bluuebunny/crossref_metadata_2025 huggingface dataset:
Caspase-1: The inflammasome and beyond
Authors: Sollberger Gabriel , Strittmatter Gerhard E , Garstkiewicz Martha , Sand Jennifer , Beer Hans-Dietmar
Published: May 2013

Caspase-1 plays a fundamental role in innate immunity and in several important inflammatory diseases as the protease activates the pro-inflammatory cytokines proIL-1β and proIL-18. Caspase-1 itself is activated in different inflammasome complexes, which assemble in response to a variety of exogenous and endogenous stressors. More recently, pyroptosis, a caspase-1-dependent type of programmed cell death, has been identified that is able to support secreted IL-1 and IL-18 in triggering an inflammatory response. Whereas these ‘canonical’ activities are well appreciated, this review also highlights less-known pathways and molecules activated by caspase-1. There is evidence that caspase-1 supports cell survival by activation of NF-κB, induction of membrane repair and regulation of unconventional secretion of certain proteins. The physiologic effects of processing of other downstream targets, such as proteins involved in glycolysis or activation of caspase-7, are less well understood. However, there is increasing evidence that caspase-1 contributes to innate and adaptive immunologic defense mechanisms, repair and pathologic conditions by the regulation of several different and partially opposing pathways.
« Dispositifs et dispositions », la transformation des pratiques alimentaires et physiques en éducation pour la santé : le cas de l’obésité et des maladies cardiovasculaires
Authors: Génolini Jean-Paul , Cazal Julien , Jacolin Nackaerts , Clément Jean-Paul
Published: May 2013

La recherche aborde d’un point de vue sociologique, le renouvellement des pratiques alimentaires et physiques de patients atteints de maladies cardio-métaboliques suite à une prise en charge en médicale. Huit dispositifs ont été analysés et 116 personnes interrogées. Elle montre, en croisant les caractéristiques des « dispositifs » et des « dispositions » des patients que l’acculturation au modèle médical de la prévention s’effectue dans une « alliance éducative » différenciée selon les maladies et les institutions; que les différentes socialisations primaires et secondaires favorisent le maintien ou l’abandon des « habitus » corporels d’hygiène alimentaire et physique.
Casual Sexual Relationships and Experiences in Emerging Adulthood
Authors: Claxton Shannon E. , van Dulmen Manfred H. M.
Published: May 2013

Casual sexual relationships and experiences (CSREs) such as hookups, one-night stands, friends with benefits relationships, and booty calls have received increasing attention in the past decade. This review examines the role of CSREs during emerging adulthood, as well as similarities and differences among the different types of CSREs. Furthermore, we examine the predictors and positive and negative consequences of engaging in CSREs. While research in the area of CSREs has provided important information about the development and course of these relationships/experiences, future research should focus on exploring these relationships/experiences using an integrated theoretical perspective and longitudinal methods, in diverse, noncollege samples.
Effects of electropulsing treatment on mechanical properties in Ti rich TiNi shape memory alloy
Authors: Cao W H , Zhang J L , Shek C H
Published: May 2013

The influence of electropulsing treatment on thermomechanical behaviour in terms of transformation temperatures and mechanical properties of a cold worked Ti rich TiNi shape memory alloy was studied. The results showed that the transformation temperatures increase with increasing current intensity. The superelasticity of the alloy is improved after the electropulsing treatment, and the hardness of the alloy decreased with increasing current intensity. The microstructure of the alloy showed that the above changes can be attributed to the decreasing dislocation density due to the current pulses.
Effect of electric contact surface treatment on microstructure and wear behaviour of ductile iron
Authors: Qi X B , Zhu S G
Published: May 2013

A study of electric contact surface treatment to ductile iron has been carried out. This technology was based on the application of the contact resistance heating between the electrode and workpiece. For comparison, the experiments of induction hardening to ductile iron were studied. The microstructure, microhardness, surface residual stress and wear properties were investigated using optical microscope, scanning electron microscope, X-ray diffraction, Vickers microhardness and rolling contact wear tests. Electric contact surface treatment resulted in the formation of fine ledeburite (white bright layer) and martensite in the ductile iron surface, in which the hardness in these areas was higher than that of induction hardened surface. The wear test results showed that the ductile iron surface after electric contact surface treatment had better wear resistance owing to the fine microstructure, high hardness and residual compressive stress.
Evolution of grain structure across joints in friction stir welded EN AW 5083 H111 plates during thermal exposure
Authors: Birol Y
Published: May 2013

The mechanisms involved in the coarsening of the grain structure across FSW joints produced in EN AW 5083 H111 plates with different pin profiles were investigated. The grain coarsening across the FSW joints invariably starts inside the shoulder flow zones and involves both abnormal growth of the grains inside the dynamically recrystallised regions as well as recrystallisation of the deformed grains outside these regions. The elliptical nugget zones produced with the threaded circular pins appear to be more stable with respect to the basin shaped counterparts obtained with the triangular pin. It takes an annealing temperature of 550°C for the former to become fully coarse grained across the joint while the joint produced with the triangular pin is largely covered with coarse grains starting at 500°C. The higher resistance of the nugget zone obtained with a threaded circular pin to grain coarsening appears to be critical in the selection of the pin profiles when the manufacturing cycle of the welded EN AW 5083 plates involves post-welding heat treatments.
Lubricated sliding wear behaviour of Al2O3–13TiO2 coatings
Authors: Deshpande P. V. , Vadiraj A. , Manivasagam G. , Bhagat P. R. , Muskawar P. N. , Sreenivasan V. S. , Anil P. M.
Published: May 2013

