bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional analysis of the jamaicamide gene cluster from the marine cyanobacterium Lyngbya majuscula and identification of possible regulatory proteins
Authors: Jones Adam C , Gerwick Lena , Gonzalez David , Dorrestein Pieter C , Gerwick William H
Published: December 2009

Background

The marine cyanobacterium Lyngbya majuscula is a prolific producer of bioactive secondary metabolites. Although biosynthetic gene clusters encoding several of these compounds have been identified, little is known about how these clusters of genes are transcribed or regulated, and techniques targeting genetic manipulation in Lyngbya strains have not yet been developed. We conducted transcriptional analyses of the jamaicamide gene cluster from a Jamaican strain of Lyngbya majuscula, and isolated proteins that could be involved in jamaicamide regulation.

Results

An unusually long untranslated leader region of approximately 840 bp is located between the jamaicamide transcription start site (TSS) and gene cluster start codon. All of the intergenic regions between the pathway ORFs were transcribed into RNA in RT-PCR experiments; however, a promoter prediction program indicated the possible presence of promoters in multiple intergenic regions. Because the functionality of these promoters could not be verified in vivo, we used a reporter gene assay in E. coli to show that several of these intergenic regions, as well as the primary promoter preceding the TSS, are capable of driving β-galactosidase production. A protein pulldown assay was also used to isolate proteins that may regulate the jamaicamide pathway. Pulldown experiments using the intergenic region upstream of jamA as a DNA probe isolated two proteins that were identified by LC-MS/MS. By BLAST analysis, one of these had close sequence identity to a regulatory protein in another cyanobacterial species. Protein comparisons suggest a possible correlation between secondary metabolism regulation and light dependent complementary chromatic adaptation. Electromobility shift assays were used to evaluate binding of the recombinant proteins to the jamaicamide promoter region.

Conclusion

Insights into natural product regulation in cyanobacteria are of significant value to drug discovery and biotechnology. To our knowledge, this is the first attempt to characterize the transcription and regulation of secondary metabolism in a marine cyanobacterium. If jamaicamide is light regulated, this mechanism would be similar to other cyanobacterial natural product gene clusters such as microcystin LR. These findings could aid in understanding and potentially assisting the management of toxin production by Lyngbya in the environment.
Salt-dependent regulation of a CNG channel subfamily in Arabidopsis
Authors: Kugler Annette , Köhler Barbara , Palme Klaus , Wolff Patricia , Dietrich Petra
Published: December 2009

Background

In Arabidopsis thaliana, the family of cyclic nucleotide-gated channels (CNGCs) is composed of 20 members. Previous studies indicate that plant CNGCs are involved in the control of growth processes and responses to abiotic and biotic stresses. According to their proposed function as cation entry pathways these channels contribute to cellular cation homeostasis, including calcium and sodium, as well as to stress-related signal transduction. Here, we studied the expression patterns and regulation of CNGC19 and CNGC20, which constitute one of the five CNGC subfamilies.

Results

GUS, GFP and luciferase reporter assays were used to study the expression of CNGC19 and CNGC20 genes from Arabidopsis thaliana in response to developmental cues and salt stress. CNGC19 and CNGC20 were differentially expressed in roots and shoots. The CNGC19 gene was predominantly active in roots already at early growth stages. Major expression was observed in the phloem. CNGC20 showed highest promoter activity in mesophyll cells surrounding the veins. Its expression increased during development and was maximal in mature and senescent leaves. Both genes were upregulated in the shoot in response to elevated NaCl but not mannitol concentrations. While in the root, CNGC19 did not respond to changes in the salt concentration, in the shoot it was strongly upregulated in the observed time frame (6-72 hours). Salt-induction of CNGC20 was also observed in the shoot, starting already one hour after stress treatment. It occurred with similar kinetics, irrespective of whether NaCl was applied to roots of intact plants or to the petiole of detached leaves. No differences in K and Na contents of the shoots were measured in homozygous T-DNA insertion lines for CNGC19 and CNGC20, respectively, which developed a growth phenotype in the presence of up to 75 mM NaCl similar to that of the wild type.

Conclusion

Together, the results strongly suggest that both channels are involved in the salinity response of different cell types in the shoot. Upon salinity both genes are upregulated within hours. CNGC19 and CNGC20 could assist the plant to cope with toxic effects caused by salt stress, probably by contributing to a re-allocation of sodium within the plant.
Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery
Authors: Dai Chen-Xin , Gao Qiang , Qiu Shuang-Jian , Ju Min-Jie , Cai Ming-Yan , Xu Yong-Feng , Zhou Jian , Zhang Bo-Heng , Fan Jia
Published: December 2009

Background

Despite well-studied tumor hypoxia in laboratory, little is known about the association with other pathophysiological events in the clinical view. We investigated the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1alpha) in hepatocellular carcinoma (HCC), and its correlations with inflammation, angiogenesis and MYC oncogene.

Methods

In a random series of 110 HCC patients, the mRNA of HIF-1alpha, inflammation related factors (COX-2, MMP7 and MMP9), angiogenesis related factors (VEGF and PDGFRA) and MYC in tumor tissue were detected by real-time RT-PCR and HIF-1alpha protein was assessed by immunohistochemistry. The correlations between HIF-1alpha mRNA and the factors mentioned previously, the relationship between HIF-1alpha and clinicopathologic features, and the prognostic value were analyzed.

