bluuebunny/crossref_metadata_2025 huggingface dataset:
Expressional profile of cardiac uncoupling protein-2 following myocardial ischemia reperfusion in losartan- and ramiprilat-treated rats
Authors: Safari Fatemeh , Bayat Gholamreza , Shekarforoush Shahnaz , Hekmatimoghaddam Seyedhossein , Anvari Zahra , Moghadam Mahdi Forouzandeh , Hajizadeh Sohrab
Published: February 2013

Background and aims:

The aim of this study was to investigate the early changes of cardiac uncoupling protein-2 (UCP2) expression following myocardial ischemia reperfusion in rats chronically treated with ramiprilat and losartan.

Methods:

Male Wistar rats were assigned into seven groups (six in each): intact (control); sham-operated; nontreated rats subjected to ischemia and reperfusion (IR); ramiprilat-treated rats with (Ram+IR) and without ischemia (Ram); losartan treated with (Los+IR) and without ischemia (Los). Quantitative evaluation of UCP2 mRNA was carried out using real-time reverse transcription-polymerase chain reaction (RT-PCR). Mitochondria were isolated, and protein expression was quantified by Western blotting.

Results:

In IR group: UCP2 protein but not mRNA level was increased in the ischemic area of the left ventricle (LV) (172% ± 26.7, p < 0.001 vs. LV of control). Following acute myocardial IR, UCP2 protein levels was increased in the ischemic area of the LV but not in RV, suggesting the local effect of ischemia on UCP2 expression. IR-induced overexpression of UCP2 was suppressed by ramiprilat and losartan.

Conclusion:

These findings suggest that losartan and ramiprilat can suppress UCP2 expression following myocardial IR, and by this mechanism may protect the myocardium against IR injury.
Side by Side: A workplace engagement program for people with younger onset dementia
Authors: Robertson Jacinta , Evans David , Horsnell Tim
Published: February 2013

This paper describes an innovative demonstration program called Side by Side that was initiated to assess the feasibility of supported workplace engagement for people with younger onset dementia. Seven people with mild dementia work one day per week beside a work-buddy in a large metropolitan hardware store. Work-buddies are store employees who have undergone dementia training. Work duties are negotiated at the start of each shift and include restocking, plant care, assembling display stock and serving customers. All participants have been able to adapt to the workplace environment and some now talk about ‘their customers’. Family carers have reported a positive impact on self-esteem and life satisfaction as a result of the workplace experience. This evaluation of feasibility has exceeded all expectations and has demonstrated that it is possible to offer meaningful activities for people with mild dementia if an appropriate framework of support is provided.
Long-distance diffusion and strongly tied bridges: The influence of the originator’s network
Authors: Bae Jonghoon , Lee Janghyuk , Baek Seok-Chul , Kang Sukwon , Noh Hyung
Published: February 2013

Network researchers have viewed a few influential individuals as driving the diffusion of ideas among individuals while paying little attention to the ways by which diffusion events came about in the first place. This study examines the role of the first adopters in the diffusion of simple ideas. To this end, it draws on the diffusion events of individual blog-posts in an online social community over a one-month period from 1 June to 30 June 2006. This study finds that an idea is likely to diffuse to remote contacts as the proportion of strong ties held by the source; that is, the idea originator, increases or as the social relations surrounding the source become dense. The analysis of this study suggests that the neighbors of the source play a pivotal role in the diffusion of simple ideas, and that an idea that is validated and supported early on by a cohesive group is likely to diffuse to remote contacts.
Independent Component Analysis and Multiresolution Asymmetry Ratio for Brain–Computer Interface
Authors: Hsu Wei-Yen
Published: February 2013

This study proposes a brain–computer interface (BCI) system for the recognition of single-trial electroencephalogram (EEG) data. With the combination of independent component analysis (ICA) and multiresolution asymmetry ratio, a support vector machine (SVM) is used to classify left and right finger lifting or motor imagery. First, ICA and similarity measures are proposed to eliminate the electrooculography (EOG) artifacts automatically. The features are then extracted from the wavelet data by means of an asymmetry ratio. Finally, the SVM classifier is used to discriminate between the features. Compared to the EEG data without EOG artifact removal, band power, and adoptive autoregressive (AAR) parameter features, the proposed system achieves promising results in BCI applications.
Give It Up
Authors: Quoidbach Jordi , Dunn Elizabeth W.
Published: February 2013

The present research provides the first evidence that temporarily giving up something pleasurable may provide an effective route to happiness. Participants were asked to eat a piece of chocolate during two lab sessions, held 1week apart. During the intervening week, we randomly assigned them to abstain from chocolate or to eat as much of it as possible, while a control group received no special instructions related to their chocolate consumption. At the second lab session, participants who had temporarily given up chocolate savored it significantly more and experienced more positive moods after eating it, compared to those in either of the other two conditions. Many cultural and religious practices entail temporarily giving up something pleasurable, and our research suggests that such self-denial may carry ironic benefits for well-being by combating hedonic adaptation.
To Give or Not to Give?
Authors: Impett Emily A. , Le Bonnie M. , Asyabi-Eshghi Behzad , Day Lisa C. , Kogan Aleksandr
Published: February 2013

