bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion tensor imaging abnormalities in depressed multiple sclerosis patients
Authors: Feinstein A. , O'Connor P. , Akbar N. , Moradzadeh L. , Scott CJM , Lobaugh NJ
Published: December 2009

Depression is common in patients with multiple sclerosis, but to date no studies have explored diffusion tensor imaging indices associated with mood change. This study aimed to determine cerebral correlates of depression in multiple sclerosis patients using diffusion tensor imaging. Sixty-two subjects with multiple sclerosis were assessed for depression with the Beck Depression Inventory (BDI-II). All subjects underwent magnetic resonance imaging. Whole brain and regional volumes were calculated for lesions (hyper/hypointense) and normal-appearing white and grey matter. Fractional anisotropy and mean diffusivity were calculated for each brain region. Magnetic resonance imaging comparisons were undertaken between depressed (Beck Depression Inventory ≥19) and non-depressed subjects. Depressed subjects (n = 30) had a higher hypointense lesion volume in the right medial inferior frontal region, a smaller normal-appearing white matter volume in the left superior frontal region, and lower fractional anisotropy and higher mean diffusivity in the left anterior temporal normal-appearing white matter and normal-appearing grey matter regions, respectively. Depressed subjects also had higher mean diffusivity in right inferior frontal hyperintense lesions. Magnetic resonance imaging variables contributed to 43% of the depression variance. We conclude that the presence of more marked diffusion tensor imaging abnormalities in the normal-appearing white matter and normal-appearing grey matter of depressed subjects highlights the importance of more subtle measures of structural brain change in the pathogenesis of depression.
Blogging as ‘therapy’? Exploring personal technologies for smoking cessation
Authors: Graham Connor , Rouncefield Mark , Satchell Christine
Published: December 2009

This article presents some early, design-oriented research findings from a study that introduced mobile blogging technologies to four people who wished to make a health-related life change — giving up smoking. We wanted to establish the nature of the relationship between blogging and quitting smoking (if any), inspired by some earlier work in the domain showing that social technologies may help with the quit process. We present an account of three participants, documenting details of how blogging technologies fitted into their (changing) lives and examples of digital content they produced. We describe, using examples from participant blogs, instances of self-expression, replacement and self-awareness. We suggest, despite all participants failing in their quit attempts, that there are possible provisional, therapeutic characteristics to such social technologies. Finally, we suggest this therapeutic process can be understood better through a concept of personal translucence.
Development, implementation and evaluation of an electronic medical record prompt for bone density testing
Authors: Rolnick Sharon J. , Jackson Jody M. , Amundson Jerry H.
Published: December 2009

The purpose of this study was to assess whether an electronic prompt promoting BMD testing affected the proportion of patients who received BMD and/or bone health medication. Rheumatology providers of patients 40+, on prednisone, with no record of BMD testing in the past 2 years, were targeted with the message: ‘This patient is at risk for osteoporosis due to prednisone use. We have no record of a recent Dexa scan.’ We also surveyed providers on the prompt’s value. The use of prednisone remained stable; BMD testing was quite low in all periods but increased slightly (non-statistically) over time, as did bone health medication use. Providers found the prompt not tailored enough to be clinically meaningful. Electronic prompts seem beneficial in theory; however, putting them into practice has challenges. While the EMR has great potential to improve care, more needs to be done to ensure optimal use.
Metal transfer characteristics of rotating arc narrow gap horizontal GMAW
Authors: Guo N. , Lin S. B. , Zhang L. , Yang C. L.
Published: December 2009

The metal transfer process in rotating arc narrow gap horizontal welding is successfully observed by the high speed photography system. Because of the difference of the arc length induced by the molten pool surface shape in the rotating arc horizontal welding, the metal transfer has certain change regularity. In the weld width direction, the transfer frequency in the area of near both sidewalls is larger than that in the centre of the groove. In a rotating period, the transfer frequency in the downward motion process is larger than that in the upward motion process. The rotating arc process can improve the metal transfer. The results indicated that the centrifugal force induced by the arc rotating has great effect on the globular transfer mode which has lower transfer frequency and larger droplet size. Regarding the spray transfer mode, it has limited effect.
Control of weld composition when welding high strength aluminium alloy using the tandem process
Authors: Pickin C. G. , Williams S. W. , Prangnell P. B. , Robson J. , Lunt M.
Published: December 2009