Results

The expression of both HIF-1alpha mRNA and protein in HCC were independent prognostic factors for overall survival (OS) (P= 0.012 andP= 0.021, respectively) and disease-free survival (DFS) (P= 0.004 andP= 0.007, respectively) as well. Besides, the high expression of HIF-1alpha mRNA and protein proposed an advanced BCLC stage and more incidence of vascular invasion. The mRNA of HIF-1alpha had significantly positive correlations to that of COX-2, PDGFRA, MMP7, MMP9, MYC, except VEGF. In addition to HIF-1alpha, COX-2 and PDGFRA were also independent prognosticators for OS (P= 0.004 andP= 0.010, respectively) and DFS (P= 0.010 andP= 0.038, respectively).

Conclusion

HIF-1alpha in HCC plays an important role in predicting patient outcome. It may influence HCC biological behaviors and affect the tumor inflammation, angiogenesis and act in concert with the oncogene MYC. Attaching importance to HIF-1alpha in HCC may improve the prognostic and therapeutic technique.
An integrated care program to prevent work disability due to chronic low back pain: a process evaluation within a randomized controlled trial
Authors: Lambeek Ludeke C , van Mechelen Willem , Buijs Peter C , Loisel Patrick , Anema Johannes R
Published: December 2009

Background

In the past decade, a considerable amount of research has been carried out to evaluate the effectiveness of innovative low back pain (LBP) interventions. Although some interventions proved to be effective, they are not always applied in daily practice. To successfully implement an innovative program it is important to identify barriers and facilitators in order to change practice routine. Because usual care is not directly aimed at return to work (RTW), we evaluated an integrated care program, combining a patient-directed and a workplace-directed intervention provided by a multidisciplinary team, including a clinical occupational physician to reduce occupational disability in chronic LBP patients. The aims of this study were to describe the feasibility of the implementation of the integrated care program, to assess the satisfaction and expectations of the involved stakeholders and to describe the needs for improvement of the program.

Methods

Eligible for this study were patients who had been on sick leave due to chronic LBP. Data were collected from the patients, their supervisors and the involved health care professionals, by means of questionnaires and structured charts, during 3-month follow-up. Implementation, satisfaction and expectations were investigated.

Results

Of the 40 patients who were eligible to participate in the integrated care program, 37 patients, their supervisors and the health care professionals actually participated in the intervention. Adherence to the integrated care program was in accordance with the protocol, and the patients, their supervisors and the health care professionals were (very) satisfied with the program. The role of the clinical occupational physician was of additional value in the RTW process. Time-investment was the only barrier for implementation reported by the multidisciplinary team.

Conclusion

The implementation of this program will not be influenced by any flaws in its application that are related to the program itself, or to the adherence of patients with chronic LBP and their health care professionals.

This program is promising in terms of feasibility, satisfaction and compliance of the patients, their supervisors and the health care professionals. Before implementation on a wider scale, the communication and the information technology of the program should be improved.

Trials Registration

[ISRCTN28478651]
Risk factors for human infection with West Nile Virus in Connecticut: a multi-year analysis
Authors: Liu Ann , Lee Vivian , Galusha Deron , Slade Martin D , Diuk-Wasser Maria , Andreadis Theodore , Scotch Matthew , Rabinowitz Peter M
Published: December 2009

Background

The optimal method for early prediction of human West Nile virus (WNV) infection risk remains controversial. We analyzed the predictive utility of risk factor data for human WNV over a six-year period in Connecticut.

Results and Discussion

Using only environmental variables or animal sentinel data was less predictive than a model that considered all variables. In the final parsimonious model, population density, growing degree-days, temperature, WNV positive mosquitoes, dead birds and WNV positive birds were significant predictors of human infection risk, with an ROC value of 0.75.

Conclusion

A real-time model using climate, land use, and animal surveillance data to predict WNV risk appears feasible. The dynamic patterns of WNV infection suggest a need to periodically refine such prediction systems.

Methods

Using multiple logistic regression, the 30-day risk of human WNV infection by town was modeled using environmental variables as well as mosquito and wild bird surveillance.
Activation of hedgehog signaling is not a frequent event in ovarian cancers
Authors: Yang Ling , He Jing , Huang Shuhong , Zhang Xiaoli , Bian Yuehong , He Nonggao , Zhang Hongwei , Xie Jingwu
Published: December 2009

The hedgehog (Hh) signaling pathway regulates many processes of development and tissue homeostasis. Activation of hedgehog signaling has been reported in about 30% of human cancer including ovarian cancer. Inhibition of hedgehog signaling has been pursued as an effective strategy for cancer treatment including an ongoing phase II clinical trial in ovarian cancer. However, the rate of hedgehog signaling activation in ovarian cancer was reported differently by different groups. To predict the successful for future clinical trials of hedgehog signaling inhibitors in ovarian cancer, we assessed hedgehog pathway activation in 34 ovarian epithelial tumor specimens through analyses of target gene expression by in-situ hybridization, immunohistochemistry, RT-PCR and real-time PCR. In contrast to previous reports, we only detected a small proportion of ovarian cancers with hedgehog target gene expression, suggesting that identification of the tumors with activated hedgehog signaling activation will facilitate chemotherapy with hedgehog signaling inhibitors.
Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo
Authors: Gu Shuchen , Papadopoulou Natalia , Gehring Eva-Maria , Nasir Omaima , Dimas Konstantinos , Bhavsar Shefalee K , Föller Michael , Alevizopoulos Konstantinos , Lang Florian , Stournaras Christos
Published: December 2009

Background

Membrane androgen receptors (mAR) have been implicated in the regulation of cell growth, motility and apoptosis in prostate and breast cancer. Here we analyzed mAR expression and function in colon cancer.

