bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling
Authors: Wang Yubing , Guo Huimin , Li Haichao , Zhang Hao , Miao Xuexia
Published: December 2012

Background

Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties.

Results

We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (P<0.05). Among the 442 TF genes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2–4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT.

Conclusions

We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice.
Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden
Authors: Zöller Bengt , Ohlsson Henrik , Sundquist Jan , Sundquist Kristina
Published: December 2012

Background

Although the heritability of atrial fibrillation (AF) has been determined, the relevance of family history of AF for the likelihood of recurrent hospitalization for AF is unknown. The aim of this nationwide study was to determine whether family history of AF is a risk factor of recurrent hospitalization for lone AF (LAF), i.e., AF with unknown etiology. The familial risk for first time LAF hospitalization was also determined and compared to the risk of recurrent hospitalization for LAF.

Methods

We examined whether family history of AF is a risk factor for recurrent hospitalization for LAF in the whole Swedish population. We linked Multigeneration Register data on individuals aged 0–60 years to Hospital Discharge Register data for the period 1987–2009 to compare LAF recurrent hospitalization risk among individuals with and without parental or sibling history of AF. We calculated hazard ratios (HRs) to determine the familial HR of recurrent hospitalization for LAF. Odds ratios (OR) were calculated for familial risk of first time LAF hospitalization.

Results

The risk of recurrent LAF hospitalization was 1.23 (95% CI 1.17-1.30) for individuals with affected parents compared to 1.30 (95% CI 1.22-1.38) for those with affected siblings. After 10 years of follow up 50% of those without and 60% of those with family history had recurrent hospitalization for LAF. The risk of recurrent LAF hospitalization in individuals with two affected parents was 1.65 (95% CI 1.44-1.90). There was an interaction between age and family history, with family history having a weaker effect on LAF hospitalization risk in older age groups. The OR for first time LAF hospitalization was 2.08 (95% CI 2.02-2.15) for offspring with affected parents and 3.23 (95% CI 3.08-3.39) for individuals with affected siblings.

Conclusions

Family history of AF is a novel risk factor for recurrent LAF hospitalization. The higher recurrence hospitalization risk in multiplex families and younger individuals suggests a genetic contribution. However, the familial risk for recurrent LAF hospitalization was much lower than the risk for first time LAF hospitalization, suggesting that familial and possibly genetic factors are more important for first time LAF hospitalization than recurrent LAF hospitalization.
Adenosine A2A receptor activation reduces recurrence and mortality from Clostridium difficileinfection in mice following vancomycin treatment
Authors: Li Yuesheng , Figler Robert A , Kolling Glynis , Bracken Tara C , Rieger Jayson , Stevenson Ralph W , Linden Joel , Guerrant Richard L , Warren Cirle Alcantara
Published: December 2012

Background

Activation of the A2Aadenosine receptor (A2AAR) decreases production of inflammatory cytokines, preventsC.difficiletoxin A-induced enteritis and, in combination with antibiotics, increases survival from sepsis in mice. We investigated whether A2AAR activation improves and A2AAR deletion worsens outcomes in a murine model ofC.difficile(strain VPI10463) infection (CDI).

Methods

C57BL/6 mice were pretreated with an antibiotic cocktail prior to infection and then treated with vancomycin with or without an A2AAR agonist. A2AAR-/-and littermate wild-type (WT) mice were similarly infected, and IFNγ and TNFα were measured at peak of and recovery from infection.

Results

Infected, untreated mice rapidly lost weight, developed diarrhea, and had mortality rates of 50-60%. Infected mice treated with vancomycin had less weight loss and diarrhea during antibiotic treatment but mortality increased to near 100% after discontinuation of antibiotics. Infected mice treated with both vancomycin and an A2AAR agonist, either ATL370 or ATL1222, had minimal weight loss and better long-term survival than mice treated with vancomycin alone. A2AAR KO mice were more susceptible than WT mice to death from CDI. Increases in cecal IFNγ and blood TNFα were pronounced in the absence of A2AARs.

Conclusion

In a murine model of CDI, vancomycin treatment resulted in reduced weight loss and diarrhea during acute infection, but high recurrence and late-onset death, with overall mortality being worse than untreated infected controls. The administration of vancomycin plus an A2AAR agonist reduced inflammation and improved survival rates, suggesting a possible benefit of A2AAR agonists in the management of CDI to prevent recurrent disease.
Pretreatment with intrathecal amitriptyline potentiates anti-hyperalgesic effects of post-injury intra-peritoneal amitriptyline following spinal nerve ligation
Authors: Cheng Kuang-I , Wang Hung-Chen , Chang Lin-Li , Wang Fu-Yen , Lai Chung-Sheng , Chou Chao-Wen , Tsai Hung-Pei , Kwan Aij-Lie
Published: December 2012

Background

Amitriptyline, a tricyclic antidepressant and potent use-dependent blocker of sodium channels, has been shown to attenuate acute and chronic pain in several preclinical modes. The purpose of this study was to investigate whether intrathecal pretreatment with amitriptyline combined with post-injury intra-peritoneal amitriptyline is more effective than post-injury treatment alone on L5 spinal nerve ligation (SNL)-induced neuropathic pain.

