bluuebunny/crossref_metadata_2025 huggingface dataset:
“Advertise in the Chippy”
Authors: Ellis Naomi , Gidlow Christopher , Davey Rachel
Published: June 2011

Background. To maximize often limited resources for health promotion interventions, it is critical to identify and consult with the target population to inform program design and implementation. Objective. To highlight the value of scoping (identifying any barriers or limitations within a target population group) in the initial social marketing phase of targeting physical activity interventions for positive mental health. Method. Semistructured focus groups were undertaken in 2 segmented population groups: Study 1—adults (aged between 20 and 50 years) from a deprived community; Study 2—older adults (50+ years of age) attending physical activity groups. Discussions centered on health, mental health, physical activity, and methods of promotion. Results. Five focus groups were conducted, 2 in study 1 (n = 17; age 38.1 ± 10.8 years) and 3 in study 2 (n = 25; age 68.1 ± 5.6 years). Themes and perspectives were consistent within each case study, but differed between them, indicating that basic segmentation during recruitment (by age, area of residence, and physical activity participation) had identified 2 distinct audience segments. Differences between groups in perceived benefits of physical activity, preferred intervention type, and appropriate terminology provided valuable insight to inform physical activity promotion. Conclusion. Focus groups offer a simple and feasible means of scoping to begin to identify and understand population segments for targeting of health promotion efforts.
Crisis Planning and Preparedness in the United States Tourism Industry
Authors: Pennington-Gray Lori , Thapa Brijesh , Kaplanidou Kyriaki , Cahyanto Ignatius , McLaughlin Elaine
Published: June 2011

An empirical exploration of disaster planning and preparedness for the industry finds a reasonably high level of planning, with noteworthy weaknesses. Based on 155 telephone interviews with tourism leaders from three industry segments (namely, lodging, attractions, and promotions), the majority of organizations surveyed had a written crisis preparedness plan which was updated regularly—often annually. Most organizations had direct communication arrangements with local emergency preparedness agencies, but connections with national agencies, notably the Federal Emergency Management Agency, were less frequent. Given that many respondents were in destinations with many visitors (in this case, Florida), perhaps most troublesome finding was the relatively low percentage of written plans addressing procedures for visitors—mentioned by barely half of the respondents—and the relatively low participation in central relocation systems—again, just half of respondents. Overall, resource allocation had a greater impact on whether an organization would engage in crisis planning and communication procedures than did crisis experience.
Modelling of hybrid laser–GMA welding: Review and challenges
Authors: Rao Z H , Liao S M , Tsai H L
Published: June 2011

Hybrid welding, which is the integration of laser beam welding (LBW) and gas metal arc welding (GMAW), may minimise the disadvantages while retaining the advantages for each of the two welding technologies and, hence, has recently received increasing interest in the welding industry. However, the hybrid welding involves very complex transport phenomena which are inherited from each of LBW and GMAW and their interactions. The development of hybrid welding has been based on the trial and error procedure and so far rather limited numerical modelling on hybrid welding is available. This paper presents an up to date literature review on modelling of the hybrid welding including LBW and GMAW. Issues and challenges for a comprehensive hybrid welding model are discussed. With the advances of numerical techniques and computers, a comprehensive hybrid welding model can be developed as a useful tool for determining key process parameters and helping the elimination/reduction of possible weld defects.
MicroRNA29a regulates the expression of the nuclear oncogene Ski
Authors: Teichler Sabine , Illmer Thomas , Roemhild Josephine , Ovcharenko Dmitriy , Stiewe Thorsten , Neubauer Andreas
Published: June 2011

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate growth and differentiation. miRNAs are frequently located at cancer-specific fragile sites in the human genome, such as chromosome 7q. The nuclear oncogene SKI is up-regulated in acute myeloid leukemia (AML) with −7/del7q. Here we asked whether loss of miRNAs on chromosome 7q may explain this up-regulation. miR-29a expression was found to be down-regulated in AML with −7/del7q. Forced expression of miR-29a down-regulated Ski and its target gene, Nr-CAM, whereas miR-29a inhibition induced Ski expression. Luciferase assays validated a functional binding site for miR-29a in the 3′ untranslated region of SKI. Finally, in samples of AML patients, we observed an inverse correlation of Ski and miR-29a expression, respectively. In conclusion, up-regulation of Ski in AML with −7/del7q is caused by loss of miR-29a. miR-29a may therefore function as an important tumor suppressor in AML by restraining expression of the SKI oncogene.
Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia
Authors: Simonsson Bengt , Gedde-Dahl Tobias , Markevärn Berit , Remes Kari , Stentoft Jesper , Almqvist Anders , Björeman Mats , Flogegård Max , Koskenvesa Perttu , Lindblom Anders , Malm Claes , Mustjoki Satu , Myhr-Eriksson Kristina , Ohm Lotta , Räsänen Anu , Sinisalo Marjatta , Själander Anders , Strömberg Ulla , Bjerrum Ole Weiss , Ehrencrona Hans , Gruber Franz , Kairisto Veli , Olsson Karin , Sandin Fredrik , Nagler Arnon , Nielsen Johan Lanng , Hjorth-Hansen Henrik , Porkka Kimmo ,   for the Nordic CML Study Group
Published: June 2011

Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg–IFN-α2b) 50 μg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg–IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg–IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg–IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg–IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg–IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
Fibrinogen β–derived Bβ15-42 peptide protects against kidney ischemia/ reperfusion injury
Authors: Krishnamoorthy Aparna , Ajay Amrendra Kumar , Hoffmann Dana , Kim Tae-Min , Ramirez Victoria , Campanholle Gabriela , Bobadilla Norma A. , Waikar Sushrut S. , Vaidya Vishal S.
Published: June 2011

Ischemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)α, Fgβ, and Fgγ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fgα and Fgγ chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fgβ chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n = 25) from healthy volunteers (n = 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate that Fgβ-derived Bβ15-42 peptide administration protects mice from I/R-induced kidney injury by aiding in epithelial cell proliferation and tissue repair. Given that kidney regeneration is a major determinant of outcome for patients with kidney damage, these results provide new opportunities for the use of Fg in diagnosis, prevention, and therapeutic interventions in kidney disease.
Immunohistochemical detection and regulation of α5nicotinic acetylcholine receptor (nAChR) subunits by FoxA2 during mouse lung organogenesis
Authors: Porter Jason L , Bukey Benjamin R , Geyer Alex J , Willnauer Charles P , Reynolds Paul R
Published: June 2011

Background

α5 nicotinic acetylcholine receptor (nAChR) subunits structurally stabilize functional nAChRs in many non-neuronal tissue types. The expression of α5 nAChR subunits and cell-specific markers were assessed during lung morphogenesis by co-localizing immunohistochemistry from embryonic day (E) 13.5 to post natal day (PN) 20. Transcriptional control of α5 nAChR expression by FoxA2 and GATA-6 was determined by reporter gene assays.

Results

Steady expression of α5 nAChR subunits was observed in distal lung epithelial cells during development while proximal lung expression significantly alternates between abundant prenatal expression, absence at PN4 and PN10, and a return to intense expression at PN20. α5 expression was most abundant on luminal edges of alveolar type (AT) I and ATII cells, non-ciliated Clara cells, and ciliated cells in the proximal lung at various periods of lung formation. Expression of α5 nAChR subunits correlated with cell differentiation and reporter gene assays suggest expression of α5 is regulated in part by FoxA2, with possible cooperation by GATA-6.

Conclusions

Our data reveal a highly regulated temporal-spatial pattern of α5 nAChR subunit expression during important periods of lung morphogenesis. Due to specific regulation by FoxA2 and distinct identification of α5 in alveolar epithelium and Clara cells, future studies may identify possible mechanisms of cell differentiation and lung homeostasis mediated at least in part by α5-containing nAChRs.
In-silico prediction of disorder content using hybrid sequence representation
Authors: Mizianty Marcin J , Zhang Tuo , Xue Bin , Zhou Yaoqi , Dunker A Keith , Uversky Vladimir N , Kurgan Lukasz
Published: June 2011

Background

Intrinsically disordered proteins play important roles in various cellular activities and their prevalence was implicated in a number of human diseases. The knowledge of the content of the intrinsic disorder in proteins is useful for a variety of studies including estimation of the abundance of disorder in protein families, classes, and complete proteomes, and for the analysis of disorder-related protein functions. The above investigations currently utilize the disorder content derived from the per-residue disorder predictions. We show that these predictions may over-or under-predict the overall amount of disorder, which motivates development of novel tools for direct and accurate sequence-based prediction of the disorder content.

Results

We hypothesize that sequence-level aggregation of input information may provide more accurate content prediction when compared with the content extracted from the local window-based residue-level disorder predictors. We propose a novel predictor, DisCon, that takes advantage of a small set of 29 custom-designed descriptors that aggregate and hybridize information concerning sequence, evolutionary profiles, and predicted secondary structure, solvent accessibility, flexibility, and annotation of globular domains. Using these descriptors and a ridge regression model, DisCon predicts the content with low, 0.05, mean squared error and high, 0.68, Pearson correlation. This is a statistically significant improvement over the content computed from outputs of ten modern disorder predictors on a test dataset with proteins that share low sequence identity with the training sequences. The proposed predictive model is analyzed to discuss factors related to the prediction of the disorder content.

