bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D Structure Development of Chikungunya Virus and its Structural Characterization – an In silico approach
Authors: Nayarisseri Anuraj , Yadav Mukesh , Rao Dowlathabad Muralidhara , Kukreja Sonam , Ahmed Sheaza , Singh Pooja 
Published: November 2010

AbstractThe 3 Dimensional structure of a protein is an expedient for structure based drug design and identifying the conformational epitopes that are foremost for designing the vaccines. Chikungunya (CHIKV) is a heat sensitive RNA virus which causes a viral disease which is transmitted in humans by human-mosquito-human transmission. Disease mostly found in the tropic and subtropical countries mainly in South India and in few other Asian countries. The primary transmission agents of Chikungunya Virus are yellow fever mosquito (Aedes aegypti) and forest day mosquito (Aedes albopictus). The forest day mosquito bites during day time and hence day time mosquito bite is the main reason for transmission. The main distinctive of the disease is a fever along with an arthritic type of pain in the joints. 3D Structure of Chikungunya virus is not encountered in the PDB Databank. A Comparative modeling method was used for the prediction of the 3D structure of Chikungunya virus. Modeled structure prvided substantial parameters under Ramachandran plot and stereochemical aspects of main chain and side chains through PROCHECK analysis. Finally the energy minimization protocols yielded a score of -12063.947 KJ/Mol and RMSD Value of 0.29oA. Structure Validation procedures proffer the use of present modeled structures for structure based drug design and other confirmative applications.
Arachidonic acid fights palmitate: new insights into fatty acid toxicity in β-cells
Authors: Ortsäter Henrik 
Published: November 2010

Saturated fatty acids are toxic to pancreatic β-cells. By inducing apoptosis, they contribute to a decrease in β-cell mass, a hallmark of Type 2 diabetes. In the present issue of Clinical Science, Keane and co-workers show that the polyunsaturated fatty acid arachidonic acid protects the β-cell against the toxic effects of palmitate. As Type 2 diabetes is characterized by subclinical inflammation, and arachidonic acid and metabolites thereof are produced during states of inflammation, it is possible that pancreatic β-cells use arachidonic acid as a compound for self-protection.
GIANT RINGS IN THE COSMIC MICROWAVE BACKGROUND SKY
Authors: Kovetz Ely D. , Ben-David Assaf , Itzhaki Nissan 
Published: November 2010

ABSTRACT
We find a unique direction in the cosmic microwave background sky around which giant rings have an anomalous mean temperature profile. This direction is in very close alignment with the afore measured anomalously large bulk flow direction. Using Monte Carlo simulations, we estimate the significance of the giant rings at the 3σ level and the alignment with the bulk flow at 2.5σ. We argue that a cosmic defect seeded by a pre-inflationary particle could explain the giant rings, the large bulk flow, and their alignment.
Biological impact of missing-value imputation on downstream analyses of gene expression profiles
Authors: Oh Sunghee , Kang Dongwan D. , Brock Guy N. , Tseng George C. 
Published: November 2010

AbstractMotivation: Microarray experiments frequently produce multiple missing values (MVs) due to flaws such as dust, scratches, insufficient resolution or hybridization errors on the chips. Unfortunately, many downstream algorithms require a complete data matrix. The motivation of this work is to determine the impact of MV imputation on downstream analysis, and whether ranking of imputation methods by imputation accuracy correlates well with the biological impact of the imputation.Methods: Using eight datasets for differential expression (DE) and classification analysis and eight datasets for gene clustering, we demonstrate the biological impact of missing-value imputation on statistical downstream analyses, including three commonly employed DE methods, four classifiers and three gene-clustering methods. Correlation between the rankings of imputation methods based on three root-mean squared error (RMSE) measures and the rankings based on the downstream analysis methods was used to investigate which RMSE measure was most consistent with the biological impact measures, and which downstream analysis methods were the most sensitive to the choice of imputation procedure.Results: DE was the most sensitive to the choice of imputation procedure, while classification was the least sensitive and clustering was intermediate between the two. The logged RMSE (LRMSE) measure had the highest correlation with the imputation rankings based on the DE results, indicating that the LRMSE is the best representative surrogate among the three RMSE-based measures. Bayesian principal component analysis and least squares adaptive appeared to be the best performing methods in the empirical downstream evaluation.Contact: ctseng@pitt.edu; guy.brock@louisville.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Norwegian house mice (Mus musculus musculus/domesticus): distributions, routes of colonization and patterns of hybridization
Authors: JONES ELEANOR P. , Van Der KOOIJ JEROEN , SOLHEIM ROAR , SEARLE JEREMY B. 
Published: November 2010

