bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific posttranslational modification regulates early events in mammary carcinoma formation
Authors: Guo Hua-Bei , Johnson Heather , Randolph Matthew , Nagy Tamas , Blalock Ryan , Pierce Michael
Published: November 2010

The expression of an enzyme, GnT-V, that catalyzes a specific posttranslational modification of a family of glycoproteins, namely a branched N-glycan, is transcriptionally up-regulated during breast carcinoma oncogenesis. To determine the molecular basis of how early events in breast carcinoma formation are regulated by GnT-V, we studied both the early stages of mammary tumor formation by using 3D cell culture and a her-2 transgenic mouse mammary tumor model. Overexpression of GnT-V in MCF-10A mammary epithelial cells in 3D culture disrupted acinar morphogenesis with impaired hollow lumen formation, an early characteristic of mammary neoplastic transformation. The disrupted acinar morphogenesis of mammary tumor cells in 3D culture caused by her-2 expression was reversed in tumors that lacked GnT-V expression. Moreover, her-2-induced mammary tumor onset was significantly delayed in the GnT-V null tumors, evidence that the lack of the posttranslational modification catalyzed by GnT-V attenuated tumor formation. Inhibited activation of both PKB and ERK signaling pathways was observed in GnT-V null tumor cells. The proportion of tumor-initiating cells (TICs) in the mammary tumors from GnT-V null mice was significantly reduced compared with controls, and GnT-V null TICs displayed a reduced ability to form secondary tumors in NOD/SCID mice. These results demonstrate that GnT-V expression and its branched glycan products effectively modulate her-2-mediated signaling pathways that, in turn, regulate the relative proportion of tumor initiating cells and the latency of her-2-driven tumor onset.
Comparative genomics of clinical and environmental
Vibrio mimicus
Authors: Hasan Nur A. , Grim Christopher J. , Haley Bradd J. , Chun Jongsik , Alam Munirul , Taviani Elisa , Hoq Mozammel , Munk A. Christine , Saunders Elizabeth , Brettin Thomas S. , Bruce David C. , Challacombe Jean F. , Detter J. Chris , Han Cliff S. , Xie Gary , Nair G. Balakrish , Huq Anwar , Colwell Rita R.
Published: November 2010

Whether
Vibrio mimicus
is a variant of
Vibrio cholerae
or a separate species has been the subject of taxonomic controversy. A genomic analysis was undertaken to resolve the issue. The genomes of
V. mimicus
MB451, a clinical isolate, and VM223, an environmental isolate, comprise ca. 4,347,971 and 4,313,453 bp and encode 3,802 and 3,290 ORFs, respectively. As in other vibrios, chromosome I (C-I) predominantly contains genes necessary for growth and viability, whereas chromosome II (C-II) bears genes for adaptation to environmental change. C-I harbors many virulence genes, including some not previously reported in
V. mimicus
, such as mannose-sensitive hemagglutinin (MSHA), and enterotoxigenic hemolysin (HlyA); C-II encodes a variant of
Vibrio
pathogenicity island 2 (VPI-2), and
Vibrio
seventh pandemic island II (VSP-II) cluster of genes. Extensive genomic rearrangement in C-II indicates it is a hot spot for evolution and genesis of speciation for the genus
Vibrio
. The number of virulence regions discovered in this study (VSP-II, MSHA, HlyA, type IV pilin, PilE, and integron integrase, IntI4) with no notable difference in potential virulence genes between clinical and environmental strains suggests these genes also may play a role in the environment and that pathogenic strains may arise in the environment. Significant genome synteny with prototypic pre-seventh pandemic strains of
V. cholerae
was observed, and the results of phylogenetic analysis support the hypothesis that, in the course of evolution,
V. mimicus
and
V. cholerae
diverged from a common ancestor with a prototypic sixth pandemic genomic backbone.
Forest transitions, trade, and the global displacement of land use
Authors: Meyfroidt Patrick , Rudel Thomas K. , Lambin Eric F.
Published: November 2010

Reducing tropical deforestation is an international priority, given its impacts on carbon emissions and biodiversity. We examined whether recent forest transitions—a shift from net deforestation to net reforestation—involved a geographic displacement of forest clearing across countries through trade in agricultural and forest products. In most of the seven developing countries that recently experienced a forest transition, displacement of land use abroad accompanied local reforestation. Additional global land-use change embodied in their net wood trade offset 74% of their total reforested area. Because the reforesting countries continued to export more agricultural goods than they imported, this net displacement offset 22% of their total reforested area when both agriculture and forestry sectors are included. However, this net displacement increased to 52% during the last 5 y. These countries thus have contributed to a net global reforestation and/or decrease in the pressure on forests, but this global environmental benefit has been shrinking during recent years. The net decrease in the pressure on forests does not account for differences in their ecological quality. Assessments of the impacts of international policies aimed at reducing global deforestation should integrate international trade in agricultural and forest commodities.
Foundational model of structural connectivity in the nervous system with a schema for wiring diagrams, connectome, and basic plan architecture
Authors: Swanson Larry W. , Bota Mihail
Published: November 2010

