bluuebunny/crossref_metadata_2025 huggingface dataset:
Chicken cyclophilin A is an inhibitory factor to influenza virus replication
Authors: Xu Chongfeng , Meng Shanshan , Liu Xiaoling , Sun Lei , Liu Wenjun
Published: January 2011

Background

The importance of enhancing influenza resistance in domestic flocks is quite clear both scientifically and economically. Chicken is very susceptible to influenza virus. It has been reported that human cellular cyclophilin A (CypA) impaired influenza virus infection in 293T cells. Whether chicken CypA (chCypA) inhibits influenza virus replication is not known. The molecular mechanism of resistance in chicken to influenza virus remains to be studied.

Results

The chCypA gene was isolated and characterized in the present study. It contained an ORF of 498 bp encoding a polypeptide of 165 amino acids with an estimated molecular mass of 17.8 kDa sharing high identity with mammalian CypA genes. The chCypA demonstrated an anti-influenza activity as expected. ChCypA protein was shown to be able to specifically interact with influenza virus M1 protein. Cell susceptibility to influenza virus was reduced by over-expression of chCypA in CEF cells. The production of recombinant influenza virus A/WSN/33 reduced to one third in chCypA expressing cells comparing to chCypA absent cells. ChCypA was widely distributed in a variety of chicken tissues. It localized in cytoplasm of chicken embryo fibroblast (CEF) cells. Avian influenza virus infection induced its translocation from cytoplasm into nucleus. ChCypA expression was not significantly up-regulated by avian influenza virus infection. The present study indicated that chCypA was an inhibitory protein to influenza virus replication, suggesting a role as an intrinsic immunity factor against influenza virus infection.

Conclusion

The present data demonstrates that chCypA possesses anti-influenza virus activity which allows the consideration of genetic improvement for resistance to influenza virus in chickens.
Human Papillomavirus in Brazilian women with and without cervical lesions
Authors: Oliveira-Silva Michelle , Lordello Camila X , Zardo Lucília MG , Bonvicino Cibele R , Moreira Miguel AM
Published: January 2011

Background

Human Papillomavirus (HPV) high-risk (HR) types are the causal factor for cervical cancer and premalignant dysplasia. Data on frequency of HPV types provide a basis to design and evaluate HPV prevention programs. Taking into account the heterogeneity of HPV types across and within populations this study aims to access the HPV frequency in Brazilian women.

Results

We identified 24 different types of HPV, including a Betapapillomavirus and a likely new type, previously reported, from 132 women positive for the virus analysed by Hybrid Capture II assay. These women were infected by a single or multiple HPV types and 142 HPV strains were identified. HR types were found in 75% of women and HPV types 16, 18, 45, 58, and 66 had the highest frequency. Significant differences in frequency of HR HPV types were found for presence of cervical lesions, and for different HPV species and women age.

Conclusions

Compared with previous studies in Brazil, our data indicated differences in frequency and HPV type diversity, a significant association of other HR-types but HPV16 and 18 and cervical lesions, and a trend for distinct distribution of HPV types by age.
Potentiation of Excitatory Transmission in Substantia Gelatinosa Neurons of Rat Spinal Cord by Inhibition of Estrogen Receptor Alpha
Authors: Zhong Yan-Qing , Li Kai-Cheng , Zhang Xu
Published: January 2011

Background:

It has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission. One of the estrogen receptor (ER) subtypes, estrogen receptor alpha (ERα), is expressed in the spinal laminae I–V, including substantia gelatinosa (SG, lamina II). However, it is unclear how ERs are involved in the modulation of nociceptive transmission.

Results:

In the present study, a selective ERα antagonist, methyl-piperidino-pyrazole (MPP), was used to test the potential functional roles of spinal ERα in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of MPP on SG neurons in the dorsal root-attached spinal cord slice prepared from adult rats. We found that MPP increased glutamatergic excitatory postsynaptic currents (EPSCs) evoked by the stimulation of either Aδ- or C-afferent fibers. Further studies showed that MPP treatment dose-dependently increased spontaneous EPSCs frequency in SG neurons, while not affecting the amplitude. In addition, the PKC was involved in the MPP-induced enhancement of synaptic transmission.

Conclusions:

These results suggest that the selective ERα antagonist MPP pre-synaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive transmission evoked by Aδ- and C-fiber stimulation could be potentiated by blocking ERα in the spinal neurons. Thus, the spinal estrogen may negatively regulate the nociceptive transmission through the activation of ERα.
Ablation of Rat TRPV1-Expressing Adelta/C-Fibers with Resiniferatoxin: Analysis of Withdrawal Behaviors, Recovery of Function and Molecular Correlates
Authors: Mitchell Kendall , Bates Brian D , Keller Jason M , Lopez Matthew , Scholl Lindsey , Navarro Julia , Madian Nicholas , Haspel Gal , Nemenov Michael I , Iadarola Michael J
Published: January 2011

Background:

Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C- and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy.

Results:

RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7–8 weeks after 5 ng, or 9–10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal.