Methods

96 adult male Sprague–Dawley rats were allocated into 4 groups: group S, Sham; group L, L5 spinal nerve
L
igation with vehicle treatment; group A, SNL and post-injury intra-peritoneal (
A
bdominal) amitriptyline twice daily × 3 days; group P, intrathecal
P
retreatment with amitriptyline, SNL and intra-peritoneal amitriptyline twice daily × 3 days. Responses to thermal and mechanical stimuli, as well as sodium channel expression in injured dorsal root ganglion (DRG) and activated glial cells in spinal dorsal horn (SDH) were measured pre-operatively and on post-operative day (POD) 4, 7, 14, 21 and 28.

Results

SNL-evoked hyper-sensitivity responses to thermal and mechanical stimuli, up-regulated Nav1.3 and down-regulated Nav1.8 expression in DRG, and activated microglia and astrocytes in SDH. In group A, intra-peritoneal amitriptyline alone alleviated thermal hypersensitivity on POD7, reversed Nav1.8 and reduced activated microglia on POD14. In group P, intrathecal pretreatment with amitriptyline not only potentiated the effect of intra-peritoneal amitriptyline on thermal hypersensitivity and Nav1.8, but attenuated mechanical hypersensitivity on POD7 and reduced up-regulated Nav1.3 on POD14. Furthermore, this treatment regimen reduced astrocyte activation on POD14.

Conclusions

Concomitant intrathecal pretreatment and post-injury intra-peritoneal amitriptyline was more effective than post-injury treatment alone on attenuation of behavioral hypersensitivity, decrease of activated microglia and astrocytes and dysregulated Nav1.3 and 1.8.
The clinical significance of Psoriasin for non-small cell lung cancer patients and its biological impact on lung cancer cell functions
Authors: Hu Mu , Ye Lin , Ruge Fiona , Zhi Xiuyi , Zhang Lijian , Jiang Wen G
Published: December 2012

Background

Psoriasin (S100A7) is a member of the S100 gene family. Alteration of Psoriasin expression has previously been reported to play an important role in cancer aggressive behaviour. The current study sought to investigate the level of Psoriasin expression at the mRNA level in a cohort of patients with non-small cell lung cancer (NSCLC), the association with clinical implication and outcomes, and the molecular and cellular impact of the protein on lung cancer cells.

Methods

Fresh frozen NSCLC cell carcinoma tissues, along with matched normal tissues were obtained from 83 NSCLC patients who received curative resection from January 2003 to December 2011. The expression of Psoriasin in the NSCLC specimens was assessed using both quantitative real time PCR (QPCR) and immunochemical staining. Knockdown and forced expression of Psoriasin in NSCLC cell lines were carried out using constructed plasmid vectors carrying either ribozyme transgenes targeting human Psoriasin or full-length coding sequence, respectively. The effect of Psoriasin on the functions of NSCLC cells was determined using a variety of in vitro cell function assays.

Results

Higher mRNA levels of Psoriasin were observed in tumour tissues when compared to both the paired normal background tissues and none paired normal tissues (p = 0.0251 and 0.0195). The mRNA level of Psoriasin was found to be higher in the squamous carcinoma (P=0.035). Higher Psoriasin expression is associated with poor prognosis. The cell function tests had supportive results to the clinical findings. Over-expression of Posriasin in lung cancer cells (SK-MES-1) resulted in an increase in in vitro growth and invasiveness. In contrast, Psoriasin knockdown suppressed cell growth and invasion (P<0.05), but increased cell adhesion (P<0.05).

Conclusions

Psoriasin expression is increased in lung cancer, more specifically in lung squamous carcinoma compared with adenocarcinoma, and is associated with poor prognosis. Psoriasin plays crucial roles in regulating the growth and invasion of lung cancer cells.
The impact of secondary hyperparathyroidism on the efficacy of antiresorptive therapy
Authors: Kincse Gyöngyvér , Varga József , Somogyi Péter , Szodoray Péter , Surányi Péter , Gaál János
Published: December 2012

Background

The aim of the present study was to assess whether the efficacy of bisphosphonate treatment is influenced by PTH levels measured in newly diagnosed osteoporotic patients and to identify the threshold value, beyond which PTH level negatively influences therapeutic efficacy.

Methods

One hundred and thirty-eight osteoporotic patients were enrolled into the study. All subjects underwent laboratory screening, bone densitometry with DEXA, and x-ray imaging. The changes in bone density were evaluated after a mean follow-up period of 13.37 ± 1.29 months. Correlation analysis was performed on the clinical data of patients, the percentage changes of BMD values, and the PTH levels measured at the beginning of study, using SPSS software.

