bluuebunny/crossref_metadata_2025 huggingface dataset:
Leading questions: Journal rankings, academic freedom and performativity: What is, or should be, the future of Leadership?
Authors: Tourish Dennis
Published: August 2011

Pressure on academics to publish articles in ‘top’ journals continues to grow. In tandem, we have seen a proliferation of journal rankings, claiming to provide a guide to the quality of journals. As editors become more preoccupied by the ranking of ‘their’ journal, they exercise performative power over authors, by setting standards for publication that exclude many while compelling those that are published to adapt to the styles, priorities and imperatives of editors. One result has been a ceaseless quest for novelty, manifest in an insistence that each paper must make a ‘distinctive’ theoretical contribution. I argue that this is producing an environment in which scholarship is increasingly mechanized and industrialized, while rendering its outputs more arcane and inaccessible to non-specialists. It also means that the academy is becoming ever more complicit in its own subordination to performative processes that it frequently criticizes when observing them in the outside, ‘real’ world of management practice. We are therefore seeing more barriers to entry for both authors and new journals — unless both conform to norms that bear an orthodox but often sterile imprint. I consider the implications of these issues for emergent journals such as Leadership, and for academic freedom, and suggest how those interested in scholarly inquiry in general and the fate of this journal in particular should respond.
Management of Long-Term Ketogenic Parenteral Nutrition
Authors: Roan Marian
Published: August 2011

The ketogenic diet (KD) is a well-accepted treatment modality for children with intractable epilepsy and for inborn errors of carbohydrate metabolism. These children, just as any other child, may be faced with short-term or long-term medical conditions that require parenteral nutrition (PN). Many institutions with KD programs have begun to institute ketogenic PN support for established KD patients who require the diet for seizure control but are acutely unable to be fed for a variety of reasons. However, there are few patients currently being treated with long-term PN providing the necessary high fat percentage to result in therapeutic levels of ketosis. In fact, there are no reported cases of the use of long-term PN to maintain a child in ketosis for seizure control, and only 1 case study documents successful use of short-term use of ketogenic PN. The case report presented is this article describes the initiation, monitoring, and long-term management of ketogenic PN resulting in ketosis in an adolescent requiring long-term PN due to inability to tolerate enteral feeds.
Enteral and Parenteral Applications of Ketogenic Diet Therapy
Authors: Zupec-Kania Beth Ann , Aldaz Vanessa , Montgomery Mary E. , Kostas Karen C.
Published: August 2011

Ketogenic diet therapy is a high-fat, low-carbohydrate, moderate-protein regimen that results in a sustained metabolic state of ketosis. The diet was originally designed in the 1920s for treatment of epilepsy, but its use has expanded in recent years to other disorders. Most individuals who undergo this therapy are able to consume the diet orally, but those with restricted oral intake require alternative methods of nutrition. Many of our patients have feeding tubes in place for receiving part or all of their nutrition. It is possible to administer the diet during an acute condition or illness in patients who have previously received their nutrition orally. This may be accomplished enterally via a feeding tube or intravenously as parenteral nutrition. This article addresses enteral and parenteral applications of ketogenic diet therapy and provides examples of the modifications that have been successfully implemented at 4 medical centers.
Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial
Authors: Hetzel J. , Eberhardt R. , Herth F.J.F. , Petermann C. , Reichle G. , Freitag L. , Dobbertin I. , Franke K.J. , Stanzel F. , Beyer T. , Möller P. , Fritz P. , Ott G. , Schnabel P.A. , Kastendieck H. , Lang W. , Morresi-Hauf A.T. , Szyrach M.N. , Muche R. , Shah P.L. , Babiak A. , Hetzel M.
Published: August 2011

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling.

A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test.

A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding.

Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.
Day–night variations in endothelial dysfunction markers and haemostatic factors in sleep apnoea
Authors: Barceló A. , Piérola J. , de la Peña M. , Esquinas C. , Sanchez-de la Torre M. , Ayllón O. , Alonso A. , Agusti A.G.N. , Barbè F.
Published: August 2011

Patients with sleep apnoea have a significant alteration in the day–night pattern of myocardial infarction and sudden cardiac death observed in the general population. The aim of this study was to investigate the influence of sleep apnoea on the diurnal variations in various haemostatic parameters (factor VII, von Willebrand factor and plasminogen activator inhibitor (PAI)-1) and markers of endothelial dysfunction (asymmetric dimethylarginine (ADMA) and soluble CD40 ligand (sCD40L)).