Conclusion:

Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control.
DREAM Regulates BDNF-Dependent Spinal Sensitization
Authors: Rivera-Arconada Ivan , Benedet Tomaso , Roza Carolina , Torres Begoβa , Barrio Jorge , Krzyzanowska Agnieszka , Avendaño Carlos , Mellström Britt , Lopez-Garcia José A , Naranjo José R
Published: January 2011

Background:

The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) controls the expression of prodynorphin and has been involved in the modulation of endogenous responses to pain. To investigate the role of DREAM in central mechanisms of pain sensitization, we used a line of transgenic mice (L1) overexpressing a Ca2+- and cAMP-insensitive DREAM mutant in spinal cord and dorsal root ganglia.

Results:

L1 DREAM transgenic mice showed reduced expression in the spinal cord of several genes related to pain, including prodynorphin and BDNF (brain-derived neurotrophic factor) and a state of basal hyperalgesia without change in A-type currents. Peripheral inflammation produced enhancement of spinal reflexes and increased expression of BDNF in wild type but not in DREAM transgenic mice. The enhancement of the spinal reflexes was reproduced in vitro by persistent electrical stimulation of C-fibers in wild type but not in transgenic mice. Exposure to exogenous BDNF produced a long-term enhancement of dorsal root-ventral root responses in transgenic mice.

Conclusions:

Our results indicate that endogenous BDNF is involved in spinal sensitization following inflammation and that blockade of BDNF induction in DREAM transgenic mice underlies the failure to develop spinal sensitization.
Estimated intelligence quotient in anorexia nervosa: a systematic review and meta-analysis of the literature
Authors: Lopez Carolina , Stahl Daniel , Tchanturia Kate
Published: January 2011

Background

It has been hypothesised that people with anorexia nervosa have a higher intelligence quotient (IQ) level than the general population. The purpose of this review was to systematically appraise the research into reported IQ levels in people with anorexia nervosa.

Methods

A search using the terms intelligence quotient, IQ, intelligence, cognition, eating disorders and anorexia was conducted in electronic databases only.

Results

In all, 30 peer-reviewed studies written in English that used well established measures of intelligence quotient (the National Adult Reading Test and Wechsler Intelligence Scales) were identified. This review established that people with anorexia nervosa score 10.8 units and 5.9 units above the average intelligence quotient of the normative population on the National Adult Reading Test and Wechsler Intelligence Scales, respectively. An association was found between Body Mass Index and intelligence quotient, as measured by the National Adult Reading Test.

Conclusions

More studies including other eating disorder categories and recovered people are needed to explore important questions regarding the role of the intelligence quotient in treatment response.
Traditional herbal medicine in Far-west Nepal: a pharmacological appraisal
Authors: Kunwar Ripu M , Shrestha Keshab P , Bussmann Rainer W
Published: January 2011

Background

Plant species have long been used as principal ingredients of traditional medicine in far-west Nepal. The medicinal plants with ethnomedicinal values are currently being screened for their therapeutic potential but their data and information are inadequately compared and analyzed with the Ayurveda and the phytochemical findings.

Methods

The present study evaluated ethnomedicinal plants and their uses following literature review, comparison, field observations, and analysis. Comparison was made against earlier standard literature of medicinal plants and ethnomedicine of the same area, the common uses of the Ayurveda and the latest common phytochemical findings. The field study for primary data collection was carried out from 2006-2008.

Results

The herbal medicine in far-west Nepal is the basis of treatment of most illness through traditional knowledge. The medicine is made available via ancient, natural health care practices such as tribal lore, home herbal remedy, and the Baidhya, Ayurveda and Amchi systems. The traditional herbal medicine has not only survived but also thrived in the trans-cultural environment with its intermixture of ethnic traditions and beliefs. The present assessment showed that traditional herbal medicine has flourished in rural areas where modern medicine is parsimoniously accessed because of the high cost and long travel time to health center. Of the 48 Nepalese medicinal plants assessed in the present communication, about half of the species showed affinity with the common uses of the Ayurveda, earlier studies and the latest phytochemical findings. The folk uses of Acacia catechu for cold and cough, Aconitum spicatum as an analgesic, Aesculus indica for joint pain, Andrographis paniculata for fever, Anisomeles indica for urinary affections, Azadirachta indica for fever, Euphorbia hirta for asthma, Taxus wallichiana for tumor control, and Tinospora sinensis for diabetes are consistent with the latest pharmacological findings, common Ayurvedic and earlier uses.

Conclusions

Although traditional herbal medicine is only a primary means of health care in far-west Nepal, the medicine has been pursued indigenously with complementing pharmacology and the Ayurveda. Therefore, further pharmacological evaluation of traditional herbal medicine deserves more attention.
An on-farm investigation of beef suckler herds using an animal welfare index (AWI)
Authors: Mazurek Mickael , Prendiville Daniel J , Crowe Mark A , Veissier Isabelle , Earley Bernadette
Published: January 2011

Background

Beef suckler farms (194 farms throughout 13 counties) were assessed once with housed cattle and once with cattle at grass using an animal welfare index (AWI). Twenty-three of the 194 farms were revisited a year later and re-evaluated using the AWI and the Tier-Gerechtheits-Index 35L/2000 (TGI35L/2000). Thirty-three indicators were collected in five categories: locomotion (5 indicators); social interactions (between animals) (7), flooring (5), environment (7) and Stockpersonship (9). Three indicators relating to the size of the farm were also collected.