Results

The mean age of the subjects was 64.82 ± 10.51 years, and the female-to-male ratio was 116/22. Baseline BMD value measured with AP DEXA scanning was 0.854 ± 0.108 g/cm2 in the L1-4 vertebrae and 0.768 ± 0.115 g/cm2 in the left femoral neck. By the end of the follow-up period, these values changed to 0.890 ± 0.111 g/cm2 and 0.773 ± 0.111 g/cm2, respectively. We found a statistically significant, negative correlation between PTH levels and the percentage changes of lumbar BMD values measured at the end of the follow-up (correlation coefficient R2 = 0.121, p < 0.0001). The analysis of frequency histograms suggested that negative effects on bone might be expected above a PTH level of 60 pg/mL (7.3 pmol/L).

Conclusion

Our findings imply that a baseline PTH level over 60 ng/mL can reduce the efficacy of bisphosphonate treatment.
Sentinel lymph node biopsy in melanoma: Our 8-year clinical experience in a single French institute (2002–2009)
Authors: Biver-Dalle Caroline , Puzenat Eve , Puyraveau Marc , Delroeux Delphine , Boulahdour Hatem , Sheppard Frances , Pelletier Fabien , Humbert Philippe , Aubin François
Published: December 2012

Background

Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma.

Methods

A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation.

Results

The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5–97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients.

Conclusion

Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated.
Prakriti (Ayurvedic concept of constitution) and variations in platelet aggregation
Authors: Bhalerao Supriya , Deshpande Tejashree , Thatte Urmila
Published: December 2012

Background

Ayurveda, the Indian traditional system of medicine describes a unique concept “prakriti”, genetically determined, categorising the population into several subgroups based on phenotypic characters like appearance, temperament and habits. The concept is claimed to be useful in predicting an individual’s susceptibility to a particular disease, prognosis of that illness and selection of therapy. The present study was carried out to study if the platelet aggregatory response and its inhibition by aspirin varied in the different prakriti subtypes.

Methods

After obtaining Institutional Ethics Committee permission, normal healthy individuals of either sex between the age group 18 to 30 years were recruited in the study. Their prakriti evaluation was done using a standardized validated questionnaire (TNMC Prakriti 2004). Their Platelet Rich Plasma was incubated with either aspirin [2.5micro-mole (μM) and 5μM] or distilled water as control for three minutes after which the aggregatory response to 5μM Adenosine Diphosphate (ADP) was measured over a period of 7 minutes.

Results

We observed that in the study population of normal healthy participants (n= 137), ADP-induced maximal platelet aggregation (MPA) was highest among the Vata-pitta prakriti individuals [Median (range), 83.33% (52.33-96)] as compared to the other prakriti types and these individuals responded better to lower dose of aspirin compared to other prakriti types.

Conclusions

Our results suggest that identifying the prakriti may help in individualising therapy or predicting proneness to a disease.
Inhibition of lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by chloroform fraction of Cudrania tricuspidata in RAW 264.7 macrophages
Authors: Yang Gabsik , Lee Kyungjin , Lee Mihwa , Ham Inhye , Choi Ho-Young
Published: December 2012

Background

Cudrania tricuspidata extract is an important traditional herbal remedy for tumors, inflammation, gastritis, and liver damage and is predominantly used in Korea, China, and Japan. However, the anti-inflammatory effects of the extract have not yet been conclusively proved.

Methods

In this study, we investigated the effects of the CHCl3 fraction (CTC) of a methanol extract of C. tricuspidata on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophage cells and mouse peritoneal macrophages, and the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in RAW 264.7 macrophage cells.

Results

We observed that the protein expression levels of inducible NO synthase and COX-2 enzymes were markedly inhibited by CTC in a concentration-dependent manner. In addition, CTC reduced the production of TNF-α, IL-1β, and IL-6 in the LPS-stimulated RAW 264.7 macrophage cells.

Conclusions

Our results show that the C. tricuspidata extract could modulate macrophage-mediated inflammatory functions such as the overproduction of cytokines, NO, and PGE2. The CTC was found to be the active fraction in this context.
Evaluation of iron and manganese-coated pumice application for the removal of as(v) from aqueous solutions
Authors: Far Leila Babaie , Souri Bubak , Heidari Masoumeh , Khoshnavazi Roshan
Published: December 2012