A new cost effective process for generating different weld element compositions has been examined. Utilising tandem welding technology, different series aluminium filler wires were mixed in a single weld pool with the result that the composition of the principal alloy elements, copper and magnesium were accurately controlled. Thermodynamic modelling was then used to predict an optimum weld bead composition for eliminating solidification cracking when welding Al2024. In order to validate the predicted target composition, the tandem process was used to control the composition of the weld bead. The presented results show that using this system to deposit a controlled ternary composition weld, solidification cracking was eliminated when welding highly constrained test pieces. In contrast, cracking was evident when using commercially available binary filler wires under the same conditions.
Tool design and stir zone grain size in AZ31 friction stir spot welds
Authors: Sun N. , Yin Y. H. , Gerlich A. P. , North T. H.
Published: December 2009

The influence of tool design and tool rotational speed variations on the torque, energy output, stir zone temperature and average grain size in the stir zones of AZ31 friction stir spot welds was investigated. The average stir zone grain size decreased by ∼1 μm in AZ31 friction stir spot welds made using a three-flat/threaded tool design and tool rotational speeds of 2250 and 3000 rev min−1. However, there was no statistically significant influence of tool design on the average grain sizes in friction stir spot welds made using tool rotational speeds of 1500 and 1000 rev min−1. There was no evidence of grain growth in the stir zones of AZ31 friction stir spot welds. Similar torque, calculated energy output and stir zone temperature values were found in AZ31 friction stir spot welds made using threaded and three-flat threaded tool designs and tool rotational speeds from 1000 to 3000 rev min−1.
Spatter reduction in gas metal arc welding of stainless steel sheets using controlled bridge transfer process
Authors: Era T. , Ueyama T. , Hirata Y.
Published: December 2009

In non-pulsed gas metal arc welding (GMAW), spatter can be reduced by controlling the short circuit current to a low level just before the re-arcing. The controlled bridge transfer (CBT) process, which optimises the accuracy of predicting the re-arcing in real time in response to the metal transfer, realises stable, low spatter level. In this research, the methods for controlling short circuit transfers to minimise spatter and realise stable arcs in GMAW of stainless sheet using argon rich shielded gases are investigated. The new CBT process has been developed by applying the specific arc length estimation method that is not affected by abnormal rise in arc voltage. This process can suppress the spatter generation caused by a fluctuation in the vibratory motion of the weld pool or inaccurate prediction of the re-arcing in the succeeding short circuit/re-arcing cycle, and thereby spatter free GMAW in the short circuit transfer mode can be carried out even on stainless steels.
Cbfb/Runx1 repression–independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11
Authors: Hyde R. Katherine , Kamikubo Yasuhiko , Anderson Stacie , Kirby Martha , Alemu Lemlem , Zhao Ling , Liu P. Paul
Published: December 2009

It is known that CBFB-MYH11, the fusion gene generated by inversion of chromosome 16 in human acute myeloid leukemia, is causative for oncogenic transformation. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not clear. Previously published reports showed that CBFB-MYH11 dominantly inhibits RUNX1 and CBFB, and such inhibition has been suggested as the mechanism for leukemogenesis. Here we show that Cbfb-MYH11 caused Cbfb/Runx1 repression–independent defects in both primitive and definitive hematopoiesis. During primitive hematopoiesis, Cbfb-MYH11 delayed differentiation characterized by sustained expression of Gata2, Il1rl1, and Csf2rb, a phenotype not found in Cbfb and Runx1 knockout mice. Expression of Cbfb-MYH11 in the bone marrow induced the accumulation of abnormal progenitor-like cells expressing Csf2rb in preleukemic mice. The expression of all 3 genes was detected in most human and murine CBFB-MYH11+ leukemia samples. Interestingly, Cbfb-MYH11+ preleukemic progenitors and leukemia-initiating cells did not express Csf2rb, although the majority of leukemia cells in our Cbfb-MYH11 knockin mice were Csf2rb+. Therefore Csf2rb can be used as a negative selection marker to enrich preleukemic progenitor cells and leukemia-initiating cells from Cbfb-MYH11 mice. These results suggest that Cbfb/Runx1 repression–independent activities contribute to leukemogenesis by Cbfb-MYH11.
Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene
Authors: Paterson Andrew D. , Rommens Johanna M. , Bharaj Bhupinder , Blavignac Jessica , Wong Isidro , Diamandis Maria , Waye John S. , Rivard Georges E. , Hayward Catherine P. M.
Published: December 2009

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder linked to a region on chromosome 10 that includes PLAU, the urokinase plasminogen activator gene. QPD increases urokinase plasminogen activator mRNA levels, particularly during megakaryocyte differentiation, without altering expression of flanking genes. Because PLAU sequence changes were excluded as the cause of this bleeding disorder, we investigated whether the QPD mutation involved PLAU copy number variation. All 38 subjects with QPD had a direct tandem duplication of a 78-kb genomic segment that includes PLAU. This mutation was specific to QPD as it was not present in any unaffected family members (n = 114), unrelated French Canadians (n = 221), or other persons tested (n = 90). This new information on the genetic mutation will facilitate diagnostic testing for QPD and studies of its pathogenesis and prevalence. QPD is the first bleeding disorder to be associated with a gene duplication event and a PLAU mutation.
Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent
Authors: Chiu Hao-Chieh , Soni Shilpa , Kulp Samuel K , Curry Heather , Wang Dasheng , Gunn John S , Schlesinger Larry S , Chen Ching-Shih
Published: December 2009