The nervous system is a biological computer integrating the body's reflex and voluntary environmental interactions (behavior) with a relatively constant internal state (homeostasis)—promoting survival of the individual and species. The wiring diagram of the nervous system's structural connectivity provides an obligatory foundational model for understanding functional localization at molecular, cellular, systems, and behavioral organization levels. This paper provides a high-level, downwardly extendible, conceptual framework—like a compass and map—for describing and exploring in neuroinformatics systems (such as our Brain Architecture Knowledge Management System) the structural architecture of the nervous system's basic wiring diagram. For this, the Foundational Model of Connectivity's universe of discourse is the structural architecture of nervous system connectivity in all animals at all resolutions, and the model includes two key elements—a set of basic principles and an internally consistent set of concepts (defined vocabulary of standard terms)—arranged in an explicitly defined schema (set of relationships between concepts) allowing automatic inferences. In addition, rules and procedures for creating and modifying the foundational model are considered. Controlled vocabularies with broad community support typically are managed by standing committees of experts that create and refine boundary conditions, and a set of rules that are available on the Web.
Paradoxical effects of constitutive human IL-32γ in transgenic mice during experimental colitis
Authors: Choi Jida , Bae Suyoung , Hong Jaewoo , Ryoo Soyoon , Jhun Hyunjhung , Hong Kwangwon , Yoon Doyoung , Lee Siyoung , Her Erk , Choi Wonhyuk , Kim Jeonghwan , Azam Tania , Dinarello Charles A. , Kim Soohyun
Published: November 2010

Inflammatory cytokines mediate inflammatory bowel diseases (IBDs) and cytokine blocking therapies often ameliorate the disease severity. IL-32 affects inflammation by increasing the production of IL-1, TNFα, and several chemokines. Here, we investigated the role of IL-32 in intestinal inflammation by generating a transgenic (TG) mouse expressing human IL-32γ (IL-32γ TG). Although IL-32γ TG mice are healthy, constitutive serum and colonic tissue levels of TNFα are elevated. Compared with wild-type (WT) mice, IL-32γ TG mice exhibited a modestly exacerbated acute inflammation early following the initiation of dextran sodium sulfate (DSS)-induced colitis. However, after 6 d, there was less colonic inflammation, reduced tissue loss, and improved survival rate compared with WT mice. Associated with attenuated tissue damage, colonic levels of TNFα and IL-6 were significantly reduced in the IL-32γ TG mice whereas IL-10 was elevated. Cultured colon explants from IL-32γ TG mice secreted higher levels of IL-10 compared with WT mice and lower levels of TNFα and IL-6. Constitutive levels of IL-32γ itself in colonic tissues were significantly lower following DSS colitis. Although the highest level of serum IL-32γ occurred on day 3 of colitis, IL-32 was below constitutive levels on day 9. The ability of IL-32γ to increase constitutive IL-10 likely reduces TNFα, IL-6, and IL-32 itself accounting for less inflammation. In humans with ulcerative colitis (UC), serum IL-32 is elevated and colonic biopsies contain IL-32 in inflamed tissues but not in uninvolved tissues. Thus IL-32γ emerges as an example of how innate inflammation worsens as well as protects intestinal integrity.
Evolution of diverse mechanisms for protecting chromosome ends by
Drosophila TART
telomere retrotransposons
Authors: George Janet A. , Traverse Karen L. , DeBaryshe P. G. , Kelley Kerry J. , Pardue Mary-Lou
Published: November 2010

The retrotransposons
HeT-A
,
TART
, and
TAHRE
, which maintain
Drosophila
telomeres, transpose specifically onto chromosome ends to form long arrays that extend the chromosome and compensate for terminal loss. Because they transpose by target-primed reverse transcription, each element is oriented so that its 5′ end serves as the extreme end of the chromosome until another element transposes to occupy the terminal position. Thus 5′ sequences are at risk for terminal erosion while the element is at the chromosome end. Here we report that
TART
elements in
Drosophila melanogaster
and
Drosophila virilis
show species-specific innovations in promoter architecture that buffer loss of sequence exposed at chromosome ends. The two elements have evolved different ways to effect this protection. The
D. virilis TART
(

TART
vir

) promoter is found in the 3′ UTR of the element directly upstream of the element transcribed. Transcription starts within the upstream element so that a “Tag” of extra sequence is added to the 5′ end of the newly transcribed RNA. This Tag provides expendable sequence to buffer end erosion of essential 5′ sequence after the RNA is reverse transcribed onto the chromosome. In contrast, the

D. melanogaster TART (TART
mel
)

promoter initiates transcription deep within the 5′ UTR, but the element is able to replace and extend the 5′ UTR sequence by copying sequence from its 3′ UTR, we believe while being reverse transcribed onto the chromosome end. Astonishingly, end-protection in

TART
vir

and

HeT-A
mel

are essentially identical (using Tags), whereas

HeT-A
vir

is clearly protected from end erosion by an as-yet-unspecified program.
First-principles Study of Field Emissions from Natrium-Encapsulated Boron-Nitride Nanotube in a Perpendicular Geometry
Authors: Gao Qiang , Hu Shuang-lin , Li Bin
Published: November 2010

The field emission from pure boron-nitride nanotube and boron-nitride nanotube encapsulated with natrium atoms with the electric field perpendicular to the axis of nanotubes is simulated based on a self-consistent method using the density-functional formalism. It has been found that the nearly-free-electron states in boron-nitride nanotube would perform very well in field emissions after natrium atom encapsulation. The characters of total energy distribution curves are analyzed to seek the function of nearly-free-electron states in the field emission, with special attention to response of the emission current to the external electric field. At last, the perpendicular emission geometry is found to possess a very sensitive response degree which is supposed to be related to specific expansion orientation of the nearly-free-electron states in this system.
Photophysical Properties of 4′-(p-aminophenyl)-2,2′:6′,2″-terpyridine
Authors: Song Peng , Sun Shi-guo , Zhou Pan-wang , Liu Jian-yong , Xu Yong-qian , Peng Xiao-jun
Published: November 2010

