bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity of recombinant Mycobacterium bovis bacille Calmette–Guèrin clones expressing T and B cell epitopes of Mycobacterium tuberculosis antigens
Authors: Mohamud Rohimah , Azlan Maryam , Yero Daniel , Alvarez Nadine , Sarmiento Maria E , Acosta Armando , Norazmi Mohd-Nor 
Published: February 2013

Abstract
Recombinant Mycobacterium bovis bacille Calmette–Guèrin (rBCG) expressing three T cell epitopes of Mycobacterium tuberculosis (MTB) Ag85B antigen (P1, P2, P3) fused to the Mtb8.4 protein (rBCG018) or a combination of these antigens fused to B cell epitopes from ESAT-6, CFP-10 and MTP40 proteins (rBCG032) were used to immunize Balb/c mice. Total IgG responses were determined against Mtb8.4 antigen and ESAT-6 and CFP-10 B cell epitopes after immunization with rBCG032. Mice immunized with rBCG032 showed a significant increase in IgG1 and IgG2a antibodies against ESAT-6 and MTP40 (P1) B cell epitopes and IgG3 against both P1 and P2 B cell epitopes of MPT40. Splenocytes from mice immunized with rBCG018 proliferated against Ag85B P2 and P3 T cell epitopes and Mtb8.4 protein whereas those from mice-immunized with rBCG032 responded against all Ag85B epitopes and the ESAT-6 B cell epitope. CD4+ and CD8+ lymphocytes from mice immunized with rBCG018 produced primarily Th1 type cytokines in response to the T cell epitopes. Similar pattern of recognition against the T cell epitopes were obtained with rBCG032 with the additional recognition of ESAT-6, CFP-10 and one of the MTP40 B cell epitopes with the same pattern of cytokines. This study demonstrates that rBCG constructs expressing either T or T and B cell epitopes of MTB induced appropriate immunogenicity against MTB.
A re-evaluation of the scratch test for locating the liver edge
Authors: Gupta Krishan , Dhawan Akash , Abel Christian , Talley Nicholas , Attia John 
Published: February 2013

Abstract

Background
A reliable and accurate estimation of liver size by physical examination is an important aspect of the clinical assessment of a patient. The scratch test uses auscultation to detect the lower liver edge by using the difference in sound transmission through the abdominal cavity over solid and hollow organs. The test is thought to be particularly useful if the abdomen is tense, distended, obese, or very tender. Although the sign is often taught to medical students and residents, the value of the technique for detecting the liver edge has become controversial.

Methods
The study was performed in two parts. In the first part, 18 patients undergoing upper abdominal ultrasound as outpatients were randomly selected and the scratch test was performed by two raters independently, followed by ultrasound (USG) as the reference standard. In the second part of the study, the two raters independently performed the scratch test on separate randomly selected patients (15 patients by rater 1, and 16 patients by rater 2), followed by USG.

Results
Agreement between raters on the scratch test was very high, with an intra-class correlation coefficient of 0.97. The agreement between the raters and the USG was 0.37 using Spearman’s rho. A Bland –Altman plot indicated that, on average, raters underestimated the distance from the right costal margin to the liver edge by only about 2.4 centimeters compared to USG. This translates into 37% and 54% of raters’ estimates falling within 2 and 3 cm of USG estimates. Each unit increase in BMI increased the discrepancy between raters and USG by 0.26 cm (p = 0.012).

Conclusion
The scratch test has very high reproducibility and overall agreement between the scratch test and USG was moderate, with a spearman’s rho of 0.37. The accuracy may potentially be improved by using the point of initial sound transmission rather than the point of maximal transmission. We conclude that the scratch test deserves further investigation.
E-cadherin gene re-expression in chronic lymphocytic leukemia cells by HDAC inhibitors
Authors: Jordaan Gwen , Liao Wei , Sharma Sanjai 
Published: February 2013

Abstract

Background
The tumor suppressor gene E-cadherin gene is frequently silenced in chronic lymphocytic leukemia (CLL) cells and results in wnt-pathway activation. We analyzed the role of histone epigenetic modifications in E-cadherin gene silencing.

Methods
CLL specimens were treated with histone deacetylase inhibitor (HDACi) MS-275 and analyzed for E-cadherin expression with western blot and RT-PCR analysis. The downstream effects of HDACi treated leukemic cells were studied by analyzing the effect on wnt-pathway signaling. HDACi induced alterations in E-cadherin splicing were investigated by transcript specific real time PCR analysis.