Conclusions

DisCon is a high-quality alternative for high-throughput annotation of the disorder content. We also empirically demonstrate that the DisCon's predictions can be used to improve binary annotations of the disordered residues from the real-value disorder propensities generated by current residue-level disorder predictors. The web server that implements the DisCon is available at http://biomine.ece.ualberta.ca/DisCon/.
Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin
Authors: Carey Robyn M , Blusztajn Jan K , Slack Barbara E
Published: June 2011

Background

The amyloid precursor protein (APP) is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ) peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a
d isintegrin a nd m etalloprotease)10 is also regulated by dynamin-dependent endocytosis.

Results

Transfection of human embryonic kidney (HEK) cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A), increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC) or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments.

Conclusions

Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two ways: by altering the putative signaling activity of the ADAM10 C-terminal fragment, and by regulating the biological function of ADAM10 substrates such as APP and N-cadherin.
Lytic activity of the virion-associated peptidoglycan hydrolase HydH5 of Staphylococcus aureusbacteriophage vB_SauS-phiIPLA88
Authors: Rodríguez Lorena , Martínez Beatriz , Zhou Yuan , Rodríguez Ana , Donovan David M , García Pilar
Published: June 2011

Background

Staphylococcus aureus is a food-borne pathogen and the most common cause of infections in hospitalized patients. The increase in the resistance of this pathogen to antibacterials has made necessary the development of new anti-staphylococcal agents. In this context, bacteriophage lytic enzymes such as endolysins and structural peptidoglycan (PG) hydrolases have received considerable attention as possible antimicrobials against gram-positive bacteria.

Results

S. aureus bacteriophage vB_SauS-phiIPLA88 (phiIPLA88) contains a virion-associated muralytic enzyme (HydH5) encoded by orf58, which is located in the morphogenetic module. Comparative bioinformatic analysis revealed that HydH5 significantly resembled other peptidoglycan hydrolases encoded by staphylococcal phages. The protein consists of 634 amino acid residues. Two putative lytic domains were identified: an N-terminal CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain (135 amino acid residues), and a C-terminal LYZ2 (lysozyme subfamily 2) domain (147 amino acid residues). These domains were also found when a predicted three-dimensional structure of HydH5 was made which provided the basis for deletion analysis. The complete HydH5 protein and truncated proteins containing only each catalytic domain were overproduced in E. coli and purified from inclusion bodies by subsequent refolding. Truncated and full-length HydH5 proteins were all able to bind and lyse S. aureus Sa9 cells as shown by binding assays, zymogram analyses and CFU reduction analysis. HydH5 demonstrated high antibiotic activity against early exponential cells, at 45°C and in the absence of divalent cations (Ca2+, Mg2+, Mn2+). Thermostability assays showed that HydH5 retained 72% of its activity after 5 min at 100°C.

Conclusions

The virion-associated PG hydrolase HydH5 has lytic activity against S. aureus, which makes it attractive as antimicrobial for food biopreservation and anti-staphylococcal therapy.
Phylogeography of Francisella tularensis subspecies holarctica from the country of Georgia
Authors: Chanturia Gvantsa , Birdsell Dawn N , Kekelidze Merab , Zhgenti Ekaterine , Babuadze George , Tsertsvadze Nikoloz , Tsanava Shota , Imnadze Paata , Beckstrom-Sternberg Stephen M , Beckstrom-Sternberg James S , Champion Mia D , Sinari Shripad , Gyuranecz Miklos , Farlow Jason , Pettus Amanda H , Kaufman Emily L , Busch Joseph D , Pearson Talima , Foster Jeffrey T , Vogler Amy J , Wagner David M , Keim Paul
Published: June 2011

Background

Francisella tularensis, the causative agent of tularemia, displays subspecies-specific differences in virulence, geographic distribution, and genetic diversity.F. tularensissubsp.holarcticais widely distributed throughout the Northern Hemisphere. In Europe,F. tularensissubsp.holarcticaisolates have largely been assigned to two phylogenetic groups that have specific geographic distributions. Most isolates from Western Europe are assigned to the B.Br.FTNF002-00 group, whereas most isolates from Eastern Europe are assigned to numerous lineages within the B.Br.013 group. The eastern geographic extent of the B.Br.013 group is currently unknown due to a lack of phylogenetic knowledge about populations at the European/Asian juncture and in Asia. In this study, we address this knowledge gap by describing the phylogenetic structure ofF. tularensissubsp.holarcticaisolates from the country of Georgia, and by placing these isolates into a global phylogeographic context.

Results

We identified a new genetic lineage ofF. tularensissubsp.holarcticafrom Georgia that belongs to the B.Br.013 group. This new lineage is genetically and geographically distinct from lineages previously described from the B.Br.013 group from Central-Eastern Europe. Importantly, this new lineage is basal within the B.Br.013 group, indicating the Georgian lineage diverged before the diversification of the other known B.Br.013 lineages. Although two isolates from the Georgian lineage were collected nearby in the Ukrainian region of Crimea, all other global isolates assigned to this lineage were collected in Georgia. This restricted geographic distribution, as well as the high levels of genetic diversity within the lineage, is consistent with a relatively older origin and localized differentiation.