Spectral and photophysical investigations of 4′-(p-aminophenyl)-2,2′:6′,2″-terpyridine (APT) have been performed in various solvents with different polarity and hydrogen-bonding ability. The emission spectra of APT are found to exhibit dual fluorescence in polar solvents, which attributes to the local excited and intramolecular charge transfer states, respectively. The two-state model is proven out for APT in polar solvent by the time-correlated single photon counting emission decay measurement. Interestingly, the linear relationships of different emission maxima and solvent polarity parameter are found for APT in protic and aprotic solvents, because of the hydrogen bond formation between APT and alcohols at the amino nitrogen N25. Furthermore, the effects of the complexation of the metal ion with tpy group of APT and the hydrogen bond formation between APT with methanol at the terpyridine nitrogen N4-N8-N14 are also presented. The appearance of new long-wave absorption and fluorescence bands indicates that a new ground state of the complexes is formed.
Vibrational Spectra and Density Functional Theory Calculations of Metallo-tetra-(tert-butyl)-tetra-azaporphyrines
Authors: Lu Tong-tong , Gao Hui-ling , He Tian-jing , Liu Fan-chen , Chen Dong-ming
Published: November 2010

The infrared absorption and 514.5 nm excited Raman spectra were measured for the metallo-tetra-(tert-butyl)-tetraazaporphyrin (MT(tBu)TAP, M=Cu, Co, Ni, Zn). The ground-state structures and vibrational spectra of MT(tBu)TAPs have been calculated at the B3LYP level of theory. The observed Raman and IR bands have been assigned based on the calculation results and by comparing with the normal metalloporphyrins. The relationship between the Raman/IR frequencies and the structures of TAP ring was investigated. The results show that the frequencies of CβCβ′ stretch (Ag), asymmetric CαNm stretch (Ag), and symmetric CαNm stretch (Bg) modes increase linearly with the decrease of the core-sizes of TAP ring. Among the three modes, the later two are more sensitive to the core-size change.
Synthesis of High Quality CuInSe2 Films with Oxygen Precursor by Non-vacuum Process
Authors: Jiang Shuai , Jiang Guo-shun , Liu Wei-feng , Zhu Chang-fei
Published: November 2010

The CuInSe2 absorber was synthesized by non-vacuum process with a simple and low-cost method, which fabricated absorber layer of thin-film solar cell. The extra amount of Se was added into the ink to help reduction of the oxide and solid Se fountain was used to provide Se atmosphere during the selenization progress. The influence of same factors was investigated, such as the time of reduction in H2, the time of selenization and the Se vapor pressure. The selenizaion, processed at 550°C for 60 min with the Se vapor pressure at 1.90 kPa, resulted in high quality CuInSe2 layer with very good chemical composition.
Controllable Electrochemical Synthesis of Silver Dendritic Nanostructures and Their SERS Properties
Authors: Hong Xun , Wang Guan-zhong , Wang Ying , Zhu Wei , Shen Xiao-shuang
Published: November 2010

Ag dendritic nanostructures were synthesized on fluorine-doped tin oxide covered glass substrates by the electrodeposition method. Results demonstrate that the size, diameter, crystallinity, and branch density of the Ag dendrites can be controlled by the applied potential, the surfactants and the concentration of AgNO3. Three kinds of typical silver dendrites were applied as substrates of the surface enhanced Raman scattering (SERS) and one of them was able to clearly detect rhodamine 6G concentrations up to 0.1 nmol/L. The differences of the SERS spectra at these Ag dendrites confirmed that the shapes and interparticle spacings have great effect on Raman enhancement, especially the interparticle spacings.
PETcofold: predicting conserved interactions and structures of two multiple alignments of RNA sequences
Authors: Seemann Stefan E. , Richter Andreas S. , Gesell Tanja , Backofen Rolf , Gorodkin Jan
Published: November 2010

Motivation: Predicting RNA–RNA interactions is essential for determining the function of putative non-coding RNAs. Existing methods for the prediction of interactions are all based on single sequences. Since comparative methods have already been useful in RNA structure determination, we assume that conserved RNA–RNA interactions also imply conserved function. Of these, we further assume that a non-negligible amount of the existing RNA–RNA interactions have also acquired compensating base changes throughout evolution. We implement a method, PETcofold, that can take covariance information in intra-molecular and inter-molecular base pairs into account to predict interactions and secondary structures of two multiple alignments of RNA sequences.

Results:  PETcofold's ability to predict RNA–RNA interactions was evaluated on a carefully curated dataset of 32 bacterial small RNAs and their targets, which was manually extracted from the literature. For evaluation of both RNA–RNA interaction and structure prediction, we were able to extract only a few high-quality examples: one vertebrate small nucleolar RNA and four bacterial small RNAs. For these we show that the prediction can be improved by our comparative approach. Furthermore, PETcofold was evaluated on controlled data with phylogenetically simulated sequences enriched for covariance patterns at the interaction sites. We observed increased performance with increased amounts of covariance.

Availability: The program PETcofold is available as source code and can be downloaded from http://rth.dk/resources/petcofold.