Background

Autophagy has been shown recently to play an important role in the intracellular survival of several pathogenic bacteria. In this study, we investigated the effect of a novel small-molecule autophagy-inducing agent, AR-12, on the survival of Francisella tularensis, the causative bacterium of tularemia in humans and a potential bioterrorism agent, in macrophages.

Methods and results

Our results show that AR-12 induces autophagy in THP-1 macrophages, as indicated by increased autophagosome formation, and potently inhibits the intracellular survival of F. tularensis (type A strain, Schu S4) and F. novicida in macrophages in association with increased bacterial co-localization with autophagosomes. The effect of AR-12 on intracellular F. novicida was fully reversed in the presence of the autophagy inhibitor, 3-methyl adenine or the lysosome inhibitor, chloroquine. Intracellular F. novicida were not susceptible to the inhibitory activity of AR-12 added at 12 h post-infection in THP-1 macrophages, and this lack of susceptibility was independent of the intracellular location of bacteria.

Conclusion

Together, AR-12 represents a proof-of-principle that intracellular F. tularensis can be eradicated by small-molecule agents that target innate immunity.
Protein-protein docking using region-based 3D Zernike descriptors
Authors: Venkatraman Vishwesh , Yang Yifeng D , Sael Lee , Kihara Daisuke
Published: December 2009

Background

Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur.

Results

We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-α RMSD ≤ 2.5 Å) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases.

Conclusion

We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods.
RFX2 is a candidate downstream amplifier of A-MYB regulation in mouse spermatogenesis
Authors: Horvath Gary C , Kistler Malathi K , Kistler W Stephen
Published: December 2009

Background

Mammalian spermatogenesis involves formation of haploid cells from the male germline and then a complex morphological transformation to generate motile sperm. Focusing on meiotic prophase, some tissue-specific transcription factors are known (A-MYB) or suspected (RFX2) to play important roles in modulating gene expression in pachytene spermatocytes. The current work was initiated to identify both downstream and upstream regulatory connections forRfx2.

Results

Searches of pachytene up-regulated genes identified high affinity RFX binding sites (X boxes) in promoter regions of several new genes:Adam5,Pdcl2, andSpag6. We confirmed a strong promoter-region X-box forAlf, a germ cell-specific variant of general transcription factor TFIIA. UsingAlfas an example of a target gene, we showed that its promoter is stimulated by RFX2 in transfected cells and used ChIP analysis to show that the promoter is occupied by RFX2 in vivo. Turning to upstream regulation of theRfx2promoter, we identified a cluster of three binding sites (MBS) for the MYB family of transcription factors. Because testis is one of the few sites ofA-mybexpression, and because spermatogenesis arrests in pachytene inA-mybknockout mice, the MBS cluster implicatesRfx2as anA-mybtarget. Electrophoretic gel-shift, ChIP, and co-transfection assays all support a role for these MYB sites inRfx2expression. Further,Rfx2expression was virtually eliminated inA-mybknockout testes. Immunohistology on testis sections showed that A-MYB expression is up-regulated only after pachytene spermatocytes have clearly moved away from the tubule wall, which correlates with onset of RFX2 expression, whereas B-MYB expression, by contrast, is prevalent only in earlier spermatocytes and spermatogonia.

Conclusion

With an expanding list of likely target genes, RFX2 is potentially an important transcriptional regulator in pachytene spermatocytes.Rfx2itself is a good candidate to be regulated by A-MYB, which is essential for meiotic progression. IfAlfis a genuine RFX2 target, thenA-myb,Rfx2, andAlfmay form part of a transcriptional network that is vital for completion of meiosis and preparation for post-meiotic differentiation.
Expansion of tandem repeats in sea anemone Nematostella vectensis proteome: A source for gene novelty?
Authors: Naamati Guy , Fromer Menachem , Linial Michal
Published: December 2009

Background

The complete proteome of the starlet sea anemone, Nematostella vectensis, provides insights into gene invention dating back to the Cnidarian-Bilaterian ancestor. With the addition of the complete proteomes of Hydra magnipapillata and Monosiga brevicollis, the investigation of proteins having unique features in early metazoan life has become practical. We focused on the properties and the evolutionary trends of tandem repeat (TR) sequences in Cnidaria proteomes.