Conclusions

We identified a new lineage ofF. tularensissubsp.holarcticafrom Georgia that appears to have an older origin than any other diversified lineages previously described from the B.Br.013 group. This finding suggests that additional phylogenetic studies ofF. tularensissubsp.holarcticapopulations in Eastern Europe and Asia have the potential to yield important new insights into the evolutionary history and phylogeography of this broadly dispersedF. tularensissubspecies.
Renal kallikrein excretion and epigenetics in human acute kidney injury: Expression, mechanisms and consequences
Authors: Kang Sun Woo , Shih Pei-an Betty , Mathew Roy O , Mahata Manjula , Biswas Nilima , Rao Fangwen , Yan Liying , Bouchard Josee , Malhotra Rakesh , Tolwani Ashita , Khandrika Srikrishna , Mehta Ravindra L , O'Connor Daniel T
Published: June 2011

Background

Renal kallikrein (KLK1) synthesis and urinary excretion are reportedly diminished during AKI (acute kidney injury) in animal models, and provision of kallikrein abrogates renal injury in this setting, but data in human AKI is limited. Therefore we first examined KLK1 renal excretion in human AKI, and then probed potential endocrine and epigenetic mechanisms for its alterations.

Methods

KLK1 enzymatic activity excretion was evaluated in urine from patients with established or incipient AKI, versus healthy/non-hospital as well as ICU controls. Endocrine control of KLK1 excretion was then probed by catecholamine and aldosterone measurements in established AKI versus healthy controls. To examine epigenetic control of KLK1 synthesis, we tested blood and urine DNA for changes in promoter CpG methylation of the KLK1 gene, as well as LINE-1 elements, by bisulfite sequencing.

Results

Patients with early/incipient AKI displayed a modest reduction of KLK1 excretion, but unexpectedly, established AKI displayed substantially elevated urine KLK1 excretion, ~11-fold higher than healthy controls, and ~3-fold greater than ICU controls. We then probed potential mechanisms of the change. Established AKI patients had lower SBP, higher heart rate, and higher epinephrine excretion than healthy controls, though aldosterone excretion was not different. Promoter KLK1 CpG methylation was higher in blood than urine DNA, while KLK1 methylation in blood DNA was significantly higher in established AKI than healthy controls, though KLK1 methylation in urine tended to be higher in AKI, directionally consistent with earlier/incipient but not later/established changes in KLK1 excretion in AKI. On multivariate ANOVA, AKI displayed coordinate changes in KLK1 excretion and promoter methylation, though directionally opposite to expectation. Control (LINE-1 repetitive element) methylation in blood and urine DNA was similar between AKI and controls.

Conclusions

Unexpectedly, increased KLK1 excretion in AKI patients was found; this increase is likely to be due in part to increments in adrenergic tone during BP depression. Epigenetic changes at KLK1 may also play a role in early changes of KLK1 expression and thus AKI susceptibility or recovery.
Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism
Authors: Serikawa Takehiro , Shimohata Takayoshi , Akashi Mami , Yokoseki Akio , Tsuchiya Miwa , Hasegawa Arika , Haino Kazufumi , Koike Ryoko , Takakuwa Koichi , Tanaka Keiko , Tanaka Kenichi , Nishizawa Masatoyo
Published: June 2011

Background

Pregnancy in patients with Parkinson disease is a rare occurrence. To the best of our knowledge, the effect of pregnancy as well as treatment in genetically confirmed autosomal recessive juvenile parkinsonism (ARJP) has never been reported. Here, we report the first case of pregnancy in a patient with ARJP associated with a parkin gene mutation, ARJP/PARK2.

Case presentation

A 27-year-old woman with ARJP/PARK2 was diagnosed as having a spontaneous dichorionic/diamniotic twin pregnancy. Exacerbation of motor disability was noted between ovulation and menstruation before pregnancy as well as during late pregnancy, suggesting that her parkinsonism might have been influenced by fluctuations in the levels of endogenous sex hormones. During the organogenesis period, she was only treated with levodopa/carbidopa, although she continued to receive inpatient hospital care for assistance in the activities of daily living. After the organogenesis period, she was administered sufficient amounts of antiparkinsonian drugs. She delivered healthy male twins, and psychomotor development of both the babies was normal at the age of 2 years.

Conclusion

Pregnancy may worsen the symptoms of ARJP/PARK2, although appropriate treatments with antiparkinsonian drugs and adequate assistance in the activities of daily living might enable successful pregnancy and birth of healthy children.
Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma
Authors: Ma Jian , Wang Shuiliang , Zhao Ming , Deng Xin-Sheng , Lee Choon-Kee , Yu Xiao-Dan , Liu Bolin
Published: June 2011

Background

Cladribine or 2-chlorodeoxyadenosine (2-CDA) is a well-known purine nucleoside analog with particular activity against lymphoproliferative disorders, such as hairy cell leukemia (HCL). Its benefits in multiple myeloma (MM) remain unclear. Here we report the inhibitory effects of cladribine on MM cell lines (U266, RPMI8226, MM1.S), and its therapeutic potential in combination with a specific inhibitor of the signal transducer and activator of transcription 3 (STAT3).