Results
Treatment of CLL specimens with histone deacetylase inhibitors (HDACi) treatment resulted in an increase of the E-cadherin RNA transcript (5 to 119 fold increase, n=10) in eight out of ten CLL specimens indicating that this gene is down regulated by histone hypoacetylation in a majority of CLL specimens. The E-cadherin re-expression in CLL specimens was noted by western blot analysis as well. Besides epigenetic silencing another mechanism of E-cadherin inactivation is aberrant exon 11 splicing resulting in an alternatively spliced transcript that lacks exon 11 and is degraded by the non-sense mediated decay (NMD) pathway. Our chromatin immunoprecipitation experiments show that HDACi increased the acetylation of histones H3 and H4 in the E-cadherin promoter region. This also affected the E-cadherin exon 11 splicing pattern as HDACi treated CLL specimens preferentially expressed the correctly spliced transcript and not the exon 11 skipped aberrant transcript. The re-expressed E- cadherin binds to β-catenin with inhibition of the active wnt-beta-catenin pathway in these cells. This resulted in a down regulation of two wnt target genes, LEF and cyclinD1 and the wnt pathway reporter.

Conclusion
The E-cadherin gene is epigenetically modified and hypoacetylated in CLL leukemic cells. Treatment of CLL specimens with HDACi MS-275 activates transcription from this silent gene with expression of more correctly spliced E-cadherin transcripts as compared to the aberrant exon11 skipped transcripts that in turn inhibits the wnt signaling pathway. The data highlights the role of epigenetic modifications in altering gene splicing patterns.
Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells
Authors: Lin Chia-Han , Lu Wei-Cheng , Wang Che-Wei , Chan Ya-Chi , Chen Mu-Kuan 
Published: February 2013

Abstract

Background
Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin.

Methods
The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting.

Results
We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells.

Conclusions
Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.
Computer game-based and traditional learning method: a comparison regarding students’ knowledge retention
Authors: Rondon Silmara , Sassi Fernanda Chiarion , Furquim de Andrade Claudia Regina 
Published: February 2013

AbstractBackgroundEducational computer games are examples of computer-assisted learning objects, representing an educational strategy of growing interest. Given the changes in the digital world over the last decades, students of the current generation expect technology to be used in advancing their learning requiring a need to change traditional passive learning methodologies to an active multisensory experimental learning methodology. The objective of this study was to compare a computer game-based learning method with a traditional learning method, regarding learning gains and knowledge retention, as means of teaching head and neck Anatomy and Physiology to Speech-Language and Hearing pathology undergraduate students.MethodsStudents were randomized to participate to one of the learning methods and the data analyst was blinded to which method of learning the students had received. Students’ prior knowledge (i.e. before undergoing the learning method), short-term knowledge retention and long-term knowledge retention (i.e. six months after undergoing the learning method) were assessed with a multiple choice questionnaire. Students’ performance was compared considering the three moments of assessment for both for the mean total score and for separated mean scores for Anatomy questions and for Physiology questions.ResultsStudents that received the game-based method performed better in the pos-test assessment only when considering the Anatomy questions section. Students that received the traditional lecture performed better in both post-test and long-term post-test when considering the Anatomy and Physiology questions.ConclusionsThe game-based learning method is comparable to the traditional learning method in general and in short-term gains, while the traditional lecture still seems to be more effective to improve students’ short and long-term knowledge retention.
A gasless laparoscopic technique of wide excision for gastric gastrointestinal stromal tumor versus open method
Authors: Lee Po-Chu , Lai Peng-Sheng , Yang Ching-Yao , Chen Chiung-Nien , Lai I-Rue , Lin Ming-Tsan 
Published: February 2013

AbstractBackgroundTraditional open surgery for gastrointestinal stromal tumors (GIST) requires a long incision. Moreover, the gas-filling laparoscopic technique used in GIST surgery still has its limitations. Therefore, we developed a gasless laparoscopic (GL) surgery for GIST and compared it with traditional open surgery.MethodsBetween October 2007 and September 2009, 62 GIST patients in the National Taiwan University Hospital received wide excisions. Of these 62 patients, 30 underwent the new procedure (GL group) and 32 had open surgery (OS group). Preoperative and postoperative clinicopathologic characteristics were compared between the groups.ResultsThere were no significant differences in preoperative characteristics or blood loss. However, the days to first flatus, postoperative hospital stay, wound length, white blood cell count at postoperative day one, and peak daily body temperature were all significantly improved in the GL group. Usage of postoperative analgesia on postoperative days one to five was also significantly lower in the GL group.ConclusionsWide-excision laparoscopy for gastric GIST can be performed more safely, more effectively, and with faster postoperative recovery using the gasless technique as compared with the open method. We, therefore, recommend this new surgical technique, which hybridizes the advantages of both the traditional open method and pure laparoscopic surgery.
Differences in wage rates for males and females in the health sector: a consideration of unpaid overtime to decompose the gender wage gap
Authors: Vecchio Nerina , Scuffham Paul A , Hilton Michael F , Whiteford Harvey A 
Published: February 2013

