bluuebunny/crossref_metadata_2025 huggingface dataset:
LIS1 Duplication
Authors: Lockrow Jason P. , Holden Kenton R. , Dwivedi Alka , Matheus Maria G. , Lyons Michael J.
Published: December 2011

Disruptions to LIS1 gene expression result in neuronal migration abnormalities. LIS1 heterozygosity is a significant cause of lissencephaly, while overexpression has recently been noted in cases of microcephaly, ventriculomegaly, and dysgenesis of the corpus callosum with normal cortical gyration. We report a partial LIS1 duplication in a child with microcephaly, neurodevelopmental delays, and profound white matter atrophy in the absence of overt lissencephaly. The duplicated genetic segment was contained entirely within the first intron of LIS1, a segment that often contains inducers of transcription. Normal gyral patterns with mild volume loss were observed at birth. Follow-up cranial imaging revealed further white matter loss, diminished sulcation, and ventriculomegaly, suggesting expanding hydrocephalus ex vacuo. The radiographic pattern has not been documented in the presence of a LIS1 gene abnormality, and suggests that altered expression of LIS1 has wider phenotypic manifestations than currently defined.
Dehiscence of Corticosteroid-Induced Abdominal Striae in a 14-Year-Old Boy Treated With Bevacizumab for Recurrent Glioblastoma
Authors: Wheeler Helen , Black Jason , Webb Suzanne , Shen Han
Published: December 2011

Corticosteroids have been the mainstay for management of cerebral edema caused by leaky angiogenic vessels associated with high-grade brain tumors since the early 1960s. Chronic corticosteroid use can cause iatrogenic Cushing syndrome, which is associated with weight gain and abdominal striae (striae distensae). The anti–vascular endothelial growth factor therapy, bevacizumab, has recently been introduced for the management of recurrent glioblastoma. Vascular endothelial growth factor plays multiple roles in wound healing, including promoting angiogenesis, acting as a chemo-attractant for inflammatory cells, and stimulating collagen production. We report the first pediatric case of a 14-year-old boy with corticosteroid-induced abdominal striae who developed ulceration and dehiscence of the striae following the introduction of bevacizumab therapy. The combination of high-dose corticosteroids and anti–vascular endothelial growth factor therapy may cause significant complications, especially in children who are susceptible to abdominal striae and therefore should be avoided.
This Far, but No Further?
Authors: Spehar Andrea
Published: December 2011

The European Union (EU) is one of the world’s most important policy promoters for gender equality. This article examines the benefits and limitations of EU gender equality policy making in two Western Balkan countries, Croatia and FYR Macedonia. Besides analyzing specific gender policy developments that can be attributed to the EU, particular focus is put on the women’s movement activists’ perceptions of the impact that accession may have on women and gender equality. The study demonstrates that while the Croatian and Macedonian EU accession processes have been beneficial to the introduction of new gender legislation and institutional mechanisms for the advancement of gender equality, the EU gender strategy has also shown serious limitations. Among these—and perhaps the most fundamental—is the strong contrast between stated goals and their actual implementation. I argue that unless profound institutional changes as well as changes in political culture take place in Croatia and Macedonia, the poor compliance with EU gender equality norms and policies will be hard to overcome.
Modeling the Transition between Dense Metal and Damaged (Microporous) Metal Viscoplasticity
Authors: Longère Patrice , Geffroy Anne-Gaëlle , Leblé Bruno , Dragon André
Published: December 2011

This article presents a physically motivated approach, which has been developed in order to describe the transition of behavior between dense metal plasticity and microporous metal plasticity in the context of dynamic plasticity and adiabatic conditions. Considering that void germination requires a certain amount of plastic deformation, a ‘primary’ hole nucleation criterion as well as a statistical law governing the ‘secondary’ hole formation kinetics has been proposed. In a consistent way, the hole nucleation criterion accounts for the accelerating effects of stress triaxiality and the delaying effects of temperature and strain rate. In addition, a modification of the GTN model was proposed, allowing for describing cavity growth under shear loading. The 3D constitutive equations were implemented as user material in the engineering finite element computation code Abaqus®. Numerical simulations were conducted considering a single finite element under uniaxial tensile loading and simple shear then notched cylindrical samples under remote uniaxial tensile loading. The numerical results clearly show the influence of the hole nucleation criteria on the ductile damage and failure.
Surgical Management of Minimally Invasive Aortic Valve Operations
Authors: Johnston William F. , Ailawadi Gorav
Published: December 2011