We studied 26 male patients with obstructive sleep apnoea syndrome (OSAS; 13 patients with severe OSAS (apnoea/hypopnoea index (AHI) >30 events·h−1) and 13 patients with mild-to-moderate OSAS (AHI <30 events·h−1)) and 12 controls of similar body mass index (BMI) and waist circumference. In each subject, six different samples were obtained over 24 h.

Although all the markers values tended to be higher in patients with severe OSAS, differences did not reach statistical significance at any time. PAI-1 levels were significantly related to BMI (p<0.001), mean (p<0.001) and minimal (p=0.047) nocturnal oxygenation saturation. ADMA levels were significantly related to arousal index (p=0.046).

The results of this study suggest that day–night variations in factor VII:antigen (Ag), von Willebrand factor:Ag, PAI-1, sCD40L and ADMA levels may be dependent on either the obesity index or metabolic dysfunction rather than on sleep apnoea alone.
Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon
Authors: Ehmann R. , Boedeker E. , Friedrich U. , Sagert J. , Dippon J. , Friedel G. , Walles T.
Published: August 2011

Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled breath of patients may represent the ideal specimen for future lung cancer screening. However, the clinical applicability of current diagnostic sensor technologies based on signal pattern analysis remains incalculable due to their inability to identify a clear target. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were applied.

Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or chronic obstructive pulmonary disease (COPD)) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders.

Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. Logistic regression identified two drugs as potential confounders.

It must be assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer. Additional research efforts are required to overcome the current technical limitations of electronic sensor technologies to engineer a clinically applicable screening tool.
Dietary factors and lung function in the general population: wine and resveratrol intake
Authors: Siedlinski M. , Boer J.M.A. , Smit H.A. , Postma D.S. , Boezen H.M.
Published: August 2011

Wine intake is associated with a better lung function in the general population, yet the source of this effect is unknown. Resveratrol, a polyphenol in wine, has anti-inflammatory properties in the lung, its effects being partially mediatedviainduction of Sirtuin (SIRT)1 activity. We assessed the impact of wine and resveratrol intake, andSIRT1single-nucleotide polymorphisms (SNPs) on lung function in the general population.

Effects of red and white wine and resveratrol intake on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were analysed in the population-based Doetinchem cohort (n=3,224). Associations of four taggingSIRT1SNPs with lung function were analysed in the Doetinchem (n=1,152) and Vlagtwedde–Vlaardingen (n=1,390) cohorts.

Resveratrol intake was associated with higher FVC levels, and white wine intake with higher FEV1levels and lower risk of airway obstruction.SIRT1SNPs were not significantly associated with level or course of lung function, either directly or indirectlyviawine or resveratrol intake.

This study shows a positive association of resveratrol intake with lung function in the general population, confirms the previously reported positive association of white wine intake with higher levels of FEV1, and additionally shows an association with a higher FEV1/FVC ratio. These effects probably do not runviaSNPs inSIRT1.
Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up
Authors: Midulla F. , Pierangeli A. , Cangiano G. , Bonci E. , Salvadei S. , Scagnolari C. , Moretti C. , Antonelli G. , Ferro V. , Papoff P.
Published: August 2011

The association between bronchiolitis and recurrent wheezing remains controversial.

In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing.

The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7versus10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0–11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2–4.9) as major independent risk factors for recurrent wheezing.

In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.
Characterisation of marsupial PHLDA2 reveals eutherian specific acquisition of imprinting
Authors: Suzuki Shunsuke , Shaw Geoffrey , Kaneko-Ishino Tomoko , Ishino Fumitoshi , Renfree Marilyn B
Published: August 2011

Background

Genomic imprinting causes parent-of-origin specific gene expression by differential epigenetic modifications between two parental genomes. We previously reported that there is no evidence of genomic imprinting of CDKN1C in the KCNQ1 domain in the placenta of an Australian marsupial, the tammar wallaby (Macropus eugenii) whereas tammar IGF2 and H19, located adjacent to the KCNQ1 domain in eutherian mammals, are imprinted. We have now identified and characterised the marsupial orthologue of PHLDA2, another gene in the KCNQ1 domain (also known as IPL or TSSC3) that is imprinted in eutherians. In mice, Phlda2 is a dose-sensitive negative regulator of placental growth, as Cdkn1c is for embryonic growth.