Abstract

Background
In Australia a persistent and sizable gender wage gap exists. In recent years this gap has been steadily widening. The negative impact of gender wage differentials is the disincentive to work more hours. This implies a substantial cost on the Australian health sector. This study aimed to identify the magnitude of gender wage differentials within the health sector. The investigation accounts for unpaid overtime. Given the limited availability of information, little empirical evidence exists that accounts for unpaid overtime.

Methods
Information was collected from a sample of 10,066 Australian full-time employees within the health sector. Initially, ordinary least-squares regression was used to identify the gender wage gap when unpaid overtime was included and then excluded from the model. The sample was also stratified by gender and then by occupation to allow for comparisons. Later the Blinder–Oaxaca decomposition method was employed to identify and quantify the contribution of individual endowments to wage differentials between males and females.

Results
The analyses of data revealed a gender wage gap that varied across occupations. The inclusion of unpaid overtime in the analysis led to a slight reduction in the wage differential. The results showed an adjusted wage gap of 16.7%.

Conclusions
Unpaid overtime made a significant but small contribution to wage differentials. Being female remained the major contributing factor to the wage gap. Given that wage differentials provide a disincentive to work more hours, serious attempts to deal with the skilled labour shortage in the health sector need to address the gender wage gap.
Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats
Authors: de Moura Leandro Pereira , Souza Pauli Luciana Santos , Cintra Dennys Esper , de Souza Claudio Teodoro , da Silva Adelino Sanchez Ramos , Marinho Rodolfo , de Melo Maria Alice Rostom , Ropelle Eduardo Rochete , Pauli José Rodrigo 
Published: February 2013

Abstract
It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging.
Protein Structure Idealization: How accurately is it possible to model protein structures with dihedral angles?
Authors: Cui Xuefeng , Li Shuai Cheng , Bu Dongbo , Alipanahi Babak , Li Ming 
Published: February 2013

AbstractBackgroundPrevious studies show that the same type of bond lengths and angles fit Gaussian distributions well with small standard deviations on high resolution protein structure data. The mean values of these Gaussian distributions have been widely used as ideal bond lengths and angles in bioinformatics. However, we are not aware of any research done to evaluate how accurately we can model protein structures with dihedral angles and ideal bond lengths and angles.Here, we introduce the protein structure idealization problem. We focus on the protein backbone structure idealization. We describe a fastO(nm/ε) dynamic programming algorithm to find an idealized protein backbone structure that is approximately optimal according to our scoring function. The scoring function evaluates not only the free energy, but also the similarity with the target structure. Thus, the idealized protein structures found by our algorithm are guaranteed to be protein-like and close to the target protein structure.We have implemented our protein structure idealization algorithm and idealized the high resolution protein structures with low sequence identities of the CULLPDB_PC30_RES1.6_R0.25 data set. We demonstrate that idealized backbone structures always exist with small changes and significantly better free energy. We also applied our algorithm to refine protein pseudo-structures determined in NMR experiments.
Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers
Authors: Li Xinyuan , Fang Pu , Mai Jietang , Choi Eric T , Wang Hong , Yang Xiao-feng 
Published: February 2013

Abstract
There are multiple sources of reactive oxygen species (ROS) in the cell. As a major site of ROS production, mitochondria have drawn considerable interest because it was recently discovered that mitochondrial ROS (mtROS) directly stimulate the production of proinflammatory cytokines and pathological conditions as diverse as malignancies, autoimmune diseases, and cardiovascular diseases all share common phenotype of increased mtROS production above basal levels. Several excellent reviews on this topic have been published, but ever-changing new discoveries mandated a more up-to-date and comprehensive review on this topic. Therefore, we update recent understanding of how mitochondria generate and regulate the production of mtROS and the function of mtROS both in physiological and pathological conditions. In addition, we describe newly developed methods to probe or scavenge mtROS and compare these methods in detail. Thorough understanding of this topic and the application of mtROS-targeting drugs in the research is significant towards development of better therapies to combat inflammatory diseases and inflammatory malignancies.
Laser Doppler Vibrometry measurements of human cadaveric tympanic membrane vibration
Authors: Beyea Jason A , Rohani Seyed Alireza , Ladak Hanif M , Agrawal Sumit K 
Published: February 2013