Contact:  gorodkin@rth.dk; backofen@informatik.uni-freiburg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Efficient change point detection for genomic sequences of continuous measurements
Authors: Muggeo Vito M. R. , Adelfio Giada
Published: November 2010

Motivation: Knowing the exact locations of multiple change points in genomic sequences serves several biological needs, for instance when data represent aCGH profiles and it is of interest to identify possibly damaged genes involved in cancer and other diseases. Only a few of the currently available methods deal explicitly with estimation of the number and location of change points, and moreover these methods may be somewhat vulnerable to deviations of model assumptions usually employed.

Results: We present a computationally efficient method to obtain estimates of the number and location of the change points. The method is based on a simple transformation of data and it provides results quite robust to model misspecifications. The efficiency of the method guarantees moderate computational times regardless of the series length and the number of change points.

Availability: The methods described in this article are implemented in the new R package cumSeg available from the Comprehensive R Archive Network at http://CRAN.R-project.org/package=cumSeg.

Contact:  vito.muggeo@unipa.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Limb-Girdle Muscular Dystrophy Type 2A Resulting From Homozygous G2338C Transversion Mutation in the Calpain-3 Gene
Authors: Peddareddygari Leema Reddy , Surgan Victoria , Grewal Raji P
Published: November 2010

Limb-girdle muscular dystrophy represents a clinically and genetically heterogeneous group of myopathies. Limb-girdle muscular dystrophy Type 2A, which is transmitted in an autosomal-recessive pattern, is caused by mutations in the calpain-3 (CAPN3) gene. A number of mutations have been reported in patients from throughout the world but not in the Asian-Indian population. We describe a genotype/phenotype analysis of an Asian-Indian patient with a history, neurologic examination, and investigations consistent with muscular dystrophy. Genetic analysis of this patient showed a homozygous G2338C transversion resulting in an amino acid change from aspartic acid 780 histidine in the CAPN3 gene confirming Limb-girdle muscular dystrophy Type 2A. Subsequent testing of the patient's family revealed that his parents and sister were heterozygous unaffected carriers. The G2338C transversion was detected as a compound heterozygous mutation in one patient in Germany. We report a homozygous case and expand the clinical spectrum of limb-girdle muscular dystrophy Type 2A to include Asian-Indians.
Microbiological and immunological effects of enteral feeding on the upper gastrointestinal tract
Authors: Smith Aileen Robertson , Macfarlane Sandra , Furrie Elizabeth , Ahmed Shakil , Bahrami Bahram , Reynolds Nigel , Macfarlane George Tennant
Published: November 2010

Enteral feeding via a percutaneous endoscopic gastrostomy tube is required for nutritional support in patients with dysphagia. Enteral tube feeding bypasses the innate defence mechanisms in the upper gastrointestinal tract. This study examined the surface-associated microbial populations and immune response in the gastric and duodenal mucosae of eight enteral nutrition (EN) patients and ten controls. Real-time PCR and fluorescence in situ hybridization were employed to assess microbiota composition and mucosal pro-inflammatory cytokine expression. The results showed that EN patients had significantly higher levels of bacterial DNA in mucosal biopsies from the stomach and duodenum (P<0.05) than the controls, and that enterobacteria were the predominant colonizing species on mucosal surfaces in these individuals. Expression of the pro-inflammatory cytokines interleukin (IL)-1α, IL-6 and tumour necrosis factor-α was significantly higher in gastric and small intestinal mucosae from patients fed normal diets in comparison with those receiving EN (P<0.05). These results indicate that EN can lead to significant bacterial overgrowth on upper gastrointestinal tract mucosae and a significantly diminished pro-inflammatory cytokine response.
Structures of cyclic dipeptides: an X-ray and computational study of cis- and trans-cyclo(Pip-Phe), cyclo(Pro-Phe) and their N-methyl derivatives
Authors: Budesinsky Milos , Cisarova Ivana , Podlaha Jaroslav , Borremans Frans , Martins José C. , Waroquier Michel , Pauwels Ewald
Published: November 2010

The crystal structures of eight cyclodipeptides are determined, incorporating pipecolic acid or proline and phenylalanine or N-methyl phenylalanine. This set of structures allows the evaluation of the effects on molecular conformation and crystal packing of imino acid ring-size, relative configuration of the two amino acids, and N-methylation. In the non-methylated compounds, hydrogen-bonding interactions form one-dimensional motifs that dominate the packing arrangement. Three compounds have more than one symmetry-independent molecule in the asymmetric unit (Z′ > 1), indicative of a broad and shallow molecular energy minimum. Density functional theory calculations reveal the interplay between inter- and intramolecular factors in the crystals. Only for the N-methylated compounds do simulations of the molecules in the isolated state succeed to reproduce the observed crystallographic conformations. Puckering of the diketopiperazine ring and the deviation from planarity of the amide bonds are not reproduced in the remaining compounds. Cluster in vacuo calculations with a central cyclodipeptide molecule surrounded by hydrogen-bound molecules establish that hydrogen bonding is of major importance but that other intermolecular interactions must also contribute substantially to the crystal structure. More advanced periodic calculations, incorporating the crystallographic environment to the full extent, are necessary to correctly describe all the conformational features of these cyclodipeptide crystals.
Hypermethylation‐mediated reduction of LMX1A expression in gastric cancer
Authors: Dong Wenjie , Feng Li , Xie Yun , Zhang Hao , Wu Yunlin
Published: November 2010