Although there is still a role for conventional sternotomy for aortic valve replacement, minimally invasive techniques are increasing in popularity and may benefit the patient with shorter postoperative course, less morbidity, and decreased overall cost. Additionally, transcatheter procedures have recently shown promising results in high-risk patients. This article provides an overview of the development of minimally invasive aortic valve operations, including a brief history of minimally invasive approaches, surgical considerations during minimally invasive aortic valve replacement, and the technical approach to performing a hemisternotomy with aortic valve replacement. In addition, the authors review transcatheter techniques, including aortic valve replacement via a sheath placed in the apex of the left ventricle or through a sheath placed in the femoral vessels. Finally, the exciting results of the PARTNER trial and the effect of these results on the future of aortic valve surgery are discussed.
Non-specific alterations of craniocervical venous drainage in multiple sclerosis revealed by cardiac-gated phase-contrast MRI
Authors: Ertl-Wagner Birgit , Koerte Inga , Kümpfel Tania , Blaschek Astrid , Laubender Ruediger P , Schick Max , Steffinger Denise , Kaufmann David , Heinen Florian , Reiser Maximilian , Alperin Noam , Hohlfeld Reinhard
Published: December 2011

Objective:

There is an on-going controversy about venous drainage abnormalities in multiple sclerosis (MS). We applied cardiac-gated phase-contrast and venographic magnetic resonance (MR) techniques to compare venous drainage patterns in patients with MS, healthy controls, and subjects with migraine.

Methods:

A total of 27 patients with MS (21 female, age 12–59 years, mean disease duration 8.4 ± 8.5 years) and 27 age- and gender-matched healthy controls (21 female, age 12–60 years) were investigated with velocity-encoded cine-phase contrast MR sequences and a 2D time-of-flight MR venography of the cervicocranial region on a 3-T MRI. The data were compared with 26 patients with chronic migraine headaches (19 female, age 17–62 years), previously investigated with the same protocol. The degree of primary and secondary venous outflow in relation to the total cerebral blood flow (tCBF) was compared both quantitatively and qualitatively. Statistical analyses were performed using linear regression models.

Results:

Secondary venous outflow was significantly increased in patients with MS compared with healthy controls, both qualitatively ( p < 0.001) and quantitatively ( p < 0.013). The observed changes were independent of age and disease duration. Very similar alterations of venous drainage were detectable with the same approach in patients with migraine, without significant differences between MS and migraine patients ( p = 0.65).

Conclusion:

Our MRI-based study suggests that patients with MS have alterations of cerebral venous drainage similar to subjects with chronic migraine. These non-disease-specific changes seem to a secondary phenomenon rather than being of primary pathogenic importance.
The Clinical Ethnographic Interview: A user-friendly guide to the cultural formulation of distress and help seeking
Authors: Arnault Denise Saint , Shimabukuro Shizuka
Published: December 2011

Transcultural nursing, psychiatry, and medical anthropology have theorized that practitioners and researchers need more flexible instruments to gather culturally relevant illness experience, meaning, and help seeking. The state of the science is sufficiently developed to allow standardized yet ethnographically sound protocols for assessment. However, vigorous calls for culturally adapted assessment models have yielded little real change in routine practice. This paper describes the conversion of the Diagnostic and Statistical Manual IV, Appendix I Outline for Cultural Formulation into a user-friendly Clinical Ethnographic Interview (CEI), and provides clinical examples of its use in a sample of highly distressed Japanese women.
“I felt so hurt and lonely”: Suicidal behavior in South Asian-Surinamese, Turkish, and Moroccan women in the Netherlands
Authors: van Bergen Diana D. , van Balkom Anton J. L. M. , Smit Johannes H. , Saharso Sawitri
Published: December 2011

Young immigrant women in the Netherlands demonstrate disproportionate rates of suicidal behavior. This study investigated the origins of suicidal behavior in South Asian-Surinamese, Turkish, and Moroccan immigrant young women in order to identify ethnic- and gender-specific patterns of suicidal behavior. Based on life story interviews of women who had been enrolled in mental health care, we constructed five typical patterns in which social, cultural, and personal factors were interconnected. Suicidal behavior was influenced by the ability and right to act autonomously with regard to strategic life choices, as well as by the questioning of cultural values of self-sacrifice and protection of honor.
Heteronormative pheromones? A feminist approach to human chemical communication
Authors: Sieben Anna
Published: December 2011