Improving animal welfare is an increasingly important aspect of livestock production systems predominantly due to increased consumer concern about the source of animal products. The objectives were (i) to evaluate animal welfare of Irish beef suckler herds using an animal welfare index (AWI), (ii) to examine correlations between parameters, how they influence the AWI and investigate the applicability of the parameters used, (iii) to investigate the impact of the activity of the farmer (full-time or part-time), the interest of the farmer and the number of animals on the AWI.

Results

The mean AWI was 65% and ranged from 54% to 83%. The grazing period represented 16.5% of the total points of the AWI. Seventy percent of the farms were rated as "Very Good" or "Excellent". There was no difference (P > 0.05) in AWI between full-time and part-time farmers. Part-time farmers had greater (P = 0.01) "social interactions": calving (P = 0.03) and weaning (P < 0.001) scores. Full-time farmers had cleaner animals (P = 0.03) and their animals had less lameness (P = 0.01). The number of animals on-farm and the interest of the Stockperson were negatively and positively correlated (P = 0.001), respectively, with the AWI. A hierarchical classification was performed to examine how the indicators influenced the AWI.

Conclusion

The AWI was easily applicable for an on-farm evaluation of welfare. The Stockpersonship was an important factor in determining the AWI (11% of the total variation) more specifically, the interest of the farmer. Part and full-time farming did not differ (P > 0.05) in AWI scores. This method could, with further development, be used in countries with both intensive and/or extensive production systems and would require substantially less resources than animal-based methods.
Impact of antigenic and genetic drift on the serologic surveillance of H5N2 avian influenza viruses
Authors: Escorcia Magdalena , Carrillo-Sánchez Karol , March-Mifsut Santiago , Chapa Joaquin , Lucio Eduardo , Nava Gerardo M
Published: January 2011

Background

Serologic surveillance of Avian Influenza (AI) viruses is carried out by the hemagglutination inhibition (HI) test using reference reagents. This method is recommended by animal health organizations as a standard test to detect antigenic differences (subtypes) between circulating influenza virus, vaccine- and/or reference- strains. However, significant discrepancies between reference antisera and field isolates have been observed during serosurveillance of influenza A viruses in pig and poultry farms. The objective of this study was to examine the effects of influenza virus genetic and antigenic drift on serologic testing using standard HI assays and reference reagents. Low pathogenic AI H5N2 viruses isolated in Mexico between 1994 and 2008 were used for phylogenetic analysis of AI hemagglutinin genes and for serologic testing using antisera produced with year-specific AI virus isolates.

Results

Phylogenetic analysis revealed significant divergence between early LPAI H5N2 viruses (1994 - 1998) and more recent virus field isolates (2002 - 2008). Results of the HI test were markedly influenced by the selection of the AI H5N2 virus (year of isolation) used as reference antigen for the assay. These analyses indicate that LPAI H5N2 viruses in Mexico are constantly undergoing genetic drift and that serosurveillance of AI viruses is significantly influenced by the antigen or antisera used for the HI test.

Conclusions

Reference viral antigens and/or antisera need to be replaced constantly during surveillance of AI viruses to keep pace with the AI antigenic drift. This strategy should improve the estimation of antigenic differences between circulating AI viruses and the selection of suitable vaccine strains.
3D-CT implanted interstitial brachytherapy for T2b nasopharyngeal carcinoma
Authors: Ren Yu-Feng , Gao Yuan-Hong , Cao Xin-Ping , Ye Wei-Jun , Teh Bin S
Published: January 2011

Background

To compare the results of external beam radiotherapy in combination with 3D- computed tomography (CT)-implanted interstitial high dose rate brachytherapy (ERT/3D-HDR-BT) versus conventional external beam radiotherapy (ERT) for the treatment of stage T2b nasopharyngeal carcinoma (NPC).

Methods

Forty NPC patients diagnosed with stage T2b NPC were treated with ERT/3D-HDR-BT under local anesthesia. These patients received a mean dose of 60 Gy, followed by 12-20 Gy administered by 3D-HDR-BT. Another 101 patients diagnosed with non-metastatic T2b NPC received a mean dose of 68 Gy by ERT alone during the same period.

Results

Patients treated with ERT/3D-HDR-BT versus ERT alone exhibited an improvement in their 5-y local failure-free survival rate (97.5% vs. 80.2%, P = 0.012) and disease-free survival rate (92.5% vs. 73.3%, P = 0.014). Using multivariate analysis, administration of 3D-HDR-BT was found to be favorable for local control (P = 0.046) and was statistically significant for disease-free survival (P = 0.021). The incidence rate of acute and chronic complications between the two groups was also compared.