LMX1A is epigenetically inactivated in cervical cancer. However, the expression and methylation status of LMX1A in gastric cancer tissues remains unknown. In the present study, we found that the expression of LMX1A was significantly decreased in gastric cancer tissues compared with normal tissues. A statistically significant inverse association was found between the LMX1A methylation status and expression of LMX1A in tumor tissues (P = 0.008). Restoration of LMX1A induced cell apoptosis and suppressed anchorage‐independent growth, suggesting LMX1A may be a potential biomarker for gastric cancer. (Cancer Sci 2011; 102: 361–366)
Molecular mechanisms of transforming growth factor‐β signaling and disease: The 59th Fujihara International Seminar, 2010
Authors: Miyazono Kohei
Published: November 2010

The Fujihara International Seminar series is supported by the Fujihara Foundation for Science, for the purpose of organizing seminars for basic and applied science, including medical science, physics, chemistry, engineering, mathematics, geology, and biology. The 59th Fujihara International Seminar was held on July 14–17, 2010 at Tomakomai, Hokkaido, Japan, focusing on molecular mechanisms of transforming growth factor (TGF)‐β signaling and disease. Recent findings on mechanisms of TGF‐β signaling, the roles of TGF‐β signaling in carcinogenesis and progression of tumors, and possible strategies of TGF‐β‐based treatment of cancer were discussed at the seminar. In particular, novel mechanisms of regulation of Smad signaling, the differential roles of Smad proteins in carcinogenesis, function of Smads in regulation of microRNA biogenesis, and treatment of cancer stem cells by targeting the TGF‐β signaling pathways were discussed. (Cancer Sci 2011; 102: 1242–1244)
Claudin‐7 down‐regulation is an important feature in oral squamous cell carcinoma
Authors: Lourenço Silvia Vanessa , Coutinho‐Camillo Cláudia Malheiros , Buim Marcilei Elisa Cavicchioli , De Carvalho Ana Carolina , Lessa Roberta Cardim , Pereira Cláudia Maria , Vettore André Luiz , Carvalho André Lopes , Fregnani José Humberto , Kowalski Luiz Paulo , Soares Fernando Augusto
Published: November 2010

Lourenço S V, Coutinho‐Camillo C M, Buim M E C, de Carvalho A C, Lessa R C, Pereira C M, Vettore A L, Carvalho A L, Fregnani J H, Kowalski L P & Soares F A  (2010) Histopathology57, 689–698  Claudin‐7 down‐regulation is an important feature in oral squamous cell carcinoma

Aims:  Claudins, a large family of essential tight junction (TJ) proteins, are abnormally regulated in human carcinomas, especially claudin‐7. The aim of this study was to investigate claudin‐7 expression and alterations in oral squamous cell carcinoma (OSCC).

Methods and results:  Expression of claudin‐7 was analysed in 132 cases of OSCC organized in a tissue microarray. Claudin‐7 mRNA transcript was evaluated using real‐time polymerase chain reaction and the methylation status of the promoter was also assessed. Claudin‐7 was negative in 58.3% of the cases. Loss of claudin‐7 protein expression was associated with recurrence (P = 0.019), tumour size (P = 0.014), clinical stage of OSCC (P = 0.055) and disease‐free survival (P = 0.015). Down‐regulation of the claudin‐7 mRNA transcripts was observed in 78% of the cases, in accordance with immunoexpression. Analysis of the methylation status of the promoter region of claudin‐7 revealed that treatment of O28 cells (that did not express claudin‐7 mRNA transcripts) with 5‐Aza‐2′‐Deoxycytidine (5‐Aza‐dC) led to the re‐expression of claudin‐7 mRNA transcript.

Conclusion:  Loss of claudin‐7 expression is associated with important subcellular processes in OSCC with impact on clinical parameters.
Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer
Authors: Stenner Markus , Weinell Antje , Ponert Tobias , Hardt Aline , Hahn Moritz , Preuss Simon F , Guntinas‐Lichius Orlando , Klussmann Jens Peter
Published: November 2010

Stenner M, Weinell A, Ponert T, Hardt A, Hahn M, Preuss S F, Guntinas‐Lichius O & Klussmann J P (2010) Histopathology 57, 699–706  Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer

Aims:  The expression of the inhibitor of apoptosis protein survivin has been shown to be a significant prognostic indicator in various human cancers. The aim was to assess its expression and prognostic value in salivary gland adenocarcinoma and muco‐epidermoid carcinoma.

Methods and results:  Survivin expression was analysed in 48 patients with parotid gland cancer (21 muco‐epidermoid, 27 adenocarcinomas) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. A high cytoplasmic expression of survivin was found in 30% of the examined tumours without any significant correlation with the patients’ clinicopathological characteristics (P > 0.05). Within all patients, the estimated overall survival rate of muco‐epidermoid carcinomas was significantly better than that of adenocarcinomas (P = 0.013). A high cytoplasmic survivin expression significantly indicated a poor 5‐year disease‐free survival rate compared to patients with a low cytoplasmic survivin expression in the whole group (P = 0.001) and in adenocarcinomas (P = 0.004). In a multivariate analysis, a high cytoplasmic survivin expression was the only independent prognostic indicator for a significantly poorer 5‐year disease‐free survival rate (P = 0.001).