Objective To determine the feasibility of measuring tympanic membrane (TM) vibrations at multiple locations on the TM to differentiate normal eardrums from those with associated ossicular pathologies. Design Cadaveric human temporal bone study. Setting Basic science laboratory. Methods A mastoidectomy and facial recess approach was performed on four cadaveric temporal bones to obtain access to the ossicles without disrupting the TM. Ossicles were palpated to ensure normal mobility and an intact ossicular chain. Laser Doppler Vibrometry (LDV) measurements were then taken on all four TMs. LDV measurements were repeated on each TM following stapes footplate fixation, incudo-stapedial joint dislocation, and malleus head fixation. Main outcome measures LDV measurements of TM vibration at the umbo, the lateral process of the malleus, and in each of the four quadrants of the TM. Results The best signal-to-noise ratios were found between 2 and 4 kHz, at the umbo, the anterior superior quadrant, the anterior inferior quadrant, and the posterior inferior quadrant. Since our goal was to assess the ossicular chain, we selected the TM locations closest to the ossicular chain (the umbo and lateral process of the malleus) for further analysis. Differences could be seen between normals and the simulated ossicular pathologies, but values were not statistically significant. Conclusions LDV measurements are technically challenging and require optimization to obtain consistent measurements. This study demonstrates the potential of LDV to differentiate ossicular pathologies behind an intact tympanic membrane. Future studies will further characterize the clinical role of this diagnostic modality.
Resolving the spatial relationship between intracellular components by dual color super resolution optical fluctuations imaging (SOFI)
Authors: Gallina Maria Elena , Xu Jianmin , Dertinger Thomas , Aizer Adva , Shav-Tal Yaron , Weiss Shimon 
Published: February 2013

Abstract

Background
Multi-color super-resolution (SR) imaging microscopy techniques can resolve ultrastructural relationships between- and provide co-localization information of- different proteins inside the cell or even within organelles at a higher resolution than afforded by conventional diffraction-limited imaging. While still very challenging, important SR colocalization results have been reported in recent years using STED, PALM and STORM techniques.

Results
In this work, we demonstrate dual-color Super Resolution Optical Fluctuations Imaging (SOFI) using a standard far-field fluorescence microscope and different color blinking quantum dots. We define the spatial relationship between hDcp1a, a processing body (P-body, PB) protein, and the tubulin cytoskeletal network. Our finding could open up new perspectives on the role of the cytoskeleton in PB formation and assembly. Further insights into PB internal organization are also reported and discussed.

Conclusions
Our results demonstrate the suitability and facile use of multi-color SOFI for the investigation of intracellular ultrastructures.
The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila
Authors: Kockmann Tobias , Gerstung Moritz , Schlumpf Tommy , Xhinzhou Zhu , Hess Daniel , Beerenwinkel Niko , Beisel Christian , Paro Renato 
Published: February 2013

Abstract
Background
The question of how cells re-establish gene expression states after cell division is still poorly understood. Genetic and molecular analyses have indicated that Trithorax group (TrxG) proteins are critical for the long-term maintenance of active gene expression states in many organisms. A generally accepted model suggests that TrxG proteins contribute to maintenance of transcription by protecting genes from inappropriate Polycomb group (PcG)-mediated silencing, instead of directly promoting transcription.

Results and discussion
Here we report a physical and functional interaction in Drosophila between two members of the TrxG, the histone methyltransferase ASH1 and the bromodomain and extraterminal family protein FSH. We investigated this interface at the genome level, uncovering a widespread co-localization of both proteins at promoters and PcG-bound intergenic elements. Our integrative analysis of chromatin maps and gene expression profiles revealed that the observed ASH1-FSH binding pattern at promoters is a hallmark of active genes. Inhibition of FSH-binding to chromatin resulted in global down-regulation of transcription. In addition, we found that genes displaying marks of robust PcG-mediated repression also have ASH1 and FSH bound to their promoters.

Conclusions
Our data strongly favor a global coactivator function of ASH1 and FSH during transcription, as opposed to the notion that TrxG proteins impede inappropriate PcG-mediated silencing, but are dispensable elsewhere. Instead, our results suggest that PcG repression needs to overcome the transcription-promoting function of ASH1 and FSH in order to silence genes.