Methods

MTS-based proliferation assays were used to determine cell viability in response to cladribine. Cell cycle progression was examined by flow cytometry analysis. Cells undergoing apoptosis were evaluated with Annexin V staining and a specific ELISA to quantitatively measure cytoplasmic histone-associated DNA fragments. Western blot analyses were performed to determine the protein expression levels and activation.

Results

Cladribine inhibited cell proliferation of MM cells in a dose-dependent manner, although the three MM cell lines exhibited a remarkably different responsiveness to cladribine. The IC50 of cladribine for U266, RPMI8226, or MM1.S cells was approximately 2.43, 0.75, or 0.18 μmol/L, respectively. Treatment with cladribine resulted in a significant G1 arrest in U266 and RPMI8226 cells, but only a minor increase in the G1 phase for MM1.S cells. Apoptosis assays with Annexin V-FITC/PI double staining indicated that cladribine induced apoptosis of U266 cells in a dose-dependent manner. Similar results were obtained with an apoptotic-ELISA showing that cladribine dramatically promoted MM1.S and RPMA8226 cells undergoing apoptosis. On the molecular level, cladribine induced PARP cleavage and activation of caspase-8 and caspase-3. Meanwhile, treatment with cladribine led to a remarkable reduction of the phosphorylated STAT3 (P-STAT3), but had little effect on STAT3 protein levels. The combinations of cladribine and a specific STAT3 inhibitor as compared to either agent alone significantly induced apoptosis in all three MM cell lines.

Conclusions

Cladribine exhibited inhibitory effects on MM cells in vitro. MM1.S is the only cell line showing significant response to the clinically achievable concentrations of cladribine-induced apoptosis and inactivation of STAT3. Our data suggest that MM patients with the features of MM1.S cells may particularly benefit from cladribine monotherapy, whereas cladribine in combination with STAT3 inhibitor exerts a broader therapeutic potential against MM.
Rural-urban differences of neonatal mortality in a poorly developed province of China
Authors: Yi Bin , Wu Li , Liu Hong , Fang Weimin , Hu Yang , Wang Youjie
Published: June 2011

Background

The influence of rural-urban disparities in children's health on neonatal death in disadvantaged areas of China is poorly understood. In this study of rural and urban populations in Gansu province, a disadvantaged province of China, we describe the characteristics and mortality of newborn infants and evaluated rural-urban differences of neonatal death.

Methods

We analyzed all neonatal deaths in the data from the Surveillance System of Child Death in Gansu Province, China from 2004 to 2009. We calculated all-cause neonatal mortality rates (NMR) and cause-specific death rates for infants born to rural or urban mothers during 2004-09. Rural-urban classifications were determined based on the residence registry system of China. Chi-square tests were used to compare differences of infant characteristics and cause-specific deaths by rural-urban maternal residence.

Results

Overall, NMR fell in both rural and urban populations during 2004-09. Average NMR for rural and urban populations was 17.8 and 7.5 per 1000 live births, respectively. For both rural and urban newborn infants, the four leading causes of death were birth asphyxia, preterm or low birth weight, congenital malformation, and pneumonia. Each cause-specific death rate was higher in rural infants than in urban infants. More rural than urban neonates died out of hospital or did not receive medical care before death.

Conclusions

Neonatal mortality declined dramatically both in urban and rural groups in Gansu province during 2004-09. However, profound disparities persisted between rural and urban populations. Strategies that address inequalities of accessibility and quality of health care are necessary to improve neonatal health in rural settings in China.
Applying the revised Chinese Job Content Questionnaire to assess psychosocial work conditions among Taiwan's hospital workers
Authors: Chien Tsair-Wei , Lai Wen-Pin , Wang Hsien-Yi , Hsu Sen-Yen , Castillo Roberto Vasquez , Guo How-Ran , Chen Shih-Chung , Su Shih-Bin
Published: June 2011

Background

For hospital accreditation and health promotion reasons, we examined whether the 22-item Job Content Questionnaire (JCQ) could be applied to evaluate job strain of individual hospital employees and to determine the number of factors extracted from JCQ. Additionally, we developed an Excel module of self-evaluation diagnostic system for consultation with experts.

Methods

To develop an Excel-based self-evaluation diagnostic system for consultation to experts to make job strain assessment easier and quicker than ever, Rasch rating scale model was used to analyze data from 1,644 hospital employees who enrolled in 2008 for a job strain survey. We determined whether the 22-item Job Content Questionnaire (JCQ) could evaluate job strain of individual employees in work sites. The respective item responding to specific groups' occupational hazards causing job stress was investigated by using skewness coefficient with its 95% CI through item-by-item analyses.