Conclusions:  The correlation between cytoplasmic survivin expression and survival in salivary gland malignancies might make this an effective tool in patient follow‐up, prognosis and targeted therapy in future.
The evidence‐based medicine model of clinical practice: scientific teaching or belief‐based preaching?
Authors: Charles Cathy , Gafni Amiram , Freeman Emily
Published: November 2010

Rationale  Evidence‐based medicine (EBM) is commonly advocated as a ‘gold standard’ of clinical practice. A prominent definition of EBM is: the integration of best research evidence with clinical expertise and patient values. Over time, various versions of a conceptual model or framework for implementing EBM (i.e. how to practice EBM) have been developed.

Aims and objectives  This paper (i) traces the evolution of the different versions of the conceptual model; (ii) tries to make explicit the underlying goals, assumptions and logic of the various versions by exploring the definitions and meaning of the components identified in each model, and the methods suggested for integrating these into clinical practice; and (iii) offers an analytic critique of the various model iterations.

Methods  A literature review was undertaken to identify, summarize, and compare the content of articles and books discussing EBM as a conceptual model to guide physicians in clinical practice.

Results  Our findings suggest that the EBM model of clinical practice, as it has evolved over time, is largely belief‐based, because it is lacking in empirical evidence and theoretical support. The model is not well developed and articulated in terms of defining model components, justifying their inclusion and suggesting ways to integrate these in clinical practice.

Conclusion  These findings are significant because without a model that clearly defines what constitutes an EBM approach to clinical practice we cannot (i) consistently teach clinicians how to do it and (ii) evaluate whether it is being done.
The value of tailored communication for person‐centred outcomes
Authors: van Dulmen Sandra
Published: November 2010

Rationale  When entering a consulting room a person becomes a patient with double needs, that is, the need to feel known and understood and the need to know and understand, also referred to as affective and instrumental needs, respectively. The fulfilment of these needs highly depends on the communication skills of both doctor and patient, which help to bridge the inherent distance that exists between these two persons. There is ample evidence that this bridge becomes stronger the more the communication is tailored to the person behind the patient. Besides, such tailored communication may also prove to be effective for reaching favourable health outcomes.

Methods  Descriptive study focusing on the value of tailored communication in promoting person‐centred instrumental and affective health outcomes.

Results  Research shows that tailored communication contributes to health outcomes known to be crucial for recovery and quality of life, that is, information recall, medication adherence, reassurance and need fulfilment.

Conclusion  There is empirical evidence for the value of tailored communication for person‐centred outcomes. Communicating in a purposeful way while at the same time respecting patients' values and feelings should therefore become the standard in health care practice.
Association of OLE RNA with bacterial membranes via an RNA–protein interaction
Authors: Block Kirsten F. , Puerta‐Fernandez Elena , Wallace Jason G. , Breaker Ronald R.
Published: November 2010

Ornate, large, extremophilic (OLE) RNAs are large, non‐coding transcripts characterized by their ornate secondary structure and presence predominantly in Gram‐positive, extremophilic bacteria. A gene for an OLE‐associated protein (OAP) is almost always located immediately downstream of the OLE gene. OAP has no extensive homology to other proteins and is predicted to form multiple transmembrane domains. We show that this protein forms a ribonucleoprotein complex with OLE RNA using at least 2:1 protein : RNA stoichiometry. A series of truncated OLE RNA constructs was used to establish that most of the RNA can be deleted without eliminating protein binding. Two primary binding sites are present within the RNA, although additional binding determinants exist and extensive structural stabilization is induced by OAP. RNA fluorescence in situ hybridization (FISH) was used in Escherichia coli to demonstrate that ribonucleoprotein complex formation localizes the RNA near cell membranes of this heterologous system. Therefore, the majority of the complex structure formed by OLE RNA may perform a biochemical function that requires membrane localization.
Is Crowsoniella relicta really a cucujiform beetle?
Authors: GE SI‐QIN , HÖRNSCHEMEYER THOMAS , FRIEDRICH FRANK , BEUTEL ROLF GEORG
Published: November 2010

Crowsoniella relicta Pace, one of the most obscure and cryptic beetle taxa, was recently transferred from Archostemata to the polyphagan series Cucujiformia. We discuss the arguments in favour of this hypothesis. The placement of the species is evaluated with a cladistic approach and two different morphological data sets: one aiming mainly to clarify the relationships of extinct and extant archostematans, and one aimed at resolving species‐level phylogeny for the suborder. The results suggest clearly that a position of Crowsoniella within a polyphagan subgroup is very unlikely, and that a placement in Archostemata is justified and should be maintained. Due to the serious lack of anatomical information, non‐destructive µ‐CT scanning of enigmatic taxa like Crowsoniella Pace and Sikhotealinia Lafer should have high priority.
Immunovirological outcomes and resistance patterns at 4 years of antiretroviral therapy use in HIV‐infected patients in Cambodia
Authors: Pujades‐Rodríguez Mar , Schramm Birgit , Som Leakena , Nerrienet Eric , Narom Prak , Chanchhaya Ngeth , Ferradini Laurent , Balkan Suna
Published: November 2010

Objectives  To report immunovirological outcomes and resistance patterns in adults treated with triple combination antiretroviral therapy (cART) for 4 years in an HIV programme of Phnom Penh, Cambodia.

Methods  It is a longitudinal study and cross‐sectional evaluation of adults receiving cART for 4 years. CD4 cell counts and HIV‐1 RNA were quantified, and resistance patterns were determined. Drug‐related toxicity was assessed by clinicians and through laboratory testing.