Results

We found that 11-16% of N. vectensis proteins contain tandem repeats. Most TRs cover 150 amino acid segments that are comprised of basic units of 5-20 amino acids. In total, the N. Vectensis proteome has about 3300 unique TR-units, but only a small fraction of them are shared with H. magnipapillata, M. brevicollis, or mammalian proteomes. The overall abundance of these TRs stands out relative to that of 14 proteomes representing the diversity among eukaryotes and within the metazoan world. TR-units are characterized by a unique composition of amino acids, with cysteine and histidine being over-represented. Structurally, most TR-segments are associated with coiled and disordered regions. Interestingly, 80% of the TR-segments can be read in more than one open reading frame. For over 100 of them, translation of the alternative frames would result in long proteins. Most domain families that are characterized as repeats in eukaryotes are found in the TR-proteomes from Nematostella and Hydra.

Conclusions

While most TR-proteins have originated from prediction tools and are still awaiting experimental validations, supportive evidence exists for hundreds of TR-units in Nematostella. The existence of TR-proteins in early metazoan life may have served as a robust mode for novel genes with previously overlooked structural and functional characteristics.
Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation
Authors: Schmeier Sebastian , MacPherson Cameron R , Essack Magbubah , Kaur Mandeep , Schaefer Ulf , Suzuki Harukazu , Hayashizaki Yoshihide , Bajic Vladimir B
Published: December 2009

Background

Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation.

Results

We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF→miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF→miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation.

Conclusions

The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process.
Inactivation of the fliY gene encoding a flagellar motor switch protein attenuates mobility and virulence of Leptospira interrogansstrain Lai
Authors: Liao Sumei , Sun Aihua , Ojcius David M , Wu Senlin , Zhao Jinfang , Yan Jie
Published: December 2009

Background

Pathogenic Leptospira species cause leptospirosis, a zoonotic disease of global importance. The spirochete displays active rotative mobility which may contribute to invasion and diffusion of the pathogen in hosts. FliY is a flagellar motor switch protein that controls flagellar motor direction in other microbes, but its role in Leptospira, and paricularly in pathogenicity remains unknown.

Results

A suicide plasmid for the fliY gene of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai that was disrupted by inserting the ampicillin resistance gene (bla) was constructed, and the inactivation of fliY gene in a mutant (fliY
-) was confirmed by PCR and Western Blot analysis. The inactivation resulted in the mRNA absence of fliP and fliQ genes which are located downstream of the fliY gene in the same operon. The mutant displayed visibly weakened rotative motion in liquid medium and its migration on semisolid medium was also markedly attenuated compared to the wild-type strain. Compared to the wild-type strain, the mutant showed much lower levels of adhesion to murine macrophages and apoptosis-inducing ability, and its lethality to guinea pigs was also significantly decreased.

Conclusion

Inactivation of fliY, by the method used in this paper, clearly had polar effects on downstream genes. The phentotypes observed, including lower pathogenicity, could be a consequence of fliY inactivation, but also a consequence of the polar effects.
The common FTOvariant rs9939609 is not associated with BMI in a longitudinal study on a cohort of Swedish men born 1920-1924
Authors: Jacobsson Josefin A , Risérus Ulf , Axelsson Tomas , Lannfelt Lars , Schiöth Helgi B , Fredriksson Robert
Published: December 2009

Background

Common FTO (fat mass and obesity associated) gene variants have recently been strongly associated with body mass index and obesity in several large studies. Here we set out to examine the association of the FTO variant rs9939609 with BMI in a 32 year follow up study of men born 1920-1924. Moreover, we analyzed the effect of physical activity on the different genotypes.

Methods

The FTO rs9936609 was genotyped using an Illumina golden gate assay. BMI was calculated using standard methods and body fat was estimated by measuring skinfold thickness using a Harpenden caliper. Physical activity was assessed using a four question medical questionnaire.

Results

FTO rs9939609 was genotyped in 1153 elderly Swedish men taking part of a population-based cohort study, the ULSAM cohort. The risk of obesity and differences in BMI according to genotype at the ages of 50, 60, 70, 77 and 82 were investigated. We found no increased risk of obesity and no association with BMI at any age with the FTO rs9939609 variant. We found however interaction between physical activity at the age of 50 years and genotype on BMI levels (p = 0.039) and there was a clear trend towards larger BMI differences between the TT and AA carriers as well as between AT and AA carriers in the less physically active subjects.