Arsenic contamination of water has been recognized as a serious environmental issue and there are reports on its epidemiological problems to human health. The objective of this study was to evaluate the performances of iron-coated pumice and manganese-coated pumice as the adsorbents for removing arsenate from aqueous solutions. The effect of various parameters such as adsorbent dose, contact time, pH and initial concentration on removal efficiency of arsenate were evaluated in batch mode. The data obtained from the kinetic studies were analyzed using kinetic models of pseudo-first-order and pseudo-second-order. In addition, two isotherm models of Freundlich and Langmuir were used to fit the experimental data. The results showed that the optimum dosage of iron-coated pumice and manganese-coated pumice for arsenate removal were 40 and 80 g/L whereas the adsorption process reached equilibrium after 80 and 100 min, respectively. The maximum removal efficiency of arsenate using the two adsorbents were both recorded in pH=3 as the removal efficiency gradually declined following every increase in pH values of the solution. Iron-coated pumice also showed to have high removal efficiency when the initial concentration of arsenate was high while the low concentration of arsenate was efficiently removed by manganese-coated pumice. Moreover, it was depicted that the adsorption kinetics by both adsorbents followed pseudo-second order equation and the uptake data of arsenate were well fitted with Langmuir isotherm model. Therefore, it could be concluded that iron and manganese-coated pumice could be considered as suitable adsorbents for arsenate removal from aqueous solutions.
Pegylated interferon α enhances recovery of memory T cells in e antigen positive chronic hepatitis B patients
Authors: Liu Yong Zhe , Hou Feng Qin , Ding Peng , Ren Yuan Yuan , Li Shi Hong , Wang Gui Qiang
Published: December 2012

Background

Interferons (IFNs) are a group of cytokines commonly used in the clinical treatment of chronic hepatitis B (CHB) patients. Their therapeutic effects are highly correlated with recovery of host antiviral immunity. Clearance of hepatitis B virus (HBV) is mediated partially by activated functional memory T cells. The aims of the present study were to investigate memory T cell status in patients with different outcomes following pegylated interferon-α (IFN-α) therapy and to identify new biomarkers for predicting antiviral immune responses.

Methods

Peripheral blood cells were isolated from 23 CHB patients who were treated with pegylated IFN-α at week 0 (baseline) and week 24. Co-expression of programmed death-1 (PD-1) and CD244 in CD45RO positive T cells, as well as a subset of CD127 and CXCR4 positive memory T cells were assessed. In addition, perforin, granzyme B, and interferon-γ (IFN-γ) expressions were also analyzed by flow cytometric analysis after intracytoplasmic cytokine staining (ICCS). Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re-challenged with exogenous HBV core antigen, and the percentage of IFN-γ expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were evaluated.

Results

At week 24, PD-1 and CD244 expression in CD8 memory T cells were down-regulated (P < 0.05,P < 0.05, respectively), along with decreased HBV DNA loads (P < 0.05), while the expressions of partial effector molecules in CD8 and CD4 memory T cells was up-regulated (P < 0.05,P < 0.05, respectively), especially in the responders. CD127 and CXCR4 were highly expressed in CD8 memory T cells after pegylated IFN-α treatment (P < 0.05), which was inversely correlated with HBV DNA loads (r = −0.47,P = 0.001). The responders had a higher IFN-γ expression in memory T cells than the non-responders did after HBV antigen re-stimulationin vitro.

Conclusion

Pegylated IFN-α treatment enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory receptors and up-regulating effector molecules. The expressions of CXCR4 and CD127 in CD8 memory T cell may be used as biomarkers for predicting the outcome of treatment.
Carbon nanoparticles induce ceramide- and lipid raft-dependent signalling in lung epithelial cells: a target for a preventive strategy against environmentally-induced lung inflammation
Authors: Peuschel Henrike , Sydlik Ulrich , Grether-Beck Susanne , Felsner Ingo , Stöckmann Daniel , Jakob Sascha , Kroker Matthias , Haendeler Judith , Gotić Marijan , Bieschke Christiane , Krutmann Jean , Unfried Klaus
Published: December 2012

Background

Particulate air pollution in lung epithelial cells induces pathogenic endpoints like proliferation, apoptosis, and pro-inflammatory reactions. The activation of the epidermal growth factor receptor (EGFR) is a key event responsible for signalling events involving mitogen activated protein kinases specific for these endpoints. The molecular events leading to receptor activation however are not well understood. These events are relevant for the toxicological evaluation of inhalable particles as well as for potential preventive strategies in situations when particulate air pollution cannot be avoided. The current study therefore had the objective to elucidate membrane-coupled events leading to EGFR activation and the subsequent signalling cascade in lung epithelial cells. Furthermore, we aimed to identify the molecular target of ectoine, a biophysical active substance which we described to prevent carbon nanoparticle-induced lung inflammation.

Methods

Membrane signalling events were investigated in isolated lipid rafts from lung epithelial cells with regard to lipid and protein content of the signalling platforms. Using positive and negative intervention approaches, lipid raft changes, subsequent signalling events, and lung inflammation were investigated in vitro in lung epithelial cells (RLE-6TN) and in vivo in exposed animals.

Results

Carbon nanoparticle treatment specifically led to an accumulation of ceramides in lipid rafts. Detailed analyses demonstrated a causal link of ceramides and subsequent EGFR activation coupled with a loss of the receptor in the lipid raft fractions. In vitro and in vivo investigations demonstrate the relevance of these events for carbon nanoparticle-induced lung inflammation. Moreover, the compatible solute ectoine was able to prevent ceramide-mediated EGFR phosphorylation and subsequent signalling as well as lung inflammation in vivo.