Is sacrificing to avoid negative outcomes in relationships always costly? The current study draws upon research and theory on approach-avoidance motivation and self-construal to test the hypothesis that individual differences in interdependent self-construal shape the outcomes of sacrificing in pursuit of avoidance goals. Seventy-three individuals in dating relationships participated in a 14-day daily experience study. Results of multilevel mediated moderation analyses showed that individuals who construed the self in less interdependent terms felt inauthentic when they sacrificed for avoidance goals, in turn, detracting from their emotional well-being and the quality of their relationships. In contrast, people high in interdependence did not feel less authentic when sacrificing for avoidance goals and were buffered against the emotional and relationship costs experienced by people low in interdependence. These findings identify a set of individuals for whom sacrificing for avoidance goals is not costly.
Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy
Authors: Pratcorona Marta , Brunet Salut , Nomdedéu Josep , Ribera Josep Maria , Tormo Mar , Duarte Rafael , Escoda Lourdes , Guàrdia Ramon , Queipo de Llano M. Paz , Salamero Olga , Bargay Joan , Pedro Carmen , Martí Josep Maria , Torrebadell Montserrat , Díaz-Beyá Marina , Camós Mireia , Colomer Dolors , Hoyos Montserrat , Sierra Jorge , Esteve Jordi
Published: February 2013

Key Points

In intermediate-risk AML, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio. Combined evaluation of NPM1 mutation and FLT3-ITD burden might contribute to identify patients who benefit from early allogeneic HSCT.
Platelets lacking PIP5KIγ have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion
Authors: Wang Yanfeng , Zhao Liang , Suzuki Aae , Lian Lurong , Min Sang H. , Wang Ziqian , Litvinov Rustem I. , Stalker Timothy J. , Yago Tadayuki , Klopocki Arkadiusz G. , Schmidtke David W. , Yin Helen , Choi John K. , McEver Rodger P. , Weisel John W. , Hartwig John H. , Abrams Charles S.
Published: February 2013

Key Points

Different isoforms of PIP5KIγ fulfill unique functions in platelets.
RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells
Authors: Ran Dan , Shia Wei-Jong , Lo Miao-Chia , Fan Jun-Bao , Knorr David A. , Ferrell Patrick I. , Ye Zhaohui , Yan Ming , Cheng Linzhao , Kaufman Dan S. , Zhang Dong-Er
Published: February 2013

Advancements in human pluripotent stem cell (hPSC) research have potential to revolutionize therapeutic transplantation. It has been demonstrated that transcription factors may play key roles in regulating maintenance, expansion, and differentiation of hPSCs. In addition to its regulatory functions in hematopoiesis and blood-related disorders, the transcription factor RUNX1 is also required for the formation of definitive blood stem cells. In this study, we demonstrated that expression of endogenous RUNX1a, an isoform of RUNX1, parallels with lineage commitment and hematopoietic emergence from hPSCs, including both human embryonic stem cells and inducible pluripotent stem cells. In a defined hematopoietic differentiation system, ectopic expression of RUNX1a facilitates emergence of hematopoietic progenitor cells (HPCs) and positively regulates expression of mesoderm and hematopoietic differentiation-related factors, including Brachyury, KDR, SCL, GATA2, and PU.1. HPCs derived from RUNX1a hPSCs show enhanced expansion ability, and the ex vivo–expanded cells are capable of differentiating into multiple lineages. Expression of RUNX1a in embryoid bodies (EBs) promotes definitive hematopoiesis that generates erythrocytes with β-globin production. Moreover, HPCs generated from RUNX1a EBs possess ≥9-week repopulation ability and show multilineage hematopoietic reconstitution in vivo. Together, our results suggest that RUNX1a facilitates the process of producing therapeutic HPCs from hPSCs.
Preferential HLA-DRB1*11–dependent presentation of CUB2-derived peptides by ADAMTS13-pulsed dendritic cells
Authors: Sorvillo Nicoletta , van Haren Simon D. , Kaijen Paul H. , ten Brinke Anja , Fijnheer Rob , Meijer Alexander B. , Voorberg Jan
Published: February 2013

Key Points

ADAMTS13 derived peptides presented on HLA-DR; implications for acquired TTP. CUB2 domain peptide binds to risk-allele HLA-DRB1*11.
Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype
Authors: Siner Joshua I. , Iacobelli Nicholas P. , Sabatino Denise E. , Ivanciu Lacramiora , Zhou Shangzhen , Poncz Mortimer , Camire Rodney M. , Arruda Valder R.
Published: February 2013

Key Points

The novel FVIII variant (FVIII-RH) has enhanced stability and procoagulant activity in both in vitro and in vivo models. FVIII-RH is efficacious and safe; thus, it is an attractive molecule for protein replacement and as a transgene in gene-therapy strategies.
An integrated pharmacokinetics ontology and corpus for text mining
Authors: Wu Heng-Yi , Karnik Shreyas , Subhadarshini Abhinita , Wang Zhiping , Philips Santosh , Han Xu , Chiang Chienwei , Liu Lei , Boustani Malaz , Rocha Luis M , Quinney Sara K , Flockhart David , Li Lang
Published: February 2013

Background

Drug pharmacokinetics parameters, drug interaction parameters, and pharmacogenetics data have been unevenly collected in different databases and published extensively in the literature. Without appropriate pharmacokinetics ontology and a well annotated pharmacokinetics corpus, it will be difficult to develop text mining tools for pharmacokinetics data collection from the literature and pharmacokinetics data integration from multiple databases.