Results

Using fluorescent mAR ligands we showed specific membrane staining in colon cell lines and mouse xenograft tumor tissues, while membrane staining was undetectable in healthy mouse colon tissues and non-transformed intestinal cells. Saturation/displacement assays revealed time- and concentration-dependent specific binding for testosterone with a KD of 2.9 nM. Stimulation of colon mAR by testosterone albumin conjugates induced rapid cytoskeleton reorganization and apoptotic responses, even in the presence of anti-androgens. The actin cytoskeleton drug cytochalasin B effectively inhibited the pro-apoptotic responses and caspase-3 activation. Interestingly, in vivo studies revealed that mAR activation resulted in a 65% reduction of tumor incidence in chemically induced Balb/c mice colon tumors.

Conclusion

Our results demonstrate for the first time that functional mARs are predominantly expressed in colon tumors and that their activation results in induction of anti-tumor responses in vitro and extensive reduction of tumor incidence in vivo.
Hypercholesterolemia and Myocardial function evaluated via Tissue Doppler Imaging
Authors: Rubinstein Jack , Pelosi Augusta , Vedre Ameeth , Kotaru Pavan , Abela George S
Published: December 2009

Objective

To establish a link between hypercholesterolemia and myocardial dysfunction.

Background

Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI).

Methods

Twenty-seven rabbits were studied: 7 were fed normal chow (group 1) and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3). Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia.

Results

Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 ± 305 mg/dl vs. 114 ± 95 mg/dl and 87 ± 37 mg/dl; p < 0.01). Myocardial cholesterol content was also higher in group 3 compared to group 2 (0.10 ± 0.04 vs. 0.06 mg/dl ± 0.02; p = 0.05). There was significant correlation between S', E'/A', E/E' and serum cholesterol (r2= 0.17 p = 0.04, r2= 0.37 p = 0.001 and r2= 0.24 p = 0.01).

Conclusion

Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective.
No association of the insulin gene VNTR polymorphism with polycystic ovary syndrome in a Han Chinese population
Authors: Xu Yuping , Wei Zhaolian , Zhang Zhiguo , Xing Qiong , Hu Pin , Zhang Xiaohui , Gao Guihua , Wang Yong , Gao Qian , Yi Long , Cao Yunxia
Published: December 2009

Background

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with an increased risk of type II diabetes mellitus. The results of previous research about the association of the VNTR polymorphism in 5-prime flanking region of the insulin (INS) gene with PCOS have been inconsistent. The present study was to investigate the association of the INS-VNTR polymorphism with PCOS in a Han Chinese population.

Methods

The -23/HphI polymorphism as a surrogate marker of the INS-VNTR length polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in 216 PCOS patients and 192 non-PCOS women as a control group. Allelic and genotypic frequencies were compared between patients and controls, and these results were analyzed in respect to clinical test data.

Results

No significant differences were observed between the cases and controls groups either in allele (P = 0.996) or genotype (P = 0.802) frequencies of INS-VNTR polymorphism; Regarding anthropometric data and hormone levels, there were no significant differences between INS-VNTR genotypes in the PCOS group, as well as in the non-PCOS group.

Conclusion

The present study demonstrated for the first time that the INS-VNTR polymorphism is not a key risk factor for sporadic PCOS in the Han Chinese women. Further studies are needed to give a global view of this polymorphism in pathogenesis of PCOS in a large-scale sample, family-based association design or well-defined subgroups of PCOS.
The construction and characterization of the bi-directional promoter between pp38 gene and 1.8-kb mRNA transcripts of Marek's disease viruses
Authors: Chen Ruiai , Ding Jiabo , Wang Bin
Published: December 2009

Background

Marek's disease virus (MDV) has a bi-directional promoter between pp38 gene and 1.8-kb mRNA transcripts. By sequencing for the promoters from 8 different strains (CVI988, 814, GA, JM, Md5, G2, RB1B and 648A), it is found, comparing with the other 7 MDV strains, CVI988 has a 5-bp (from -628 to -632) deletion in this region, which caused a Sp1 site destroyed. In order to analysis the activity of the promoter, the complete bi-directional promoters from GA and CVI988 were, respectively, cloned into pCAT-Basic vector in both directions for the recombinants pPGA(pp38)-CAT, pPGA(1.8 kb)-CAT, pPCVI(pp38)-CAT and pPCVI(1.8 kb)-CAT. The complete promoter of GA was divided into two single-direction promoters from the replication of MDV genomic DNA, and cloned into pCAT-Basic for pdPGA(pp38)-CAT and pdPGA(1.8 kb)-CAT as well. The above 6 recombinants were then transfected into chicken embryo fibroblasts (CEFs) infected with MDV, and the activity of chloramphenicol acetyltransferase (CAT) was measured from the lysed CEFs 48 h post transfection.