Conclusion

The data identify a so far unknown event in pro-inflammatory signalling and contribute to the understanding of particle cell interaction and therefore to risk identification and risk assessment of inhalable xenobiotics. Moreover, as this cellular reaction can be prevented by the well tolerated substance ectoine, a molecular preventive strategy for susceptible persons against airway inflammation is proposed.
Clinical outcome for patients with dedifferentiated chondrosarcoma: a report of 9 cases at a single institute
Authors: Yokota Kazuya , Sakamoto Akio , Matsumoto Yoshihiro , Matsuda Shuichi , Harimaya Katsumi , Oda Yoshinao , Iwamoto Yukihide
Published: December 2012

Background

Dedifferentiated chondrosarcomas consist of two distinguishable components: low-grade chondrosarcoma components and high-grade dedifferentiated components.

Materials and methods

Nine cases (4 males, 5 females) of dedifferentiated chondrosarcoma were treated in our institute. The average age was 58.6 (range, 37–86) years. The tumor location was the long bone in 7 cases (femur, n=5; humerus, n=1; tibia, n=1) and the pelvic bone in 2 cases. The average time from appearance of symptoms to treatment was 9.4 (range, 1–40) months.

Results and discussion

On plain radiographs, matrix mineralization was seen in all 9 cases (100%). Bone destruction was observed in 5 of 9 cases (56%), while pathological fracture was seen in one femur case (11%). Lung metastasis was observed in all cases (initially in 5 cases; during the treatment course in 4 cases). Surgery was performed in 8 cases, with local recurrence occurring in 2 of those cases (time to recurrence, 2 and 10 months). Chemotherapy was administered in 4 cases, but did not result in significant improvement. All 9 cases died of lung metastases, with a median survival time of 10 (range, 3.4-18.8) months. The presence of initial metastasis at diagnosis was a significant unfavorable prognostic factor.

Conclusion

The prognosis of dedifferentiated chondrosarcoma is dismal. With the lack of convincing evidence of the benefit of chemotherapy, complete surgical excision is the initial recommended treatment.
Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection
Authors: Tamayev Robert , Akpan Nsikan , Arancio Ottavio , Troy Carol M , D’Adamio Luciano
Published: December 2012

Background

Mutations in either Aβ Precursor protein (APP) or genes that regulate APP processing, such as BRI2/ITM2B and PSEN1/PSEN2, cause familial dementias. Although dementias due to APP/PSEN1/PSEN2 mutations are classified as familial Alzheimer disease (FAD) and those due to mutations in BRI2/ITM2B as British and Danish dementias (FBD, FDD), data suggest that these diseases have a common pathogenesis involving toxic APP metabolites. It was previously shown that FAD mutations in APP and PSENs promote activation of caspases leading to the hypothesis that aberrant caspase activation could participate in AD pathogenesis.

Results

Here, we tested whether a similar mechanism applies to the Danish BRI2/ITM2B mutation. We have generated a genetically congruous mouse model of FDD, called FDDKI, which presents memory and synaptic plasticity deficits. We found that caspase-9 is activated in hippocampal synaptic fractions of FDDKI mice and inhibition of caspase-9 activity rescues both synaptic plasticity and memory deficits.

Conclusion

These data directly implicate caspase-9 in the pathogenesis of Danish dementia and suggest that reducing caspase-9 activity is a valid therapeutic approach to treating human dementias.
New analogues of 13-hydroxyocatdecadienoic acid and 12-hydroxyeicosatetraenoic acid block human blood platelet aggregation and cyclooxygenase-1 activity
Authors: Hirz Taghreed , Khalaf Ali , El-Hachem Nehme , Mrad May F , Abdallah Hassan , Créminon Christophe , Grée René , Merhi Raghida Abou , Habib Aïda , Hachem Ali , Hamade Eva
Published: December 2012

Background

Thromboxane A2 is derived from arachidonic acid through the action of cyclooxygenases and thromboxane synthase. It is mainly formed in blood platelets upon activation and plays an important role in aggregation. Aspirin is effective in reducing the incidence of complications following acute coronary syndrome and stroke. The anti-thrombotic effect of aspirin is obtained through the irreversible inhibition of cyclooxygenases. Analogues of 12-hydroxyeicosatetraenoic acid and 13-hydroxyocatdecadienoic acid were shown previously to modulate platelet activation and to block thromboxane receptors.

Results and discussion

We synthesized 10 compounds based on the structures of analogues of 12-hydroxyeicosatetraenoic acid and 13-hydroxyocatdecadienoic acid and evaluated their effect on platelet aggregation triggered by arachidonic acid. The structure activity relationship was evaluated. Five compounds showed a significant inhibition of platelet aggregation and highlighted the importance of the lipidic hydrophobic hydrocarbon chain and the phenol group. Their IC50 ranged from 7.5 ± 0.8 to 14.2 ± 5.7 μM (Mean ± S.E.M.). All five compounds decreased platelet aggregation and thromboxane synthesis in response to collagen whereas no modification of platelet aggregation in response to thromboxane receptor agonist, U46619, was observed. Using COS-7 cells overexpressing human cyclooxygenase-1, we showed that these compounds are specific inhibitors of cyclooxygenase-1 with IC50 ranging from 1.3 to 12 μM. Docking observation of human recombinant cyclooxygenase-1 supported a role of the phenol group in the fitting of cyclooxygenase-1, most likely related to hydrogen bonding with the Tyr 355 of cyclooxygenase-1.

