bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Calcium/Calmodulin/Kinase System and Arrhythmogenic Afterdepolarizations in Bradycardia-Related Acquired Long-QT Syndrome
Authors: Qi XiaoYan , Yeh Yung-Hsin , Chartier Denis , Xiao Ling , Tsuji Yukiomi , Brundel Bianca J.J.M. , Kodama Itsuo , Nattel Stanley 
Published: April 2009

Background—Sustained bradycardia is associated with long-QT syndrome in human beings and causes spontaneous torsades de pointes in rabbits with chronic atrioventricular block (CAVB), at least partly by downregulating delayed-rectifier K+-current to cause action potential (AP) prolongation. We addressed the importance of altered Ca2+handling, studying underlying mechanisms and consequences.Methods and Results—We measured ventricular cardiomyocyte [Ca2+]i(Indo1-AM), L-type Ca2+-current (ICaL) and APs (whole-cell perforated-patch), and Ca2+-handling protein expression (immunoblot). CAVB increased AP duration, cell shortening, systolic [Ca2+]itransients, and caffeine-induced [Ca2+]irelease, and CAVB cells showed spontaneous early afterdepolarizations (EADs).ICaLdensity was unaffected by CAVB, but inactivation was shifted to more positive voltages, increasing the activation-inactivation overlap zone forICaLwindow current. Ca2+-calmodulin–dependent protein kinase-II (CaMKII) autophosphorylation was enhanced in CAVB, indicating CaMKII activation. CAVB also enhanced CaMKII-dependent phospholamban-phosphorylation and accelerated [Ca2+]i-transient decay, consistent with phosphorylation-induced reductions in phospholamban inhibition of sarcoplasmic reticulum (SR) Ca2+-ATPase as a contributor to enhanced SR Ca2+loading. The CaMKII-inhibitor KN93 reversed CAVB-induced changes in caffeine-releasable [Ca2+]iandICaLinactivation voltage and suppressed CAVB-induced EADs. Similarly, the calmodulin inhibitor W7 suppressed CAVB-inducedICaLinactivation voltage shifts and EADs, and a specific CaMKII inhibitory peptide preventedICaLinactivation voltage shifts. The SR Ca2+-uptake inhibitor thapsigargin and the SR Ca2+release inhibitor ryanodine also suppressed CAVB-induced EADs, consistent with an important role for SR Ca2+loading and release in arrhythmogenesis. AP-duration changes reached a maximum after 1 week of bradypacing, but peak alterations in CaMKII and [Ca2+]irequired 2 weeks, paralleling the EAD time course.Conclusions—CAVB-induced remodeling enhances [Ca2+]iload and activates the Ca2+-calmodulin-CaMKII system, producing [Ca2+]i-handling abnormalities that contribute importantly to CAVB-induced arrhythmogenic afterdepolarizations.
Convective-Scale Downdrafts in the Principal Rainband of Hurricane Katrina (2005)
Authors: Didlake Anthony C. , Houze Robert A. 
Published: April 2009

AbstractAirborne Doppler radar data collected during the Hurricane Rainband and Intensity Change Experiment (RAINEX) document downdrafts in the principal rainband of Hurricane Katrina (2005). Inner-edge downdrafts (IEDs) originating at 6–8-km altitude created a sharp reflectivity gradient along the inner boundary of the rainband. Low-level downdrafts (LLDs) evidently driven by precipitation drag originated at 2–4 km within the heavy rain cells of each convective element. The IED and LLD were spatially separated by but closely associated with the updrafts within the rainband. The IED was forced aloft by pressure perturbations formed in response to the adjacent buoyant updrafts. Once descending, the air attained negative buoyancy via evaporative cooling from the rainband precipitation. A convective-scale tangential wind maximum tended to occur in the radial inflow at lower levels in association with the IED, which enhanced the inward flux of angular momentum at lower levels. Convergence at the base of the downdrafts on the upwind end of the principal rainband contributed to the principal rainband growing in length. New updraft elements triggered by this convergence led to the formation of new IED and LLD pockets, which were subsequently advected downwind around the storm by the vortex winds while additional new cells continued to form on the upwind end of the band. These processes sustained the principal rainband and helped to make it effectively stationary relative to the storm center, thus maintaining its impact on the hurricane dynamics over an extended period.
Femoral Avulsion of the Medial Patellofemoral Ligament after Primary Traumatic Patellar Dislocation Predicts Subsequent Instability in Men
Authors: Sillanpää Petri J , Peltola Erno , Mattila Ville M. , Kiuru Martti , Visuri Tuomo , Pihlajamäki Harri 
Published: April 2009