Results

Each of those 22 items on the questionnaire was examined to have five factors. The prevalence rate of Chinese hospital workers with high job strain was 16.5%.

Conclusions

Graphical representations of four quadrants, item-by-item bar chart plots and skewness 95% CI comparison generated in Excel can help employers and consultants of an organization focusing on a small number of key areas of concern for each worker in job strain.
Hypericum lanceolatum (Hypericaceae) as a potential source of new anti-malarial agents: a bioassay-guided fractionation of the stem bark
Authors: Zofou Denis , Kowa Théodora K , Wabo Hippolyte K , Ngemenya Moses N , Tane Pierre , Titanji Vincent PK
Published: June 2011

Background

Malaria is a major public health threat in Africa, and traditional medicine continues to play a key role in its control especially in rural areas. A bioassay-guided fractionation was carried out in order to evaluate the anti-malarial potential and the safety of the methanol extract of the Hypericum lanceolatum stem bark.

Methods

The anti-plasmodial activity was assayed by the lactate dehydrogenase method (pLDH) against the multidrug-resistant W2mef laboratory strain, and a field isolate (SHF4) of Plasmodium falciparum. Cytotoxicity tests were carried out using the LLC-MK2 monkey kidney epithelial cells.

Results

Five compounds were isolated from the most active and least cytotoxic ethylacetate sub-extract: betulinic acid (HLT1), 2,2',5,6'-tetrahydroxybenzophenone (HLT2), 5-hydroxy-3-methoxyxanthone (HLT3), 3-hydroxy-5-methoxyxanthone (HLT4) and HLT0 (yet to be identified). Three of the tested compounds presented significant anti-plasmodial activities (with 50% inhibitory concentration, IC50 < 5 μM), with 5-hydroxy-3-methoxyxanthone exerting the highest activity, followed by HLT0 and betulinic acid. All the compounds with significant anti-plasmodial activity were non-cytotoxic, except betulinic acid which showed a 50% cytotoxic concentration, CC50 of 25 μg/mL.

Conclusions

These findings justify the use of H. lanceolatum stem bark as anti-malarial by traditional healers of Western Cameroon, and could constitute a good basis for further studies towards development of new drug candidates or phytomedicines for malaria.
Mobile phones and head tumours. The discrepancies in cause-effect relationships in the epidemiological studies - how do they arise?
Authors: Levis Angelo G , Minicuci Nadia , Ricci Paolo , Gennaro Valerio , Garbisa Spiridione
Published: June 2011

Background

Whether or not there is a relationship between use of mobile phones (analogue and digital cellulars, and cordless) and head tumour risk (brain tumours, acoustic neuromas, and salivary gland tumours) is still a matter of debate; progress requires a critical analysis of the methodological elements necessary for an impartial evaluation of contradictory studies.

Methods

A close examination of the protocols and results from all case-control and cohort studies, pooled- and meta-analyses on head tumour risk for mobile phone users was carried out, and for each study the elements necessary for evaluating its reliability were identified. In addition, new meta-analyses of the literature data were undertaken. These were limited to subjects with mobile phone latency time compatible with the progression of the examined tumours, and with analysis of the laterality of head tumour localisation corresponding to the habitual laterality of mobile phone use.

Results

Blind protocols, free from errors, bias, and financial conditioning factors, give positive results that reveal a cause-effect relationship between long-term mobile phone use or latency and statistically significant increase of ipsilateral head tumour risk, with biological plausibility. Non-blind protocols, which instead are affected by errors, bias, and financial conditioning factors, give negative results with systematic underestimate of such risk. However, also in these studies a statistically significant increase in risk of ipsilateral head tumours is quite common after more than 10 years of mobile phone use or latency. The meta-analyses, our included, examining only data on ipsilateral tumours in subjects using mobile phones since or for at least 10 years, show large and statistically significant increases in risk of ipsilateral brain gliomas and acoustic neuromas.

Conclusions

Our analysis of the literature studies and of the results from meta-analyses of the significant data alone shows an almost doubling of the risk of head tumours induced by long-term mobile phone use or latency.
Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression
Authors: McConnell Brice V , Koto Karen , Gutierrez-Hartmann Arthur
Published: June 2011

Background

LIM kinase 1 (LIMK1) is expressed in both cytoplasmic and nuclear compartments, and is a key regulator of cytoskeletal organization involved in cell migration and proliferation. LIMK1 levels are increased in several human cancers, with LIMK1 over-expression in prostate and breast cancer cells leading to tumor progression. While it has been presumed that the mechanism by which LIMK1 promotes cancer progression is via its cytoplasmic effects, the role of nuclear vs cytoplasmic LIMK1 in the tumorigenic process has not been examined.