Conclusion

Here we found that the well established obesity risk allele for a common variant in FTO does not associate with increased BMI levels in a Swedish population of adult men which reached adulthood before the appearance of today's obesogenic enviroment. There is an interaction between physical activity and the effect of the FTO genotype on BMI levels suggesting that lack of physical activity is a requirement for an association of FTO gene variants to obesity.
Association of ADAM33 gene polymorphisms with COPD in a northeastern Chinese population
Authors: Wang Xinyan , Li Lei , Xiao Jinling , Jin Chengzhen , Huang Kun , Kang Xiaowen , Wu Xiaomei , Lv Fuzhen
Published: December 2009

Background

Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma since its first association with the disease in Caucasian populations. Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD. The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and COPD in a Han population in northeastern China.

Methods

A total of 312 COPD patients and a control group of 319 healthy volunteers were recruited for this study. Eight polymorphic loci (V4, T+1, T2, T1, S2, S1, Q-1, and F+1) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

Statistically significant differences in the distributions of the T2G, T1G, S2C, and Q-1G alleles between patients and controls were observed (P< 0.001, odds ratio (OR) = 2.81, 95% confidence interval (CI) = 2.19-3.61;P< 0.001, OR = 2.60, 95% CI = 2.06-3.30;P= 0.03, OR = 1.31, 95% CI = 1.02-1.69; andP< 0.001, OR = 1.93, 95% CI = 1.50-2.50, respectively). Haplotype analysis showed that the frequencies of the CGGGGAGC, CGGGGAGT, CGGGCAGC, and CGGGGGGC haplotypes were significantly higher in the case group than in the control group (P= 0.0002, 0.0001, 0.0005, and 0.0074, respectively). In contrast, the haplotype CGAAGAGC was more common in the control group than in the case group (P< 0.0001).

Conclusion

These preliminary results suggest an association between ADAM33 polymorphisms and COPD in a Chinese Han population.
Synthesis and expression of CDw75 antigen in human colorectal cancer
Authors: Costa-Nogueira Clotilde , Villar-Portela Susana , Cuevas Elisa , Gil-Martín Emilio , Fernández-Briera Almudena
Published: December 2009

Background

Increased ST6Gal I activity has been associated with the α(2,6)sialylation enhancement of membrane glycoconjugates observed in metastatic colorectal carcinomas (CRC). Siaα(2,6)Galβ(1,4)GlcNAc sequence, known as CDw75, is a sialylated carbohydrate determinant generated by the ST6Gal I. This epitope has been reported to be associated with the progression of gastric and colorectal tumours, hence there are only a few conclusive studies to date.

Methods

By radioisotopic techniques we evaluated the ST6Gal I activity in healthy, transitional and tumour tissues from 43 patients with CRC. By immunohistochemistry we assessed the CDw75 expression in 25 colorectal adenomas, 43 tumours, 13 transitional and 28 healthy tissues of CRC patients.

Results

ST6Gal I activity was likewise found to be statistically higher in tumour tissue respect to healthy tissue from CRC patients. CDw75 expression was positive in 20% of colorectal adenomas. Furthermore, 70% of tumour specimens and 8.3% of transitional specimens were positive for CDw75 expression, whereas none of the healthy ones showed the presence of the epitope.

Conclusion

The major contribution of this study is the inclusion of data from transitional tissue and the analysis of CDw75 antigen expression in CRC and in colorectal adenomas, little known so far. ST6Gal I activity and CDw75 antigen expression were increased in CRC. Although their comparison did not reach the statistical significance, a great extent of patients showed both, an enhanced tumour ST6Gal I activity and an increased CDw75 expression in the tumour tissue. So, these two variables may play a role in malignant transformation. The expression of CDw75 in colorectal adenomas suggests that this antigen may be a tumour marker in CRC.
The effectiveness of health coaching, home blood pressure monitoring, and home-titration in controlling hypertension among low-income patients: protocol for a randomized controlled trial
Authors: Bennett Heather , Laird Kelsey , Margolius David , Ngo Victoria , Thom David H , Bodenheimer Thomas
Published: December 2009

Background

Despite the many antihypertensive medications available, two-thirds of patients with hypertension do not achieve blood pressure control. This is thought to be due to a combination of poor patient education, poor medication adherence, and "clinical inertia." The present trial evaluates an intervention consisting of health coaching, home blood pressure monitoring, and home medication titration as a method to address these three causes of poor hypertension control.

Methods/Design

The randomized controlled trial will include 300 patients with poorly controlled hypertension. Participants will be recruited from a primary care clinic in a teaching hospital that primarily serves low-income populations.

An intervention group of 150 participants will receive health coaching, home blood pressure monitoring, and home-titration of antihypertensive medications during 6 months. The control group (n = 150) will receive health coaching plus home blood pressure monitoring for the same duration. A passive control group will receive usual care. Blood pressure measurements will take place at baseline, and after 6 and 12 months. The primary outcome will be change in systolic blood pressure after 6 and 12 months. Secondary outcomes measured will be change in diastolic blood pressure, adverse events, and patient and provider satisfaction.