Results

The results showed the activity of the divided promoters was decreased on both directions. In 1.8-kb mRNA direction, it is nearly down to 2.4% (19/781) of the whole promoter, while it keeps 65% (34/52) activity in pp38 direction. The deletion of Sp1 site in CVI988 causes the 20% activity decreased, and has little influence in pp38 direction.

Conclusion

The present study confirmed their result, and the promoter for the 1.8-kb mRNA transcripts is a much stronger promoter than that in the orientation for pp38.
Inferring a transcriptional regulatory network of the cytokinesis-related genes by network component analysis
Authors: Chen Shun-Fu , Juang Yue-Li , Chou Wei-Kang , Lai Jin-Mei , Huang Chi-Ying F , Kao Cheng-Yan , Wang Feng-Sheng
Published: December 2009

Background

Network Component Analysis (NCA) is a network structure-driven framework for deducing regulatory signal dynamics. In contrast to principal component analysis, which can be employed to select the high-variance genes, NCA makes use of the connectivity structure from transcriptional regulatory networks to infer dynamics of transcription factor activities. Using the budding yeast Saccharomyces cerevisiae as a model system, we aim to deduce regulatory actions of cytokinesis-related genes, using precise spatial proximity (midbody) and/or temporal synchronicity (cytokinesis) to avoid full-scale computation from genome-wide databases.

Results

NCA was applied to infer regulatory actions of transcription factor activity from microarray data and partial transcription factor-gene connectivity information for cytokinesis-related genes, which were a subset of genome-wide datasets. No literature has so far discussed the inferred results through NCA are independent of the scale of the gene expression dataset. To avoid full-scale computation from genome-wide databases, four cytokinesis-related gene cases were selected for NCA by running computational analysis over the transcription factor database to confirm the approach being scale-free. The inferred dynamics of transcription factor activity through NCA were independent of the scale of the data matrix selected from the four cytokinesis-related gene sets. Moreover, the inferred regulatory actions were nearly identical to published observations for the selected cytokinesis-related genes in the budding yeast; namely, Mcm1, Ndd1, and Fkh2, which form a transcription factor complex to control expression of the CLB2 cluster (i.e. BUD4, CHS2, IQG1, and CDC5).

Conclusion

In this study, using S. cerevisiae as a model system, NCA was successfully applied to infer similar regulatory actions of transcription factor activities from two various microarray databases and several partial transcription factor-gene connectivity datasets for selected cytokinesis-related genes independent of data sizes. The regulated action for four selected cytokinesis-related genes (BUD4, CHS2, IQG1, and CDC5) belongs to the M-phase or M/G1 phase, consistent with the empirical observations that in S. cerevisiae, the Mcm1-Ndd1-Fkh2 transcription factor complex can regulate expression of the cytokinesis-related genes BUD4, CHS2, IQG1, and CDC5. Since Bud4, Iqg1, and Cdc5 are highly conserved between human and yeast, results obtained from NCA for cytokinesis in the budding yeast can lead to a suggestion that human cells should have the transcription regulator(s) as the budding yeast Mcm1-Ndd1-Fkh2 transcription factor complex in controlling occurrence of cytokinesis.
Spectral affinity in protein networks
Authors: Voevodski Konstantin , Teng Shang-Hua , Xia Yu
Published: December 2009

Background

Protein-protein interaction (PPI) networks enable us to better understand the functional organization of the proteome. We can learn a lot about a particular protein by querying its neighborhood in a PPI network to find proteins with similar function. A spectral approach that considers random walks between nodes of interest is particularly useful in evaluating closeness in PPI networks. Spectral measures of closeness are more robust to noise in the data and are more precise than simpler methods based on edge density and shortest path length.

Results

We develop a novel affinity measure for pairs of proteins in PPI networks, which uses personalized PageRank, a random walk based method used in context-sensitive search on the Web. Our measure of closeness, which we call PageRank Affinity, is proportional to the number of times the smaller-degree protein is visited in a random walk that restarts at the larger-degree protein. PageRank considers paths of all lengths in a network, therefore PageRank Affinity is a precise measure that is robust to noise in the data. PageRank Affinity is also provably related to cluster co-membership, making it a meaningful measure. In our experiments on protein networks we find that our measure is better at predicting co-complex membership and finding functionally related proteins than other commonly used measures of closeness. Moreover, our experiments indicate that PageRank Affinity is very resilient to noise in the network. In addition, based on our method we build a tool that quickly finds nodes closest to a queried protein in any protein network, and easily scales to much larger biological networks.

Conclusion

We define a meaningful way to assess the closeness of two proteins in a PPI network, and show that our closeness measure is more biologically significant than other commonly used methods. We also develop a tool, accessible at http://xialab.bu.edu/resources/pnns, that allows the user to quickly find nodes closest to a queried vertex in any protein network available from BioGRID or specified by the user.
Primary mucinous adenocarcinoma in a defunctionalized urinary bladder: a case report
Authors: Taneous Mary , Ramalingam Preetha , Mode Donald G , Heiner Jared G , Terris Martha K , Lee Jeffrey R
Published: December 2009

Introduction

Malignancies are rare in defunctionalized bladders and are thought to arise from metaplasia secondary to chronic inflammation. Transitional cell and squamous cell carcinomas are the most common but there are three reported cases of mucinous adenocarcinoma.