Results  After 4 years of cART start, the cumulative probability of retention in care was 0.80 and survival among patients not lost to follow‐up was 0.85. A total of 349 patients (98% of eligible) participated in the cross‐sectional evaluation. Ninety per cent were receiving first‐line therapy, 29% stavudine‐ and 58% zidovudine‐containing regimens (compared with 94% and 3% at cART initiation). Ninety‐three per cent of patients were clinically asymptomatic, and severe lipodystrophy and dyslipidemia were diagnosed in 7.2% and 4.0%, respectively. Good treatment adherence was reported by 83% of patients. Median CD4 T‐cell count was 410 cells/μl [IQR 290–511], and 90% of patients had >200 cells/μl. Only 15 (4%) patients had detectable HIV viral load (eight had <200 CD4 cells/μl), five had thymidine analogue mutations, and nine were resistant to two drug classes. In an intention‐to‐treat analysis, 26.1% (95% CI 22.0–30.5) of patients had failed first‐line therapy.

Conclusions  In this Cambodian cohort of adults who started cART at an advanced stage of HIV disease, we observed good clinical and immunovirological outcomes and self‐reported treatment adherence at 4 years of therapy.
Genetic variability in Plasmodium vivax aldolase gene in Korean isolates and the sensitivity of the Binax Now malaria test
Authors: Cho Chi‐Hyun , Nam Myoung Hyun , Kim Jang Su , Han Eun Taek , Lee Won Ja , Oh Jun Seo , An Seong Soo A. , Lim Chae Seung
Published: November 2010

Introduction of rapid malaria diagnostic tests (RDT) initiated numerous field evaluations in various epidemiologic settings. But the efficiency of some RTD kits based on aldolase raised reservations for direct implementation of RDT into clinical settings. We performed Binax Now malaria test in 84 Korean Plasmodium vivax isolates and compared it with the traditional Giemsa stain microscopy test as the reference standard. The sensitivity of Binax Now was 62.0% for P. vivax cases (52/84, 95% CI 51.2–71.6%) with 100.0% specificity (50/50, 95% confidence interval 92.9–100%). After the aldolase gene sequence analysis of 84 isolates, two synonymous mutations in aldolase gene were identified in both Binax Now positive and negative samples. No significant association between the mutations and Binax Now malaria tests was found. Thus, the genetic variability would not explain the poor performance of P. vivax RDTs by detecting aldolase in ROK isolates.
Would rational use of antibiotics be compromised in the era of test‐based management of malaria?
Authors: Baiden Frank , Webster Jayne , Owusu‐Agyei Seth , Chandramohan Daniel
Published: November 2010

Editorial: L’utilisation rationnelle des antibiotiques sera‐t‐elle compromise dans l’ère de la prise en charge de la malaria basée sur les tests?

L’OMS a publié des directives révisées sur le traitement de la malaria qui recommandent la confirmation parasitologique avant le début du traitement des patients fébriles, y compris les enfants de moins de cinq ans. Le respect des nouvelles directives conduirait à un grand nombre de maladies fébriles confirmées comme étant non‐malariques. Sans les compétences et la capacité de distinguer les causes de fièvre non malarique dans les régions à pauvres ressources, la tendance serait pour les cliniciens à recourir à l’utilisation présomptueuse d’antibiotiques dans tous les cas à test négatif. Une augmentation significative de l’utilisation inappropriée des antibiotiques en Afrique subsaharienne va accroître le problème mondial de la résistance aux antibiotiques. Des interventions ciblées sont nécessaires pour améliorer l’utilisation rationnelle des antibiotiques dans l’ère de la prise en charge de la malaria basée sur les tests. Cela comprend des modifications appropriées dans les directives actuelles de la PCIME, l’équipement et la reformation du personnel dans les services de soins primaires, l’établissement de systèmes de surveillance sentinelle pour déterminer l’étiologie de la maladie fébrile non‐malarique et les profils de sensibilité aux antibiotiques, ainsi qu’un mécanisme efficace pour la diffusion des données de surveillance afin d’améliorer le diagnostic et la prise en charge des maladies fébriles chez les enfants.
Epigenetic and physiological effects of gibberellin inhibitors and chemical pruners on the floral transition of azalea
Authors: Meijón Mónica , Jesús Cañal María , Valledor Luis , Rodríguez Roberto , Feito Isabel
Published: November 2010

The ability to control the timing of flowering is a key strategy in planning the production of ornamental species such as azaleas; however, it requires a thorough understanding of floral transition. DNA methylation is involved in controlling the functional state of chromatin and gene expression during floral induction pathways in response to environmental and developmental signals. Plant hormone signalling is also known to regulate suites of morphogenic processes in plants and its role in flowering‐time control is starting to emerge as a key controlling step. This work investigates if the gibberellin (GA) inhibitors and chemical pinching applied in improvement of azalea flowering alter the dynamics of DNA methylation or the levels of polyamines (PAs), GAs and cytokinins (CKs) during floral transition, and whether these changes could be related to the effects observed on flowering ability. DNA methylation during floral transition and endogenous content of PAs, GAs and CKs were analysed after the application of GA synthesis inhibitors (daminozide, paclobutrazol and chlormequat chloride) and a chemical pruner (fatty acids). The application of GA biosynthesis inhibitors caused alterations in levels of PAs, GAs and CKs and in global DNA methylation levels during floral transition; also, these changes in plant growth regulators and DNA methylation were correlated with flower development. DNA methylation, PA, GA and CK levels can be used as predictive markers of plant floral capacity in azalea.
Strain filtering and transmission of a mixed infection in a social insect
Authors: ULRICH Y. , SADD B. M. , SCHMID‐HEMPEL P.
Published: November 2010