Discussion

The present study is designed to assess whether the 3-pronged approach of health coaching, home blood pressure monitoring, and home medication titration can successfully improve blood pressure, and if so, whether this effect persists beyond the period of the intervention.

Trial Registration

ClinicalTrials.gov identifier: NCT01013857
Researching the mental health needs of hard-to-reach groups: managing multiple sources of evidence
Authors: Dowrick Christopher , Gask Linda , Edwards Suzanne , Aseem Saadia , Bower Peter , Burroughs Heather , Catlin Amy , Chew-Graham Carolyn , Clarke Pam , Gabbay Mark , Gowers Simon , Hibbert Derek , Kovandzic Marija , Lamb Jonathan , Lovell Karina , Rogers Anne , Lloyd-Williams Mari , Waheed Waquas ,   the AMP Group
Published: December 2009

Background

Common mental health problems impose substantial challenges to patients, carers, and health care systems. A range of interventions have demonstrable efficacy in improving the lives of people experiencing such problems. However many people are disadvantaged, either because they are unable to access primary care, or because access does not lead to adequate help. New methods are needed to understand the problems of access and generate solutions. In this paper we describe our methodological approach to managing multiple and diverse sources of evidence, within a research programme to increase equity of access to high quality mental health services in primary care.

Methods

We began with a scoping review to identify the range and extent of relevant published material, and establish key concepts related to access. We then devised a strategy to collect - in parallel - evidence from six separate sources: a systematic review of published quantitative data on access-related studies; a meta-synthesis of published qualitative data on patient perspectives; dialogues with local stakeholders; a review of grey literature from statutory and voluntary service providers; secondary analysis of patient transcripts from previous qualitative studies; and primary data from interviews with service users and carers.

We synthesised the findings from these diverse sources, made judgements on key emerging issues in relation to needs and services, and proposed a range of potential interventions. These proposals were debated and refined using iterative electronic and focus group consultation procedures involving international experts, local stakeholders and service users.

Conclusions

Our methods break new ground by generating and synthesising multiple sources of evidence, connecting scientific understanding with the perspectives of users, in order to develop innovative ways to meet the mental health needs of under-served groups.
Macromolecular and elemental composition analysis and extracellular metabolite balances of Pichia pastoris growing at different oxygen levels
Authors: Carnicer Marc , Baumann Kristin , Töplitz Isabelle , Sánchez-Ferrando Francesc , Mattanovich Diethard , Ferrer Pau , Albiol Joan
Published: December 2009

Background

Analysis of the cell operation at the metabolic level requires collecting data of different types and to determine their confidence level. In addition, the acquired information has to be combined in order to obtain a consistent operational view. In the case ofPichia pastoris, information of its biomass composition at macromolecular and elemental level is scarce particularly when different environmental conditions, such as oxygen availability or, genetic backgrounds (e.g. recombinant protein productionvs. non production conditions) are compared.

Results

P. pastoriscells growing in carbon-limited chemostat cultures under different oxygenation conditions (% O2in the bioreactor inlet gas: 21%, 11% and 8%, corresponding to normoxic, oxygen-limiting and hypoxic conditions, respectively), as well as under recombinant protein (antibody fragment, Fab) producing and non-producing conditions, were analyzed from different points of view. On the one hand, the macromolecular and elemental composition of the biomass was measured using different techniques at the different experimental conditions and proper reconciliation techniques were applied for gross error detection of the measured substrates and products conversion rates. On the other hand, fermentation data was analyzed applying elemental mass balances. This allowed detecting a previously missed by-product secreted under hypoxic conditions, identified as arabinitol (aka. arabitol). After identification of this C5 sugar alcohol as a fermentation by-product, the mass balances of the fermentation experiments were validated.

Conclusions

After application of a range of analytical and statistical techniques, a consistent view of growth parameters and compositional data ofP. pastoriscells growing under different oxygenation conditions was obtained. The obtained data provides a first view of the effects of oxygen limitation on the physiology of this microorganism, while recombinant Fab production seems to have little or no impact at this level of analysis. Furthermore, the results will be highly useful in other complementary quantitative studies ofP. pastorisphysiology, such as metabolic flux analysis.
Transforming growth factor-beta inhibits aromatase gene transcription in human trophoblast cells via the Smad2 signaling pathway
Authors: Zhou Hong , Fu Guodong , Yu Hui , Peng Chun
Published: December 2009

Background

Transforming growth factor-beta (TGF-beta) is known to exert multiple regulatory functions in the human placenta, including inhibition of estrodial production. We have previously reported that TGF-beta1 decreased aromatase mRNA levels in human trophoblast cells. The objective of this study was to investigate the molecular mechanisms underlying the regulatory effect of TGF-beta1 on aromatase expression.