Results

Tammar PHLDA2 is highly expressed in the yolk sac placenta compared to other fetal tissues, confirming a similar expression pattern to that of mouse Phlda2. However, tammar PHLDA2 is biallelically expressed in both the fetus and yolk sac placenta, so it is not imprinted. The lack of imprinting in tammar PHLDA2 suggests that the acquisition of genomic imprinting of the KCNQ1 domain in eutherian mammals, accompanied with gene dosage reduction, occurred after the split of the therian mammals into the marsupials and eutherians.

Conclusions

Our results confirm the idea that acquisition of genomic imprinting in the KCNQ1 domain occurred specifically in the eutherian lineage after the divergence of marsupials, even though imprinting of the adjacent IGF2-H19 domain arose before the marsupial-eutherian split. These data are consistent with the hypothesis that genomic imprinting of the KCNQ1 domain may have contributed to the evolution of more complex placentation in the eutherian lineage by reduction of the gene dosage of negative regulators for both embryonic and placental growth.
SAMQA: error classification and validation of high-throughput sequenced read data
Authors: Robinson Thomas , Killcoyne Sarah , Bressler Ryan , Boyle John
Published: August 2011

Background

The advances in high-throughput sequencing technologies and growth in data sizes has highlighted the need for scalable tools to perform quality assurance testing. These tests are necessary to ensure that data is of a minimum necessary standard for use in downstream analysis. In this paper we present the SAMQA tool to rapidly and robustly identify errors in population-scale sequence data.

Results

SAMQA has been used on samples from three separate sets of cancer genome data from The Cancer Genome Atlas (TCGA) project. Using technical standards provided by the SAM specification and biological standards defined by researchers, we have classified errors in these sequence data sets relative to individual reads within a sample. Due to an observed linearithmic speedup through the use of a high-performance computing (HPC) framework for the majority of tasks, poor quality data was identified prior to secondary analysis in significantly less time on the HPC framework than the same data run using alternative parallelization strategies on a single server.

Conclusions

The SAMQA toolset validates a minimum set of data quality standards across whole-genome and exome sequences. It is tuned to run on a high-performance computational framework, enabling QA across hundreds gigabytes of samples regardless of coverage or sample type.
Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby
Authors: Wong Emily SW , Papenfuss Anthony T , Heger Andreas , Hsu Arthur L , Ponting Chris P , Miller Robert D , Fenelon Jane C , Renfree Marilyn B , Gibbs Richard A , Belov Katherine
Published: August 2011

Background

The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby.

Results

We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor diversity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed.

Conclusion

This is the first study comparing the transcriptomes of two thymuses from a single individual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system.
The tammar wallaby major histocompatibility complex shows evidence of past genomic instability
Authors: Siddle Hannah V , Deakin Janine E , Coggill Penny , Wilming Laurens G , Harrow Jennifer , Kaufman Jim , Beck Stephan , Belov Katherine
Published: August 2011

Background

The major histocompatibility complex (MHC) is a group of genes with a variety of roles in the innate and adaptive immune responses. MHC genes form a genetically linked cluster in eutherian mammals, an organization that is thought to confer functional and evolutionary advantages to the immune system. The tammar wallaby (Macropus eugenii), an Australian marsupial, provides a unique model for understanding MHC gene evolution, as many of its antigen presenting genes are not linked to the MHC, but are scattered around the genome.

Results

Here we describe the 'core' tammar wallaby MHC region on chromosome 2q by ordering and sequencing 33 BAC clones, covering over 4.5 MB and containing 129 genes. When compared to the MHC region of the South American opossum, eutherian mammals and non-mammals, the wallaby MHC has a novel gene organization. The wallaby has undergone an expansion of MHC class II genes, which are separated into two clusters by the class III genes. The antigen processing genes have undergone duplication, resulting in two copies of TAP1 and three copies of TAP2. Notably, Kangaroo Endogenous Retroviral Elements are present within the region and may have contributed to the genomic instability.