I analyse scientific articles on human pheromones from a critical feminist perspective, using new materialist feminist theories, in particular, the work of Judith Butler, Karen Barad and Annemarie Mol. Pheromones were defined by Karlson and Lüscher in 1959 as ‘substances which are secreted to the outside by an individual and received by a second individual of the same species, in which they release a specific reaction – for example, a definite behavior or a developmental process’. In humans, it remains unclear whether substances act as pheromones. With reference to Butler, I show how heteronormativity as a discourse influences research on two potential human pheromones, androstadienone and estratetraenol. I argue that experiments on these two substances have been set up to combine sex-specificity, heterosexuality and reproduction. In these experiments, only the inconsistent effects of androstadienone and estratetraenol were demonstrated. With reference to Barad, I interpret this inconsistency as an indicator of ‘resistant matter’. I argue that in order to experimentally show ‘heteronormative pheromones’ materialities (pheromones) have to merge with discourse (heteronormativity). Androstadienone and estratetraenol partly refuse this collaboration. Finally, I refer to Mol's concept of multiple realities and discuss whether alternative, non-heteronormative effects of pheromones occur instead.
Critical features of short break and community support services to families and disabled young people whose behaviour is severely challenging
Authors: McConkey Roy , Gent Clare , Scowcroft Emma
Published: December 2011

Parenting a child with severely challenging behaviours is very stressful and threatens family well-being. Short break (respite) services are commonly provided as a support to families but surprisingly little attention has been paid to adapting these services when children and families have complex needs. This article describes the model of service that has evolved in three separate locations which successfully provides overnight short breaks and/or community-based support to families. The model was documented and validated through individual and group interviews with a range of stakeholders – around 30 in all. The services are embedded within multi-agency partnerships and four particular features are highlighted: the values and ethos underpinning the service; the service procedures; the organization of short breaks; and the role of an intensive support/outreach service. The rationale for complex service models is discussed and the key lessons for replicating this model are reviewed.
The impact of social policy on changes in professional practice within learning disability services: different standards for children and adults? A two-part examination
Authors: Race David G. , Malin Nigel A.
Published: December 2011

This is the second of two articles examining links between policy developments and changes in professional practice within learning disability services in England. The first article focused on policy foundations over the last 30 years, and concluded that there was a developing gap in professional inputs between children’s and adult services. This article, written one year into the Coalition government, argues that its policies – especially the large-scale reduction in public expenditure, but also the decline in support for inclusion of children in mainstream education, the rapid growth of academies, and proposals for the reorganization of the NHS – have exacerbated the trends identified earlier. In addition, local authorities, though outwardly compliant, have variously interpreted their responsibilities under the personalization agenda, in particular in relation to individual budgets, and this has resulted in assessments of need being based on ‘service hours’ rather than service quality and staff qualifications.
Subluxation-related ulnar neuropathy (SUN) syndrome related to distal radioulnar joint instability
Authors: Malone P. S. C. , Hutchinson C. E. , Kalson N. S. , Twining C. J. , Terenghi G. , Lees V. C.
Published: December 2011

Ulnar neuropathy coexistent with distal radioulnar joint (DRUJ) instability has previously been observed in our practice. The aim of this study was to define this phenomenon and investigate the hypothesis that the cause of this intermittent, positional ulnar neuropathy is related to kinking of the ulnar nerve about the DRUJ. Ulna neuropathy was present in 10/51 (19.6%) of a historical cohort of patients who presented with DRUJ instability. Nine subsequent patients with DRUJ instability and coexistent ulnar neuropathy underwent 3-T magnetic resonance imaging to better understand the mechanism of the observed syndrome. Both 3D qualitative and quantitative analyses were used to assess the presence of nerve ‘kinking’, displacing the nerve from its normal course and causing nerve compression/distraction in the distal forearm and Guyon’s canal. Results of the quantitative analysis were statistically significant ( p < 0.05). The clinical features of the condition have been delineated and termed subluxation-related ulnar neuropathy or SUN syndrome. The imaging study was a level II diagnostic study.
Traction radiography for the diagnosis of scapholunate ligament tears: an experimental cadaver study
Authors: Hohendorff B. , Burkhart K. J. , Stein G. , Mühldorfer-Fodor M. , Müller L. P.
Published: December 2011

The aim of this experimental cadaver study was to verify that thumb traction radiography can be used to diagnose scapholunate interosseous ligament (SLIL) injury. Eight cadaver forearms were positioned vertically so that the thumb could be held in a Chinese finger trap and traction force applied using a 5 kg weight. Fluoroscopy was performed with the thumb unloaded and under traction, and then unloaded and under traction after division of the SLIL. The scapholunate joint gaps were measured electronically. The difference between the unloaded and loaded wrists with sectioned SLIL was not statistically significant. These results suggest that thumb traction radiography might not reliably detect acute, complete SLIL tears.
Comprehensive analysis of tandem amino acid repeats from ten angiosperm genomes
Authors: Zhou Yuan , Liu Jing , Han Lei , Li Zhi-Gang , Zhang Ziding
Published: December 2011

Background

The presence of tandem amino acid repeats (AARs) is one of the signatures of eukaryotic proteins. AARs were thought to be frequently involved in bio-molecular interactions. Comprehensive studies that primarily focused on metazoan AARs have suggested that AARs are evolving rapidly and are highly variable among species. However, there is still controversy over causal factors of this inter-species variation. In this work, we attempted to investigate this topic mainly by comparing AARs in orthologous proteins from ten angiosperm genomes.