Conclusions

In conclusion, the compounds we synthesized at first based on the structures of analogues of 12 lipoxygenase metabolites showed a role of the phenol group in the anti-platelet and anti-cyclooxygenase-1 activities. These compounds mediate their effects via blockade of cyclooxygenase-1.
A novel monoclonal antibody of human stem cell factor inhibits umbilical cord blood stem cell ex vivo expansion
Authors: Fan Jie , Ding Xinxin , Jiang Yongping
Published: December 2012

Stem cell factor (SCF) activates hematopoietic stem cell (HSC) self-renewal and is being used to stimulate the ex vivo expansion of HSCs. The mechanism by which SCF supports expansion of HSCs remains poorly understood. In cord blood ex vivo expansion assays, a newly produced anti-SCF monoclonal antibody (clone 23C8) was found to significantly inhibit the expansion of CD34+ cells. This antibody appears to bind directly to a part of SCF that is critical for biological activity toward expansion of CD34+ cells, which is located in the first 104 amino acids from the NH2-terminus.
Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
Authors: Zha Xianfeng , Yan Xiaojuan , Shen Qi , Zhang Yuping , Wu Xiuli , Chen Shaohua , Li Bo , Yang Lijian , Geng Suxia , Weng Jianyu , Du Xin , Li Yangqiu
Published: December 2012

A previous study has demonstrated a significant decrease in the TCRζ gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCRζ-regulating factors, the distribution of the TCRζ 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), FcεRIγ and ZAP-70 genes. TCRζ 3'-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 14 healthy individuals, 40 patients with CML and 22 patients with CML in complete remission (CML-CR) by RT-PCR. The expression level of the TCRζ, FcεRIγ, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCRζ gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRIγ and ASF/SF-2 genes was found in the CML group. Two types of splicing forms were detected in all of the healthy individual CML-CR cases: wild type (WT) TCRζ 3'-UTR and alternatively splieced (AS) TCRζ 3'-UTR which have been alternatively splieced in the WT TCRζ 3'-UTR . However, 35% of the CML cases contained only the wild type TCRζ 3'-UTR isoform. Based on the TCRζ 3'-UTR isoform expression characteristic, we divided the patients with CML into two subgroups: the WT+AS-CML group, containing patients that express only the wild type TCRζ 3'-UTR, and the WT+AS+CML group, which contained patients that expressed two TCRζ 3'-UTR isoforms. A significantly different ASF/SF-2 and FcεRIγ gene expression pattern was found between the WT+AS-and WT+AS+CML groups. We concluded that defective TCRζ expression may be characterized in the WT+AS-and WT+AS+CML subgroups by the different gene expression pattern. The overexpression of ASF/SF2, which alternatively splices the TCRζ 3’-UTR, is thought to participate in feedback regulation. The characteristics of TCRζ 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.
Unusual osseous presentation of blastomycosis in an immigrant child: a challenge for European pediatricians
Authors: Codifava Margherita , Guerra Azzurra , Rossi Giulio , Paolucci Paolo , Iughetti Lorenzo
Published: December 2012

Background

Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. Blastomycosis can originate a "metastatic disease" in the skin, bones, genitourinary tract and central nervous system. Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis. Direct visualization of single broadbased budding yeast with specific stains in sputum or tissue samples at microscopy is the primary method for diagnosis, while culture is timeconsuming and other methods are unreliable.

Case presentation

We report a case of severe osteoarticular Blastomycosis occurring in a 3-years-old presented to our Emergency Department with pain and swelling of the left knee, successfully treated with surgical curettage and antifungal therapy. To our knowledge this is the first case reported in Europe.

Conclusions

Blastomycosis represents a challenge for European physicians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas.
Access to kidney transplantation: outcomes of the non-referred
Authors: AlBugami Meteb M , Panek Romuald , Soroka Steven , Tennankore Karthik , Kiberd Bryce A
Published: December 2012

Background

There is a concern that some, especially older people, are not referred and could benefit from transplantation.

Methods

We retrospectively examined consecutive incident end stage renal disease (ESRD) patients at our center from January 2006 to December 2009. At ESRD start, patients were classified into those with or without contraindications using Canadian eligibility criteria. Based on referral for transplantation, patients were grouped as CANDIDATE (no contraindication and referred), NEITHER (no contraindication and not referred) and CONTRAINDICATION. The Charlson Comorbidity Index (CCI) was used to assess comorbidity burden.