Description

A comprehensive pharmacokinetics ontology was constructed. It can annotate all aspects of in vitro pharmacokinetics experiments and in vivo pharmacokinetics studies. It covers all drug metabolism and transportation enzymes. Using our pharmacokinetics ontology, a PK-corpus was constructed to present four classes of pharmacokinetics abstracts: in vivo pharmacokinetics studies, in vivo pharmacogenetic studies, in vivo drug interaction studies, and in vitro drug interaction studies. A novel hierarchical three level annotation scheme was proposed and implemented to tag key terms, drug interaction sentences, and drug interaction pairs. The utility of the pharmacokinetics ontology was demonstrated by annotating three pharmacokinetics studies; and the utility of the PK-corpus was demonstrated by a drug interaction extraction text mining analysis.

Conclusions

The pharmacokinetics ontology annotates both in vitro pharmacokinetics experiments and in vivo pharmacokinetics studies. The PK-corpus is a highly valuable resource for the text mining of pharmacokinetics parameters and drug interactions.
The relationship of Vascular endothelial growth factor gene polymorphisms and clinical outcome in advanced gastric cancer patients treated with FOLFOX: VEGF polymorphism in gastric cancer
Authors: Oh Sung Yong , Kwon Hyuk-Chan , Kim Sung Hyun , Lee Suee , Lee Ji Hyun , Hwang Jung-Ah , Hong Seung Hyun , Graves Christian A , Camphausen Kevin , Kim Hyo-Jin , Lee Yeon-Su
Published: February 2013

Background

The aim of this study is to evaluate the associations between vascular endothelial growth factor (VEGF) Single-nucleotide polymorphisms (SNPs) and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX).

Methods

Genomic DNA was isolated from whole blood, and six VEGF (−2578C/A, -2489C/T, -1498 T/C, -634 G/C, +936C/T, and +1612 G/A) gene polymorphisms were analyzed by PCR. Levels of serum VEGF were measured using enzyme-linked immunoassays.

Results

Patients with G/G genotype for VEGF -634 G/C gene polymorphism showed a lower response rate (22.2%) than those with G/C or C/C genotype (32.3%, 51.1%; P = 0.034). Patients with the VEGF -634 G/C polymorphism G/C + C/C genotype had a longer progression free survival (PFS) of 4.9 months, compared with the PFS of 3.5 months for those with the G/G (P = 0.043, log-rank test). By multivariate analysis, this G/G genotype of VEGF -634 G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, P = 0.017).

Conclusion

Our data suggest that G/G genotype of VEGF -634 G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients.
Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3as a novel lung cancer-related gene
Authors: Wu Mingsong , Tu Tao , Huang Yunchao , Cao Yi
Published: February 2013

Background

To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes.

Methods

Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression.

Results

Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration and proliferation in vitro.

Conclusions

The two libraries of differentially expressed genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer-related gene. ERGIC3 may play an active role in the development and progression of lung cancer.
Cost-effectiveness of laser Doppler imaging in burn care in the Netherlands
Authors: Hop M Jenda , Hiddingh Jakob , Stekelenburg Carlijn M , Kuipers Hedwig C , Middelkoop Esther , Nieuwenhuis Marianne K , Polinder Suzanne , van Baar Margriet E ,   the LDI study group
Published: February 2013

Background

Early accurate assessment of burn depth is important to determine the optimal treatment of burns. The method most used to determine burn depth is clinical assessment, which is the least expensive, but not the most accurate.

Laser Doppler imaging (LDI) is a technique with which a more accurate (>95%) estimate of burn depth can be made by measuring the dermal perfusion. The actual effect on therapeutic decisions, clinical outcomes and the costs of the introduction of this device, however, are unknown. Before we decide to implement LDI in Dutch burn care, a study on the effectiveness and cost-effectiveness of LDI is necessary.

Methods/design

A multicenter randomised controlled trial will be conducted in the Dutch burn centres: Beverwijk, Groningen and Rotterdam. All patients treated as outpatient or admitted to a burn centre within 5 days post burn, with burns of indeterminate depth (burns not obviously superficial or full thickness) and a total body surface area burned of ≤ 20% are eligible. A total of 200 patients will be included. Burn depth will be diagnosed by both clinical assessment and laser Doppler imaging between 2–5 days post burn in all patients. Subsequently, patients are randomly divided in two groups: ‘new diagnostic strategy’ versus ‘current diagnostic strategy’. The results of the LDI-scan will only be provided to the treating clinician in the ‘new diagnostic strategy’ group. The main endpoint is the effect of LDI on wound healing time.

In addition we measure: a) the effect of LDI on other patient outcomes (quality of life, scar quality), b) the effect of LDI on diagnostic and therapeutic decisions, and c) the effect of LDI on total (medical and non-medical) costs and cost-effectiveness.