Results

Angiosperm AAR content is positively correlated with the GC content of the protein coding sequence. However, based on observations from fungal AARs and insect AARs, we argue that the applicability of this kind of correlation is limited by AAR residue composition and species' life history traits. Angiosperm AARs also tend to be fast evolving and structurally disordered, supporting the results of comprehensive analyses of metazoans. The functions of conserved long AARs are summarized. Finally, we propose that the rapid mRNA decay rate, alternative splicing and tissue specificity are regulatory processes that are associated with angiosperm proteins harboring AARs.

Conclusions

Our investigation suggests that GC content is a predictor of AAR content in the protein coding sequence under certain conditions. Although angiosperm AARs lack conservation and 3D structure, a fraction of the proteins that contain AARs may be functionally important and are under extensive regulation in plant cells.
Origin of multiple periodicities in the Fourier power spectra of the Plasmodium falciparum genome
Authors: Nunes Miriam CS , Wanner Elizabeth F , Weber Gerald
Published: December 2011

Background

Fourier transforms and their associated power spectra are used for detecting periodicities and protein-coding genes and is generally regarded as a well established technique. Many of the periodicities which have been found with this method are quite well understood such as the periodicity of 3 nt which is associated to codon usage. But what is the origin of the peculiar frequency multiplesk/21 which were reported for a tiny section of chromosome 2 inP. falciparum? Are these present in other chromosomes and perhaps in related organisms? And how should we interpret fractional periodicities in genomes?

Results

We applied the binary indicator power spectrum to all chromosomes ofP. falciparum, and found that the frequency overtonesk/21 are present only in non-coding sections. We did not find such frequency overtones in any other related genomes. Furthermore, the frequency overtones were identified as artifacts of the way the genome is encoded into a numerical sequence, that is, they are frequency aliases. By choosing a different way to encode the sequence the overtones do not appear. In view of these results, we revisited early applications of this technique to proteins where frequency overtones were reported.

Conclusions

Some authors hinted recently at the possibility of mapping artifacts and frequency aliases in power spectra. However, in the case ofP. falciparumthe frequency aliases are particularly strong and can mask the 1/3 frequency which is used for gene detecting. This shows that albeit being a well known technique, with a long history of application in proteins, few researchers seem to be aware of the problems represented by frequency aliases.
Maximum predictive power of the microarray-based models for clinical outcomes is limited by correlation between endpoint and gene expression profile
Authors: Zhao Chen , Shi Leming , Tong Weida , Shaughnessy John D , Oberthuer André , Pusztai Lajos , Deng Youping , Symmans W Fraser , Shi Tieliu
Published: December 2011

Background

Microarray data have been used for gene signature selection to predict clinical outcomes. Many studies have attempted to identify factors that affect models' performance with only little success. Fine-tuning of model parameters and optimizing each step of the modeling process often results in over-fitting problems without improving performance.

Results

We propose a quantitative measurement, termed consistency degree, to detect the correlation between disease endpoint and gene expression profile. Different endpoints were shown to have different consistency degrees to gene expression profiles. The validity of this measurement to estimate the consistency was tested with significance at a p-value less than 2.2e-16 for all of the studied endpoints. According to the consistency degree score, overall survival milestone outcome of multiple myeloma was proposed to extend from 730 days to 1561 days, which is more consistent with gene expression profile.

Conclusion

For various clinical endpoints, the maximum predictive powers of different microarray-based models are limited by the correlation between endpoint and gene expression profile of disease samples as indicated by the consistency degree score. In addition, previous defined clinical outcomes can also be reassessed and refined more coherent according to related disease gene expression profile. Our findings point to an entirely new direction for assessing the microarray-based predictive models and provide important information to gene signature based clinical applications.
Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers
Authors: Luo Hongmei , Sun Chao , Sun Yongzhen , Wu Qiong , Li Ying , Song Jingyuan , Niu Yunyun , Cheng Xianglin , Xu Hongxi , Li Chuyuan , Liu Juyan , Steinmetz André , Chen Shilin
Published: December 2011

Background

Panax notoginseng (Burk) F.H. Chen is important medicinal plant of the Araliacease family. Triterpene saponins are the bioactive constituents in P. notoginseng. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the Panax species are largely unknown.

Results

Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for P. notoginseng root. These reads were processed and assembled by 454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST) similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS), which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old P. notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif.