Case presentation

We report a 57-year-old Caucasian man presenting with penile discharge for 30 years following ileal conduit surgery for neurogenic bladder, and who was found to have primary mucinous adenocarcinoma of his defunctionalized bladder.

Conclusion

Although urinary diversion without cystectomy is less common in current urologic practice, there are many patients with longstanding defunctionalized bladders. While there are no established surveillance protocols, defunctionalized bladder patients with urethral discharge should be evaluated.
Influenza A (H1N1) in Rome, Italy in family: three case reports
Authors: Lisena Francesco , Bordi Licia , Carletti Fabrizio , Castilletti Concetta , Ferraro Federica , Lalle Eleonora , Lanini Simone , Ruscitti Luca Enrico , Fusco Francesco Maria
Published: December 2009

Introduction

A new Influenza A virus H1N1 appeared in March-April 2009, and thousands of cases are being reported worldwide. In the initial months, several imported cases were reported in many European countries, while some countries reported local chains of transmission. We describe the first cluster of in-country transmission of the new Influenza A H1N1 which occurred in Italy, involving 3 patients.

Case presentation

Patient 1, a 11-year-old male child developed fever, cough, and general malaise 4 days after returning from a travel to Mexico. Some days later, the 69-year-old grandfather (patient 2), who did not travel to Mexico, and the 33-month-old brother (patient 3) of patient 1 developed mild influenza symptoms. PCR tests resulted positive for Influenza A, and sequence analysis confirmed infection with the Influenza A (H1N1) strain for all three patients. Some problems were experienced in the administration of chemoprophylaxis and therapy in the patient 3. The chemoprophylaxis policies in other family members are described, too.

Conclusion

Some interesting facts emerge from the analysis of this cluster. The transmission of Influenza A H1N1 virus seems to be dependent on strict contacts. Patient 2 and patient 3 did not take the chemoprophylaxis properly. The problems in the administration of chemoprophylaxis and therapy to patient 3 suggest that in infants specific individual-based strategies for assuring the correct administration are advisable.
Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding
Authors: Schick Kerstin S , Fertmann Jan M , Jauch Karl-Walter , Hoffmann Johannes N
Published: December 2009

Introduction

Prothrombin complex concentrates are recommended for rapid reversal of vitamin K anticoagulants. As they normalize levels of vitamin K dependent clotting factors and re-establish hemostasis, they may also be used as adjunctive therapy in patients with major bleeding. The aim of this study was to retrospectively evaluate the efficacy of prothrombin complex concentrates in the surgical setting.

Methods

The case notes of 50 patients requiring urgent oral anticoagulation reversal (n = 12) or with severe perioperative coagulopathic bleeding (n = 38) who received an infusion of prothrombin complex concentrate (Beriplex P/N(R) 500) at the surgical department of the University of Munich Hospital, Germany were retrospectively reviewed. Efficacy of prothrombin complex concentrate application was evaluated using the Quick test, reported as an international normalized ratio, hemodynamic measurements and requirement for blood products. Safety assessments included whole blood hemoglobin levels and specific parameters of organ dysfunction.

Results

Baseline characteristics were comparable, except that mean baseline international normalized ratio and hemoglobin levels were significantly higher (P < 0.01) in anticoagulation reversal than in bleeding patients. In anticoagulation reversal, the international normalized ratio was significantly reduced (from 2.8 +/- 0.2 at baseline to 1.5 +/- 0.1, P < 0.001) after one prothrombin complex concentrate infusion (median dose 1500 IU; lower quartile 1,000, upper quartile 2,000). No major bleeding was observed during surgery after prothrombin complex concentrate administration. Only one patient received platelets and red blood cell transfusion after prothrombin complex concentrate administration. In bleeding patients, infusion of prothrombin complex concentrate (median dose 2,000 IU; lower quartile 2,000, upper quartile 3,000) significantly reduced the INR from 1.7 +/- 0.1 at baseline to 1.4 +/- 0.1 (P < 0.001). This decrease was unrelated to fresh frozen plasma or vitamin K administration. Bleeding stopped after prothrombin complex concentrate administration in 4/11 (36%) patients with surgical bleeding and 26/27 (96%) patients with diffuse bleeding. Hemoglobin levels increased significantly from baseline in bleeding patients (P < 0.05) and mean arterial pressure stabilized (P < 0.05). No thrombotic events or changes in organ function were reported in any patient.

Conclusions

Prothrombin complex concentrate application effectively reduced international normalized ratios in anticoagulation reversal, allowing surgical procedures and interventions without major bleeding. In bleeding patients, the improvement in coagulation after prothrombin complex concentrate administration was judged to be clinically significant.
Vestibulo-ocular monitoring as a predictor of outcome after severe traumatic brain injury
Authors: Schlosser Hans-Georg , Lindemann Jan-Nikolaus , Vajkoczy Peter , Clarke Andrew H
Published: December 2009

Introduction

Based on the knowledge that traumatic brainstem damage often leads to alteration in brainstem functions, including the vestibulo-ocular reflex, the present study is designed to determine whether prediction of outcome in the early phase after severe traumatic brain injury is possible by means of vestibulo-ocular monitoring.