The influence of Cu and Ni nanoparticle suspensions (2 wt-%) in commercially available engine oil (15W40) has been investigated on friction and wear behaviour of Al2O3–13TiO2 coatings. Lab synthesised nano-Cu and Ni suspensions have been compared with one commercially available nano-Cu suspension. Results show that lab synthesised Cu and Ni increases the oil viscosity by 12 and 20% for Ni and Cu respectively. However, the commercially available nano-Cu has reduced the viscosity by 8%. Lab synthesised Cu and Ni showed slightly reduced friction coefficient with significantly higher mass loss compared to virgin base oil and commercially available nano-Cu. The abrasive nature of these particles may possibly predominate in higher viscosity medium generating steady wear particles from the softer counterpart. Commercially available nano-Cu shows higher and irregular friction profile with mass loss equal to base oil possibly due to reduced viscosity.
Control of post-translational modifications in antithrombin during murine post-natal development by miR-200a
Authors: Teruel Raúl , Martínez-Martínez Irene , Guerrero José A , González-Conejero Rocío , de la Morena-Barrio María E , Salloum-Asfar Salam , Arroyo Ana B , Águila Sonia , García-Barberá Nuria , Miñano Antonia , Vicente Vicente , Corral Javier , Martínez Constantino
Published: May 2013

Background

Developmental haemostatic studies may help identifying new elements involved in the control of key haemostatic proteins like antithrombin, the most relevant endogenous anticoagulant.

Results

In this study, we showed a significant reduction of sialic acid content in neonatal antithrombin compared with adult antithrombin in mice. mRNA levels of St3gal3 and St3gal4, two sialyltransferases potentially involved in antithrombin sialylation, were 85% lower in neonates in comparison with adults. In silico analysis of miRNAs overexpressed in neonates revealed that mir-200a might target these sialyltransferases. Moreover, in vitro studies in murine primary hepatocytes sustain this potential control.

Conclusions

These data suggest that in addition to the direct protein regulation, microRNAs may also modulate qualitative traits of selected proteins by an indirect control of post-translational processes.
Physiological stressors and invasive plant infections alter the small RNA transcriptome of the rice blast fungus, Magnaporthe oryzae
Authors: Raman Vidhyavathi , Simon Stacey A , Romag Amanda , Demirci Feray , Mathioni Sandra M , Zhai Jixian , Meyers Blake C , Donofrio Nicole M
Published: May 2013

Background

The rice blast fungus, Magnaporthe oryzae is a destructive pathogen of rice and other related crops, causing significant yield losses worldwide. Endogenous small RNAs (sRNAs), including small interfering RNAs (siRNAs) and microRNAs (miRNAs) are critical components of gene regulation in many eukaryotic organisms. Recently several new species of sRNAs have been identified in fungi. This fact along with the availability of genome sequence makes M. oryzae a compelling target for sRNA profiling. We have examined sRNA species and their biosynthetic genes in M. oryzae, and the degree to which these elements regulate fungal stress responses. To this end, we have characterized sRNAs under different physiological stress conditions, which had not yet been examined in this fungus.

Results

The resulting libraries are composed of more than 37 million total genome matched reads mapping to intergenic regions, coding sequences, retrotransposons, inverted, tandem, and other repeated regions of the genome with more than half of the small RNAs arising from intergenic regions. The 24 nucleotide (nt) size class of sRNAs was predominant. A comparison to transcriptional data of M. oryzae undergoing the same physiological stresses indicates that sRNAs play a role in transcriptional regulation for a small subset of genes. Support for this idea comes from generation and characterization of mutants putatively involved in sRNAs biogenesis; our results indicate that the deletion of Dicer-like genes and an RNA-Dependent RNA Polymerase gene increases the transcriptional regulation of this subset of genes, including one involved in virulence.

Conclusions

Various physiological stressors and in planta conditions alter the small RNA profile of the rice blast fungus. Characterization of sRNA biosynthetic mutants helps to clarify the role of sRNAs in transcriptional control.
Ligation-assisted endoscopic enucleation for the diagnosis and resection of small gastrointestinal tumors originating from the muscularis propria: a preliminary study
Authors: Guo Jintao , Liu Zhijun , Sun Siyu , Wang Sheng , Ge Nan , Liu Xiang , Wang Guoxin , Yang Xianghong
Published: May 2013

Background

Ligation-assisted endoscopic enucleation (EE-L) was developed for the pathological diagnosis and resection of small gastrointestinal tumors originating from the muscularis propria. The technique combines endoscopic band ligation and endoscopic enucleation. The aim of this study was to evaluate the efficacy and safety of EE-L in the diagnosis and resection of gastrointestinal tumors originating from the muscularis propria.

Methods

A total of 43 patients were eligible for inclusion in this study from June 2009 to June 2011. Endoscopic ligation was first performed to force the tumor to assume a polypoid form with a pseudostalk. EE-L was then performed until the tumor was completely enucleated from the muscularis propria. Wound closure was performed using clips and adhesive tissue.