Conclusions

It is possible that the treatment modality enhances local control due to improved conformal dose distributions and the escalated radiation dose applied.
Adjuvant therapy for T3N0 rectal cancer in the total mesorectal excision era- identification of the high risk patients
Authors: Zhu Ji , Xu Ye , Gu Weilie , Peng Junjie , Cai Gang , Cai Guoxiang , Sun Wenjie , Shen Weiqi , Cai Sanjun , Zhang Zhen
Published: January 2011

Background

Adjuvant therapy for T3N0 rectal cancer was controversial with respect to both radiation and the use of a combined regimen of chemotherapy. We evaluated both clinical features and biomarkers and sought to determine risk factors for those patients retrospectively.

Methods

A total of 122 patients with T3N0 rectal cancer were analyzed in this study from January 2000 to December 2005. Clinicopathologic and biomarkers were used to predict local recurrence (LR), disease-free survival (DFS), and overall survival (OS).

Results

The median follow-up interval was 45.4 months. Five-year LR, DFS, and OS rates were 10.4%, 68.3%, and 88.7%. Having a lower tumor location and showing low P21 and high CD44v6 expression were identified as risk factors for LR: patients with two or three of these risk factors had a higher 5-year LR rate (19.3%) than did patients with none or one of these risk factors (6.8%) (p = 0.05). A poorer DFS was related to low P21 nor high CD44v6 expression but not to tumor location: the 5-year DFS rates were 79.3% for those with neither, 65.9% for those with either one or the other, and 16.9% for those with both (p = 0.00).

Conclusions

The prognostic model including tumor location, P21 and CD44v6 expressions could help to distinguish these patients with high risk T3N0 patients and determine whether adjuvant therapy was beneficial.
Comparison of side effects of oxytetracycline and talc pleurodesis: an experimental study
Authors: Gözübüyük Alper , Özpolat Berkant , Çiçek Ali Fuat , Çaylak Hasan , Yücel Orhan , Kavaklı Kuthan , Gürkök Sedat , Genç Onur
Published: January 2011

Background

Chemical pleurodesis is widely recommended in the treatment of refractory pleural effusion or pulmonary air leak of different etiologies. Although several agents have been used, many questions have remained unanswered about their toxicity. Talc is the most commonly used agent for the treatment, with rare, serious complications reported. Oxytetracycline pleurodesis in clinical practice has been described in a few studies, but literature reveals no experimental studies using this agent. We performed a prospective, randomized, observer-blinded, controlled study to evaluate the changes in lung histology and systemic response to pleurodesis with oxytetracycline and talc in acute and subacute phases in a rat model.

Methods

Forty-two male albino Wistar rats were divided into three groups and 3 subgroups with 7 animals in each. Group 1 was given oxytetracycline, 35 mg/kg; Group 2 was given talc slurry, 60 mg/kg in 0.5 mL saline solution, and Group 3 was given only 0.5 mL saline intrapleurally. In subgroups "a" the nimls were sacrificed at the postoperative 72nd hour and, in subgroups "b", on the postoperative day 7. The surfaces were graded by microscopic examination.

Results

Oxytetracycline produced alveolar collapse, hemorrhage, edema, inflammation at the postoperative 72nd hour and hemorrhage on the postoperative day 7, while talc produced significant edema, inflammation, proliferation, fibrosis at the postoperative 72nd hour and hemorrhage, edema, inflammation, proliferation, and fibrosis on the postoperative day 7 (p < 0,0042). Talc produced significant edema compared to oxytetracycline on the postoperative day 7. On contralateral side, oxytetracycline and talc produced significant hemorrhage on the postoperative day 7 (p < 0.0042).

Conclusions

Both agents were shown to produce pulmonary lesions. In acute phase, the pulmonary side effects of oxytetracycline were more pronounced, whereas the side effects of talc were prolonged to subacute phase. We propose that the occasional side effects in humans may be related to these changes as were observed in our rat model, and like talc, oxytetracycline must be used cautiously in patients with limited respiratory function.
Inference of hierarchical regulatory network of estrogen-dependent breast cancer through ChIP-based data
Authors: Gu Fei , Hsu Hang-Kai , Hsu Pei-Yin , Wu Jiejun , Ma Yilin , Parvin Jeffrey , Huang Tim H-M , Jin Victor X
Published: January 2011

Background

Global profiling of in vivo protein-DNA interactions using ChIP-based technologies has evolved rapidly in recent years. Although many genome-wide studies have identified thousands of ERα binding sites and have revealed the associated transcription factor (TF) partners, such as AP1, FOXA1 and CEBP, little is known about ERα associated hierarchical transcriptional regulatory networks.

Results

In this study, we applied computational approaches to analyze three public available ChIP-based datasets: ChIP-seq, ChIP-PET and ChIP-chip, and to investigate the hierarchical regulatory network for ERα and ERα partner TFs regulation in estrogen-dependent breast cancer MCF7 cells. 16 common TFs and two common new TF partners (RORA and PITX2) were found among ChIP-seq, ChIP-chip and ChIP-PET datasets. The regulatory networks were constructed by scanning the ChIP-peak region with TF specific position weight matrix (PWM). A permutation test was performed to test the reliability of each connection of the network. We then used DREM software to perform gene ontology function analysis on the common genes. We found that FOS, PITX2, RORA and FOXA1 were involved in the up-regulated genes.