Conclusions

The wallaby MHC has been extensively remodeled since the American and Australian marsupials last shared a common ancestor. The instability is characterized by the movement of antigen presenting genes away from the core MHC, most likely via the presence and activity of retroviral elements. We propose that the movement of class II genes away from the ancestral class II region has allowed this gene family to expand and diversify in the wallaby. The duplication of TAP genes in the wallaby MHC makes this species a unique model organism for studying the relationship between MHC gene organization and function.
The balance between intrahepatic IL-17+ T cells and Foxp3+ regulatory T cells plays an important role in HBV-related end-stage liver disease
Authors: Niu Yinghua , Liu Hongli , Yin Donglin , Yi Ruitian , Chen Tianyan , Xue Hong'an , Zhang Shulin , Lin Shumei , Zhao Yingren
Published: August 2011

Backgroud

IL-17+ T helper cells and Foxp3+ regulatory T cells are CD4+ T helper cells with reciprocally regulated differentiation and function. Their frequency and function vary in patients with chronic hepatitis B. In this study, we investigated the balance between IL-17+ T cells and Foxp3+ regulatory T cells and illustrated their function in the aggravation of chronic hepatitis B (CHB).

Results

Twenty-six patients with chronic HBV -related liver failure (CLF), thirty-one patients with acute on chronic HBV-related liver failure (ACLF) and twelve normal controls were enrolled in our study. The expressions of IL-17, Foxp3, CD4, CD8 and perforin in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes. The frequency of liver IL-17+ T cells on liver inflammatory cells and their proportion in the total CD4+ T cell population increased markedly in the ACLF group, while the frquency of Foxp3+ T cells and their proportion in the total CD4+ T cell population did not show a significant difference in the two HBV infection groups. In addition, the ACLF group showed a dramatically higher IL-17+ /Foxp3+ ratio than the CLF group. CD4+ T cells increased significantly in the liver of patients with ACLF, compared with those in the liver of patients with CLF.

Conclusions

Our findings suggest that intrahepatic IL-17+ T cells play an important role in the development of chronic HBV and that the imbalance between IL-17+ and Foxp3+ T cells in the liver may lead to progression of the disease but the mechanism should be further explored.
Immunome database for marsupials and monotremes
Authors: Wong Emily SW , Papenfuss Anthony T , Belov Katherine
Published: August 2011

Background

To understand the evolutionary origins of our own immune system, we need to characterise the immune system of our distant relatives, the marsupials and monotremes. The recent sequencing of the genomes of two marsupials (opossum and tammar wallaby) and a monotreme (platypus) provides an opportunity to characterise the immune gene repertoires of these model organisms. This was required as many genes involved in immunity evolve rapidly and fail to be detected by automated gene annotation pipelines.

Description

We have developed a database of immune genes from the tammar wallaby, red-necked wallaby, northern brown bandicoot, brush-tail possum, opossum, echidna and platypus. The resource contains 2,235 newly identified sequences and 3,197 sequences which had been described previously. This comprehensive dataset was built from a variety of sources, including EST projects and expert-curated gene predictions generated through a variety of methods including chained-BLAST and sensitive HMMER searches. To facilitate systems-based research we have grouped sequences based on broad Gene Ontology categories as well as by specific functional immune groups. Sequences can be extracted by keyword, gene name, protein domain and organism name. Users can also search the database using BLAST.

Conclusion

The Immunome Database for Marsupials and Monotremes (IDMM) is a comprehensive database of all known marsupial and monotreme immune genes. It provides a single point of reference for genomic and transcriptomic datasets. Data from other marsupial and monotreme species will be added to the database as it become available. This resource will be utilized by marsupial and monotreme immunologists as well as researchers interested in the evolution of mammalian immunity.
Transcripts that associate with the RNA binding protein, DEAD-END (DND1), in embryonic stem (ES) cells
Authors: Zhu Rui , Iacovino Michelina , Mahen Elisabeth , Kyba Michael , Matin Angabin
Published: August 2011

Background

The RNA binding protein, DEAD END (DND1), is essential for maintaining viable germ cells in vertebrates. It is also a testicular germ cell tumor susceptibility factor in mice. DND1 has been shown to interact with the 3'-untranslated region (3'-UTR) of mRNAs such as P27 and LATS2. Binding of DND1 to the 3'-UTRs of these transcripts blocks the inhibitory function of microRNAs (miRNA) from these transcripts and in this way DND1 helps maintain P27 and LATS2 protein expression. We found that DND1 is also expressed in embryonic stem (ES) cells. Because ES cells share similar gene expression patterns as germ cells, we utilized ES cells to identify additional candidate mRNAs that associate with DND1.