Discussion

This trial will contribute to our current knowledge on the use of LDI in burn care and will provide evidence on its cost-effectiveness.

Trial registration

NCT01489540
Diurnal temperature range and childhood asthma: a time-series study
Authors: Xu Zhiwei , Huang Cunrui , Su Hong , Turner Lyle R , Qiao Zhen , Tong Shilu
Published: February 2013

Background

Hot and cold temperatures have been associated with childhood asthma. However, the relationship between daily temperature variation and childhood asthma is not well understood. This study aimed to examine the relationship between diurnal temperature range (DTR) and childhood asthma.

Methods

A Poisson generalized linear model combined with a distributed lag non-linear model was used to examine the relationship between DTR and emergency department admissions for childhood asthma in Brisbane, from January 1st 2003 to December 31st 2009.

Results

There was a statistically significant relationship between DTR and childhood asthma. The DTR effect on childhood asthma increased above a DTR of 10°C. The effect of DTR on childhood asthma was the greatest for lag 0–9 days, with a 31% (95% confidence interval: 11% – 58%) increase of emergency department admissions per 5°C increment of DTR. Male children and children aged 5–9 years appeared to be more vulnerable to the DTR effect than others.

Conclusions

Large DTR may trigger childhood asthma. Future measures to control and prevent childhood asthma should include taking temperature variability into account. More protective measures should be taken after a day of DTR above10°C.
Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site
Authors: Eisermann Kurtis , Broderick Carly J , Bazarov Anton , Moazam Mustafa M , Fraizer Gail C
Published: February 2013

Background

Vascular Endothelial Growth Factor (VEGF) is regulated by a number of different factors, but the mechanism(s) behind androgen-mediated regulation of VEGF in prostate cancer are poorly understood.

Results

Three novel androgen receptor (AR) binding sites were discovered in the VEGF promoter and in vivo binding of AR to these sites was demonstrated by chromatin immunoprecipitation. Mutation of these sites attenuated activation of the VEGF promoter by the androgen analog, R1881 in prostate cancer cells. The transcription factors AR and Sp1 were shown to form a nuclear complex and both bound the VEGF core promoter in chromatin of hormone treated CWR22Rv1 prostate cancer cells. The importance of the Sp1 binding site in hormone mediated activation of VEGF expression was demonstrated by site directed mutagenesis. Mutation of a critical Sp1 binding site (Sp1.4) in the VEGF core promoter region prevented activation by androgen. Similarly, suppression of Sp1 binding by Mithramycin A treatment significantly reduced VEGF expression.

Conclusions

Our mechanistic study of androgen mediated induction of VEGF expression in prostate cancer cells revealed for the first time that this induction is mediated through the core promoter region and is dependent upon a critical Sp1 binding site. The importance of Sp1 binding suggests that therapy targeting the AR-Sp1 complex may dampen VEGF induced angiogenesis and, thereby, block prostate cancer progression, helping to maintain the indolent form of prostate cancer.
Proteins from Tuber magnatum Pico fruiting bodies naturally grown in different areas of Italy
Authors: Vita Federico , Lucarotti Valentina , Alpi Emanuele , Balestrini Raffaella , Mello Antonietta , Bachi Angela , Alessio Massimo , Alpi Amedeo
Published: February 2013

Background

A number of Tuber species are ecologically important. The fruiting bodies of some of these also have value as a cooking ingredient due to the fact that they possess exceptional flavor and aromatic properties. In particular, T. magnatum fruiting bodies (commonly known as truffles), are greatly appreciated by consumers. These grow naturally in some parts of Italy. However, the quality of these fruiting bodies varies significantly depending on the area of origin due to differences in environmental growth conditions. It is therefore useful to be able to characterize them. A suitable method to reach this goal is to identify proteins which occur in the fruiting bodies that are specific to each area of origin. In this work protein profiles are described for samples coming from different areas and collected in two successive years. To our knowledge this is the first time that proteins of T. magnatum have been thoroughly examined.

Results

Using two dimensional electrophoresis, reproducible quantitative differences in the protein patterns (total 600 spots) of samples from different parts of Italy (accession areas) were revealed by bioinformatic analysis. 60 spots were chosen for further analysis, out of which 17 could probably be used to distinguish a sample grown in one area from a sample grown in another area. Mass spectrometry (MS) protein analysis of these seventeen spots allowed the identification of 17 proteins of T. magnatum.

Conclusions

The results indicate that proteomic analysis is a suitable method for characterizing those differences occurring in samples and induced by the different environmental conditions present in the various Italian areas where T. magnatum can grow. The positive protein identification by MS analysis has proved that this method can be applied with success even in a species whose genome, at the moment, has not been sequenced.
Papillary carcinoma of the duodenum combined with right renal carcinoma: a case report
Authors: Zhang Xuan , Zhou Zhen-hong , Cai Shou-wang , Dong Jia-hong
Published: February 2013