We also conducted the ERα and Pol-II ChIP-seq experiments in tamoxifen resistance MCF7 cells (denoted as MCF7-T in this study) and compared the difference between MCF7 and MCF7-T cells. The result showed very little overlap between these two cells in terms of targeted genes (21.2% of common genes) and targeted TFs (25% of common TFs). The significant dissimilarity may indicate totally different transcriptional regulatory mechanisms between these two cancer cells.

Conclusions

Our study uncovers new estrogen-mediated regulatory networks by mining three ChIP-based data in MCF7 cells and ChIP-seq data in MCF7-T cells. We compared the different ChIP-based technologies as well as different breast cancer cells. Our computational analytical approach may guide biologists to further study the underlying mechanisms in breast cancer cells or other human diseases.
SVM classifier to predict genes important for self-renewal and pluripotency of mouse embryonic stem cells
Authors: Xu Huilei , Lemischka Ihor R , Ma'ayan Avi
Published: January 2011

Background

Mouse embryonic stem cells (mESCs) are derived from the inner cell mass of a developing blastocyst and can be cultured indefinitely in-vitro. Their distinct features are their ability to self-renew and to differentiate to all adult cell types. Genes that maintain mESCs self-renewal and pluripotency identity are of interest to stem cell biologists. Although significant steps have been made toward the identification and characterization of such genes, the list is still incomplete and controversial. For example, the overlap among candidate self-renewal and pluripotency genes across different RNAi screens is surprisingly small. Meanwhile, machine learning approaches have been used to analyze multi-dimensional experimental data and integrate results from many studies, yet they have not been applied to specifically tackle the task of predicting and classifying self-renewal and pluripotency gene membership.

Results

For this study we developed a classifier, a supervised machine learning framework for predicting self-renewal and pluripotency mESCs stemness membership genes (MSMG) using support vector machines (SVM). The data used to train the classifier was derived from mESCs-related studies using mRNA microarrays, measuring gene expression in various stages of early differentiation, as well as ChIP-seq studies applied to mESCs profiling genome-wide binding of key transcription factors, such as Nanog, Oct4, and Sox2, to the regulatory regions of other genes. Comparison to other classification methods using the leave-one-out cross-validation method was employed to evaluate the accuracy and generality of the classification. Finally, two sets of candidate genes from genome-wide RNA interference screens are used to test the generality and potential application of the classifier.

Conclusions

Our results reveal that an SVM approach can be useful for prioritizing genes for functional validation experiments and complement the analyses of high-throughput profiling experimental data in stem cell research.
Targeted protein depletion in Saccharomyces cerevisiae by activation of a bidirectional degron
Authors: Jungbluth Marc , Renicke Christian , Taxis Christof
Published: January 2011

Background

Tools for in vivo manipulation of protein abundance or activity are highly beneficial for life science research. Protein stability can be efficiently controlled by conditional degrons, which induce target protein degradation at restrictive conditions.

Results

We used the yeast Saccharomyces cerevisiae for development of a conditional, bidirectional degron to control protein stability, which can be fused to the target protein N-terminally, C-terminally or placed internally. Activation of the degron is achieved by cleavage with the tobacco etch virus (TEV) protease, resulting in quick proteolysis of the target protein. We found similar degradation rates of soluble substrates using destabilization by the N- or C-degron. C-terminal tagging of essential yeast proteins with the bidirectional degron resulted in deletion-like phenotypes at non-permissive conditions. Developmental process-specific mutants were created by N- or C-terminal tagging of essential proteins with the bidirectional degron in combination with sporulation-specific production of the TEV protease.

Conclusions

We developed a system to influence protein abundance and activity genetically, which can be used to create conditional mutants, to regulate the fate of single protein domains or to design artificial regulatory circuits. Thus, this method enhances the toolbox to manipulate proteins in systems biology approaches considerably.
Benign perimesencephalic hemorrhage occurring after previous aneurysmal subarachnoid hemorrhage: a case report
Authors: Singleton Richard H , Kostov Dean B , Kanaan Hilal A , Horowitz Michael B
Published: January 2011

Introduction

Both aneurysmal subarachnoid hemorrhage and benign perimesencephalic hemorrhage are well-described causes of spontaneous subarachnoid hemorrhage that arise as a result of different pathologic processes. To the best of the authors' knowledge, there have been no reports of both vascular pathologies occurring in the same individual.

Case presentation

A 51-year-old Caucasian woman with a history of aneurysmal subarachnoid hemorrhage presented five years after her initial treatment with ictal headache, meningismus, nausea and emesis similar to her previous bleeding event. Computed tomographic imaging revealed perimesencephalic bleeding remote from her previously coiled anterior communicating artery aneurysm. Both immediate and delayed diagnostic angiography revealed no residual filling of the previously coiled aneurysm and no other vascular anomalies, consistent with benign perimesencephalic hemorrhage. The patient had an uneventful hospital course and was discharged to home in good condition.