Results

All 43 tumors were completely enucleated. The mean enucleation time was 7.2 minutes (range, 5–11 minutes). No perforation, massive hemorrhage, or peritonitis requiring further endoscopic or surgical intervention occurred. Histopathology, 19 lesions were identified as gastrointestinal stromal tumors and 24 lesions were identified as leiomyomas. The mean follow-up time was 20.4 months (range, 14–38 months). No recurrence has occurred during the follow-up period.

Conclusions

EE-L appears to be a safe, effective, and relatively simple method for the histologic diagnosis and removal of small gastrointestinal tumors originating from the muscularis propria.
ST9 MRSA strains carrying a variant of type IX SCCmec identified in the Thai community
Authors: Lulitanond Aroonlug , Ito Teruyo , Li Shanshuang , Han Xiao , Ma Xiao Xue , Engchanil Chulapan , Chanawong Aroonwadee , Wilailuckana Chotechana , Jiwakanon Netchanok , Hiramatsu Keiichi
Published: May 2013

Background

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in Thailand occur most frequently in healthcare facilities. However, reports of community-associated MRSA are limited.

Methods

We characterized 14 MRSA isolates from outpatients (O-1 to O-14) by phenotypic and genotypic methods and compared them with 5 isolates from inpatients (I-1 to I-5). Thai MRSA isolates from a healthcare worker (N-1) and a pig (P-1) were also included as ST9 MRSA strains from other sources.

Results

All MRSA isolates from the outpatients and inpatients were multidrug-resistant (resistant to ≥3 classes of antimicrobials). All of them except strains O-2 and I-3 carried type III SCCmec and belonged to agrI, coagulase IV, spa type t037 or t233, which related to ST239. The strain O-2 (JCSC6690) carried type IX SCCmec and belonged to agrII, coagulaseXIc, spa type t337 and ST9, whereas the strain I-3 carried a type III SCCmec and belonged to ST1429. Nucleotide sequence determination revealed that the type IX SCCmec element in strain O-2 was distinct from that in a Thai ST398 strain (JCSC6943) previously identified in 2011; nucleotide identities of ccrA and ccrB were 93 and 91%, respectively and several open reading frames (ORFs) at the joining regions were different. PCR experiments suggested that strain O-2 and N-1 carried similar SCCmec element, whereas that of strain P-1 was different, suggesting that distinct ST9-MRSA–IX clones might be spreading in this province.

Conclusions

The SCCmecIX-ST9 MRSA clones of distinct SCCmec subtypes might have emerged in the Thai community and might also have disseminated into the hospital.
Genetic association between selected cytokine genes and glioblastoma in the Han Chinese population
Authors: Jin Tianbo , Li Xiaolan , Zhang Jiayi , Wang Hong , Geng Tingting , Li Gang , Gao Guodong , Chen Chao
Published: May 2013

Background

Glioblastoma (GBM) is the most malignant brain tumor. Many abnormal secretion and expression of cytokines have been found in GBM, initially speculated that the occurrence of GBM may be involved in these abnormal secretion of cytokines. This study aims to detect the association of cytokine genes with GBM.

Methods

We selected seven tag single nucleotide polymorphisms (tSNPs) in six cytokine genes, which previously reported to be associated with brain tumors, and analyzed their association with GBM in a Han Chinese population using χ2 test and genetic model analysis.

Results

We found two risk tSNPs and one protective tSNP. By χ2 test, the rs1801275 in IL-4R showed an increased risk of GBM. In the genetic model analysis, the genotype “TC” of rs20541 in IL-13 gene showed an increased risk of GBM in over-dominant model (OR = 2.00; 95% CI, 1.13-3.54, p = 0.015); the genotype “CT” of rs1800871 in the IL-10 gene showed a decrease risk in the over-dominant model (OR = 0.57; 95% CI, 0.33 – 0.97; p = 0.037). The genotype “AG” of rs1801275 in the IL-4R gene showed an increase risk in over-dominant model (OR = 2.29; 95% CI, 1.20 - 4.35; p = 0.0081) We further analyzed whether the six cytokine genes have a different effect on the disease in gender specific population, and found that the allele “G” of rs2243248 in the IL-4 gene showed a decrease risk of GBM in female (OR = 0.35, 95% CI, 0.13 - 0.94, p = 0.0032), but the allele “T” showed a decrease risk in male (OR = 0.30, 95% CI, 0.17 - 0.53, p = 0.0032).

Conclusions

Our findings, combined with previously reported results, suggest that cytokine genes have potential role in GBM development, which may be useful to early prognostics for GBM in the Han Chinese population.
Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells
Authors: Charalambous Christiana , Pitta Chara A , Constantinou Andreas I
Published: May 2013

Background

Soy phytoestrogens, such as daidzein and its metabolite equol, have been proposed to be responsible for the low breast cancer rate in Asian women. Since the majority of estrogen receptor positive breast cancer patients are treated with tamoxifen, the basic objective of this study is to determine whether equol enhances tamoxifen’s anti-tumor effect, and to identify the molecular mechanisms involved.

Methods

For this purpose, we examined the individual and combined effects of equol and tamoxifen on the estrogen-dependent MCF-7 breast cancer cells using viability assays, annexin-V/PI staining, cell cycle and western blot analysis.