Results

ES cells are readily amenable to genetic modification and easier to culture in vitro compared to germ cells. Therefore, for the purpose of our study, we made a genetically modified, stable, human embryonic stem (hES) cell line that expresses hemagluttinin (HA)-tagged DND1 in a doxycycline (dox) regulatable manner. This line expresses modest levels of HA-DND1 and serves as a good system to study DND1 function in vitro. We used this stable cell line to identify the transcripts that physically interact with DND1. By performing ribonucleoprotein immunoprecipitation (RIP) followed by RT-PCR, we identified that transcripts encoding pluripotency factors (OCT4, SOX2, NANOG, LIN28), cell cycle regulators (TP53, LATS2) and apoptotic factors (BCLX, BAX) are specifically associated with the HA-DND1 ribonucleoprotein complex. Surprisingly, in many cases, bioinformatics analysis of the pulled-down transcripts did not reveal the presence of known DND1 interacting motifs.

Conclusions

Our results indicate that the inducible ES cell line system serves as a suitable in vitro system to identify the mRNA targets of DND1. The RIP-RT results hint at the broad spectrum of mRNA targets that interact with DND1 in ES cells. Based on what is known about DND1 function, our results suggest that DND1 may impose another level of translational regulation to modulate expression of critical factors in ES cells.
The resistance of the yeast Saccharomyces cerevisiae to the biocide polyhexamethylene biguanide: involvement of cell wall integrity pathway and emerging role for YAP1
Authors: Elsztein Carolina , de Lucena Rodrigo M , de Morais Marcos A
Published: August 2011

Background

Polyhexamethylene biguanide (PHMB) is an antiseptic polymer that is mainly used for cleaning hospitals and pools and combating Acantamoeba infection. Its fungicide activity was recently shown by its lethal effect on yeasts that contaminate the industrial ethanol process, and on the PE-2 strain of Saccharomyces cerevisiae, one of the main fermenting yeasts in Brazil. This pointed to the need to know the molecular mechanism that lay behind the cell resistance to this compound. In this study, we examined the factors involved in PHMB-cell interaction and the mechanisms that respond to the damage caused by this interaction. To achieve this, two research strategies were employed: the expression of some genes by RT-qPCR and the analysis of mutant strains.

Results

Cell Wall integrity (CWI) genes were induced in the PHMB-resistant Saccharomyces cerevisiae strain JP-1, although they are poorly expressed in the PHMB-sensitive Saccharomyces cerevisiae PE2 strain. This suggested that PHMB damages the glucan structure on the yeast cell wall. It was also confirmed by the observed sensitivity of the yeast deletion strains, Δslg1, Δrom2, Δmkk2, Δslt2, Δknr4, Δswi4 and Δswi4, which showed that the protein kinase C (PKC) regulatory mechanism is involved in the response and resistance to PHMB. The sensitivity of the Δhog1 mutant was also observed. Furthermore, the cytotoxicity assay and gene expression analysis showed that the part played by YAP1 and CTT1 genes in cell resistance to PHMB is unrelated to oxidative stress response. Thus, we suggested that Yap1p can play a role in cell wall maintenance by controlling the expression of the CWI genes.

Conclusion

The PHMB treatment of the yeast cells activates the PKC1/Slt2 (CWI) pathway. In addition, it is suggested that HOG1 and YAP1 can play a role in the regulation of CWI genes.
Identification of two distinct genes at the vertebrate TRPC2 locus and their characterisation in a marsupial and a monotreme
Authors: Frankenberg Stephen , Schneider Nanette Y , Fletcher Terrence P , Shaw Geoffrey , Renfree Marilyn B
Published: August 2011

Background

The vomeronasal organ (VNO) detects pheromones via two large families of vomeronasal receptors: vomeronasal receptor 1 (V1R) and vomeronasal receptor 2 (V2R). Both VRs have a common receptor activation cascade involving transient receptor potential channel, subfamily C, member 2 (TRPC2).

Results

We characterised the TRPC2 locus in a marsupial, the tammar wallaby (Macropus eugenii), and identified two independently regulated genes not previously recognised as distinct. 3'-located exons comprise bona fide TRPC2 whilst 5'-located exons, previously identified as part of TRPC2, comprise a distinct gene, which we term XNDR (X RCC1 N-terminal d omain-r elated). The two genes show contrasting expression patterns in the tammar: TRPC2 is specifically expressed in adult and developing VNO, whereas XNDR is widely expressed in many tissues suggesting a non-VNO-specific role. Strong expression of TRPC2 was detected only after about day 30 post-partum, suggesting that the VNO may not be functional during early pouch life of the tammar. Similarly restricted expression of TRPC2 and widespread expression of XNDR was also detected in the platypus. Bioinformatic analysis of the genomes of a wide range of species suggests that the identity of XNDR and TRPC2 as distinct genes is conserved among vertebrates. Finally, we analysed the promoter of mammalian TRPC2 and identified a conserved binding site for NHLH1, a transcription factor previously implicated in VNO receptor neuron development.