AbstractWe investigated the distributions and routes of colonization of two commensal subspecies of house mouse in Norway: Mus musculus domesticus and M. m. musculus. Five nuclear markers (Abpa, D11 cenB2, Btk, SMCY and Zfy2) and a morphological feature (tail length) were used to differentiate the two subspecies and assess their distributions, and mitochondrial (mt) D‐loop sequences helped to elucidate their colonization history. M. m. domesticus is the more widespread of the two subspecies, occupying the western and southern coast of Norway, while M. m. musculus is found along Norway’s southeastern coast and east from there to Sweden. Two sections of the hybrid zone between the two subspecies were localized in Norway. However, hybrid forms also occur well away from that hybrid zone, the most prevalent of which are mice with a M. m. musculus‐type Y chromosome and an otherwise M. m. domesticus genome. MtDNA D‐loop sequences of the mice revealed a complex phylogeography within M. m. domesticus, reflecting passive human transport to Norway, probably during the Viking period. M. m. musculus may have colonized earlier. If so, that leaves open the possibility that M. m. domesticus replaced M. m. musculus from much of Norway, with the widely distributed hybrids a relict of this process. Overall, the effects of hybridization are evident in house mice throughout Norway.
The mTOR pathway affects proliferation and chemosensitivity of urothelial carcinoma cells and is upregulated in a subset of human bladder cancers
Authors: Makhlin Igor , Zhang Jiaru , Long Christopher J. , Devarajan Karthik , Zhou Yan , Klein‐Szanto Andres J. , Huang Min , Chernoff Jonathan , Boorjian Stephen A. 
Published: November 2010

What’s known on the subject? and What does the study add? Prior to publication of our paper, evidence had suggested elevated activity of the mTOR pathway in urothelial carcinoma. Separate studies had in addition demonstrated that mTOR inhibition sensitized certain cancer cells to cisplatin therapy. We therefore evaluated the efficacy of mTOR inhibition using in vitro and in vivo models of bladder cancer, and investigated whether mTOR inhibition accentuates the response of bladder cancer cells to cisplatin, which is currently the most effective systemic treatment for metastatic bladder cancer.We found that mTOR blockade inhibits urothelial carcinoma cell proliferation, and enhances the therapeutic efficacy of cisplatin. Our data support a functional relevance for the mTOR signaling pathway in bladder cancer, and provide evidence to suggest the potential for mTOR inhibitors to be used in combination with cisplatin‐based chemotherapy regimens.OBJECTIVE• To investigate whether mammalian target of rapamycin (mTOR) inhibition by rapamycin is therapeutically efficacious in combination with cisplatin for bladder cancer.MATERIALS AND METHODS• Using a panel of human urothelial carcinoma cell lines, we determined the effect of rapamycin on cell viability, cell‐cycle progression, signalling and apoptosis.• The effect of mTOR inhibition on chemosensitivity was investigated by treating cells with rapamycin, alone, or with cisplatin.• The effect of rapamycin or cisplatin treatment was assessed in xenograft mice inoculated with urothelial carcinoma cells.• Expression of p‐mTOR in human bladder cancer specimens was assessed using a tissue microarray.RESULTS• Treatment with rapamycin significantly decreased cell viability in UMUC3 (P= 0.004) and 253J (P < 0.001) cells. It induced arrest in the G0‐G1 phase and decreased activation of p‐mTOR and its downstream effector, p‐S6K, in both cell lines.• Treatment with rapamycin increased the ability of cisplatin to inhibit cell viability in UMUC3 (P= 0.002) and 253J (P= 0.03) cells. No evidence for apoptosis induction was noted after treatment with rapamycin alone.• Mouse xenografts of UMUC3 cells revealed that rapamycin significantly prolonged survival and enhanced the therapeutic efficacy of cisplatin.• In patient urothelial carcinoma specimens, p‐mTOR expression was increased in cancer vs non‐tumour bladder tissue in 65/203 (32.0%) tumours.CONCLUSIONS• mTOR blockade inhibits urothelial carcinoma cell proliferation and enhances the effectiveness of cisplatin.• Suppression of the mTOR pathway has the potential to be a therapeutic target in bladder cancer for selected patients.
Spousal support decreases the negative impact of pain on mental quality of life in women with interstitial cystitis/painful bladder syndrome
Authors: Ginting Jessica V. , Tripp Dean A. , Nickel J. Curtis , Fitzgerald Mary Pat , Mayer Robert 
Published: November 2010