Results

We found that equol (>50 μM) and 4-hydroxy-tamoxifen (4-OHT; >100 nM) significantly reduced the MCF-7 cell viability. Furthermore, the combination of equol (100 μM) and 4-OHT (10 μM) induced apoptosis more effectively than each compound alone. Subsequent treatment of MCF-7 cells with the pan-caspase inhibitor Z-VAD-FMK inhibited equol- and 4-OHT-mediated apoptosis, which was accompanied by PARP and α-fodrin cleavage, indicating that apoptosis is mainly caspase-mediated. These compounds also induced a marked reduction in the bcl-2:bax ratio, which was accompanied by caspase-9 and caspase-7 activation and cytochrome-c release to the cytosol. Taken together, these data support the notion that the combination of equol and tamoxifen activates the intrinsic apoptotic pathway more efficiently than each compound alone.

Conclusions

Consequently, equol may be used therapeutically in combination treatments and clinical studies to enhance tamoxifen’s effect by providing additional protection against estrogen-responsive breast cancers.
Alterations of the genes involved in the PI3K and estrogen-receptor pathways influence outcome in human epidermal growth factor receptor 2-positive and hormone receptor-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy
Authors: Takada Mamoru , Higuchi Toru , Tozuka Katsunori , Takei Hiroyuki , Haruta Masayuki , Watanabe Junko , Kasai Fumio , Inoue Kenichi , Kurosumi Masafumi , Miyazaki Masaru , Sato-Otsubo Aiko , Ogawa Seishi , Kaneko Yasuhiko
Published: May 2013

Background

Chemotherapy with trastuzumab is widely used for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but a significant number of patients with the tumor fail to respond, or relapse. The mechanisms of recurrence and biomarkers that indicate the response to the chemotherapy and outcome are not fully investigated.

Methods

Genomic alterations were analyzed using single-nucleotide polymorphism arrays in 46 HER2 immunohistochemistry (IHC) 3+ or 2+/fluorescent in situ hybridization (FISH)+ breast cancers that were treated with neoadjuvant chemotherapy with paclitaxel, cyclophosphamid, epirubicin, fluorouracil, and trastuzumab. Patients were classified into two groups based on presence or absence of alterations of 65 cancer-associated genes, and the two groups were further classified into four groups based on genomic HER2 copy numbers or hormone receptor status (HR+/−). Pathological complete response (pCR) and relapse-free survival (RFS) rates were compared between any two of the groups.

Results and discussion

The pCR rate was 54% in 37 patients, and the RFS rate at 3 years was 72% (95% CI, 0.55-0.89) in 42 patients. The analysis disclosed 8 tumors with nonamplified HER2 and 38 tumors with HER2 amplification, indicating the presence of discordance in tumors diagnosed using current HER2 testing. The 8 patients showed more difficulty in achieving pCR (P=0.019), more frequent relapse (P=0.018), and more frequent alterations of genes in the PI3K pathway (P=0.009) than the patients with HER2 amplification. The alterations of the PI3K and estrogen receptor (ER) pathway genes generally indicated worse RFS rates. The prognostic significance of the alterations was shown in patients with a HR+ tumor, but not in patients with a HR- tumor when divided. Alterations of the PI3K and ER pathway genes found in patients with a HR+ tumor with poor outcome suggested that crosstalk between the two pathways may be involved in resistance to the current chemotherapy with trastuzumab.

Conclusions

We recommend FISH analysis as a primary HER2 testing because patients with IHC 2+/3+ and nonamplified HER2 had poor outcome. We also support concurrent use of trastuzumab, lapatinib, and cytotoxic and anti-hormonal agents for patients having HR+ tumors with alterations of the PI3K and ER pathway genes.
Improved emollient use reduces atopic eczema symptoms and is cost neutral in infants: before-and-after evaluation of a multifaceted educational support programme
Authors: Mason James M , Carr Julie , Buckley Carolyn , Hewitt Steve , Berry Phillip , Taylor Josh , Cork Michael J
Published: May 2013

Background

Parents and carers of children with eczema often underuse emollient therapy, essential to repairing and protecting the defective skin barrier in atopic eczema. Educational interventions delivered by specialist dermatology nurses in hospital settings have been shown to improve emollient use and reduce symptoms of atopic eczema, but benefits of community-based interventions are uncertain. Support and information about appropriate care may often be inadequate for patients and carers in the community.

Methods

A multifaceted educational support programme was evaluated as a method of increasing emollient use and reducing atopic eczema in children. Support provided for parents and carers included an educational DVD, online daily diary and telephone helpline. The before and after study included 136 British children and their parents, providing baseline and 12 week follow-up data while receiving the programme. Measures included emollient use, POEM and PEST scores, and cost of care.

Results

Average emollient use increased by 87.6 g (95% CI: 81.9 to 119.5 g, p = 0.001) from baseline with the change being immediate and persistent. The POEM score reduced on average by 5.38 (95% CI: 4.36 to 6.41, p = 0.001), a 47% reduction from baseline. Similarly the PEST score reduced on average by 0.61 (95% CI: 0.47 to 0.75, p = 0.001), a 48% reduction from baseline. Sleep disturbance was reduced by 1.27 nights per week (95% CI: 0.85 to 1.68, p = 0.001) and parental feeling of control improved by 1.32 points (95% CI: 1.16 to 1.48, p = 0.001). From the NHS perspective, the programme was cost neutral overall within the study period.