Results

To determine if cytoplasmic or nuclear LIMK1 expression correlated with breast cancer, we performed immunohistochemical (IHC) analysis of breast tissue microarrays (TMAs), The IHC analysis of breast TMAs revealed that 76% of malignant breast tissue samples strongly expressed LIMK1 in the cytoplasm, with 52% of these specimens also expressing nuclear LIMK1. Only 48% of benign breast samples displayed strong cytoplasmic LIMK1 expression and 27% of these expressed nuclear LIMK1. To investigate the respective roles of cytoplamsic and nuclear LIMK1 in breast cancer progression, we targeted GFP-LIMK1 to cytoplasmic and nuclear subcellular compartments by fusing nuclear export signals (NESs) or nuclear localization sequences (NLS), respectively, to the amino-terminus of GFP-LIMK1. Stable pools of MDA-MB-231 cells were generated by retroviral transduction, and fluorescence microscopy revealed that GFP alone (control) and GFP-LIMK1 were each expressed in both the cytoplasm and nucleus of MDA-MB-231 cells, whereas NLS-GFP-LIMK1 was expressed in the nucleus and NES-GFP-LIMK1 was expressed in the cytoplasm. Western blot analyses revealed equal expression of GFP-LIMK1 and NES-GFP-LIMK1, with NLS-GFP-LIMK1 expression being less but equal to endogenous LIMK1. Also, Western blotting revealed increased levels of phospho-cofilin, phospho-FAK, phospho-paxillin, phospho-Src, phospho-AKT, and phospho-Erk1/2 in cells expressing all GFP-LIMK1 fusions, compared to GFP alone. Invasion assays revealed that all GFP-LIMK1 fusions increased MDA-MB-231 cell invasion ~1.5-fold, compared to GFP-only control cells. Tumor xenograft studies in nude mice revealed that MDA-MB-231 cells stably expressing GFP-LIMK, NLS-GFP-LIMK1 and NES-GFP-LIMK1 enhanced tumor growth 2.5-, 1.6- and 4.7-fold, respectively, compared to GFP-alone.

Conclusion

Taken together, these data demonstrate that LIMK1 activity in both the cytoplasmic and nuclear compartments promotes breast cancer progression, underscoring that nuclear LIMK1 contributes to the transforming function of LIMK1.
Ovarian endometriomas and IVF: a retrospective case-control study
Authors: Bongioanni Francesca , Revelli Alberto , Gennarelli Gianluca , Guidetti Daniela , Delle Piane Luisa Delle , Holte Jan
Published: June 2011

We performed this retrospective case-control study analyzing 428 first-attempt in vitro fertilization (IVF) cycles, among which 254 involved women with a previous or present diagnosis of ovarian endometriosis. First, the results of these 254 cycles were compared with 174 cycles involving patients with proven non-endometriotic tubal infertility having similar age and body mass index. Women with ovarian endometriosis had a significantly higher cancellation rate, but similar pregnancy, implantation and delivery rates as patients with tubal infertility. Second, among the women with ovarian endometriosis, the women with a history of laparoscopic surgery for ovarian endometriomas prior to IVF and no visual endometriosis at ovum pick-up (n = 112) were compared with the non-operated women and visual endometriomas at ovum pick-up (n = 142). Patients who underwent ovarian surgery before IVF had significantly shorter period, lower antral follicle count and required higher gonadotropin doses than patients with non-operated endometriomas. The two groups of women with a previous or present ovarian endometriosis did, however, have similar pregnancy, implantation and live birth rates. In conclusion, ovarian endometriosis does not reduce IVF outcome compared with tubal factor. Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins.
Self-organized chains of nanodots induced by an off-normal incident beam
Authors: Lee Seungjun , Wang Lumin , Lu Wei
Published: June 2011

We propose a model to show that under off-normal bombardment of an incident ion beam, a solid surface may spontaneously form nanoscale dots lining up into chains perpendicular to the incident beam direction. These dots demonstrate a highly ordered hexagonal pattern. We attribute the self-organization behavior to surface instability under concurrent surface kinetics and to a shadow effect that causes the self-alignment of dots. The fundamental mechanism may be applicable to diverse systems, suggesting an effective approach for nanofabrication.
Modeling of polyethylene, poly(l-lactide), and CNT composites: a dissipative particle dynamics study
Authors: Wang Yao-Chun , Ju Shin-Pon , Huang Tien Jung , Wang Hung-Hsiang
Published: June 2011

Dissipative particle dynamics (DPD), a mesoscopic simulation approach, is used to investigate the effect of volume fraction of polyethylene (PE) and poly(l-lactide) (PLLA) on the structural property of the immiscible PE/PLLA/carbon nanotube in a system. In this work, the interaction parameter in DPD simulation, related to the Flory-Huggins interaction parameter χ, is estimated by the calculation of mixing energy for each pair of components in molecular dynamics simulation. Volume fraction and mixing methods clearly affect the equilibrated structure. Even if the volume fraction is different, micro-structures are similar when the equilibrated structures are different. Unlike the blend system, where no relationship exists between the micro-structure and the equilibrated structure, in the di-block copolymer system, the micro-structure and equilibrated structure have specific relationships.
Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy
Authors: Wong Raymond , Balachandran Ahalya , Mao Annie YQ , Dobson Wendy , Gray-Owen Scott , Cochrane Alan
Published: June 2011

Background

RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK) family of SR protein kinases on HIV-1 expression and RNA processing was examined.