Study Type – Symptom prevalence (case series)Level of Evidence 4What’s known on the subject? and What does the study add?Research has demonstrated that significant others influence the course of pain experienced by individuals with chronic pain. Generally, spousal responses to pain behaviour are associated with higher levels of pain, disability, and depression.The present research discusses novel findings regarding how spousal responses to patient pain behaviour influences the impact of pain on mental quality of life in women with IC/PBS. These findings go beyond correlations, and begin to untangle the circumstances under which pain influences mental quality of life. Women with IC/PBS would benefit from spouse‐led distraction as a way to help them cope with their pain.OBJECTIVE• To examine whether spousal responses to patient pain would alter the association between pain and patient health‐related quality of life (HRQL), depression and disability.METHODS• Ninety‐six women with IC/PBlS (mean age = 50.6 (13.8); mean time since diagnosis = 6.2 years) completed questionnaires on demographics, depressive symptoms (Center for Epidemiological Studies‐Depression Scale), disability (Pain Disability Index), HRQL (Medical Outcomes Study Short Form 12) and a measure of perceived spousal responses to their pain (Multidimensional Pain Inventory).• A repeated measures multivariate analysis of variance examined association changes between pain and adjustment variables at high, moderate and low levels of negative, solicitous and distracting spousal responses.RESULTS• The association between pain and all outcome variables did not vary as a function of levels of solicitous and negative spousal responses.• However, the association between pain and mental HRQL was stronger at lower levels (β=−1.25) of distracting responses than it was at moderate (β=−0.66) and higher (β=−0.06) levels.CONCLUSION• Distracting spousal responses act to ‘buffer’ the deleterious effects of pain on mental HRQL for women suffering from IC/PBlS. Spousal support training may be a useful HRQL intervention.
The learning curve for reducing complications of robotic‐assisted laparoscopic radical prostatectomy by a single surgeon
Authors: Ou Yen‐Chuan , Yang Chi‐Rei , Wang John , Yang Chun‐Kuang , Cheng Chen‐Li , Patel Vipul R. , Tewari Ashutosh K. 
Published: November 2010

Study Type – Therapy (case series)Level of Evidence 4 What’s known on the subject? and What does the study add? Between December 2005 and January 2010, 200 consecutive patients with prostate cancer received RALP performed by a single surgeon. Only one case with Clavien grade II complication due to gouty arthritis. The complication rate was 1%. We suggested that patient with history of gouty arthritis need to prescribe preventive colchicine.OBJECTIVE

To analyse the learning curve for reducing complications of robotic‐assisted laparoscopic radical prostatectomy (RALP) performed by a single surgeon in Taiwan.

PATIENTS AND METHODS

Complication rates were prospectively assessed in 200 consecutive patients undergoing RALP (Group I: cases 1–50; Group II: cases 51–100; Group III: cases 101–150 and Group IV: cases 151–200).
Complications were classified using the Clavien system: grade I: deviation normal postoperative course without treatment; grade II: drug or bedside treatment; grade III: endoscopic or surgical intervention; grade IV: life‐threatening problem; and grade V: death.
Operative parameters and peri‐operative complications were evaluated, including operative and console time, blood loss and transfusion rate, Gleason scores, positive surgical margin (PSM) rate, specimen volume, tumour size, tumour percentage, node positive rate and intra‐ and postoperative complications.