Conclusion

A community-based multifaceted educational support programme greatly increased emollient use, reducing symptoms of atopic eczema and general practitioner contacts, without increasing cost. Significant benefits may accrue to the families and carers of children with atopic eczema due to improved sleep patterns and greater feeling of control. PEST, a new simple measure of acute and remitting atopic eczema severity designed to help parents and children to monitor and manage eczema, merits further evaluation.
Antibacterial, antidiarrhoeal, and cytotoxic activities of methanol extract and its fractions of Caesalpinia bonducella (L.) Roxb leaves
Authors: Billah Muhammad Mutassim , Islam Rafikul , Khatun Hajera , Parvin Shahnaj , Islam Ekramul , Islam SM Anisul , Mia Akbar Ali
Published: May 2013

Background

Caesalpinia bonducella is an important medicinal plant for its traditional uses against different types of diseases. Therefore, the present study investigated the antimicrobial, antidiarrhoeal, and cytotoxic activities of the methanol extract and ethyl acetate, chloroform, and petroleum ether (pet. ether) fractions of C. bonducella leaves.

Methods

The antibacterial potentialities of methanol extract and its fractions of C. bonducella leaves were investigated by the disc diffusion method against four gram-positive and five gram-negative bacteria at 300, 500 and 800 μg/disc. Kanamycin (30 μg/disc) was used as the standard drug. Antidiarrhoeal activities of leaf extracts were evaluated at two doses (200 and 400 mg/kg) and compared with loperamide in a castor oil-induced diarrhoeal model in rat. The fractions were subjected to a brine shrimp lethality test to evaluate their cytotoxicity.

Results

The methanol extract and other three fractions exhibited better activities at higher concentrations. Amongst, the chloroform fraction showed maximum activity at all three concentrations (300, 500, and 800 μg/disc) against almost all bacteria. S. aureus and P. aeruginosa showed better sensitivities to all extracts at all three concentrations excluding the pet. ether fraction. Bacillus megaterium and Klebsiella spp. were two bacteria amongst nine that showed lowest sensitivity to the extracts. Maximum zone of inhibition (25-mm) was obtained by the methanol extract at an 800 μg/disc concentration against S. aureus. In the antidiarrhoeal test, all fractions exhibited dose-dependent actions, which were statistically significant (p < 0.05). Ethyl acetate fraction exerted maximum inhibition (51.11%) against defecation, whereas 57.75% inhibition was obtained for loperamide. Moderate cytotoxicity was found for the methanol extract and its three fractions compared with the standard drug vincristine sulfate in the brine shrimp bioassay. In the present study, the LC50 values of the methanol crude extract and ethyl acetate, chloroform, pet. ether fractions and vincristine sulfate were 223.87, 281.84, 112.2, 199.53, and 12.59 μg/mL, respectively. Therefore, the ethyl acetate fraction showed maximum cytotoxicity, whereas minimum cytotoxicity was observed for the chloroform fraction.

Conclusion

The present study revealed that the ethyl acetate fraction of the C. bonducella leaves has significant antidiarrhoeal properties. The methanol extract and other three fractions of the C. bonducella leaves possess potent antibacterial activities along with moderate cytotoxicities that may lead to new drug development.
Interactions by 2D Gel Electrophoresis Overlap (iGEO): a novel high fidelity
approach to identify constituents of protein complexes
Authors: Yoshigi Masaaki , Pronovost Stephen M , Kadrmas Julie L
Published: May 2013

Background

Here we describe a novel approach used to identify the constituents of
protein complexes with high fidelity, using the integrin-associated
scaffolding protein PINCH as a test case. PINCH is comprised of five LIM
domains, zinc-finger protein interaction modules. In Drosophila
melanogaster, PINCH has two known high-affinity binding
partners—Integrin-linked kinase (ILK) that binds to LIM1 and Ras
Suppressor 1 (RSU1) that binds to LIM5—but has been postulated to bind
additional proteins as well.

Results

To purify PINCH complexes, in parallel we fused different affinity tags
(Protein A and Flag) to different locations within the PINCH sequence (N-
and C-terminus). We expressed these tagged versions of PINCH both in cell
culture (overexpressed in Drosophila S2 cell culture in the
presence of endogenous PINCH) and in vivo (at native levels in
Drosophila lacking endogenous PINCH). After affinity
purification, we analyzed PINCH complexes by a novel 2D-gel electrophoresis
analysis, iGEO (interactions by 2D Gel Electrophoresis Overlap), with mass
spectrometric identification of individual spots of interest. iGEO allowed
the identification of protein partners that associate with PINCH under two
independent purification strategies, providing confidence in the
significance of the interaction. Proteins identified by iGEO were validated
against a highly inclusive list of candidate PINCH interacting proteins
identified in previous analyses by MuDPIT mass spectrometry.

