allelic Homologous Recombination (AHR) within the affected region. However, recombination rate estimates for 22q11.2 region show that neither average recombination rates in the 22q11.2 region or within LCR22-2 (the LCR implicated in most deletions and duplications), are significantly below chromosome 22 averages. Furthermore, LCR22-2, the repeat most frequently implicated in rearrangements, is also the LCR22 with the highest levels of AHR. In addition, we find recombination events in the 22q11.2 region to cluster within families. Within this context, the same chromosome recombines twice in one family; first by AHR and in the next generation by NAHR resulting in an individual affected with the del22q11.2 syndrome.

Conclusion
We show in the context of a first high resolution pedigree map of the 22q11.2 region that NAHR within LCR22 leading to duplications and deletions cannot be explained exclusively under a hypothesis of low AHR rates. In addition, we find that AHR recombination events cluster within families. If normal and aberrant recombination are mechanistically related, the fact that LCR22s undergo frequent AHR and that we find familial differences in recombination rates within the 22q11.2 region would have obvious health-related implications.