Background The clinical relevance of medial patellofemoral ligament (MPFL) injury location in primary patellar dislocation has not been studied. Hypothesis Prognosis after primary traumatic patellar dislocation may vary by MPFL injury location. Study Design Cohort study; Level of evidence, 3. Methods The initial magnetic resonance imaging (MRI) findings in 53 patients with identical nonoperative management were retrospectively analyzed for medial restraint injuries. The MPFL injury sites were classified as follows: femoral, midsubstance, and patellar. Magnetic resonance imaging was used to assess initial and control articular cartilage lesions in the patellofemoral joint. After a mean follow-up of 7 years, 42 patients were evaluated for redislocations, subjective symptoms, and functional limitations. Results Based on the initial MRIs, MPFL rupture was classified as femoral in 35 patients, midsubstance in 11, and patellar in 7. At follow-up, 15 patients reported an unstable patella (13 femoral, 1 patellar, 1 midsubstance; P =. 01) and 9 reported patellar redislocations (8 femoral, 1 midsubstance; P =. 05). The proportion of patients who regained their preinjury activity level was significantly smaller among those with femoral MPFL injury than among those with midsubstance or patellar MPFL injury (P =. 05). The median Kujala score was as follows: 90 for femoral, 91 for patellar, and 96 for midsubstance (P =. 76). Control MRI showed full-thickness patellofemoral cartilage lesions in 50% of the patients, unrelated to MPFL injury location. Conclusion An MPFL avulsion at the femoral attachment in primary traumatic patellar dislocations predicts subsequent patellar instability. The authors suggest that MPFL injury location be taken into account when planning treatment of primary traumatic patellar dislocation.
Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential
Authors: Kent David G. , Copley Michael R. , Benz Claudia , Wöhrer Stefan , Dykstra Brad J. , Ma Elaine , Cheyne John , Zhao Yongjun , Bowie Michelle B. , Zhao Yun , Gasparetto Maura , Delaney Allen , Smith Clayton , Marra Marco , Eaves Connie J. 
Published: April 2009

Abstract
Hematopoietic stem cells (HSCs) are generally defined by their dual properties of pluripotency and extensive self-renewal capacity. However, a lack of experimental clarity as to what constitutes extensive self-renewal capacity coupled with an absence of methods to prospectively isolate long-term repopulating cells with defined self-renewal activities has made it difficult to identify the essential components of the self-renewal machinery and investigate their regulation. We now show that cells capable of repopulating irradiated congenic hosts for 4 months and producing clones of cells that can be serially transplanted are selectively and highly enriched in the CD150+ subset of the EPCR+CD48−CD45+ fraction of mouse fetal liver and adult bone marrow cells. In contrast, cells that repopulate primary hosts for the same period but show more limited self-renewal activity are enriched in the CD150− subset. Comparative transcriptome analyses of these 2 subsets with each other and with HSCs whose self-renewal activity has been rapidly extinguished in vitro revealed 3 new genes (VWF, Rhob, Pld3) whose elevated expression is a consistent and selective feature of the long-term repopulating cells with durable self-renewal capacity. These findings establish the identity of a phenotypically and molecularly distinct class of pluripotent hematopoietic cells with lifelong self-renewal capacity.
Cellular and subcellular localization of Marlin-1 in the brain
Authors: Vidal René L , Valenzuela José I , Luján Rafael , Couve Andrés 
Published: April 2009

Abstract

Background
Marlin-1 is a microtubule binding protein that associates specifically with the GABAB1 subunit in neurons and with members of the Janus kinase family in lymphoid cells. In addition, it binds the molecular motor kinesin-I and nucleic acids, preferentially single stranded RNA. Marlin-1 is expressed mainly in the central nervous system but little is known regarding its cellular and subcellular distribution in the brain.