Conclusions

Two functionally distinct vertebrate genes-XNDR and TRPC2 - occupy a genomic locus that was previously defined as a single gene in the mouse. The former is widely expressed with a putative role in DNA repair, while the latter shows VNO-specific expression under the probable regulation of NHLH1.
The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma
Authors: Lieber Justus , Eicher Carmen , Wenz Julia , Kirchner Bettina , Warmann Steven W , Fuchs Jörg , Armeanu-Ebinger Sorin
Published: August 2011

Background

The primary goal of current chemotherapy in hepatoblastoma (HB) is reduction of tumour volume and vitality to enable complete surgical resection and reduce risk of recurrence or metastatic disease. Drug resistance remains a major challenge for HB treatment. In some malignancies inhibition of anti-apoptotic pathways using small BH3 mimetic molecules like ABT-737 shows synergistic effects in combination with cystotoxic agents in vitro. Now we analysed toxicology and synergistic effects of this approach in HB cells and HB xenografts.

Methods

Viability was monitored in HB cells (HUH6 and HepT1) and fibroblasts treated with paclitaxel, ABT-737 and a combination of both in a MTT assay. HUH6 xenotransplants in NOD/LtSz-scid IL2Rγnull mice (NSG) were treated accordingly. Tumour volume and body weight were monitored. Xenografted tumours were analysed by histology and immunohistochemistry (Ki-67 and TUNEL assay).

Results

ABT-737 reduced viability in HUH6 and HepT1 cells cultures at concentrations above 1 μM and also enhanced the cytotoxic effect of paclitaxel when used in combination. Thereby paclitaxel could be reduced tenfold to achieve similar reduction of viability of tumour cells. In contrast no toxicity in fibroblasts was observed at the same regiments. Subcutaneous HB (HUH6) treated with paclitaxel (12 mg/kg body weight, n = 7) led to delayed tumour growth in the beginning of the experiment. However, tumour volume was similar to controls (n = 5) at day 25. Combination treatment with paclitaxel and ABT-737 (100 mg/kg, n = 8) revealed significantly 10 fold lower relative tumour volumes compared to control and paclitaxel groups. Paclitaxel dependent toxicity was observed in this mice strain.

Conclusions

Our results demonstrate enhancement of chemotherapy by using modulators of apoptosis. Further analyses should include improved pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce toxicological effects. Sensitising HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens.
Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B
Authors: Yang Ya , Ge Ping J , Jiang Long , Li Feng L , Zhu Qin Y
Published: August 2011

Background

Our previous studies showed that Salvianolic acid B (Sal B) inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and such anti-cancer effects might be related to the inhibition of angiogenesis. This study was aimed to further investigate the anti-proliferative effect of Sal B on the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the possible mechanisms of action with respect to angiogenesis inhibition.

Methods

Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4, and premalignant leukoplakia cells were treated with different concentrations of Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to evaluate the expression of 96 genes known to be involved in modulating the biological processes of angiogenesis. Real-time reverse transcription-polymerase chain reaction analysis was conducted to confirm the cDNA microarray data.

Results

Sal B induced growth inhibition in OSCC cell lines but had limited effects on premalignant cells. A total of 17 genes showed a greater than 3-fold change when comparing Sal B treated OSCC cells to the control. Among these genes, HIF-1α, TNFα and MMP9 are specifically inhibited, expression of THBS2 was up-regulated.

Conclusions

Sal B has inhibitory effect on OSCC cell growth. The antitumor effect can be attributed to anti-angiogenic potential induced by a decreased expression of some key regulator genes of angiogenesis. Sal B may be a promising modality for treating oral squamous cell carcinoma.
Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes
Authors: Akhtar Nahid , Miller Mark JS , Haqqi Tariq M
Published: August 2011

Background

Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of theUncariatomentosa,Boswellia spp.,Lepidium meyenii and L-Leucineon the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants.

Methods

Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-Leucinemixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits.

Results

HLM tested in thesein vitrostudies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-Leucinemixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β.