Conclusions

The iGEO strategy confirmed a core complex comprised of PINCH, RSU1, ILK, and
ILK binding partner Parvin. Our iGEO method also identified five novel
protein partners that specifically interacted with PINCH in
Drosophila S2 cell culture. Because of the improved
reproducibility of 2D-GE methodology and the increasing affordability of the
required labeling reagents, iGEO is a method that is accessible to most
moderately well-equipped biological laboratories. The biochemical
co-purifications inherent in iGEO allow for rapid and unambiguous
identification of the constituents of protein complexes, without the need
for extensive follow-up experiments.
Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice
Authors: Kalli Francesca , Machiorlatti Rodolfo , Battaglia Florinda , Parodi Alessia , Conteduca Giuseppina , Ferrera Francesca , Proietti Michele , Tardito Samuele , Sanguineti Marina , Millo Enrico , Fenoglio Daniela , De Palma Raffaele , Inghirami Giorgio , Filaci Gilberto
Published: May 2013

Background

Cancer vaccines are considered a promising therapeutic approach. However, their clinical results are not yet satisfactory. This may be due to the the difficulty of selection of an efficient tumor associated antigen (TAA) and immunization protocol. Indeed, the weak antigenicity of many TAA impairs the design of robust procedures, therefore a systematic analysis to identify the most efficient TAA is mandatory. Here, we performed a study to compare different gp100 vaccination strategies to identify the best strategy to provide a 100% protection against experimental melanoma in a reproducible manner.

Methods

C57BL/6J mice were challenged subcutaneously with B16F10 melanoma cells, after vaccination with: a) mouse or human gp10025-33 peptide plus CpG adjuvant; b) mouse or human gp100 gene; c) mouse or human gp10025-33 peptide-pulsed dendritic cells (DC). Alternatively, a neutralizing anti-IL-10 monoclonal antibody (mAb) was subcutaneously administered at the site of tumor challenge to counteract regulatory cells. Finally, combinatorial treatment was performed associating human gp10025-33 peptide-pulsed DC vaccination with administration of the anti-IL-10 mAb.

Results

Vaccination with human gp10025-33 peptide-pulsed DC was the most effective immunization protocol, although not achieving a full protection. Administration of the anti-IL-10 mAb showed also a remarkable protective effect, replicated in mice challenged with a different tumor, Anaplastic Large Cell Lymphoma. When immunization with gp10025-33 peptide-pulsed DC was associated with IL-10 counteraction, a 100% protective effect was consistently achieved. The analysis on the T-cell tumor infiltrates showed an increase of CD4+granzyme+ T-cells and a decreased number of CD4+CD25+Foxp3+ Treg elements from mice treated with either gp10025-33 peptide-pulsed DC vaccination or anti-IL-10 mAb administration. These data suggest that processes of intratumoral re-balance between effector and regulatory T cell subpopulations may play a critical protective role in immunotherapy protocols.

Conclusions

Here we demonstrate that, in the setting of a cancer vaccine strategy, a comparative analysis of different personalized approaches may favour the unveiling of the most effective protocol. Moreover, our findings suggest that counteraction of IL-10 activity may be critical to revert the intratumoral environment promoting Treg polarization, thus increasing the effects of a vaccination against selected TAA.
Depression as a non-causal variable risk marker in coronary heart disease
Authors: Meijer Anna , Zuidersma Marij , de Jonge Peter
Published: May 2013

Background

After decades of investigations, explanations for the prospective association between depression and coronary heart disease (CHD) are still incomplete.

Discussion

Depression is often suggested to be causally related to CHD. Based on the available literature, we would rather argue that depression can best be regarded as a variable risk marker, that is, a variable that fluctuates together with mechanisms leading to poor cardiovascular fitness. Despite numerous efforts, no evidence is found that manipulation of depression alters cardiovascular outcomes - a key premise for determining causality. To explain the concept of a variable risk marker, we discuss several studies on the heterogeneity of depression suggesting that depression is particularly harmful for the course of cardiovascular disease when it appears to be a physiological consequence of the cardiovascular disease itself.

We conclude that instead of depression being a causal risk factor for CHD, the association between depression and CHD is likely confounded, at least by the cardiac disease itself.
Using allometric procedures to substantiate the plastochrone method for eelgrass leaf growth assessments
Authors: Echavarría-Heras Héctor , Solana-Arellano Elena , Leal-Ramírez Cecilia , Castillo Oscar
Published: May 2013

Estimation of leaf productivity in eelgrass (Zostera marina L.) is crucial for evaluating the ecological role of this important seagrass species. Although leaf marking techniques are widely used to obtain estimates of leaf productivity, the accuracy of these assessments, has been questioned mainly because these fail to account for leaf growth bellow the reference mark and also because they apparently disregard the contribution of mature leaf tissues to the growth rate of leaves. On the other hand, the plastochrone method is a simpler technique that has been considered to effectively capture growth in a more realistic way, thereby providing more accurate assessments of both above- and below-ground productivities. But since the actual values of eelgrass growth rates are difficult to obtain, the worth of the plastochrone method has been largely vindicated because it produces assessments that overestimate productivity as compared to estimates obtained by leaf marking. Additionally, whenever eelgrass leaf biomass can be allometrically scaled in terms of matching leaf length in a consistent way, the associated leaf growth rates can be also projected allometrically. In this contribution, we used that approach to derive an authentication of the plastochrone method and formally demonstrate that, as has been claimed to occur for leaf marking approaches, the plastochrone method itself underestimates actual values of eelgrass leaf growth rates. We also show that this unavoidable bias is mainly due to the inadequacy of single-leaf biomass assessments in providing a proxy for the growth of all leaf tissue in a shoot over a given interval. Moreover, the derived formulae give conditions under which assessments of leaf growth rates using the plastochrone method would systematically underestimate matching values obtained by leaf marking procedures. And, assessments of leaf growth rates obtained by using the present data show that plastochrone method estimations underestimated corresponding proxies obtained allometrically (27%), or through leaf marking (35%). Allometric projection is recommended as a simpler and more effective procedure to reduce the bias in eelgrass leaf productivity estimations that associates to the use of plastochrone methods.
Effects of southern rice black-streaked dwarf virus on the development and fecundity of its vector, Sogatella furcifera
Authors: Tu Zhi , Ling Bing , Xu Donglin , Zhang Maoxin , Zhou Guohui
Published: May 2013