Methods

Vestibulo-ocular monitoring is based on video-oculographic recording of eye movements during galvanic labyrinth polarization. The integrity of vestibulo-ocular reflex is determined from the eye movement response during vestibular galvanic labyrinth polarization stimulation. Vestibulo-ocular monitoring is performed within three days after traumatic brain injury and the oculomotor response compared to outcome after six months (Glasgow Outcome Score).

Results

Twenty-seven patients underwent vestibulo-ocular monitoring within three days after severe traumatic brain injury. One patient was excluded from the study. In 16 patients oculomotor response was induced, in the remaining 11 patients no oculomotor response was observed. The patients' outcome was classified as Glasgow Outcome Score 1-2 or as Glasgow Outcome Score 3 to 5. Statistical testing supported the hypothesis that those patients with oculomotor response tended to recover (exact two-sided Fisher-Test (P < 10-3)).

Conclusions

The results indicate that vestibulo-ocular monitoring with galvanic labyrinth polarization performed during the first days after traumatic brain injury helps to predict favourable or unfavourable outcome. As an indicator of brainstem function, vestibulo-ocular monitoring provides a useful, complementary approach to the identification of brainstem lesions by imaging techniques.
Using a Replica of Leeuwenhoek's Microscope to Teach the History of Science and to Motivate Students to Discover the Vision and the Contributions of the First Microscopists
Authors: Sepel Lenira M.N. , Loreto Elgion L.S. , Rocha João B.T.
Published: December 2009

The history of science should be incorporated into science teaching as a means of improving learning and also to increase the students' understanding about the nature of science. In biology education, the history of microscopy deserves a special place. The discovery of this instrument not only opened a new and fantastic microworld but also led to the development of one unifying principle of biological sciences (i.e., cell theory). The microscopes of Leeuwenhoek and Hooke opened windows into the microworld of living organisms. In the present work, the knowledge of these themes was analyzed in a group of students beginning an undergraduate biology course. Our data suggest that the history of microscopy is poorly treated at the secondary school level. We propose a didactic activity using a replica of Leeuwenhoek's microscope made with Plexiglas and a lens obtained from a key chain laser pointer or from a broken CD drive. The proposed activity motivated students to learn about microscopy and helped them to appreciate scientific knowledge from a historical perspective.
Linking Assessment Questions to a Research Article to Stimulate Self-directed Learning and Develop High-order Cognitive Skills in an Undergraduate Module of Molecular Genetics
Authors: Wu Jinlu
Published: December 2009

Assessment plays a crucial role in the learning process, but current assessments focus on assessment of learning rather than assessment for learning. In this study, a novel method for open-book continuous assessment (CA) was developed. The aim was to encourage students to learn beyond the textbook by challenging students with questions linked to a research article. Research articles closely related to lecture contents were selected and released to students before the CA for perusal. CA questions were set at three different levels to assess conceptual understanding, application, and synthesis. The CA was administered to first-year undergraduate students majoring in life science as part of Molecular Genetics, a compulsory module. It contributed 10% of the student's grade for the module. Students’ CA scores indicated that the majority could answer correctly all the questions. Students’ feedback on the CA showed that most of them praised the CA model for its novelty, motivation, and application. Only a few criticized it due to its poor coverage of lecture contents. Overall, this CA went beyond the traditional role of assessments in the assignment of scores and stimulated curiosity and self-directed learning.
From Genes to Proteins to Behavior: A Laboratory Project That Enhances Student Understanding in Cell and Molecular Biology
Authors: Aronson Benjamin D. , Silveira Linda A.
Published: December 2009

In the laboratory, students can actively explore concepts and experience the nature of scientific research. We have devised a 5-wk laboratory project in our introductory college biology course whose aim was to improve understanding in five major concepts that are central to basic cellular, molecular biology, and genetics while teaching molecular biology techniques. The project was focused on the production of adenine in Saccharomyces cerevisiae and investigated the nature of mutant red colonies of this yeast. Students created red mutants from a wild-type strain, amplified the two genes capable of giving rise to the red phenotype, and then analyzed the nucleotide sequences. A quiz assessing student understanding in the five areas was given at the start and the end of the course. Analysis of the quiz showed significant improvement in each of the areas. These areas were taught in the laboratory and the classroom; therefore, students were surveyed to determine whether the laboratory played a role in their improved understanding of the five areas. Student survey data demonstrated that the laboratory did have an important role in their learning of the concepts. This project simulated steps in a research project and could be adapted for an advanced course in genetics.
Kathleen Nolan
Authors: Mays Hoopes Laura L.
Published: December 2009

Note from the Editor

Educator Highlights for CBE-LSE show how professors at different kinds of institutions educate students in life sciences with inspiration and panache. If you have a particularly creative teaching portfolio yourself, or if you wish to nominate an inspiring colleague to be profiled, please email Laura Hoopes at lhoopes@pomona.edu .
Did the author of Psalm 30 have cyclothymia or bipolar disorder?
Authors: Stein George
Published: December 2009

Psalm 30 is a short psalm used as a song for the dedication of the Temple. It contains a description in religious terminology of two abrupt changes of mood which seem to resemble the mood switches of affective disorder. Examples quoted here are verses 30:3–5 and 30:8–12.
Empirical typology of bipolar I mood episodes
Authors: Solomon David A. , Leon Andrew C. , Endicott Jean , Coryell William H. , Li Chunshan , Fiedorowicz Jess G. , Keller Martin B.
Published: December 2009

Background

Much remains unknown about the phenomenology of bipolar I disorder.