RESULTS

RALP console time was gradually lowered from Group I to Group IV (P < 0.05). Significantly less blood loss occurred after every 50 cases of RALP (Group I 275 mL, Group II 179 mL, Group III 145 mL, Group IV 102 mL, P < 0.001).
Blood transfusion incidence was 8%, 4%, 2% and 0% in Groups I, II, III and IV, respectively.
Complication rates were 18%, 12%, 18% and 0% in Groups I, II, III and IV, respectively.
Major complications (grade III–IV) were 6%, 2%, 4% and 0% in Groups I, II, III and IV, respectively.
Bowel injury occurred in three cases (Group II: 1; Group III: 2); one received intra‐operative repair without sequelae and two received a transient colostomy and later colostomy closure.

CONCLUSIONS

The learning curve for every 50 cases of RALP showed significantly less blood loss and blood transfusion rate.
The learning curve for significantly decreasing complications is 150 cases.
Prognostic significance of lymphovascular invasion in radical prostatectomy specimens
Authors: Yee David S. , Shariat Shahrokh F. , Lowrance William T. , Maschino Alexandra C. , Savage Caroline J. , Cronin Angel M. , Scardino Peter T. , Eastham James A. 
Published: November 2010

Study Type – Prognosis (case series)Level of Evidence 4 What’s known on the subject? and What does the study add? The reported incidence of lymphovascular invasion (LVI) in radical prostatectomy specimens ranges from 5% to 53%. Although LVI has a strong and significant association with adverse clinicopathologic features, it has almost uniformly not been found to be a predictor of biochemical recurrence (BR) on multivariate analysis.This study confirms that LVI is associated with features of aggressive disease and is an independent predictor of BCR. Given that LVI may play a role in the metastatic process, it may be useful in clinical decision‐making regarding adjuvant therapy for patients treated with RP.OBJECTIVESTo determine whether lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens has prognostic significance.The study examined whether LVI is associated with clinicopathological characteristics and biochemical recurrence (BCR).PATIENTS AND METHODSLVI was evaluated based on routine pathology reports on 1298 patients treated with RP for clinically localized prostate cancer between 2004 and 2007.LVI was defined as the unequivocal presence of tumour cells within an endothelium‐lined space.The association between LVI and clinicopathological features was assessed with univariate logistic regression. Cox regression was used to test the association between LVI and BCR.RESULTSLVI was identified in 10% (129/1298) of patients.The presence of LVI increased with advancing pathological stage: 2% (20/820) in pT2N0 patients, 16% (58/363) in pT3N0 patients and 17% (2/12) in pT4N0 patients; and was highest in patients with pN1 disease (52%; 49/94).Univariate analysis showed an association between LVI and higher preoperative prostate‐specific antigen levels and Gleason scores, and a greater likelihood of extraprostatic extension, seminal vesicle invasion, lymph node metastasis and positive surgical margins (all P < 0.001).With a median follow‐up of 27 months, LVI was significantly associated with an increased risk of BCR after RP on univariate (P < 0.001) and multivariate analysis (hazard ratio, 1.77; 95% confidence interval, 1.11–2.82; P= 0.017).As a result of the relatively short follow‐up, the predictive accuracy of the standard clinicopathological features was high (concordance index, 0.880), and inclusion of LVI only marginally improved the predictive accuracy (0.884).CONCLUSIONSAlthough associated with features of aggressive disease and BCR, LVI added minimally to established predictors on short follow‐up.Further study of cohorts with longer follow‐up is warranted to help determine its prognostic significance.
Copines‐1, ‐2, ‐3, ‐6 and ‐7 show different calcium‐dependent intracellular membrane translocation and targeting
Authors: Perestenko Pavel V. , Pooler Amy M. , Noorbakhshnia Maryam , Gray Adrian , Bauccio Charlotte , Jeffrey McIlhinney Robert Andrew 
Published: November 2010