We report a case of papillary carcinoma of the duodenum combined with right renal carcinoma. A 58-year-old man underwent a physical examination that revealed intrahepatic and extrahepatic bile duct dilatation on B ultrasound. Intrahepatic bile duct dilatation could be seen on magnetic resonance imaging (MRI), but the head of the pancreas and distal bile duct showed no tumor signals, which led to a diagnosis of periampullary carcinoma and right renal carcinoma. Considering the trauma of pancreaticoduodenectomy combined with renal resection operation is greater, we carried out the laparoscopic right renal radical resection first, and then a pylorus-preserving pancreaticoduodenectomy was performed. However, postoperative intra-abdominal infections and bleeding occurred; our patient improved after vascular interventional microcoil embolization for the treatment of hemostasis. The second operation for celiac necrotic tissue elimination, jejunal fistulization and peritoneal lavage and drainage was performed 14 days latter. Our patient improved gradually and was discharged on the 58th postoperative day. There has been no tumor recurrence after a follow-up of 26 months.
MST1, a key player, in enhancing fast skeletal muscle atrophy
Authors: Wei Bin , Dui Wen , Liu Dong , Xing Yan , Yuan Zengqiang , Ji Guangju
Published: February 2013

Background

Skeletal muscle undergoes rapid atrophy upon denervation and the underlying mechanisms are complicated. FOXO3a has been implicated as a major mediator of muscle atrophy, but how its subcellular location and activity is controlled during the pathogenesis of muscle atrophy remains largely unknown. MST1 (Mammalian Sterile 20-like kinase 1) is identified as a central component of the Hippo signaling pathway. MST1 has been shown to mediate phosphorylation of FOXO3a at Ser207. Whether this MST1-FOXO signaling cascade exerts any functional consequence on cellular homeostasis remains to be investigated.

Result

We identified that MST1 kinase was expressed widely in skeletal muscles and was dramatically up-regulated in fast- but not slow-dominant skeletal muscles immediately following denervation. The results of our histological and biochemical studies demonstrated that deletion of MST1 significantly attenuated denervation-induced skeletal muscle wasting and decreased expression of Atrogin-1 and LC3 genes in fast-dominant skeletal muscles from three- to five-month-old adult mice. Further studies indicated that MST1, but not MST2, remarkably increased FOXO3a phosphorylation level at Ser207 and promoted its nuclear translocation in atrophic fast-dominant muscles.

Conclusions

We have established that MST1 kinase plays an important role in regulating denervation-induced skeletal muscle atrophy. During the early stage of muscle atrophy, the up-regulated MST1 kinase promoted progression of neurogenic atrophy in fast-dominant skeletal muscles through activation of FOXO3a transcription factors.
Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
Authors: Paterniti Irene , Impellizzeri Daniela , Crupi Rosalia , Morabito Rossana , Campolo Michela , Esposito Emanuela , Cuzzocrea Salvatore
Published: February 2013

Background

Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. Moreover, several data have suggested that PEA reduced inflammation and tissue injury associated with spinal cord trauma and showed a regulatory role for peroxisome proliferator-activated receptor (PPAR)-α signaling in the neuroprotective effect of PEA. However, several other mechanisms could explain the anti-inflammatory and anti-hyperalgesic effects of PEA, including the activation of PPAR-δ and PPAR-γ. The aim of the present study was to carefully investigate the exact contribution of PPAR-δ and PPAR-γ in addition to PPAR-α, in the protective effect of PEA on secondary inflammatory damage associated with an experimental model of spinal cord injury (SCI).

Methods

SCI was induced in mice through a spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy, and PEA (10 mg/kg, intraperitoneally, 1 and 6 hours after SCI) was injected into wildtype mice and into mice lacking PPAR-α (PPAR-αKO). To deepen the ability of specific PPAR-δ and PPAR-γ antagonists to reverse the effect of PEA, mice were administered GSK0660 or GW9662, 30 minutes before PEA injection.

Results

Genetic ablation of PPAR-α in mice exacerbated spinal cord damage, while PEA-induced neuroprotection seemed be abolished in PPARαKO mice. Twenty-four hours after spinal cord damage, immunohistological and biochemical studies were performed on spinal cord tissue. Our results indicate that PPAR-δ and PPAR-γ also mediated the protection induced by PEA. In particular, PEA was less effective in PPAR-αKO, GSK0660-treated or GW9662-pretreated mice, as evaluated by the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, proinflammmatory cytokine, inducible nitric oxide synthase expression and motor function. PEA is also able to restore PPAR-δ and PPAR-γ expression in spinal cord tissue.

Conclusion

This study indicates that PPAR-δ and PPAR-γ can also contribute to the anti-inflammatory activity of PEA in SCI.
Role of SUMO-1 and SUMO interacting motifs in rhesus TRIM5α-mediated restriction
Authors: Lukic Zana , Goff Stephen P , Campbell Edward M , Arriagada Gloria
Published: February 2013

Background

TRIM5α is a member of the tripartite motif family of proteins that restricts retroviral infection in a species-specific manner. The restriction requires an interaction between the viral capsid lattice and the B30.2/SPRY domain of TRIM5α. Previously, we determined that two SUMO interacting motifs (SIMs) present in the B30.2/SPRY domain of human TRIM5α (huTRIM5α) were important for the restriction of N-tropic Murine Leukemia Virus. Here, we examined whether SUMO expression and the SIM1 and SIM2 motifs in rhesus monkey TRIM5α (rhTRIM5α) are similarly important for Human Immunodeficiency Type 1 (HIV-) restriction.