Aims

To determine the type of bipolar I mood episodes that occur over time, and their relative frequency.

Method

A total of 219 individuals with Research Diagnostic Criteria bipolar I disorder were prospectively followed for up to 25 years (median 20 years). Psychopathology was assessed with the Longitudinal Interval Follow-up Evaluation.

Results

Overall, 1208 mood episodes were prospectively observed. The episodes were empirically classified as follows: major depression, 30.9% (n= 373); minor depression, 13.0% (n= 157); mania, 20.4% (n= 246); hypomania, 10.4% (n= 126); cycling, 17.3% (n= 210); cycling plus mixed state, 7.8% (n= 94); and mixed, 0.2% (n= 2).

Conclusions

Cycling episodes constituted 25% of all episodes. Work groups revising ICD–10 and DSM–IV should add a category for bipolar I cycling episode.
Treatment of ischaemic heart disease and stroke in individuals with psychosis under universal healthcare
Authors: Kisely Stephen , Campbell Leslie Anne , Wang Yan
Published: December 2009

Background

Most data on the quality of vascular care for individuals with psychiatric conditions come from countries without universal healthcare.

Aims

To investigate the treatment of people with psychosis admitted for ischaemic heart disease or stroke under universal healthcare.

Method

A population-based study of administrative data comparing Canadians with and without a history of schizophrenia or related psychosis (n= 65 039).

Results

Of 49 248 admissions for ischaemic heart disease, 1285 had a history of psychosis. Despite a higher 1-year mortality, they were less likely to receive guideline-consistent treatment: e.g. coronary artery bypass grafting (adjusted odds ratio (OR) = 0.35, 95% CI 0.25–0.48), beta-blockers (adjusted OR = 0.82, 95% CI 0.71–0.95) and statins (adjusted OR = 0.51, 95% CI 0.41–0.63). Of 15 791 admissions for stroke, 594 had a history of psychosis. Despite higher 1-year mortality rates, they were less likely to receive cerebrovascular arteriography or warfarin.

Conclusions

People with a history of psychosis do not receive equitable levels of vascular care under universal healthcare.
Combined Resistance and Aerobic Exercise Program Reverses Muscle Loss in Men Undergoing Androgen Suppression Therapy for Prostate Cancer Without Bone Metastases: A Randomized Controlled Trial
Authors: Galvão Daniel A. , Taaffe Dennis R. , Spry Nigel , Joseph David , Newton Robert U.
Published: December 2009

Purpose

Androgen suppression therapy (AST) results in musculoskeletal toxicity that reduces physical function and quality of life. This study examined the impact of a combined resistance and aerobic exercise program as a countermeasure to these AST-related toxicities.

Patients and Methods

Between 2007 and 2008, 57 patients with prostate cancer undergoing AST (commenced > 2 months prior) were randomly assigned to a program of resistance and aerobic exercise (n = 29) or usual care (n = 28) for 12 weeks. Primary end points were whole body and regional lean mass. Secondary end points were muscle strength and function, cardiorespiratory capacity, blood biomarkers, and quality of life.

Results

Analysis of covariance was used to compare outcomes for groups at 12 weeks adjusted for baseline values and potential confounders. Patients undergoing exercise showed an increase in lean mass compared with usual care (total body, P = .047; upper limb, P < .001; lower limb, P = .019) and similarly better muscle strength (P < .01), 6-meter walk time (P = .024), and 6-meter backward walk time (P = .039). Exercise also improved several aspects of quality of life including general health (P = .022) and reduced fatigue (P = .021) and decreased levels of C-reactive protein (P = .008). There were no adverse events during the testing or exercise intervention program.

Conclusion

A relatively brief exposure to exercise significantly improved muscle mass, strength, physical function, and balance in hypogonadal men compared with normal care. The exercise regimen was well tolerated and could be recommended for patients undergoing AST as an effective countermeasure to these common treatment-related adverse effects.
Revised Tumor and Node Categorization for Rectal Cancer Based on Surveillance, Epidemiology, and End Results and Rectal Pooled Analysis Outcomes
Authors: Gunderson Leonard L. , Jessup John Milburn , Sargent Daniel J. , Greene Frederick L. , Stewart Andrew
Published: December 2009

Purpose

The sixth edition of the American Joint Committee on Cancer (AJCC) rectal cancer staging subdivided stage II into IIA (T3N0) and IIB (T4N0) and stage III into IIIA (T1-2N1M0), IIIB (T3-4N1M0), and IIIC (anyTN2M0). Subsequent analyses supported revised substaging of stage III as a result of improved survival with T1-2N2 versus T3-4N2 and survival of T4N1 more similar to T3-4N2 than T3N1. The AJCC Hindgut Taskforce sought population-based validation that depth of invasion interacts with nodal status to affect survival.