Results
Here we have studied the localization of Marlin-1 in the rodent brain and cultured neurons combining immunohistochemistry, immunofluorescence and pre-embedding electron microscopy. We demonstrate that Marlin-1 is enriched in restricted areas of the brain including olfactory bulb, cerebral cortex, hippocampus and cerebellum. Marlin-1 is abundant in dendrites and axons of GABAergic and non-GABAergic hippocampal neurons. At the ultrastructural level, Marlin-1 is present in the cytoplasm and the nucleus of CA1 neurons in the hippocampus. In the cytoplasm it associates to microtubules in the dendritic shaft and occasionally with the Golgi apparatus, the endoplasmic reticulum (ER) and dendritic spines. In the nucleus, clusters of Marlin-1 associate to euchromatin.

Conclusion
Our results demonstrate that Marlin-1 is expressed in discrete areas of the brain. They also confirm the microtubule association at the ultrastructural level in neurons. Together with the abundance of the protein in dendrites and axons they are consistent with the emerging role of Marlin-1 as an intracellular protein linking the cytoskeleton and transport. Our study constitutes the first detailed description of the cellular and subcellular distribution of Marlin-1 in the brain. As such, it will set the basis for future studies on the functional implications of Marlin-1 in protein trafficking.
Systematic comparison of SCOP and CATH: a new gold standard for protein structure analysis
Authors: Csaba Gergely , Birzele Fabian , Zimmer Ralf 
Published: April 2009

Abstract

Background
SCOP and CATH are widely used as gold standards to benchmark novel protein structure comparison methods as well as to train machine learning approaches for protein structure classification and prediction. The two hierarchies result from different protocols which may result in differing classifications of the same protein. Ignoring such differences leads to problems when being used to train or benchmark automatic structure classification methods. Here, we propose a method to compare SCOP and CATH in detail and discuss possible applications of this analysis.

Results
We create a new mapping between SCOP and CATH and define a consistent benchmark set which is shown to largely reduce errors made by structure comparison methods such as TM-Align and has useful further applications, e.g. for machine learning methods being trained for protein structure classification. Additionally, we extract additional connections in the topology of the protein fold space from the orthogonal features contained in SCOP and CATH.

Conclusion
Via an all-to-all comparison, we find that there are large and unexpected differences between SCOP and CATH w.r.t. their domain definitions as well as their hierarchic partitioning of the fold space on every level of the two classifications. A consistent mapping of SCOP and CATH can be exploited for automated structure comparison and classification.

Availability
Benchmark sets and an interactive SCOP-CATH browser are available at http://www.bio.ifi.lmu.de/SCOPCath.
A systematic classification of Plasmodium falciparum P-loop NTPases: structural and functional correlation
Authors: Gangwar Deepti , Kalita Mridul K , Gupta Dinesh , Chauhan Virander S , Mohmmed Asif 
Published: April 2009

AbstractBackgroundThe P-loop NTPases constitute one of the largest groups of globular protein domains that play highly diverse functional roles in most of the organisms. Even with the availability of nearly 300 different Hidden Markov Models representing the P-loop NTPase superfamily, not many P-loop NTPases are known inPlasmodium falciparum. A number of characteristic attributes of the genome have resulted into the lack of knowledge about this functionally diverse, but important class of proteins.MethodIn the study, protein sequences with characteristic motifs of NTPase domain (Walker A and Walker B) are computationally extracted from theP. falciparumdatabase. A detailed secondary structure analysis, functional classification, phylogenetic and orthology studies of the NTPase domain of repertoire of 97P. falciparumP-loop NTPases is carried out.ResultsBased upon distinct sequence features and secondary structure profile of the P-loop domain of obtained sequences, a cladistic classification is also conceded: nucleotide kinases and GTPases, ABC and SMC family, SF1/2 helicases, AAA+ and AAA protein families. Attempts are made to identify any ortholog(s) for each of these proteins in otherPlasmodiumsp. as well as its vertebrate host,Homo sapiens. A number ofP. falciparumP-loop NTPases that have no homologue in the host, as well as those annotated as hypothetical proteins and lack any characteristic functional domain are identified.ConclusionThe study suggests a strong correlation between sequence and secondary structure profile of P-loop domains and functional roles of these proteins and thus provides an opportunity to speculate the role of many hypothetical proteins. The study provides a methodical framework for the characterization of biologically diverse NTPases in theP. falciparumgenome.The efforts made in the analysis are first of its kind; and the results augment to explore the functional role of many of these proteins from the parasite that could provide leads to identify novel drug targets against malaria.
Ace-1 duplication in Anopheles gambiae: a challenge for malaria control
Authors: Djogbénou Luc , Labbé Pierrick , Chandre Fabrice , Pasteur Nicole , Weill Mylène 
Published: April 2009