Results

We found that mutation of SIM1 and SIM2 of rhTRIM5α abolished the restriction of HIV-1 virus. Further, knockdown of SUMO-1 in rhTRIM5α expressing cells abolished restriction of HIV-1. These results may be due, in part, to the ability of SUMO-1 to stabilize rhTRIM5α protein expression, as SUMO-1 knockdown increased rhTRIM5α turnover and the mutations in SIM1 and SIM2 led to more rapid degradation than the wild type protein. The NF-κB signaling ability of rhTRIM5α was also attenuated by SUMO-1 knockdown. Finally, upon inhibition of CRM1-dependent nuclear export with Leptomycin B (LMB), wild type rhTRIM5α localized to SUMO-1 bodies in the nucleus, while the SIM1 and SIM2 mutants did not localize to SUMO-1.

Conclusions

Our results suggest that the rhTRIM5α B30.2/SPRY domain is not only important for the recognition of the HIV-1 CA, but it is also important for its association with SUMO-1 or SUMO-1 modified proteins. These interactions help to maintain TRIM5α protein levels and its nuclear localization into specific nuclear bodies.
XRCC1 codon 399Gln polymorphism is associated with radiotherapy-induced acute dermatitis and mucositis in nasopharyngeal carcinoma patients
Authors: Li Haijun , You Yanjie , Lin Canfeng , Zheng Mingzhang , Hong Chaoqun , Chen Jiongyu , Li Derui , Au William W , Chen Zhijian
Published: February 2013

Background

To evaluate the association between single nucleotide polymorphisms (SNPs) at the 194 and 399 codons of XRCC1, and the risk of severe acute skin and oral mucosa reactions in nasopharyngeal carcinoma patients in China.

Methods

114 patients with nasopharyngeal carcinoma were sequentially recruited in this study. Heparinized peripheral blood samples were taken for SNPs analysis before the start of radiation treatment. SNPs in XRCC1 (194Arg/Trp and 399Arg/Gln) gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Dermatitis at upper neck and oral mucositis were clinically recorded according to the Common Terminology Criteria for Adverse Events v.3.0.

Results

The variant allele frequencies were 0.289 for XRCC1 194Trp and 0.263 for XRCC1 399Gln. Of the 114 patients, 24 experienced grade 3 acute dermatitis and 48 had grade 3 acute mucositis. The XRCC1 399Arg/Gln was significantly associated with the development of grade 3 dermatitis (Odds Ratio, 2.65; 95% CI, 1.04–6.73; p = 0.037, χ2 = 4.357). In addition, it was also associated with higher incidence of grade 3 mucositis with a borderline statistical significance (Odds Ratio, 2.11; 95% CI, 0.951–4.66; p = 0.065, χ2 = 3.411). The relationship between XRCC1 194Arg/Trp and acute dermatitis, and mucositis was not found.

Conclusions

Our investigation shows, for the first time, that patients with the XRCC1 399Arg/Gln genotype were more likely to experience severe acute dermatitis and oral mucositis. With further validation, the information can be used to determine personalized radiotherapy strategy.
Structural changes in femoral bone tissue of rats after subchronic peroral exposure to selenium
Authors: Martiniaková Monika , Boboňová Ivana , Omelka Radoslav , Grosskopf Birgit , Stawarz Robert , Toman Róbert
Published: February 2013

Background

The role of selenium (Se) on bone microarchitecture is still poorly understood. The present study aims to investigate the macroscopic and microscopic structures of femoral bone tissue in adult male rats after subchronic peroral administration of Se.

Methods

Twenty one-month-old male Wistar rats were randomly divided into two experimental groups. In the first group (Se group) young males were exposed to 5 mg Na2SeO3/L in drinking water, for 90 days. Ten one-month-old males without Se administration served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy.

Results

The body weight, femoral length and cortical bone thickness were significantly decreased in Se group rats. These rats also displayed different microstructure in the middle part of the femur, both in medial and lateral views, where vascular canals expanded into the central area of the bone while, in control rats, these canals occurred only near the endosteal surfaces. Additionally, a smaller number of primary and secondary osteons was identified in Se group rats. Histomorphometric analyses revealed significant increases for area, perimeter, maximum and minimum diameters of primary osteons’ vascular canals but significant reductions for all measured variables of Haversian canals and secondary osteons.

Conclusions

Se negatively affected the macroscopic and microscopic structures of femoral bone tissue in adult male rats. The results contribute to the knowledge on damaging impact of Se on bone.
Study on the stability and antioxidant effect of the Allium ursinumwatery extract
Authors: Putnoky Salomeia , Caunii Angela , Butnariu Monica
Published: February 2013

Background

Organosulfur compounds usually present a reduced stability especially in the presence of oxygen. This research aimed to study the stability and antioxidant potential of the Allium ursinum watery extract.

Results

The decrease of the antioxidant capacity verifies an exponential relation which may be formally associated to a kinetically pseudomonomolecular process. The exponential regression equation allows the half-life of the degradation process to be determined, this being 14 hours and 49 minutes in a watery environment at room temperature.