Conclusion

Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery.
Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil
Authors: Siqueira Erika RF , Oliveira Cláudia PMS , Muniz Maria TC , Silva Filipe , Pereira Leila MMB , Carrilho Flair J
Published: August 2011

Background/Aim

Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil.

Method

One hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week.

Results

Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the MTHFR genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03).

Conclusion

Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.
Numerical simulation of strain-adaptive bone remodelling in the ankle joint
Authors: Bouguecha Anas , Weigel Nelly , Behrens Bernd-Arno , Stukenborg-Colsman Christina , Waizy Hazibullah
Published: August 2011

Background

The use of artificial endoprostheses has become a routine procedure for knee and hip joints while ankle arthritis has traditionally been treated by means of arthrodesis. Due to its advantages, the implantation of endoprostheses is constantly increasing. While finite element analyses (FEA) of strain-adaptive bone remodelling have been carried out for the hip joint in previous studies, to our knowledge there are no investigations that have considered remodelling processes of the ankle joint. In order to evaluate and optimise new generation implants of the ankle joint, as well as to gain additional knowledge regarding the biomechanics, strain-adaptive bone remodelling has been calculated separately for the tibia and the talus after providing them with an implant.

Methods

FE models of the bone-implant assembly for both the tibia and the talus have been developed. Bone characteristics such as the density distribution have been applied corresponding to CT scans. A force of 5,200 N, which corresponds to the compression force during normal walking of a person with a weight of 100 kg according to Stauffer et al., has been used in the simulation. The bone adaptation law, previously developed by our research team, has been used for the calculation of the remodelling processes.

Results

A total bone mass loss of 2% in the tibia and 13% in the talus was calculated. The greater decline of density in the talus is due to its smaller size compared to the relatively large implant dimensions causing remodelling processes in the whole bone tissue. In the tibia, bone remodelling processes are only calculated in areas adjacent to the implant. Thus, a smaller bone mass loss than in the talus can be expected. There is a high agreement between the simulation results in the distal tibia and the literature regarding.

Conclusions

In this study, strain-adaptive bone remodelling processes are simulated using the FE method. The results contribute to a better understanding of the biomechanical behaviour of the ankle joint and hence are useful for the optimisation of the implant geometry in the future.
High content of long-chain n-3 polyunsaturated fatty acids in red blood cells of Kenyan Maasai despite low dietary intake
Authors: Knoll Nadja , Kuhnt Katrin , Kyallo Florence M , Kiage-Mokua Beatrice N , Jahreis Gerhard
Published: August 2011

Background

Increasing land restrictions and a reduced livestock-to-human ratio during the 20th century led the Maasai to lead a more sedentary, market-orientated lifestyle. Although plant-derived food nowadays contributes substantially to their diet, dairy products being high in saturated fatty acids (SFA) and low in polyunsaturated fatty acids (PUFA) still are an important energy source. Since reliable data regarding the Maasai diet date back to the 1980s, the study objective was to document current diet practices in a Kenyan Maasai community and to investigate the fatty acid distribution in diet and red blood cells.

Methods

A cross-sectional study was conducted among 26 Maasai (20 women, 6 men) from Loodokilani, Kajiado District, Kenya. Food intake was described by the subjects via 24-h recall, and both food and blood samples were analysed.

Results

Two main foods - milk and ugali - constituted the Maasai diet in this region. A total of 0.9 L of milk and 0.6 kg of ugali were consumed per person and day to yield an energy intake of 7.6 MJ/d per person. A major proportion of ingested food contributing 58.3% to the total dietary energy (en%) was plant-derived, followed by dairy products representing 41.1 en%. Fat consumed (30.5 en%) was high in SFA (63.8%) and low in PUFA (9.2%). Long-chain n-3 PUFA (EPA, DPA and DHA) made up only 0.15% of the ingested fatty acids, but 5.9% of red blood cell fatty acids.