Mixed‐genotype infections have attracted considerable attention as drivers of pathogen evolution. However, experimental approaches often overlook essential features of natural host–parasite interactions, such as host heterogeneity, or the effects of between‐host selection during transmission. Here, following inoculation of a mixed infection, we analyse the success of different strains of a trypanosome parasite throughout the colony cycle of its bumblebee host. We find that most colonies efficiently filter the circulating infection before it reaches the new queens, the only offspring that carry infections to the next season. A few colonies with a poor filtering ability thus contributed disproportionately to the parasite population in the next season. High strain diversity but not high infection intensity within colony was associated with an increased probability of transmission of the infection to new queens. Interestingly, the representation of the different strains changed dramatically over time, so that long‐term parasite success could not be predicted from short‐term observations. These findings highlight the shaping of within‐colony parasite diversity through filtering as a crucial determinant of year‐to‐year pathogen transmission and emphasize the importance of host ecology and heterogeneity for disease dynamics.
Limited gene flow may enhance adaptation to local optima in isolated populations of the Roesel’s bush cricket (Metrioptera roeselii)
Authors: CASSEL‐LUNDHAGEN A. , KAŇUCH P. , LOW M. , BERGGREN Å.
Published: November 2010

Variation in morphological traits along latitudinal gradients often manifests as size clines. In insects, both positive and negative correlations are seen, and the mechanism behind the response is unclear. We studied variation in seven morphological traits of Roesel’s bush cricket,Metrioptera roeselii, sampled from seven latitude‐matched‐pair populations that were either geographically isolated from or connected to the species continuous distribution range. The aim was to examine whether morphological traits differed between isolated and continuous populations, and whether latitudinal variation was apparent. The data were used to indicate whether variation in trait means originates from plastic responses to the environment or genetic adaptation to local conditions. To evaluate the influence of gene flow on trait means, we analysed the genetic variation in seven microsatellites. Data showed that individuals from isolated populations display a positive relationship between latitude and body size, whereas individuals from continuous populations show little or no such relationship. The combined morphological and genetic data suggest that the isolated populations have adapted to local optima, while gene flow between continuous populations appears to counteract this process.
Testing the molecular and evolutionary causes of a ‘leapfrog’ pattern of geographical variation in coloration
Authors: CADENA C. D. , CHEVIRON Z. A. , FUNK W. C.
Published: November 2010

Understanding the mechanisms accounting for the evolution of phenotypic diversity is central to evolutionary biology. We use molecular and phenotypic data to test hypotheses for ‘leapfrog’ patterns of geographical variation, in which phenotypically similar, disjunct populations are separated by distinct populations of the same species. Phylogenetic reconstructions revealed independent evolution of melanic plumage characters in different populations in the Neotropical avian genus Arremon. Thus, phenotypic similarities between distant populations cannot be explained by close phylogenetic affinity. Nor can they be attributed to recurring mutations in the MC1R gene, a locus involved in melanic pigmentation. A coalescent analysis indicates that plumage traits have become fixed at a faster rate than expected under genetic drift, suggesting that selection underlies their repeated evolution. In contrast to views that genetic drift drives phenotypic differentiation in Neotropical montane birds, our results imply that geographical variation preceding speciation may reflect the action of deterministic selective processes.
Altitudinal and seasonal variation in microsatellite allele frequencies of Drosophila buzzatii
Authors: BARKER J. S. F. , FRYDENBERG J. , SARUP P. , LOESCHCKE V.
Published: November 2010

Variation in climate, particularly temperature, is known to affect the genetic composition of populations. Although there have been many studies of latitudinal variation, comparisons of populations across altitudes or seasons, particularly for animal species, are less common. Here, we study genetic variation (microsatellite markers) in populations of Drosophila buzzatii collected along altitudinal gradients and in different seasons. We found no differences in genetic variation between 2 years or between seasons within years. However, there were numerous cases of significant associations between allele frequencies or expected heterozygosities and altitude, with more than half showing nonlinear relationships. While these associations indicate possible selection and local altitudinal adaptation, direct tests gave strong evidence for selection affecting two loci and weaker evidence for five other loci. Two loci that are located within an inversion (including the one with strongest evidence for selection) show a linear increase in genetic diversity with altitude, likely due to thermal selection. Parallel associations with altitude here and with latitude in Australian populations indicate that selection is operating on chromosomal regions marked by some of the loci.
Prognostic variables and nomograms for renal cell carcinoma
Authors: Flanigan Robert C , Polcari Anthony J , Hugen Cory M
Published: November 2010

The term renal cell carcinoma (RCC) is used to describe a heterogeneous group of tumors that vary histologically, genetically and molecularly. Extensive research has been conducted to identify characteristics that predict outcomes among patients with RCC. In addition to histological subtype these include tumor size, patient age, mode of presentation and various hematological indices, among others. Several groups have incorporated these clinical and pathological features into nomograms which help the clinician better define individual patient prognosis and direct the optimum therapeutic approach. In the present article we review these prognostic variables and nomograms for RCC.