Background

Southern rice black-streaked dwarf virus (SRBSDV) threatens rice production in China and Vietnam. The virus is vectored by the migrating white-backed planthopper (WBPH, Sogatella furcifera) in a circulative, propagative, and persistent manner. A persistently-transmitted plant virus might affect its vector’s development and fecundity directly by infecting the vector itself and/or indirectly altering the host plant. This study evaluated the direct and indirect effects of SRBSDV on WBPH performance to better understand the virus–vector–host plant relationship in terms of its effects on the biological parameters of the vector.

Methods

Three experimental WBPH populations were established. Viruliferous and non-viruliferous populations were fed on SRBSDV-infected rice seedlings for 48 h as first-instar nymphs; infection status was confirmed by RT–PCR after they died. The control population was fed on healthy rice. Each insect was individually transferred to a healthy rice plant grown in a glass tube at 20°C, 25°C, or 28°C. Life parameters, including nymphal duration, survival rate, adult sex ratio, macropterous proportion, longevity, and oviposition amounts, of each population were measured at each temperature.

Results

The life parameter data indicated that SRBSDV and infected rice plants adversely influenced WBPH; the effects were temperature dependent. Compared with the control population, viruliferous populations showed significant changes, including prolonged nymphal stages and reduced survival rates at 20°C, while the non-viruliferous population had higher survival rates at 20°C and lower rates at 28°C compared with the control. Both populations had significantly shorter adult life spans at 25°C and lower oviposition amounts at 28°C relative to the control.

Conclusions

Both SRBSDV-infection and feeding on infected rice plants affected vector performance. Although a longer nymphal period benefits viral acquisition and transmission by nymphs and might increase rice infection rate, in general, SRBSDV infection of the vectors and host plants was unfavorable to WBPH population expansion.
Heterogenous nuclear ribonucleoprotein Q increases protein expression from HIV-1 Rev-dependent transcripts
Authors: Vincendeau Michelle , Nagel Daniel , Brenke Jara K , Brack-Werner Ruth , Hadian Kamyar
Published: May 2013

Background

Heterogenous nuclear ribonucleoproteins (hnRNPs) control many processes of the gene expression machinery including mRNA transcription, splicing, export, stability and translation. Recent data show interaction of the HIV-1 Rev regulatory protein with a subset of hnRNP proteins, that includes hnRNP Q, suggesting that hnRNPs can contribute to regulation of HIV-1 gene expression by Rev.

Findings

In this work we address the effect of hnRNP Q on Rev-dependent gene expression. We show that hnRNP Q overexpression increased levels of proteins produced from a Rev-dependent reporter gene in the presence of Rev. Increased protein levels did not correlate with changes in either the levels or the nucleocytoplasmic distribution of Rev-dependent reporter mRNAs. Similar observations were made in persistently HIV-1 infected HeLa cells. In these cells, hnRNP Q overexpression increased levels of the HIV-1 Gag-p24 protein, while levels of viral Rev-dependent mRNAs were not affected.

Conclusion

Our data indicate that hnRNP Q can stimulate the protein production of Rev-dependent mRNAs without changing mRNA levels and mRNA export, respectively. This suggests that hnRNP Q can boost HIV gene expression at the level of protein production.
Ethno-medicinal study of plants used for treatment of human and livestock ailments by traditional healers in South Omo, Southern Ethiopia
Authors: Tolossa Ketema , Debela Etana , Athanasiadou Spiridoula , Tolera Adugna , Ganga Gebeyehu , Houdijk Jos GM
Published: May 2013

Background

Plants have traditionally been used for treatment of human and livestock ailments in Ethiopia by different ethnic and social groups. However, this valuable source of knowledge is not adequately documented, which impedes their widespread use, evaluation and validation. Here, we recorded indigenous knowledge and standard practices for human and livestock disease control, of three ethnic groups (Aari, Maale and Bena-Tsemay) in South Omo Zone of Southern Nations, Nationalities and Peoples Regional State, Ethiopia.

Methods

A cross-sectional study was carried out using a semi-structured questionnaire to document knowledge of 50 traditional healers (40 male and 10 female) in medicinal plant use for treatment of human and livestock ailments. Descriptive statistics were used to analyze and summarize the ethno-botanical data.

Results

Ninety-one plants, with claimed medicinal properties against a total of 34 human and livestock ailments, were reported and botanically identified as belonging to 57 genera and 33 plant families. Most of the plant species reported belonged to one of seven major families:Lamiaceae,Solanaceae,Menispermiaceae, Fabaceae,Asteraceae,PlumbaginaceaeandGeraniaceae. Woody plants (shrubs 21% and trees 29%) were the major growth form used, whilst roots (40%) and leaves (35%) were the major plant parts used in the study areas. Healers mostly practice oral administration of plant preparations (65%). Multiple medicinal plants were cited against particular ailments, and mixing of two or more different medicinal plants (14.3%) against a single ailment was also commonly reported.