Conclusion

The study indicates the Maasai diet is rich in SFA and low in PUFA. Nevertheless, red blood cells are composed of comparable proportions of long-chain n-3 PUFA to populations consuming higher amounts of this fatty acid group.
Reduction of neutrophil activity decreases early microvascular injury after subarachnoid haemorrhage
Authors: Friedrich Victor , Flores Rowena , Muller Artur , Bi Weina , Peerschke Ellinor IB , Sehba Fatima A
Published: August 2011

Background

Subarachnoid haemorrhage (SAH) elicits rapid pathological changes in the structure and function of parenchymal vessels (≤ 100 μm). The role of neutrophils in these changes has not been determined. This study investigates the role of neutrophils in early microvascular changes after SAH

Method

Rats were either untreated, treated with vinblastine or anti-polymorphonuclear (PMN) serum, which depletes neutrophils, or treated with pyrrolidine dithiocarbamate (PDTC), which limits neutrophil activity. SAH was induced by endovascular perforation. Neutrophil infiltration and the integrity of vascular endothelium and basement membrane were assessed immunohistochemically. Vascular collagenase activity was assessed by in situ zymography.

Results

Vinblastine and anti-PMN serum reduced post-SAH accumulation of neutrophils in cerebral vessels and in brain parenchyma. PDTC increased the neutrophil accumulation in cerebral vessels and decreased accumulation in brain parenchyma. In addition, each of the three agents decreased vascular collagenase activity and post-SAH loss of vascular endothelial and basement membrane immunostaining.

Conclusions

Our results implicate neutrophils in early microvascular injury after SAH and indicate that treatments which reduce neutrophil activity can be beneficial in limiting microvascular injury and increasing survival after SAH.
Promoting smoking cessation in Pakistani and Bangladeshi men in the UK: pilot cluster randomised controlled trial of trained community outreach workers
Authors: Begh Rachna A , Aveyard Paul , Upton Penney , Bhopal Raj S , White Martin , Amos Amanda , Prescott Robin J , Bedi Raman , Barton Pelham , Fletcher Monica , Gill Paramjit , Zaidi Qaim , Sheikh Aziz
Published: August 2011

Background

Smoking prevalence is high among Pakistani and Bangladeshi men in the UK, but there are few tailored smoking cessation programmes for Pakistani and Bangladeshi communities. The aim of this study was to pilot a cluster randomised controlled trial comparing the effectiveness of Pakistani and Bangladeshi smoking cessation outreach workers with standard care to improve access to and the success of English smoking cessation services.

Methods

A pilot cluster randomised controlled trial was conducted in Birmingham, UK. Geographical lower layer super output areas were used to identify natural communities where more than 10% of the population were of Pakistani and Bangladeshi origin. 16 agglomerations of super output areas were randomised to normal care controls vs. outreach intervention. The number of people setting quit dates using NHS services, validated abstinence from smoking at four weeks, and stated abstinence at three and six months were assessed. The impact of the intervention on choice and adherence to treatments, attendance at clinic appointments and patient satisfaction were also assessed.

Results

We were able to randomise geographical areas and deliver the outreach worker-based services. More Pakistani and Bangladeshi men made quit attempts with NHS services in intervention areas compared with control areas, rate ratio (RR) 1.32 (95%CI: 1.03-1.69). There was a small increase in the number of 4-week abstinent smokers in intervention areas (RR 1.30, 95%CI: 0.82-2.06). The proportion of service users attending weekly appointments was lower in intervention areas than control areas. No difference was found between intervention and control areas in choice and adherence to treatments or patient satisfaction with the service. The total cost of the intervention was £124,000; an estimated cost per quality-adjusted life year (QALY) gained of £8,500.

Conclusions

The intervention proved feasible and acceptable. Outreach workers expanded reach of smoking cessation services in diverse locations of relevance to Pakistani and Bangladeshi communities. The outreach worker model has the potential to increase community cessation rates and could prove cost-effective, but needs evaluating definitively in a larger, appropriately powered, randomised controlled trial. These future trials of outreach interventions need to be of sufficient duration to allow embedding of new models of service delivery.

Trial registration

Current Controlled Trials ISRCTN82127540
Combining multivariate analysis and monosaccharide composition modeling to identify plant cell wall variations by Fourier Transform Near Infrared spectroscopy
Authors: Smith-Moritz Andreia M , Chern Mawsheng , Lao Jeemeng , Sze-To Wing Hoi , Heazlewood Joshua L , Ronald Pamela C , Vega-Sánchez Miguel E
Published: August 2011

We outline a high throughput procedure that improves outlier detection in cell wall screens using FT-NIR spectroscopy of plant leaves. The improvement relies on generating a calibration set from a subset of a mutant population by taking advantage of the Mahalanobis distance outlier scheme to construct a monosaccharide range predictive model using PLS regression. This model was then used to identify specific monosaccharide outliers from the mutant population.