Conclusion

This study is the first to present a large-scale EST dataset for P. notoginseng root acquired by next-generation sequencing (NGS) technology. The candidate genes involved in triterpene saponin biosynthesis, including the putative CYP450s and UGTs, were obtained in this study. Additionally, the identification of SSRs provided plenty of genetic makers for molecular breeding and genetics applications in this species. These data will provide information on gene discovery, transcriptional regulation and marker-assisted selection for P. notoginseng. The dataset establishes an important foundation for the study with the purpose of ensuring adequate drug resources for this species.
Predicting sequence and structural specificities of RNA binding regions recognized by splicing factor SRSF1
Authors: Wang Xin , Juan Liran , Lv Junjie , Wang Kejun , Sanford Jeremy R , Liu Yunlong
Published: December 2011

Background

RNA-binding proteins (RBPs) play diverse roles in eukaryotic RNA processing. Despite their pervasive functions in coding and noncoding RNA biogenesis and regulation, elucidating the sequence specificities that define protein-RNA interactions remains a major challenge. Recently, CLIP-seq (Cross-linking immunoprecipitation followed by high-throughput sequencing) has been successfully implemented to study the transcriptome-wide binding patterns of SRSF1, PTBP1, NOVA and fox2 proteins. These studies either adopted traditional methods like Multiple EM for Motif Elicitation (MEME) to discover the sequence consensus of RBP's binding sites or used Z-score statistics to search for the overrepresented nucleotides of a certain size. We argue that most of these methods are not well-suited for RNA motif identification, as they are unable to incorporate the RNA structural context of protein-RNA interactions, which may affect to binding specificity. Here, we describe a novel model-based approach--RNAMotifModeler to identify the consensus of protein-RNA binding regions by integrating sequence features and RNA secondary structures.

Results

As an example, we implemented RNAMotifModeler on SRSF1 (SF2/ASF) CLIP-seq data. The sequence-structural consensus we identified is a purine-rich octamer 'AGAAGAAG' in a highly single-stranded RNA context. The unpaired probabilities, the probabilities of not forming pairs, are significantly higher than negative controls and the flanking sequence surrounding the binding site, indicating that SRSF1 proteins tend to bind on single-stranded RNA. Further statistical evaluations revealed that the second and fifth bases of SRSF1octamer motif have much stronger sequence specificities, but weaker single-strandedness, while the third, fourth, sixth and seventh bases are far more likely to be single-stranded, but have more degenerate sequence specificities. Therefore, we hypothesize that nucleotide specificity and secondary structure play complementary roles during binding site recognition by SRSF1.

Conclusion

In this study, we presented a computational model to predict the sequence consensus and optimal RNA secondary structure for protein-RNA binding regions. The successful implementation on SRSF1 CLIP-seq data demonstrates great potential to improve our understanding on the binding specificity of RNA binding proteins.
The order of expression is a key factor in the production of active transglutaminase in Escherichia coli by co-expression with its pro-peptide
Authors: Liu Song , Zhang Dongxu , Wang Miao , Cui Wenjing , Chen Kangkang , Du Guocheng , Chen Jian , Zhou Zhemin
Published: December 2011

Background

Streptomyces transglutaminase (TGase) is naturally synthesized as zymogen (pro-TGase), which is then processed to produce active enzyme by the removal of its N-terminal pro-peptide. This pro-peptide is found to be essential for overexpression of soluble TGase in E. coli. However, expression of pro-TGase by E. coli requires protease-mediated activation in vitro. In this study, we developed a novel co- expression method for the direct production of active TGase in E. coli.

Results

A TGase from S. hygroscopicus was expressed in E. coli only after fusing with the pelB signal peptide, but fusion with the signal peptide induced insoluble enzyme. Therefore, alternative protocol was designed by co-expressing the TGase and its pro-peptide as independent polypeptides under a single T7 promoter using vector pET-22b(+). Although the pro-peptide was co-expressed, the TGase fused without the signal peptide was undetectable in both soluble and insoluble fractions of the recombinant cells. Similarly, when both genes were expressed in the order of the TGase and the pro-peptide, the solubility of TGase fused with the signal peptide was not improved by the co-expression with its pro-peptide. Interestingly, active TGase was only produced by the cells in which the pro-peptide and the TGase were fused with the signal peptide and sequentially expressed. The purified recombinant and native TGase shared the similar catalytic properties.

Conclusions

Our results indicated that the pro-peptide can assist correct folding of the TGase inter-molecularly in E. coli, and expression of pro-peptide prior to that of TGase was essential for the production of active TGase. The co-expression strategy based on optimizing the order of gene expression could be useful for the expression of other functional proteins that are synthesized as a precursor.
Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India
Authors: Jain Vidhan , Lucchi Naomi W , Wilson Nana O , Blackstock Anna J , Nagpal Avinash C , Joel Pradeep K , Singh Mrigendra P , Udhayakumar Venkatachalam , Stiles Jonathan K , Singh Neeru
Published: December 2011

Background

The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM associated mortality. Recognizing the importance of angiopoietins (ANG) in the pathogenesis of CM, a retrospective investigation was carried out in a hospital cohort of malaria patients with Plasmodium infection in central India to determine if these factors could be suitable markers of CM associated severity.