Abstract

Background
Insecticide resistance is a rapid and recent evolutionary phenomenon with serious economic and public health implications. In the mosquito Anopheles gambiae s.s., main vector of malaria, resistance to organophosphates and carbamates is mainly due to a single amino-acid substitution in acetylcholinesterase 1 (AChE1). This mutation entails a large fitness cost. However, a resistant duplicated allele of the gene encoding AChE1 (ace-1), potentially associated to a lower fitness cost, recently appeared in An. gambiae.

Methods
Using molecular phenotype data collected from natural populations from West Africa, the frequency of this duplicated allele was investigated by statistical inference. This method is based on the departure from Hardy-Weinberg phenotypic frequency equilibrium caused by the presence of this new allele.

Results
The duplicated allele, Ag-ace-1

D
, reaches a frequency up to 0.65 in Ivory Coast and Burkina Faso, and is potentially present in Benin. A previous study showed that Ag-ace-1

D
, present in both M and S molecular forms in different West Africa countries, was generated by a single genetic event. This single origin and its present distribution suggest that this new allele is currently spreading.

Conclusion
The spread of this less costly resistance allele could represent a major threat to public health, as it may impede An. gambiae control strategies, and thus increases the risk of malaria outbreaks.
Research collaboration in Tehran University of Medical Sciences: two decades after integration
Authors: Majdzadeh Reza , Nedjat Saharnaz , Gholami Jaleh , Nedjat Sima , Maleki Katayoun , Qorbani Mostafa , Shokoohi Mostafa , Ashoorkhani Mahnaz 
Published: April 2009

Abstract

Background
In 1985 medical schools were integrated into the Ministry of Health, and the Ministry of Health and Medical Education was created in Iran. Under this infrastructure education, research and service provision are unified, and it is expected that collaboration between researchers and decision makers become easier in such an integrated context.
The question here is how the researchers behavior in the biggest medical university of the country towards collaboration is, i.e. how much do decision makers participate in different stages of research? Which factors affect it?

Methodology
The samples under study were all Tehran University of Medical Sciences (TUMS) completed research projects that had gotten grants in 2004 and were over by the time this study was done. Two questionnaires were designed for this study: i) the research checklist which was filled for 301 projects, ii) the researcher's questionnaire, which was sent to principle investigators, 208 of which were collected. Multiple linear regression analysis was used for evaluating the potential factors affecting individuals 'collaboration score'.

Results
Only 2.2 percent of TUMS' projects initiated in 2004 have had collaboration as a joint PI or co-investigator from non-academic organizations. The principle investigators mean collaboration score was 2.09, where 6 was the total score. So the collaboration score obtained was 35%. The 'type of research' had significant association with the collaboration score which is shown in the linear regression; collaboration was seen more in clinical (p = 0.007) and health system researches (p = 0.001) as compared to basic research.

Conclusion
The present study shows that not many individuals collaborated as co-investigators from outside the university. This finding shows that research policy makers need to introduce interventions in this field. And assessment of barriers to collaboration and its facilitating factors should be considered in order to make it actually happen.
Inhibitory effects of adenovirus mediated tandem expression of RhoA and RhoC shRNAs in HCT116 cells
Authors: Liu Xiang-ping , Wang Hai-bo , Yang Kun , Sui Ai-hua , Shi Qiang , Qu Shen 
Published: April 2009

Abstract

Background
RhoA and RhoC are deregulated by over expression in many human tumors, including colorectal cancer. Some reports show that they play a pivotal role in the carcinogenesis, tumor development and infiltration metastasis. In this study, for the first time we constructed recombinant adenovirus to investigate the inhibitory effects of RhoA and RhoC shRNAs in tandem expression on the cell proliferation and invasion of colorectal cancer HCT116 cells.