Conclusions

This report for the first time identifies benign perimesencephalic hemorrhage occurring in the setting of previous aneurysmal subarachnoid hemorrhage. The presence of a previously treated aneurysm can complicate the process of diagnosing benign perimesencephalic hemorrhage. Fortunately, in this case, the previously treated anterior communicating artery aneurysm was remote from the perimesencephalic hemorrhage and could be ruled out as a source. The patient's prior aneurysmal subarachnoid hemorrhage did not worsen the anticipated good outcome associated with benign perimesencephalic hemorrhage.
Cholesteatoma of the concha bullosa: a case report
Authors: Cukurova Ibrahim , Demirhan Erhan , Arslan Ilker B , Cumurcu Suheyla
Published: January 2011

Introduction

Cholesteatoma is a relatively common disease within the middle ear cavity, but rarely it manifests in the paranasal sinuses. There is, to the best of our knowledge, only one other published case of cholesteatoma inside the concha bullosa in the English language literature.

Case presentation

An 81-year-old Caucasian woman was admitted to our hospital complaining of nasal obstruction, headache and diplopia. After endoscopic and radiological evaluation a transnasal endoscopic approach was chosen. The diagnosis of cholesteatoma was established by histopathological evaluation of the mass inside the concha bullosa.

Conclusion

Although it is rarely seen, cholesteatoma should be considered in the differential diagnosis of slow-growing and destructive paranasal masses.
New cytogenetically visible copy number variant in region 8q21.2
Authors: Manvelyan Marina , Cremer Friedrich W , Lancé Jeannette , Kläs Rüdiger , Kelbova Christina , Ramel Christian , Reichenbach Herbert , Schmidt Catharina , Ewers Elisabeth , Kreskowski Katharina , Ziegler Monika , Kosyakova Nadezda , Liehr Thomas
Published: January 2011

Background

Cytogenetically visible unbalanced chromosomal abnormalities (UBCA), reported for >50 euchromatic regions of almost all human autosomes, are comprised of a few megabases of DNA, and carriers are in many cases clinically healthy. It may be speculated, that some of the UBCA may be similar or identical to copy number variants (CNV) of the human genome.

Results

Here we report on a yet unreported cytogenetically visible copy number variant (CNV) in the long arm of chromosome 8, region 8q21.2, detected in three unrelated clinically healthy carriers.

Conclusion

The first description of a cytogenetically visible CNV/UBCA in 8q21.2 shows that banding cytogenetics is far from being outdated. It is a cost efficient, up-to-date method for a single cell specific overview on the whole genome, still prepared to deliver unexpected findings.
Primate-specific evolution of noncoding element insertion into PLA2G4Cand human preterm birth
Authors: Plunkett Jevon , Doniger Scott , Morgan Thomas , Haataja Ritva , Hallman Mikko , Puttonen Hilkka , Menon Ramkumar , Kuczynski Edward , Norwitz Errol , Snegovskikh Victoria , Palotie Aarno , Peltonen Leena , Fellman Vineta , DeFranco Emily A , Chaudhari Bimal P , Oates John , Boutaud Olivier , McGregor Tracy L , McElroy Jude J , Teramo Kari , Borecki Ingrid , Fay Justin C , Muglia Louis J
Published: January 2011

Background

The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance.

Methods

We performed a comparative genomics screen of highly conserved noncoding elements and identifiedPLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) inPLA2G4Cin US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers.

Results

Detailed structural and phylogenic analysis ofPLA2G4Csuggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affectPLA2G4Cactivity.

Conclusions

Our findings suggest that variation inPLA2G4Cmay influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.
Synthesis-View: visualization and interpretation of SNP association results for multi-cohort, multi-phenotype data and meta-analysis
Authors: Pendergrass Sarah A , Dudek Scott M , Crawford Dana C , Ritchie Marylyn D
Published: January 2011

Background

Initial genome-wide association study (GWAS) discoveries are being further explored through the use of large cohorts across multiple and diverse populations involving meta-analyses within large consortia and networks. Many of the additional studies characterize less than 100 single nucleotide polymorphisms (SNPs), often include multiple and correlated phenotypic measurements, and can include data from multiple-sites, multiple-studies, as well as multiple race/ethnicities. New approaches for visualizing resultant data are necessary in order to fully interpret results and obtain a broad view of the trends between DNA variation and phenotypes, as well as provide information on specific SNP and phenotype relationships.

Results

The Synthesis-View software tool was designed to visually synthesize the results of the aforementioned types of studies. Presented herein are multiple examples of the ways Synthesis-View can be used to report results from association studies of DNA variation and phenotypes, including the visual integration of p-values or other metrics of significance, allele frequencies, sample sizes, effect size, and direction of effect.