Methods

To determine if TGF-beta regulates aromatase gene transcription, several reporter constructs containing different lengths of the placental specific promoter of the human aromatase gene were generated. JEG-3 cells were transiently transfected with a promoter construct and treated with or without TGF-beta1. The promoter activity was measured by luciferase assays. To examine the downstream signaling molecule mediating the effect of TGF-beta on aromatase transcription, cells were transiently transfected with dominant negative mutants of TGF-beta type II (TbetaRII) and type I receptor (ALK5) receptors before TGF-beta treatment. Smad2 activation was assessed by measuring phophorylated Smad2 protein levels in cytosolic and nuclear fractions. Smad2 expression was silenced using a siRNA expression construct. Finally, aromatase mRNA half-life was determined by treating cells with actinomycin D together with TGF-beta1 and measuring aromatase mRNA levels at various time points after treatment.

Results and Discussion

TGF-beta1 inhibited the aromatase promoter activity in a time- and dose-dependent manner. Deletion analysis suggests that the TGF-β1 response element resides between -422 and -117 nucleotides upstream from the transcription start site where a Smad binding element was found. The inhibitory effect of TGF-beta1 was blocked by dominant negative mutants of TbetaRII and ALK5. TGF-beta1 treatment induced Smad2 phosphorylation and translocation into the nucleus. On the other hand, knockdown of Smad2 expression reversed the inhibitory effect of TGF-beta1 on aroamtase transcription. Furthermore, TGF-beta1 accelerated the degradation of aromatase mRNA.

Conclusion

Our results demonstrate that TGF-beta1 exerts regulatory effects on aromatase gene at both transcriptional and post-transcriptional levels. The transcriptional regulation of aromatase gene by TGF-beta1 is mediated by the canonical TGF-beta pathway involving TbetaRII, ALK5 and Smad2. These findings further support the role of TGF-beta1 in regulating human placental functions and pregnancy.
Seven mistakes and potential solutions in epidemiology, including a call for a World Council of Epidemiology and Causality
Authors: Bhopal Raj
Published: December 2009

All sciences make mistakes, and epidemiology is no exception. I have chosen 7 illustrative mistakes and derived 7 solutions to avoid them. The mistakes (Roman numerals denoting solutions) are:

Failing to provide the context and definitions of study populations. (I Describe the study population in detail)

Insufficient attention to evaluation of error. (II Don't pretend error does not exist.)

Not demonstrating comparisons are like-for-like. (III Start with detailed comparisons of groups.)

Either overstatement or understatement of the case for causality. (IV Never say this design cannot contribute to causality or imply causality is ensured by your design.)

Not providing both absolute and relative summary measures. (V Give numbers, rates and comparative measures, and adjust summary measures such as odds ratios appropriately.)

In intervention studies not demonstrating general health benefits. (VI Ensure general benefits (mortality/morbidity) before recommending application of cause-specific findings.)

Failure to utilise study data to benefit populations. (VII Establish a World Council on Epidemiology to help infer causality from associations and apply the work internationally.)

Analysis of these and other common mistakes is needed to benefit from the increasing discovery of associations that will be multiplying as data mining, linkage, and large-scale scale epidemiology become commonplace.
The effects of HIF-1alpha on gene expression profiles of NCI-H446 human small cell lung cancer cells
Authors: Wan Jun , Ma Jinben , Mei Ju , Shan Genfa
Published: December 2009

Background

Gene targeted therapy refers to any therapy focused on one of the many biological features of the tumor. Such features are mediated by specific genes that are involved in tumor metastasis, recurrence, poor response to chemotherapy and others. Hypoxia is an important pathognomonic feature of many malignant tumors including SCLC (small cell lung cancer). HIF-1alpha, which is induced by hypoxia, is the most important regulatory factor of many specific genes that can influence the biological features of tumors.

Methods

In this study, we tried to elucidate the changes in gene expression profiles of SCLC NCI-H446 cells mediated by HIF-1alpha. According to different treatments of cells, three experimental pairwise comparisons were designed: hypoxia group vs. control group, Ad5-HIF-1alpha group vs. Ad5 group, and Ad5-siHIF-1 alpha group Vs Ad5 group.

Results

Results from the analysis of gene expression profiles indicated that there were 65 genes upregulated and 28 genes downregulated more than two-fold in all three experimental pairwise comparisons. These genes were involved in transport, signal-transduction, cell adhesion/motility, growth factor/cytokines, transcription, inflammatory response, metabolic process, in addition to others. SOCS1, IGFBP5, IL-6 and STAT3 were also upregulated at protein level. SOCS1 could significantly induce apoptosis and suppress growth of NCI-H446 cells but HIF-1alpha could induce growth and suppress apoptosis.