Methods
The recombinant adenovirus carrying RhoA and RhoC shRNAs in tandem expression was transfected into HCT116. The mRNA transcription and protein expressions of RhoA and RhoC were examined by RT-FQPCR and Western blot respectively. Cellular proliferation inhibitory activity was determined by methyl thiazolyl tetrazolium (MTT) assay and invasive and migrating potential was detected through in vitro Matrigel coated invasion and migration assay.

Results
Both mRNA and proteins Levels of RhoA and RhoC were significantly reduced in HCT116 cells transfected with Ad-A1+A2+C1+C2 than those in Ad-HK group and control one. The relative RhoA and RhoC mRNA transcriptions were decreased to 40% and 36% (P < 0.05), while proteins expression reducing 42% and 35%, respectively (P < 0.05). Growth curves analysis showed that alive cell number in the Ad-A1+A2+C1+C2 group was lower than others in the third to sixth day and transwell chamber analysis showed that migration/invasion activity was significantly suppressed in Ad-A1+A2+C1+C2 group.

Conclusion
Our results indicate recombinant adenovirus carrying RhoA and RhoC shRNAs in tandem expression may inhibit the growth and invasion of HCT116 cells. Application of such vector to inhibit one or more genes may be a new method to cancer therapy.
The mean and the biological variation of insulin resistance does not differ between polycystic ovary syndrome and type 2 diabetes
Authors: Cho Li Wei , Jayagopal V , Kilpatrick E S , Atkin S L 
Published: April 2009

Background There is an assumption that the mean and biological variation of insulin resistance (IR) is less in polycystic ovary syndrome (PCOS), and intuitively higher in type 2 diabetes (T2DM). To test this hypothesis we compared the mean and biological variation in IR in PCOS to that of T2DM and to age- and weight-matched controls. Methods Twelve PCOS, 11 matched healthy women; 12 postmenopausal diet-controlled T2DM and 11 matched healthy postmenopausal women were recruited. Blood samples were collected at 4-d intervals on 10 consecutive occasions. The biological variability of IR was derived on duplicate samples. Results Mean and biological variability of HOMA-IR for PCOS did not differ from T2DM. Both measures were higher than the matched controls. There was no difference in insulin or IR measures between the body mass index matched pre- and postmenopausal women. Percentage β cell function were 208.8%, 62.3%, 106.5% and 111.9%, respectively, in PCOS, postmenopausal women with T2DM, healthy premenopausal and healthy postmenopausal women. Conclusions The progression from PCOS to the development of T2DM is unlikely to be due to a further increase in IR (or variability), but rather the progressive failure of pancreatic beta cells with a decrease in insulin production. The clinical trial registration number for this study is ISRCTN65353256.
Controlled study on folate status following folic acid supplementation and discontinuation in women of child-bearing age
Authors: Bakker D Joyce , de Jong-van den Berg Lolkje T W , Fokkema M Rebecca 
Published: April 2009

Background To decrease the incidence of neural tube defects, active efforts are currently undertaken to promote folic acid (FA) intake among women. In 2003, the Food and Drug Administration approved the proposal of introducing an oral contraceptive (OC) and FA combination pill. It is unknown whether these pills will reduce neural tube defect incidence for couples who do not become pregnant soon after discontinuation. We studied FA kinetics up to 12 weeks discontinuation of eight weeks 500 μg/d FA in 27 healthy Dutch women of child-bearing age. Methods In this controlled study, women were assigned to an intervention group ( n = 13) or a control group ( n = 14). The total study duration was 20 weeks, during which the subjects had to give blood on nine occasions (week –8 [baseline], –4, 0, 1, 2, 3, 4, 8 and 12) for analyses of serum and erythrocyte folate, and plasma total homocysteine. The intervention group received 500 μg/d FA during the first eight weeks, and discontinued the intake from weeks 0 to 12. No supplements were supplied to the control group. Results Serum folate and plasma total homocysteine returned to baseline after 12 weeks of FA discontinuation, erythrocyte folate did not. Conclusion An FA/OC combination pill seems to be of value for only a minor portion of women. Active efforts to stimulate women of child-bearing age to take FA remain essential.