Conclusions

To truly allow a user to visually integrate multiple pieces of information typical of a genetic association study, innovative views are needed to integrate multiple pieces of information. As a result, we have created "Synthesis-View" software for the visualization of genotype-phenotype association data in multiple cohorts. Synthesis-View is freely available for non-commercial research institutions, for full details seehttps://chgr.mc.vanderbilt.edu/synthesisview.
Pyrethroid resistance in southern African Anopheles funestus extends to Likoma Island in Lake Malawi
Authors: Hunt RH , Edwardes M , Coetzee M
Published: January 2011

Background

A mosquito survey was carried out on the island of Likoma in Lake Malawi with a view to collecting baseline data to determine the feasibility of implementing an integrated malaria vector control programme. No vector control interventions are currently being applied on the island apart from the sporadic use of treated and untreated bed nets.

Results

Large numbers of Anopheles funestus were found resting inside houses. WHO susceptibility tests were carried out on wild caught females and 1-5 day old F-1 female progeny. Wild caught females were tested on deltamethrin (77.8% mortality) and bendiocarb (56.4% mortality). Female progeny were tested on deltamethrin (41.4% mortality), permethrin (40.4%), bendiocarb (52.5%), propoxur (7.4%), malathion, fenitrothion, DDT, dieldrin (all 100%) and pirimiphos-methyl (98.9%). The malaria parasite rate was 4.9%. A small number of Anopheles arabiensis were also collected.

Conclusion

This locality is 1,500 km north of the currently known distribution of pyrethroid resistant An. funestus in southern Africa. The susceptibility results mirror those found in southern Mozambique and South African populations, but are markedly different to An. funestus populations in Uganda, indicating that the Malawi resistance has spread from the south.
Hashimoto thyroiditis is more frequent than expected when diagnosed by cytology which uncovers a pre-clinical state
Authors: Staii Anca , Mirocha Sarah , Todorova-Koteva Kristina , Glinberg Simone , Jaume Juan C
Published: January 2011

Background

Our Thyroid-Multidisciplinary Clinic is a large referral site for thyroid diseases. Thyroid biopsies are mainly performed for thyroid cancer screening. Yet, Hashimoto thyroiditis (HT) is being too frequently diagnosed. The prevalence of HT is reported as 0.3-1.2% or twice the prevalence of type 1 diabetes. However, the prevalence of HT confirmed by cytology is still uncertain. To evaluate different aspects of thyroid physiopathology including prevalence of Hashimoto's, a database of clinical features, ultrasound images and cytology results of patients referred for FNA of thyroid nodules was prospectively developed.

Methods

We retrospectively studied 811 consecutive patients for whom ultrasound guided thyroid FNA biopsies were performed at our clinic over 2.5 year period (Mar/2006-Sep/2008).

Results

The analysis of our database revealed that from 761 patients, 102 (13.4%) had HT, from whom 56 (7.4%) were euthyroid or had sub-clinical (non-hypothyroid) disease, and 46 (6%) were clinically hypothyroid.

Conclusions

This is the first study to show such a high prevalence of HT diagnosed by ultrasound-guided FNA. More strikingly, the prevalence of euthyroid HT, appears to be >5% similar to that of type 2 diabetes. Based on our results, there might be a need to follow up on cytological Hashimoto's to monitor for thyroid failure, especially in high risk states, like pregnancy. The potential risk for thyroid cancer in patients with biopsy-proven inflammation of thyroid epithelium remains to be established prospectively. However, it may explain the increased risk for thyroid cancer observed in patients with elevated but within normal TSH.
Science, institutional archives and open access: an overview and a pilot survey on the Italian cancer research institutions
Authors: Poltronieri Elisabetta , Truccolo Ivana , Di Benedetto Corrado , Castelli Mauro , Mazzocut Mauro , Cognetti Gaetana
Published: January 2011

Background

The Open Archive Initiative (OAI) refers to a movement started around the '90s to guarantee free access to scientific information by removing the barriers to research results, especially those related to the ever increasing journal subscription prices. This new paradigm has reshaped the scholarly communication system and is closely connected to the build up of institutional repositories (IRs) conceived to the benefit of scientists and research bodies as a means to keep possession of their own literary production. The IRs are high-value tools which permit authors to gain visibility by enabling rapid access to scientific material (not only publications) thus increasing impact (citation rate) and permitting a multidimensional assessment of research findings.

Methods

A survey was conducted in March 2010 to mainly explore the managing system in use for archiving the research finding adopted by the Italian Scientific Institutes for Research, Hospitalization and Health Care (IRCCS) of the oncology area within the Italian National Health Service (Servizio Sanitario Nazionale, SSN). They were asked to respond to a questionnaire intended to collect data about institutional archives, metadata formats and posting of full-text documents. The enquiry concerned also the perceived role of the institutional repository DSpace ISS, built up by the Istituto Superiore di Sanità (ISS) and based on a XML scheme for encoding metadata. Such a repository aims at acting as a unique reference point for the biomedical information produced by the Italian research institutions. An in-depth analysis has also been performed on the collection of information material addressed to patients produced by the institutions surveyed.