Conclusions

Through this research, we are trying to find novel functional genes that are mediated by HIF-1alpha and provide the theoretical basis for new therapeutic targets. HIF-1 alpha maybe upregulate the expression of SOCS1 through mediation of STAT3 and IL-6. In addition, SOCS1 could significantly induce apoptosis and suppress growth of NCI-H446 cells. This was contrary to HIF-1alpha and it indicated that there might be an antagonism effect between HIF-1alpha and SOCS1 on regulating growth and apoptosis of NCI-H446 cells.
Acute interstitial nephritis during rifampicin therapy can be a paradoxical response: a case report
Authors: van der Meulen Jan , de Jong Gijs MT , Westenend Pieter J
Published: December 2009

An 18-year-old Ethiopian woman presented with debilitating back pain and high fever. X-ray examinations showed diffuse pulmonary tuberculosis and a psoas abscess. After starting rifampicin, isoniazid, ethambutol and pyrazinamide, acute interstitial nephritis developed that spontaneously recovered. According to Harrison's Online rifampicin should have been causative, but the spontaneous recovery excluded that possibility. The clinical course fit the diagnosis of a paradoxical response, for which recently risk factors have been described. Thus, a paradoxical response should be added to the list of causes of interstitial nephritis in tuberculosis patients and in such cases rifampicin could be continued.
Normalization of systemic arterial hypertension following removal of posterior fossa hemangioblastoma: a case report
Authors: Saberi Hooshang , Meybodi Ali Tayebi , Zeinalizadeh Mehdi
Published: December 2009

The concept of compression of the rostral ventrolateral medulla as a cause for hypertension is gaining more and more interest. This report is about a 36-year-old male with a three years history of hypertension who presented with a posterior fossa mass suggestive of a hemangioblastoma. Laboratory and imaging studies ruled out the presence of von Hippel-Lindau disease and/or concomitant pheochromocytoma. Post-surgical blood pressure monitoring revealed a 40 mmHg decline in blood pressure. It could be hypothesized that alleviation the compressive effect of the tumour on the rostral ventrolateral medulla as proposed by previous studies could be a contributing factor.
Recessive congenital myotonia resulting from maternal isodisomy of chromosome 7: a case report
Authors: Bulli Cristina , Battistella Pier Antonio , Bordignon Marta , Bramanti Placido , Novelli Giuseppe , Sangiuolo Federica
Published: December 2009

Autosomal dominant (Thomsen) and recessive (Becker) congenital myotonia are two different non dystrophic disorders, due to allelic mutations of the muscle chloride channel gene, located on chromosome 7q35. More than two thirds of the muscle chloride channel gene mutations occur independently in unique families and cause the recessive form of the disease. Becker disease is more common and severe than Thomsen disease. Here, we report on the clinical and molecular data of the first patient with maternal uniparental disomy for chromosome 7 and recessive congenital myotonia. The proband is a 15-year-old male, homozygous for a missense mutation within muscle chloride channel gene, showing few characteristic signs of the Silver Russell Syndrome.
Resistance exercise training lowers HbA1c more than aerobic training in adults with type 2 diabetes
Authors: Bweir Salameh , Al-Jarrah Muhammed , Almalty Abdul-Majeed , Maayah Mikhled , Smirnova Irina V , Novikova Lesya , Stehno-Bittel Lisa
Published: December 2009

Background

The aim of this study was to compare the effects of 10 weeks of resistance or treadmill exercises on glycemic indices levels prior to and immediately following exercise in adults with type 2 diabetes.

Research Design and Method

Twenty inactive subjects (mean age 53.5 years) with type 2 diabetes enrolled in the study. Baseline HbA1c, blood glucose levels, heart rate, and blood pressure were measured for each subject prior to the initiation of the exercise program. Subsequently, subjects were matched to age, waist circumference and sex and assigned to either isocaloric resistance or treadmill exercise groups, which met 3 times per week for 10 weeks.

Results

Both groups showed a reduction in pre and post-exercise blood glucose and HbA1c values. There was no change in resting blood pressure or heart rate in either group during the course of the 10 week intervention. The group receiving resistance exercises showed significant differences in the daily pre-exercise plasma glucose readings between the beginning and end of the exercise protocol (p < 0.001). There were significant improvements in the mean HbA1c reading pre and post training in both groups (p < 0.001). However, the greater reduction was noted in the resistance exercise group, and at 10 weeks their HbA1c levels were significantly lower than the group that received treadmill exercises (p < 0.006).

Conclusion

Ten weeks of resistance exercises were associated with a significantly better glycemic control in adults with type 2 diabetes compared to treadmill exercise.