Conclusions

The watery extract of Allium ursinum changes its proprieties in time. This might be explained by the network of hydrogen bonds in a watery environment which has a protective effect on the dissolved allicin molecule.
Atypical rearrangement involving 3′-IGH@ and a breakpoint at least 400 Kb upstream of an intact MYC in a CLL patient with an apparently balanced t(8;14)(q24.1;q32) and negative MYC expression
Authors: Amarillo Ina , Bui Peter H , Kantarci Sibel , Rao Nagesh , Shackley Brit S , García Rolando , Tirado Carlos A
Published: February 2013

The t(8;14)(q24.1;q32), the cytogenetic hallmark of Burkitt’s lymphoma, is also found, but rarely, in cases of chronic lymphocytic leukemia (CLL). Such translocation typically results in a MYC-IGH@ fusion subsequently deregulating and overexpressing MYC on der 14q32. In CLL, atypical rearrangements resulting in its gain or loss, within or outside of IGH@ or MYC locus, have been reported, but their clinical significance remains uncertain. Herein, we report a 67 year-old male with complex cytogenetic findings of apparently balanced t(8;14) and unreported complex rearrangements of IGH@ and MYC loci. His clinical, morphological and immunophenotypic features were consistent with the diagnosis of CLL.

Interphase FISH studies revealed deletions of 11q22.3 and 13q14.3, and an extra copy of IGH@, indicative of rearrangement. Karyotype analysis showed an apparently balanced t(8;14)(q24.1;q32). Sequential GPG-metaphase FISH studies revealed abnormal signal patterns: rearrangement of IGH break apart probe with the 5’-IGH@ on derivative 8q24.1 and the 3’-IGH@ retained on der 14q; absence of MYC break apart-specific signal on der 8q; and, the presence of unsplit 5’-MYC-3’ break apart probe signals on der 14q. The breakpoint on 8q24.1 was found to be at least 400 Kb upstream of 5’ of MYC. In addition, FISH studies revealed two abnormal clones; one with 13q14.3 deletion, and the other, with concurrent 11q deletion and atypical rearrangements. Chromosome microarray analysis (CMA) detected a 7.1 Mb deletion on 11q22.3-q23.3 including ATM, a finding consistent with FISH results. While no significant copy number gain or loss observed on chromosomes 8, 12 and 13, a 455 Kb microdeletion of uncertain clinical significance was detected on 14q32.33. Immunohistochemistry showed co-expression of CD19, CD5, and CD23, positive ZAP-70 expression and absence of MYC expression. Overall findings reveal an apparently balanced t(8;14) and atypical complex rearrangements involving 3’-IGH@ and a breakpoint at least 400 Kb upstream of MYC, resulting in the relocation of the intact 5’-MYC-3’ from der 8q, and apposition to 3’-IGH@ at der 14q. This case report provides unique and additional cytogenetic data that may be of clinical significance in such a rare finding in CLL. It also highlights the utility of conventional and sequential metaphase FISH in understanding complex chromosome anomalies and their association with other clinical findings in patients with CLL. To the best of our knowledge, this is the first CLL reported case with such an atypical rearrangement in a patient with a negative MYC expression.
Development of a transoral robotic surgery program in Canada
Authors: Nichols Anthony C , Fung Kevin , Chapeskie Corina , Dowthwaite Samuel A , Basmaji John , Dhaliwal Sandeep , Szeto Christopher CT , Palma David A , Theurer Julie A , Corsten Martin A , Odell Michael , Barrett John W , Franklin Jason H , Yoo John
Published: February 2013

Due to significant differences in healthcare structure between the United States and Canada, there are unique barriers to adopting new medical technology in Canada. In this article, we describe our experience developing a transoral robotic surgery (TORS) program at Western University. Specifically, we outline the steps that were necessary to obtain institutional and multidisciplinary team approval, financial support, as well as surgeon and allied healthcare personnel training. This experience can potentially be used as a roadmap for other Canadian institutions pursuing a TORS program.
Does HPV type affect outcome in oropharyngeal cancer?
Authors: Nichols Anthony C , Dhaliwal Sandeep S , Palma David A , Basmaji John , Chapeskie Corina , Dowthwaite Samuel , Franklin Jason H , Fung Kevin , Kwan Keith , Wehrli Brett , Howlett Chris , Siddiqui Iram , Salvadori Marina I , Winquist Eric , Ernst Scott , Kuruvilla Sara , Read Nancy , Venkatesan Varagur , Todorovic Biljana , Hammond J Alex , Koropatnick James , Mymryk Joe S , Yoo John , Barrett John W
Published: February 2013

Background

An epidemic of human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC) has been reported worldwide largely due to oral infection with HPV type-16, which is responsible for approximately 90% of HPV-positive cases. The purpose of this study was to determine the rate of HPV-positive oropharyngeal cancer in Southwestern Ontario, Canada.

Methods

A retrospective search identified ninety-five patients diagnosed with OPSCC. Pre-treatment biopsy specimens were tested for p16 expression using immunohistochemistry and for HPV-16, HPV-18 and other high-risk subtypes, including 31,33,35,39,45,51,52,56,58,59,67,68, by real-time qPCR.