Results

Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication.

Conclusions

Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.
Novel norovirus recombinants and GII.4 sub-lineages associated with outbreaks between 2006 and 2010 in Belgium
Authors: Mathijs Elisabeth , Denayer Sarah , Palmeira Leonor , Botteldoorn Nadine , Scipioni Alexandra , Vanderplasschen Alain , Thiry Etienne , Dierick Katelijne
Published: June 2011

Background

Noroviruses (NoVs) are an important cause of acute gastroenteritis in humans worldwide. To gain insight into the epidemiologic patterns of NoV outbreaks and to determine the genetic variation of NoVs strains circulating in Belgium, stool samples originating from patients infected with NoVs in foodborne outbreak investigations were analysed between December 2006 and December 2010.

Results

NoVs were found responsible of 11.8% of all suspected foodborne outbreaks reported in the last 4 years and the number of NoV outbreaks reported increased along the years representing more than 30% of all foodborne outbreaks in 2010. Genogroup II outbreaks largely predominated and represented more than 90% of all outbreaks. Phylogenetic analyses were performed with 63 NoV-positive samples for the partial polymerase (N = 45) and/or capsid gene (N = 35) sequences. For 12 samples, sequences covering the ORF1-ORF2 junction were obtained. A variety of genotypes was found among genogroups I and II; GII.4 was predominant followed in order of importance by GII.2, GII.7, GII.13, GI.4 and GI.7. In the study period, GII.4 NoVs variants 2006a, 2006b, 2007, 2008 and 2010 were identified. Moreover, phylogenetic analyses identified different recombinant NoV strains that were further characterised as intergenotype (GII.e/GII.4 2007, GII.e/GII.3 and GII.g/GII.1) and intersub-genotype (GII.4 2006b/GII.4 2007 and GII.4 2010/GII.4 2010b) recombinants.

Conclusions

NoVs circulating in the last 4 years in Belgium showed remarkable genetic diversity either by small-scale mutations or genetic recombination. In this period, GII.4 2006b was successfully displaced by the GII.4 2010 subtype, and previously reported epidemic GII.b recombinants seemed to have been superseded by GII.e recombinants in 2009 and GII.g recombinants in 2010. This study showed that the emergence of novel GII.4 variants together with novel GII recombinants could lead to an explosion in NoV outbreaks, likewise to what was observed in 2008 and 2010. Among recombinants detected in this study, two hitherto unreported strains GII.e/GII.3 and GII.g/GII.1 were characterised. Surveillance will remain important to monitor contemporaneously circulating strains in order to adapt preventive and curative strategies.
Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancer
Authors: Wang Rui , Lu Meng , Chen Haiquan , Chen Sufeng , Luo Xiaoyang , Qin Ying , Zhang Jie
Published: June 2011

Background

Monocyte recruited into the tumor and maturation to tumor-associated macrophage (TAM). Interleukin-10(IL-10) is a potent immunosuppressive cytokine, which can be secreted from both primary tumor and stromal cells. However, there are controversies regarding its role in the progression of cancer. So it is important to isolate TAM from tumor cells to study the role of IL-10 in the progress of cancer. The aim of our study was to determine whether IL-10 expressed by TAM correlated with clinicopathological factors in NSCLC.

Methods

TAM in NSCLC was isolated by short-term culture in serum free medium with the modification to literature reports. The mRNA expression levels of IL-10, cathepsin B, cathepsin S, which were closely related with TAM according to the literatures, were evaluated by Quantitative real-time RT-PCR in 63 NSCLC. The relationships between their expression levels and clinicopathological features were investigated.

Results

We successfully achieved up to 95% purity of TAM, derived from 63 primary lung cancer tissues. TAM expressed high levels of IL-10, cathepsin B in NSCLC. High levels of IL-10 in TAM significantly correlated with stage, tumor size, lymph node metastasis, lymphovascular invasion or histologic poor differentiation.

Conclusions

Our results revealed that TAM with high levels of IL-10 expression may play an important role in the progression of non-small cell lung cancer. The data also suggested that TAMs may involve in tumor immunosuppression through overexpressed IL-10. Additionally, the phenotype of isolated TAM can be potentially used to predict clinicopathological features as well.