Methods

Surveillance, Epidemiology, and End Results (SEER) population-based data from January 1992 to December 2004 for 35,829 patients with rectal cancer were compared with rectal pooled analysis data (3,791 patients). T4N0 cancers were stratified by tumors that perforate visceral peritoneum (T4a) versus tumors that invade or are adherent to adjacent organs or structures (T4b). N1 and N2 were stratified by number of positive nodes as follows: N1a/N1b (one v two to three nodes) and N2a/N2b (four to six v ≥ seven nodes). Five-year observed and relative survival rates were obtained for each TN category.

Results

SEER rectal cancer analyses confirm that T1-2N2 cancers have better prognosis than T3-4N2, T4bN1 have similar prognosis to T4N2, T1-2N1 have similar prognosis to T2N0/T3N0, and T1-2N2a have similar prognosis to T2N0/T3N0 (T1N2a) or T4aN0 (T2N2a). Prognosis for T4a lesions is better than T4b by N category. The number of positive nodes affects prognosis.

Conclusion

This SEER population-based rectal cancer analysis validates the rectal pooled analyses and supports the shift of T1-2N2 lesions from IIIC to IIIA or IIIB and T4bN1 from IIIB to IIIC. SEER outcomes support subdividing T4, N1, and N2 and revised substaging of stages II and III. Survival by TN category suggests a complex biologic interaction between depth of invasion and nodal status.
Assessment of the Applicability of EU Biomass Technologies in Turkey
Authors: Bascetincelik Ali , Ozturk H. Huseyin , Ekinci Kamil , Kaya Durmuş , Kacira Murat , Karaca Cengiz
Published: December 2009

An assessment of the applicability of EU biomass technologies in Turkey is presented. SWOT analysis was applied for the implementation of EU biomass technology in Turkey. Market overview, EU biomass technologies implementation in Turkey, market competition and comparison with competing fuels, manufacturers-distribution channels-sales networks, application areas, investment incentives-financing techniques, the changing market conditions and critical success factors were assessed in this study. An ultimate objective of this study is to transfer the European experience and practices relative to the overall framework of managing agricultural waste.
Consensus miRNA expression profiles derived from interplatform normalization of microarray data
Authors: Bargaje Rhishikesh , Hariharan Manoj , Scaria Vinod , Pillai Beena
Published: December 2009

Eukaryotic gene expression is controlled at the post-transcriptional level by small noncoding RNAs called microRNAs (miRNA). miRNAs play important roles during early development and participate in gene regulatory circuits in the cell. Different high-throughput expression analysis methods including microarrays, bead-based detection, and small RNA cloning have been applied to quantitatively detect miRNAs in various tissues, cell types, and biological conditions. High-throughput expression data was collected from public repositories and processed to create a database of miRNA expression profiles. Several commonly used normalization methods were compared to identify suitable methods for cross-platform comparison of high-throughput miRNA expression data. The database provides interlaboratory and interplatform validated reference expression levels for miRNAs. The normalized expression profiles were validated by querying for well-established features of miRNA expression. Firstly, expression profiles of several tissue-specific miRNAs showed good agreement between the database and previously reported profiles. We have also identified a set of miRNAs that are constitutively expressed across mammalian tissues. Secondly, we used the database to compare the expression patterns of miRNAs belonging to the let-7 family, where the divergence in expression patterns implies that they may have diversified functionally. Lastly, we compared expression profiles of intronic and clustered miRNAs. Expression profiles of intronic miRNAs and clustered miRNAs showed either very good, or in certain cases, very poor correlation with the host gene. Interplatform comparison of miRNA expression profiles thus provides a resource of consensus expression profiles that can be used in the future for studying miRNA function and regulation.
Effects of chemical modification on the potency, serum stability, and immunostimulatory properties of short shRNAs
Authors: Ge Qing , Dallas Anne , Ilves Heini , Shorenstein Joshua , Behlke Mark A. , Johnston Brian H.
Published: December 2009

Small hairpin RNAs (shRNAs) with 19-base-pair, or shorter, stems (short shRNAs [sshRNAs]) have been found to constitute a class whose mechanism of action appears to be distinct from that of small interfering RNAs (siRNAs) or longer shRNAs. These sshRNAs can be as active as canonical siRNAs or longer shRNAs. Their activity is affected by whether the antisense strand is positioned 5′ or 3′ to the loop (L or R sshRNAs, respectively). Dicer seems not to be involved in the processing of sshRNAs, although the mechanism of target gene suppression by these hairpins is through Ago2-mediated mRNA cleavage. In this study, the effects of chemical modifications on the potency, serum stability, and innate immune response of sshRNAs were investigated. Deoxynucleotide substitution and 2′-O-methyl (2′-OMe) modification in the sense strand and loop did not affect silencing activity, but, unlike with siRNAs, when placed in the antisense strand these modifications were detrimental. Conjugation with bulky groups at the 5′-end of L sshRNAs or 3′-end of R sshRNAs had a negative impact on the potency. Unmodified sshRNAs in dimer form or with blunt ends were immunostimulatory. Some modifications such as 3′-end conjugation and phosphorothioate linkages on the backbone of the sshRNAs could also induce inflammatory cytokine production. However, 2′-OMe substitution of sshRNAs abrogated the innate immune response and improved the serum stability of the hairpins.