Results

Fifty-nine tumours (62%) were positive for p16 expression and fifty (53%) were positive for known high-risk HPV types. Of the latter, 45 tumors (90%) were identified as HPV-16 positive, and five tumors (10%) were positive for other high-risk HPV types (HPV-18 (2), HPV-67 (2), HPV-33 (1)). HPV status by qPCR and p16 expression were extremely tightly correlated (p < 0.001, Fishers exact test). Patients with HPV-positive tumors had improved 3-year overall (OS) and disease-free survival (DFS) compared to patients with HPV-negative tumors (90% vs 65%, p = 0.001; and 85% vs 49%, p = 0.005; respectively). HPV-16 related OPSCC presented with cervical metastases more frequently than other high-risk HPV types (p = 0.005) and poorer disease-free survival was observed, although this was not statistically significant.

Conclusion

HPV-16 infection is responsible for a significant proportion of OPSCC in Southwestern Ontario. Other high-risk subtypes are responsible for a smaller subset of OPSCC that present less frequently with cervical metastases and may have a different prognosis.
The skin prick test – European standards
Authors: Heinzerling Lucie , Mari Adriano , Bergmann Karl‐Christian , Bresciani Megon , Burbach Guido , Darsow Ulf , Durham Stephen , Fokkens Wytske , Gjomarkaj Mark , Haahtela Tari , Bom Ana Todo , Wöhrl Stefan , Maibach Howard , Lockey Richard
Published: February 2013

Skin prick testing is an essential test procedure to confirm sensitization in IgE‐mediated allergic disease in subjects with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and food and drug allergy. This manuscript reviews the available evidence including Medline and Embase searches, abstracts of international allergy meetings and position papers from the world allergy literature. The recommended method of prick testing includes the appropriate use of specific allergen extracts, positive and negative controls, interpretation of the tests after 15 – 20 minutes of application, with a positive result defined as a wheal ≥3 mm diameter. A standard prick test panel for Europe for inhalants is proposed and includes hazel (Corylus avellana), alder (Alnus incana), birch (Betula alba), plane (Platanus vulgaris), cypress (Cupressus sempervirens), grass mix (Poa pratensis, Dactilis glomerata, Lolium perenne, Phleum pratense, Festuca pratensis, Helictotrichon pretense), Olive (Olea europaea), mugwort (Artemisia vulgaris), ragweed (Ambrosia artemisiifolia), Alternaria alternata (tenuis), Cladosporium herbarum, Aspergillus fumigatus, Parietaria, cat, dog, Dermatophagoides pteronyssinus, Dermatophagoides farinae, and cockroach (Blatella germanica). Standardization of the skin test procedures and standard panels for different geographic locations are encouraged worldwide to permit better comparisons for diagnostic, clinical and research purposes.
Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling
Authors: Clarke Michael , Lohan Amanda J , Liu Bernard , Lagkouvardos Ilias , Roy Scott , Zafar Nikhat , Bertelli Claire , Schilde Christina , Kianianmomeni Arash , Bürglin Thomas R , Frech Christian , Turcotte Bernard , Kopec Klaus O , Synnott John M , Choo Caleb , Paponov Ivan , Finkler Aliza , Heng Tan Chris Soon , Hutchins Andrew P , Weinmeier Thomas , Rattei Thomas , Chu Jeffery SC , Gimenez Gregory , Irimia Manuel , Rigden Daniel J , Fitzpatrick David A , Lorenzo-Morales Jacob , Bateman Alex , Chiu Cheng-Hsun , Tang Petrus , Hegemann Peter , Fromm Hillel , Raoult Didier , Greub Gilbert , Miranda-Saavedra Diego , Chen Nansheng , Nash Piers , Ginger Michael L , Horn Matthias , Schaap Pauline , Caler Lis , Loftus Brendan J
Published: February 2013

Background

The Amoebozoa constitute one of the primary divisions of eukaryotes, encompassing taxa of both biomedical and evolutionary importance, yet its genomic diversity remains largely unsampled. Here we present an analysis of a whole genome assembly of Acanthamoeba castellanii (Ac) the first representative from a solitary free-living amoebozoan.

Results

Ac encodes 15,455 compact intron-rich genes, a significant number of which are predicted to have arisen through inter-kingdom lateral gene transfer (LGT). A majority of the LGT candidates have undergone a substantial degree of intronization and Ac appears to have incorporated them into established transcriptional programs. Ac manifests a complex signaling and cell communication repertoire, including a complete tyrosine kinase signaling toolkit and a comparable diversity of predicted extracellular receptors to that found in the facultatively multicellular dictyostelids. An important environmental host of a diverse range of bacteria and viruses, Ac utilizes a diverse repertoire of predicted pattern recognition receptors, many with predicted orthologous functions in the innate immune systems of higher organisms.

Conclusions

Our analysis highlights the important role of LGT in the biology of Ac and in the diversification of microbial eukaryotes. The early evolution of a key signaling facility implicated in the evolution of metazoan multicellularity strongly argues for its emergence early in the Unikont lineage. Overall, the availability of an Ac genome should aid in deciphering the biology of the Amoebozoa and facilitate functional genomic studies in this important model organism and environmental host.