Methods

Patients enrolled in the study were clinically characterized as healthy controls (HC), mild malaria (MM), CM survivors (CMS) and CM non-survivors (CMNS) based on their malaria status and hospital treatment outcome. Plasma ANG-1 and ANG-2 levels were assessed using sandwich ELISA. Receiver operating characteristic (ROC) curve analysis was used to calculate area under the curve (AUC) for each biomarker in order to assess predictive accuracy of individual biomarkers.

Results

The plasma levels of ANG-1 were lower in CMS and CMNS compared to control groups (mild malaria and healthy controls) at the time of hospital admission. On the contrary, ANG-2 levels positively correlated with malaria severity and were significantly higher in CMNS. The ratio of ANG-2/ANG-1 was highest in CMNS compared to other groups. Receiver operating characteristic curves revealed that compared to ANG-1 (AUC = 0.35), ANG-2 (AUC = 0.95) and ratio of ANG-2/ANG-1 (AUC = 0.90) were better markers to discriminate CMNS from MM cases. However, they were less specific in predicting fatal outcome amongst CM cases at the time of hospital admission.

Conclusion

These results suggest that at the time of admission plasma levels of ANG-2 and ratio of ANG-2/ANG-1 are clinically informative biomarkers to predict fatal CM from MM cases while they have limited usefulness in discriminating fatal CM outcomes in a pool of CM cases in endemic settings of Central India.
Dynamic expression of CEACAM7 in precursor lesions of gastric carcinoma and its prognostic value in combination with CEA
Authors: Zhou Jinfeng , Zhang Liyun , Gu Yong , Li Kai , Nie Yongzhan , Fan Daiming , Feng Yichao
Published: December 2011

Background

The significance of carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) expression in gastric carcinoma and precancerous lesions and its correlation with CEA expression has rarely been previously investigated.

Methods

CEACAM7 and CEA expression was detected by immunohistochemistry in consecutive sections of 345 subjects with gastric carcinoma and precancerous lesions. Laser confocal analysis was performed to determine CEACAM7 and CEA localization. Correlation between CEACAM7 and CEA expression with clinicopathological parameters was statistically analyzed.

Results

CEACAM7 expression correlated with pathologic grading (P = 0.006), Lauren's classification (P = 0.023), and CEA expression (Spearman R = 0.605, P < 0.001) in gastric carcinoma. CEACAM7 co-localized with CEA predominantly in the cytoplasmic membrane of cancerous cells. CEA expression was correlated with lymph node metastasis (P = 0.031). CEACAM7 and CEA expression increased progressively from precursor lesions to gastric carcinomas. A combination of CEACAM7 and CEA expression was determined to be an independent predictor for patients with gastric carcinoma by multivariate analysis (P = 0.001).

Conclusions

CEACAM7 expression correlates with tumor differentiation and CEA expression in gastric carcinoma. CEACAM7 and CEA expression may synergistically promote gastric carcinogenesis. Combined CEACAM7 and CEA expression analysis can be a useful postoperative predictor for patients with gastric carcinoma.
Adaptive collision resolution for efficient RFID tag identification
Authors: Chen Yung-Chun , Yeh Kuo-Hui , Lo NaiWei , Li Yingjiu , Winata Enrico
Published: December 2011

In large-scale RFID systems, all of the communications between readers and tags are via a shared wireless channel. When a reader intends to collect all IDs from numerous existing tags, a tag identification process is invoked by the reader to collect the tags' IDs. This phenomenon results in tag-to-reader signal collisions which may suppress the system performance greatly. To solve this problem, we design an efficient tag identification protocol in which a significant gain is obtained in terms of both identification delay and communication overhead. A k-ary tree-based abstract is adopted in our proposed tag identification protocol as underlying architecture for collision resolution. Instead of just recognizing whether tag collision happens at each interrogation time period, the reader can further obtain the reason of why the collision occurs in the current tag inquiry operation. With this valuable information, we can reduce tag signal collisions significantly and at the same time avoid all of the tag idle scenarios during a tag identification session. The rigorous performance analysis and evaluation show that our proposed tag identification protocol outperforms existing tree-based schemes.
Oncostatin M Induces Heat Hypersensitivity by gp130-Dependent Sensitization of TRPV1 in Sensory Neurons
Authors: Langeslag Michiel , Constantin Cristina E , Andratsch Manfred , Quarta Serena , Mair Norbert , Kress Michaela
Published: December 2011

Oncostatin M (OSM) is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out ( SNS-gp130−/−) and gp130 floxed ( gp130fl/fl) mice.

Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130f/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130−/− mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo.

The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.
A transcriptional dynamic network during Arabidopsis thaliana pollen development
Authors: Wang Jigang , Qiu Xiaojie , Li Yuhua , Deng Youping , Shi Tieliu
Published: December 2011

Background

To understand transcriptional regulatory networks (TRNs), especially the coordinated dynamic regulation between transcription factors (TFs) and their corresponding target genes during development, computational approaches would represent significant advances in the genome-wide expression analysis. The major challenges for the experiments include monitoring the time-specific TFs' activities and identifying the dynamic regulatory relationships between TFs and their target genes, both of which are currently not yet available at the large scale. However, various methods have been proposed to computationally estimate those activities and regulations. During the past decade, significant progresses have been made towards understanding pollen development at each development stage under the molecular level, yet the regulatory mechanisms that control the dynamic pollen development processes remain largely unknown. Here, we adopt Networks Component Analysis (NCA) to identify TF activities over time couse, and infer their regulatory relationships based on the coexpression of TFs and their target genes during pollen development.

Results

We carried out meta-analysis by integrating several sets of gene expression data related toArabidopsis thalianapollen development (stages range from UNM, BCP, TCP, HP to 0.5 hr pollen tube and 4 hr pollen tube). We constructed a regulatory network, including 19 TFs, 101 target genes and 319 regulatory interactions. The computationally estimated TF activities were well correlated to their coordinated genes' expressions during the development process. We clustered the expression of their target genes in the context of regulatory influences, and inferred new regulatory relationships between those TFs and their target genes, such as transcription factor WRKY34, which was identified that specifically expressed in pollen, and regulated several new target genes. Our finding facilitates the interpretation of the expression patterns with more biological relevancy, since the clusters corresponding to the activity of specific TF or the combination of TFs suggest the coordinated regulation of TFs to their target genes.

Conclusions

Through integrating different resources, we constructed a dynamic regulatory network ofArabidopsis thalianaduring pollen development with gene coexpression and NCA. The network illustrated the relationships between the TFs' activities and their target genes' expression, as well as the interactions between TFs, which provide new insight into the molecular mechanisms that control the pollen development.
Could petroleum biodegradation be a joint achievement of aerobic and anaerobic microrganisms in deep sea reservoirs?
Authors: da Cruz Georgiana F , de Vasconcellos Suzan P , Angolini Célio FF , Dellagnezze Bruna M , Garcia Isabel NS , de Oliveira Valéria M , dos Santos Neto Eugenio V , Marsaioli Anita J
Published: December 2011

Several studies suggest that petroleum biodegradation can be achieved by either aerobic or anaerobic microorganisms, depending on oxygen input or other electron acceptors and appropriate nutrients. Evidence from in vitro experiments with samples of petroleum formation water and oils from Pampo Field indicate that petroleum biodegradation is more likely to be a joint achievement of both aerobic and anaerobic bacterial consortium, refining our previous observations of aerobic degradation. The aerobic consortium depleted, in decreasing order, hydrocarbons > hopanes > steranes > tricyclic terpanes while the anaerobic consortium depleted hydrocarbons > steranes > hopanes > tricyclic terpanes. The oxygen content of the mixed consortia was measured from time to time revealing alternating periods of microaerobicity (O2 ~0.8 mg.L-1) and of aerobicity (O2~6.0 mg.L-1). In this experiment, the petroleum biodegradation changed from time to time, alternating periods of biodegradation similar to the aerobic process and periods of biodegradation similar to the anaerobic process. The consortia showed preferences for metabolizing hydrocarbons > hopanes > steranes > tricyclic terpanes during a 90-day period, after which this trend changed and steranes were more biodegraded than hopanes. The analysis of aerobic oil degrading microbiota by the 16S rRNA gene clone library detected the presence of Bacillus, Brevibacterium, Mesorhizobium and Achromobacter, and the analysis of the anaerobic oil degrading microbiota using the same technique detected the presence of Bacillus and Acinetobacter (facultative strains). In the mixed consortia Stenotrophomonas, Brevibacterium, Bacillus, Rhizobium, Achromobacter and 5% uncultured bacteria were detected. This is certainly a new contribution to the study of reservoir biodegradation processes, combining two of the more important accepted hypotheses.
Severity of depression and response to antidepressants: GENPOD randomised controlled trial
Authors: Wiles Nicola J. , Mulligan Jean , Peters Tim J. , Cowen Philip J. , Mason Victoria , Nutt David , Sharp Deborah , Tallon Debbie , Thomas Laura , O'Donovan Michael C. , Lewis Glyn
Published: December 2011

Background

Antidepressant prescribing is widespread. Nonetheless, response to antidepressants is variable. If it was possible to predict response to medication and thus tailor treatment accordingly, this would not only improve patient outcomes but may also have economic benefits.