Conclusion

This study showed that traditional medicine, mainly involving the use of medicinal plants, is playing a significant role in meeting the primary healthcare needs of the three ethnic groups. Acceptance of traditional medicine and limited access to modern healthcare facilities could be considered as the main factors for the continuation of the practice. Documented knowledge of the traditional healers can be used to support the country’s human and livestock health care system and improve lives and livelihoods. Information generated will be used in future studies to validate bioactivity of selected medicinal plants used by traditional healers, so to increase their acceptability in health care systems both nationally and internationally.
Cell cycle-dependent localization of CHK2 at centrosomes during mitosis
Authors: Chouinard Guillaume , Clément Isabelle , Lafontaine Julie , Rodier Francis , Schmitt Estelle
Published: May 2013

Background

Centrosomes function primarily as microtubule-organizing centres and play a crucial role during mitosis by organizing the bipolar spindle. In addition to this function, centrosomes act as reaction centers where numerous key regulators meet to control cell cycle progression. One of these factors involved in genome stability, the checkpoint kinase CHK2, was shown to localize at centrosomes throughout the cell cycle.

Results

Here, we show that CHK2 only localizes to centrosomes during mitosis. Using wild-type and CHK2−/− HCT116 human colon cancer cells and human osteosarcoma U2OS cells depleted for CHK2 with small hairpin RNAs we show that several CHK2 antibodies are non-specific and cross-react with an unknown centrosomal protein(s) by immunofluorescence. To characterize the localization of CHK2, we generated cells expressing inducible GFP-CHK2 and Flag-CHK2 fusion proteins. We show that CHK2 localizes to the nucleus in interphase cells but that a fraction of CHK2 associates with the centrosomes in a Polo-like kinase 1-dependent manner during mitosis, from early mitotic stages until cytokinesis.

Conclusion

Our findings demonstrate that a subpopulation of CHK2 localizes at the centrosomes in mitotic cells but not in interphase. These results are consistent with previous reports supporting a role for CHK2 in the bipolar spindle formation and the timely progression of mitosis.
Developing a diagnostic checklist of traditional Chinese medicine symptoms and signs for psoriasis: a Delphi study
Authors: Yang Xuesong , Chongsuvivatwong Virasakdi , McNeil Edward , Ye Jianzhou , Ouyang Xiaoyong , Yang Enpin , Sriplung Hutcha
Published: May 2013

Background

Psoriasis is a chronic inflammatory skin disease with a genetic basis. Its ill-defined causes make it difficult to diagnose. This study aims to develop a diagnostic checklist for psoriasis classification in the context of traditional Chinese medicine.

Methods

A Delphi study was conducted with three rounds by a panel of 16 dermatology experts to develop a checklist for traditional Chinese medicine symptoms and signs of psoriasis. Dermatology experts in psoriasis research, nine in Yunnan and seven in Beijing, were selected as the expert panel. The initial list of symptoms and signs in psoriasis was developed by reviewing the literature retrieved from Chinese and English journals. Experts rated each item of the list on a 5-point Likert scale. The list was revised and re-evaluated in the same manner for a total of 3 rounds before it was finalized.

Results

One hundred and thirty items were extracted from the literature review. After three rounds of expert ratings, 96 items were retained with eight domains: color, type and shape of skin lesion, physical expression, tongue and coating, pulse, associated factors, and living environment. Intraclass correlation coefficient and Kappa statistics indicated an inter-rater agreement in the final checklist.

Conclusion

A checklist containing 96 items in 8 domains was developed for psoriasis diagnosis using traditional Chinese medicine symptoms and signs.
Normal cognition in transgenic BRI2-Aβ mice
Authors: Kim Jungsu , Chakrabarty Paramita , Hanna Amanda , March Amelia , Dickson Dennis W , Borchelt David R , Golde Todd , Janus Christopher
Published: May 2013

Background

Recent research in Alzheimer’s disease (AD) field has been focused on the potential role of the amyloid-β protein that is derived from the transmembrane amyloid precursor protein (APP) in directly mediating cognitive impairment in AD. Transgenic mouse models overexpressing APP develop robust AD-like amyloid pathology in the brain and show various levels of cognitive decline. In the present study, we examined the cognition of the BRI2-Aβ transgenic mouse model in which secreted extracellular Aβ1-40, Aβ1-42 or both Aβ1-40/Aβ1-42 peptides are generated from the BRI-Aβ fusion proteins encoded by the transgenes. BRI2-Aβ mice produce high levels of Aβ peptides and BRI2-Aβ1-42 mice develop amyloid pathology that is similar to the pathology observed in mutant human APP transgenic models.

Results

Using established behavioral tests that reveal deficits in APP transgenic models, BRI2-Aβ1-42 mice showed completely intact cognitive performance at ages both pre and post amyloid plaque formation. BRI2-Aβ mice producing Aβ1-40 or both peptides were also cognitively intact.

Conclusions

These data indicate that high levels of Aβ1-40 or Aβ1-42, or both produced in the absence of APP overexpression do not reproduce memory deficits observed in APP transgenic mouse models. This outcome is supportive of recent data suggesting that APP processing derivatives or the overexpression of full length APP may contribute to cognitive decline in APP transgenic mouse models. Alternatively, Aβ aggregates may impact cognition by a mechanism that is not fully recapitulated in these BRI2-Aβ mouse models.