Results

Of the 437 patients, 133 (30.4%) were CANDIDATE (mean age 50 and CCI 3.0), 59 (13.5%) were NEITHER (age 76 and CCI 4.4), and 245 (56.1%) were CONTRAINDICATION (age 65 and CCI 5.5). Age was the best discriminator between NEITHER and CANDIDATES (c-statistic 0.96, P <0.0001) with CCI being less discriminative (0.692, P <0.001). CANDIDATES had excellent survival whereas those patients designated NEITHER and CONTRAINDICATION had high mortality rates. NEITHER patients died or developed a contraindication at very high rates. By 1.5 years 50% of the NEITHER patients were no longer eligible for a transplant.

Conclusions

There exists a relatively small population of incident patients not referred who have no contraindications. These are older patients with significant comorbidity who have a small window of opportunity for kidney transplantation.
Effects of EPA supplementation on plasma fatty acids composition in hypertriglyceridemic subjects with FABP2 and PPARα genotypes
Authors: Pishva Hamideh , Amini Mohsen , Eshraghian Mohammad Reza , Hosseini Saeed , Mahboob Soltan Ali
Published: December 2012

Background

Fatty acid binding protein 2 (FABP2) and peroxisome proliferator-activated receptor α (PPARα) are involved in cellular uptake and metabolism of fatty acids. Polymorphism of FABP2 and PPARα may influence plasma levels of fatty acids in those who take supplemental eicosapentaenoic acid (EPA). The purpose of this study was to study the potential associations between the Ala54/Thr polymorphism in FABP2 protein and the Leu162/Val in exon 5 and G/C in intron 7 of PPARα with plasma fatty acids composition after EPA supplementation.

Methods

Twenty three FABP2 Ala54 and twenty three Thr54 carriers with hypertriglyceridemia were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wks. Plasma fatty acids composition was determined and changes from the baseline were measured.

Results

Although EPA supplementation increased the level of plasma EPA and ω-3 fatty acids in both carriers of FABP2 and PPARα genes, these effects were more pronounced in Thr54 and Val162 carriers. EPA supplementation decreased the level of some n-6 fatty acids such as arachidonic acid.

Conclusion

EPA consumption has more favorable effects on blood n-3 fatty acids and can change the level of plasma n-3 fatty acids, particularly EPA. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for preventing cardiovascular diseases. Finally, diets and micronutrient recommendations should be individualized for high risk people.
Citrullinated fibronectin inhibits apoptosis and promotes the secretion of pro-inflammatory cytokines in fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Fan Lieying , Wang Qiang , Liu Rongqing , Zong Ming , He Dongyi , Zhang Hui , Ding Yuanyuan , Ma Jianwei
Published: December 2012

Introduction

Rheumatoid arthritis (RA) is characterized by synovial lining hyperplasia, in which there may be an imbalance between the growth and death of fibroblast-like synoviocytes (FLSs). Antibodies against citrullinated proteins are proposed to induce RA. This study aimed to investigate the pathogenic role of citrullinated fibronectin (cFn) in RA.

Methods

The distribution of fibronectin (Fn) and cFn in synovial tissues from RA and osteoarthritis (OA) patients was examined by immunohistochemical and double immunofluorescence analysis. FLSs were isolated from RA and OA patients and treated with Fn or cFn. Apoptosis was detected by flow cytometry and TUNEL assay. The expression of survivin, caspase-3, cyclin-B1, Bcl-2 and Bax was detected by real-time PCR. The secretion of proinflammatory cytokines was measured by ELISA.

Results

Fn formed extracellular aggregates that were specifically citrullinated in synovial tissues of RA patients, but no Fn deposits were observed in those of OA patients. Fn induced the apoptosis of RA and OA FLSs while cFn inhibited the apoptosis of RA and OA FLSs. Fn significantly increased the expression of caspase-3 and decreased the expression of survivin and cyclin-B1 in FLSs from RA and OA patients. cFn significantly increased the expression of survivin in RA FLSs. Furthermore, cFn increased the secretion of TNF-α and IL-1 by FLSs.

Conclusions

cFn plays a potential pathophysiologic role in RA by inhibiting apoptosis and increasing proinflammatory cytokine secretion of FLSs.
Silencing of microRNA-101 prevents IL-1β-induced extracellular matrix degradation in chondrocytes
Authors: Dai Linghui , Zhang Xin , Hu Xiaoqing , Zhou Chunyan , Ao Yingfang
Published: December 2012

Introduction

Extracellular matrix (ECM) degradation leads to malfunction of the cartilage in osteoarthritis (OA). Inflammatory cytokine interleukin-1 beta (IL-1β) functions in ECM degradation and prevents ECM synthesis by down-regulating the key transcription factor, Sox9, and consequently inhibiting ECM gene expression. Evidence reveals that microRNAs (miRNA) have been associated with OA, but little is known of their function in chondrocyte ECM degradation. This study aimed to identify possible miRNAs that mediate IL-1β-induced down-regulation of Sox9 as well as its known down-stream genes, collagen type II and aggrecan.