Aims

To test the hypothesis that individuals with more severe depression would benefit more from noradrenaline reuptake inhibitors (NARIs) than selective serotonin reuptake inhibitors (SSRIs) compared with individuals with less severe depression.

Method

Individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory (BDI) were randomised to either an SSRI (citalopram 20mg daily) or a NARI (reboxetine 4mg twice daily). Randomisation was by means of a remote automated telephone system. The main outcome was depressive symptoms measured by the BDI total score 6 weeks after randomisation. (Trial registration: ISRCTN31345163.)

Results

In total, 601 participants were randomised (citalopram:n= 298, reboxetine:n= 303). Ninety-one per cent were followed up at 6 weeks (citalopram:n= 274, reboxetine:n= 272). There was little evidence to support an interaction between treatment and severity of depression (interaction term: 0.02, 95% CI −0.59 to 0.62,P= 0.96). Adjustment for potential confounders (age, gender, employment status, history of depression, number of life events and social support) did not affect the findings (interaction term: 0.06, 95% CI −0.54 to 0.66,P= 0.85).

Conclusions

Treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care.
Microtubule depolymerization induces traction force increase through two distinct pathways
Authors: Rape Andrew , Guo Wei-hui , Wang Yu-li
Published: December 2011

Traction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microscopy to cells cultured on micropatterned polyacrylamide hydrogels to obtain samples of homogeneous shape and size. Control cells and cells treated with a focal adhesion kinase (FAK) inhibitor showed similar increases in traction forces, indicating that the response is independent of FAK. Surprisingly, pharmacological inhibition of myosin II did not prevent the increase of residual traction forces upon nocodazole treatment. This increase was abolished upon pharmacological inhibition of FAK. These results suggest two distinct pathways for the regulation of traction forces. First, microtubule depolymerization activates a myosin-II-dependent mechanism through a FAK-independent pathway. Second, microtubule depolymerization also enhances traction forces through a myosin-II-independent, FAK-regulated pathway. Traction forces are therefore regulated by a complex network of complementary signals and force-generating mechanisms.
SMRT analysis of MTOC and nuclear positioning reveals the role of EB1 and LIC1 in single-cell polarization
Authors: Hale Christopher M. , Chen Wei-Chiang , Khatau Shyam B. , Daniels Brian R. , Lee Jerry S. H. , Wirtz Denis
Published: December 2011

In several migratory cells, the microtubule-organizing center (MTOC) is repositioned between the leading edge and nucleus, creating a polarized morphology. Although our understanding of polarization has progressed as a result of various scratch-wound and cell migration studies, variations in culture conditions required for such assays have prevented a unified understanding of the intricacies of MTOC and nucleus positioning that result in cell polarization. Here, we employ a new SMRT (for sparse, monolayer, round, triangular) analysis that uses a universal coordinate system based on cell centroid to examine the pathways regulating MTOC and nuclear positions in cells plated in a variety of conditions. We find that MTOC and nucleus positioning are crucially and independently affected by cell shape and confluence; MTOC off-centering correlates with the polarization of single cells; acto-myosin contractility and microtubule dynamics are required for single-cell polarization; and end binding protein 1 and light intermediate chain 1, but not Par3 and light intermediate chain 2, are required for single-cell polarization and directional cell motility. Using various cellular geometries and conditions, we implement a systematic and reproducible approach to identify regulators of MTOC and nucleus positioning that depend on extracellular guidance cues.
Multifocal Primary Bone Sarcoma in the Elderly: A Rare Case and Review of the Literature
Authors: Duckworth A D , Beggs I , Salter D M , Patton J T , Porter D E
Published: December 2011

To our knowledge there are no reports of a primary multifocal spindle cell sarcoma affecting both long bones of the lower limb in an elderly patient. An 83-year-old man presented with a progressively painful right ankle, without a history of trauma. Radiographs demonstrated a pathological fracture through a mixed lytic and sclerotic lesion in the distal tibia. Staging investigations, including bone scintigraphy and magnetic resonance imaging, revealed a second lytic lesion in the right distal femur. A provisional diagnosis of metastatic disease was favoured and intramedullary nailing was considered. However, computed tomography of the chest, abdomen and pelvis, and relevant blood tests revealed no evidence of a primary malignancy. Open biopsy of the tibial lesion showed high-grade pleomorphic spindle cells consistent with a primary bone sarcoma. The patient was treated successfully with a right trans-femoral amputation. In conclusion, we recommend early bone biopsy to allow accurate diagnosis and appropriate skeletal management in elderly patients.