Results

The survey respondents were 6 out of 9. The results reveal the use of different practices and standard among the institutions concerning: the type of documentation collected, the software adopted, the use and format of metadata and the conditions of accessibility to the IRs.

Conclusions

The Italian r esearch institutions in the field of oncology are moving the first steps towards the philosophy of OA. The main effort should be the implementation of common procedures also in order to connect scientific publications to researchers curricula. In this framework, an important effort is represented by the project of ISS aimed to set a common interface able to allow migration of data from partner institutions to the OA compliant repository DSpace ISS.
Transcription factor c-Myb promotes the invasion of hepatocellular carcinoma cells via increasing osteopontin expression
Authors: Chen Rong-Xin , Xia Yun-Hong , Xue Tong-Chun , Ye Sheng-Long
Published: January 2011

Background

Specific gene expression is tightly regulated by various transcription factors. Osteopontin (OPN) is a phosphoprotein that mediates hepatocellular carcinoma (HCC) progression and metastasis. However, the mechanism of OPN up-regulation in HCC metastasis remains to be clarified.

Methods

Oligonucleotide array-based transcription factor assays were applied to compare different activities of transcription factors in two human HCC cell lines with different OPN expression levels. The effects of one selected transcription factor on OPN expression were further evaluated.

Results

Eleven transcription factors were over-expressed in metastatic HCC cell line HCCLM6 cells whereas twelve transcription factors were down-regulated. Electrophoretic mobility shift assays (EMSA) and reporter gene assays showed that one of up-regulated transcription factors c-Myb could bind the OPN promoter and increase its transcription activity. In addition, small interfering RNA targeting c-Myb could inhibit OPN expression and significantly decrease migration and invasion of HCCLM6 cells in vitro.

Conclusion

Our data first demonstrate that c-Myb has a functionally important role in the regulation of OPN expression in HCC cells, suggesting that c-Myb might be a new target to control HCC metastasis.
‘Foot’ and ‘surgeon’: a tale of two definitions
Authors: Menz Hylton B , Borthwick Alan M , Potter Mike J , Landorf Karl B , Munteanu Shannon E
Published: January 2011

Recent events in the USA and UK have raised questions about the appropriate definition and application of the terms ‘foot’ and ‘surgeon’. In this editorial, we explore these issues and clarify our use of these terms in the journal.
Preliminary observations of muscle fibre cross sectional area of flexor digitorum brevis in cadaver feet with and without claw toes
Authors: Locke Jackie , Baird Stuart A , Frankis Jamie
Published: January 2011

Background

In order to facilitate normal gait, toes require to be in a rectus position during the propulsive phase. This requires a correct balance and sequence of activity of the intrinsic musculature of the feet. Alteration of this balance and sequence may lead to the development of claw toes. Atrophy of the lumbricals occurs in the development of claw toes, but it is not known if changes occur in any other intrinsic muscles, including flexor digitorum brevis. This study set out to investigate whether hypertrophic changes were evident in flexor digitorum brevis in feet with claw toes.

Methods

Four cadaver feet were investigated, two with rectus toes and two with claw toes. Flexor digitorum brevis was removed from each, and seven anatomically significant tissue sections from each muscle were routinely processed, cut and stained. One hundred and sixty muscle fibre cross sectional areas were measured from each section.

Results

The mean age of the donors was 81.5 years, and three of the four were female. Results showed that the cross sectional area of fibres from feet with claw toes was 417 μg2 significantly greater (p < 0.01) than the cross sectional area of fibres from feet with rectus toes, which was 263 μg2.

Conclusions

Although this study has several limitations, preliminary observations reveal that flexor digitorum brevis muscle fibre cross sectional area is significantly reduced in feet with claw toes. This would indicate a relationship between muscle fibre atrophy of flexor digitorum brevis and clawing of the lesser toes.
Comparison of ankle and subtalar joint complex range of motion during barefoot walking and walking in Masai Barefoot Technology sandals
Authors: Roberts Sophie , Birch Ivan , Otter Simon
Published: January 2011

Background

Masai Barefoot Technology (MBT, Switzerland) produce footwear which they claim simulate walking barefoot on soft undulating ground. This paper reports an investigation into the effect of MBT sandals on the motion of the ankle and subtalar joint complex during walking.

Methods

Range of motion data was collected in the sagittal, frontal and transverse plane from the ankle and subtalar joint complex from 32 asymptomatic subjects using the CODA MPX30 motion analysis system during both barefoot walking and walking in the MBT sandal. Shod and un‐shod data were compared using the Wilcoxon signed ranks test.

Results

A significantly greater range of motion in the frontal and sagittal planes was recorded when walking in the MBT sandal (p = 0.031, and p = 0.015 respectively). In the transverse plane, no significant difference was found (p = 0.470).

Conclusions

MBT sandals increase the range of motion of the ankle and subtalar joint complex in the frontal and sagittal planes. MBT footwear could therefore have a role to play in the management of musculoskeletal disorders where an increase in frontal and sagittal plane range of motion is desirable.