Methods

The miRNAs were predicted based on three classical databases. The expression levels of the predicted miRNAs were assessed in IL-1β stimulated chondrocytes by real-time PCR. A luciferase reporter was used to test the binding of the miRNAs to the 3' untranslated regions (3'UTR) of Sox9. The predicted miRNAs were transfected into chondrocytes to validate their relationship with Sox9. Functional analysis of the miRNAs on chondrocytes ECM degradation was performed at both the mRNA and protein levels after miRNA transfection and IL-1β treatment.

Results

Six miRNAs were predicted to target Sox9, and their expression in IL-1β-stimulated chondrocytes was revealed by real-time PCR. The luciferase reporter assay indicated that only miR-101 could bind to the 3'UTR of Sox9. The expression of Sox9 was likewise negatively regulated by miR-101 in rat chondrocytes. Functional analysis showed that miR-101 could aggravate chondrocyte ECM degradation, whereas miR-101 inhibition could reverse IL-1β-induced ECM degradation.

Conclusion

miR-101 participates in IL-1β-induced chondrocyte ECM degradation. Down-regulating miR-101 expression can prevent the IL-1β-induced ECM degradation in chondrocytes. miR-101 probably functions by directly targeting Sox9 mRNA.
Derivation of HLA types from shotgun sequence datasets
Authors: Warren René L , Choe Gina , Freeman Douglas J , Castellarin Mauro , Munro Sarah , Moore Richard , Holt Robert A
Published: December 2012

The human leukocyte antigen (HLA) is key to many aspects of human physiology and medicine. All current sequence-based HLA typing methodologies are targeted approaches requiring the amplification of specific HLA gene segments. Whole genome, exome and transcriptome shotgun sequencing can generate prodigious data but due to the complexity of HLA loci these data have not been immediately informative regarding HLA genotype. We describe HLAminer, a computational method for identifying HLA alleles directly from shotgun sequence datasets (http://www.bcgsc.ca/platform/bioinfo/software/hlaminer). This approach circumvents the additional time and cost of generating HLA-specific data and capitalizes on the increasing accessibility and affordability of massively parallel sequencing.
A prestack basis pursuit seismic inversion
Authors: Zhang Rui , Sen Mrinal K , Srinivasan Sanjay
Published: December 2012

Resolving thin layers and clearly delineating layer boundaries in inverted seismic sections are very important goals for exploration and production. Many seismic inversion methods based on a least-squares optimization approach with Tikhonov-type regularization can lead to unfocused transitions between adjacent layers. A basis pursuit inversion (BPI) algorithm based on the [Formula: see text] norm optimization method can, however, resolve sharp boundaries between layers. We have formulated a BPI algorithm for amplitude-versus-angle inversion and investigated its potential to improve contrasts between layers. Like the BPI for poststack case, the sparse layer constraint, rather than the sparse spike constraint, is used to construct the model space as a wedge dictionary. All the elements of the dictionary are bed reflectivities, which include solutions consisting of thin beds as well. With this dictionary, we use an [Formula: see text] norm optimization framework to derive three reflectivities, namely, [Formula: see text], [Formula: see text], and [Formula: see text]. Although BPI does not require a starting model, high-resolution absolute velocities ([Formula: see text], [Formula: see text]) and density ([Formula: see text]) can be obtained by incorporating initial models in the BPI derived reflectivities. Tests on synthetic and field data show that the BPI algorithm can indeed detect and enhance layer boundaries by effectively removing the wavelet interference.
Rethinking Comparison
Authors: Jullien François
Published: December 2012

Comparison of Chinese and Western civilizations cannot proceed on the basis of influences but only of originary distinctions. Even the most general categories remain unassimilable and must be understood in terms of contrasts. An exterior, “utopic” or “atopic” perspective that takes nothing for granted mutually highlights Chinese and Western cultures. China, for instance, exhibits no disjuncture between sacred and profane, hence no canon in the Western sense. Even difference is too relative a term; cultures must be grasped in terms of separations, of how they stand apart from one another, making diversity an irreducible resource. “Being,” “truth,” and “time” are all Western categories whose aspects are presented altogether differently in Chinese. Displacement, in the sense of Michel Foucault or Gilles Deleuze, still premises a norm. So does any notion of a rooted cultural absolute. Everything is subject to understanding, via dialogue rather than intuition, and with continued alertness to the unthought within each culture.
The Struggle for Origins: Old English in Nineteenth-Century America
Authors: Modarelli Michael
Published: December 2012

The founding of the United States brought with it many conceptions of Englishness, among them the historical connection to an Anglo-Saxon past. To explain the importance of Anglo-Saxonism in the American nineteenth century, Modarelli argues that the northern American states, mostly under the influence of German Romanticism, looked back to the northern Saxons as a mythical origin of American culture, while the southern states, spurred in part by Walter Scott’s popular reversal of the Norman-Saxon equation, followed a more cavalier mythology. As nineteenth-century historical texts employed Norman-Saxon dichotomies for nationalist purposes, various nations manipulated the Anglo-Saxon myth for nation-building purposes. America was no different. Ultimately, its relation to its Anglo-Saxon past became a struggle for its own national heritage.