The copines are a family of C2‐ and von Willebrand factor A‐domain‐containing proteins that have been proposed to respond to increases in intracellular calcium by translocating to the plasma membrane. The copines have been reported to interact with a range of cell signalling and cytoskeletal proteins, which may therefore be targeted to the membrane following increases in cellular calcium. However, neither the function of the copines, nor their actual movement to the plasma membrane, has been fully established in mammalian cells. Here, we show that copines‐1, ‐2, ‐3, ‐6 and ‐7 respond differently to a methacholine‐evoked intracellular increase in calcium in human embryonic kidney cell line‐293 cells, and that their membrane association requires different levels of intracellular calcium. We demonstrate that two of these copines associate with different intracellular vesicles following calcium entry into cells, and identify a novel conserved amino acid sequence that is required for their membrane translocation in living cells. Our data show that the von Willebrand factor A‐domain of the copines modulates their calcium sensitivity and intracellular targeting. Together, these findings suggest a different set of roles for the members of this protein family in mediating calcium‐dependent processes in mammalian cells.Structured digital abstract
MINT‐8049236: Copine‐6 (uniprotkb:Q9Z140) and transferrin (uniprotkb:P02787) colocalize (MI:0403) by fluorescence microscopy (MI:0416)
MINT‐8049176: CD2 (uniprotkb:P06729) and Copine‐2 (uniprotkb:P59108) colocalize (MI:0403) by fluorescence microscopy (MI:0416)
Automatic Affective Appraisal of Sexual Penetration Stimuli in Women with Vaginismus or Dyspareunia
Authors: Huijding Jorg , Borg Charmaine , Weijmar-Schultz Willibrord , de Jong Peter J. 
Published: November 2010

ABSTRACT

Introduction
Current psychological views are that negative appraisals of sexual stimuli lie at the core of sexual dysfunctions. It is important to differentiate between deliberate appraisals and more automatic appraisals, as research has shown that the former are most relevant to controllable behaviors, and the latter are most relevant to reflexive behaviors. Accordingly, it can be hypothesized that in women with vaginismus, the persistent difficulty to allow vaginal entry is due to global negative automatic affective appraisals that trigger reflexive pelvic floor muscle contraction at the prospect of penetration.

Aims
To test whether sexual penetration pictures elicited global negative automatic affective appraisals in women with vaginismus or dyspareunia and to examine whether deliberate appraisals and automatic appraisals differed between the two patient groups.

Methods
Women with persistent vaginismus (N = 24), dyspareunia (N = 23), or no sexual complaints (N = 30) completed a pictorial Extrinsic Affective Simon Task (EAST), and then made a global affective assessment of the EAST stimuli using visual analogue scales (VAS).

Main Outcome Measures
The EAST assessed global automatic affective appraisals of sexual penetration stimuli, while the VAS assessed global deliberate affective appraisals of these stimuli.

Results
Automatic affective appraisals of sexual penetration stimuli tended to be positive, independent of the presence of sexual complaints. Deliberate appraisals of the same stimuli were significantly more negative in the women with vaginismus than in the dyspareunia group and control group, while the latter two groups did not differ in their appraisals.

Conclusion
Unexpectedly, deliberate appraisals seemed to be most important in vaginismus, whereas dyspareunia did not seem to implicate negative deliberate or automatic affective appraisals. These findings dispute the view that global automatic affect lies at the core of vaginismus and indicate that a useful element in therapeutic interventions may be the modification of deliberate global affective appraisals of sexual penetration (e.g., via counter-conditioning).
Genome‐wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus
Authors: Medema Marnix H. , Alam Mohammad T. , Heijne Wilbert H. M. , van den Berg Marco A. , Müller Ulrike , Trefzer Axel , Bovenberg Roel A. L. , Breitling Rainer , Takano Eriko 
Published: November 2010

SummaryTo increase production of the important pharmaceutical compound clavulanic acid, a β‐lactamase inhibitor, both random mutagenesis approaches and rational engineering of Streptomyces clavuligerus strains have been extensively applied. Here, for the first time, we compared genome‐wide gene expression of an industrial S. clavuligerus strain, obtained through iterative mutagenesis, with that of the wild‐type strain. Intriguingly, we found that the majority of the changes contributed not to a complex rewiring of primary metabolism but consisted of a simple upregulation of various antibiotic biosynthesis gene clusters. A few additional transcriptional changes in primary metabolism at key points seem to divert metabolic fluxes to the biosynthetic precursors for clavulanic acid. In general, the observed changes largely coincide with genes that have been targeted by rational engineering in recent years, yet the presence of a number of previously unexplored genes clearly demonstrates that functional genomic analysis can provide new leads for strain improvement in biotechnology.