bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic evaluation of a peracetic-acid-based high performance disinfectant
Authors: Humphreys Paul N , Finan Peter , Rout Simon , Hewitt James , Thistlethwaite Peter , Barnes Sophie , Pilling Sally
Published: February 2013

The importance of environmental contamination in the spread of healthcare associated infections (HAI) has generated a need for high performance disinfectants. Currently chlorine-based disinfectants are the products of choice, a position reflected in UK guidance. The aim of this research was to evaluate a peracetic acid (PAA) generating disinfectant to determine if it provided a realistic alternative to commonly used chlorine-based disinfectants. The European standards framework was employed in this study and enhanced where appropriate by reducing the contact times, increasing the organic and microbial challenge, and changing the organisms involved. When tested against bacteria and spores PAA provided similar or better performance than currently employed levels of chlorine. This was particularly the case in the presence of an organic challenge or dried surface contamination. The chlorine disinfectants only demonstrated superior performance in the case of fungal spores. These results suggest that PAA generating products provide an effective alternative to chlorine-based products up to 10,000 ppm free available chlorine. These products have superior performance in situations with spore borne, surface contamination and high organic challenge. In cases where filamentous fungi are a concern, high levels of PAA (>5,000 ppm) would be required to match the performance of chlorine based disinfectants.
The BLADE-ON-PETIOLE genes of Arabidopsis are essential for resistance induced by methyl jasmonate
Authors: Canet Juan Vicente , Dobón Albor , Fajmonová Jana , Tornero Pablo
Published: February 2013

Background

NPR1 is a gene of Arabidopsis thaliana required for the perception of salicylic acid. This perception triggers a defense response and negatively regulates the perception of jasmonates. Surprisingly, the application of methyl jasmonate also induces resistance, and NPR1 is also suspected to be relevant. Since an allelic series of npr1 was recently described, the behavior of these alleles was tested in response to methyl jasmonate.

Results

The response to methyl jasmonate of different npr1s alleles and NPR1 paralogs null mutants was measured by the growth of a pathogen. We have also tested the subcellular localization of some npr1s, along with the protein-protein interactions that can be measured in yeast. The localization of the protein in npr1 alleles does not affect the response to methyl jasmonate. In fact, NPR1 is not required. The genes that are required in a redundant fashion are the BOPs. The BOPs are paralogs of NPR1, and they physically interact with the TGA family of transcription factors.

Conclusions

Some npr1 alleles have a phenotype in this response likely because they are affecting the interaction between BOPs and TGAs, and these two families of proteins are responsible for the resistance induced by methyl jasmonate in wild type plants.
Associations between dietary patterns and gene expression profiles of healthy men and women: a cross-sectional study
Authors: Bouchard-Mercier Annie , Paradis Ann-Marie , Rudkowska Iwona , Lemieux Simone , Couture Patrick , Vohl Marie-Claude
Published: February 2013

Background

Diet regulates gene expression profiles by several mechanisms. The objective of this study was to examine gene expression in relation with dietary patterns.

Methods

Two hundred and fifty four participants from the greater Quebec City metropolitan area were recruited. Two hundred and ten participants completed the study protocol. Dietary patterns were derived from a food frequency questionnaire (FFQ) by factor analysis. For 30 participants (in fasting state), RNA was extracted from peripheral blood mononuclear cells (PBMCs) and expression levels of 47,231 mRNA transcripts were assessed using the Illumina Human-6 v3 Expression BeadChips®. Microarray data was pre-processed with Flexarray software and analysed with Ingenuity Pathway Analysis (IPA).

Results

Two dietary patterns were identified. The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats. When individuals with high scores for the Prudent dietary pattern where compared to individuals with low scores, 2,083 transcripts were differentially expressed in men, 1,136 transcripts in women and 59 transcripts were overlapping in men and women. For the Western dietary pattern, 1,021 transcripts were differentially expressed in men with high versus low scores, 1,163 transcripts in women and 23 transcripts were overlapping in men and women. IPA reveals that genes differentially expressed for both patterns were present in networks related to the immune and/or inflammatory response, cancer and cardiovascular diseases.

Conclusion

Gene expression profiles were different according to dietary patterns, which probably modulate the risk of chronic diseases.

Trial Registration

NCT:NCT01343342
Silica induces NLRP3 inflammasome activation in human lung epithelial cells
Authors: Peeters Paul M , Perkins Timothy N , Wouters Emiel FM , Mossman Brooke T , Reynaert Niki L
Published: February 2013

Background

In myeloid cells the inflammasome plays a crucial role in innate immune defenses against pathogen- and danger-associated patterns such as crystalline silica. Respirable mineral particles impinge upon the lung epithelium causing irreversible damage, sustained inflammation and silicosis. In this study we investigated lung epithelial cells as a target for silica-induced inflammasome activation.

Methods

A human bronchial epithelial cell line (BEAS-2B) and primary normal human bronchial epithelial cells (NHBE) were exposed to toxic but nonlethal doses of crystalline silica over time to perform functional characterization of NLRP3, caspase-1, IL-1β, bFGF and HMGB1. Quantitative RT-PCR, caspase-1 enzyme activity assay, Western blot techniques, cytokine-specific ELISA and fibroblast (MRC-5 cells) proliferation assays were performed.

Results

We were able to show transcriptional and translational upregulation of the components of the NLRP3 intracellular platform, as well as activation of caspase-1. NLRP3 activation led to maturation of pro-IL-1β to secreted IL-1β, and a significant increase in the unconventional release of the alarmins bFGF and HMGB1. Moreover, release of bFGF and HMGB1 was shown to be dependent on particle uptake. Small interfering RNA experiments using siNLRP3 revealed the pivotal role of the inflammasome in diminished release of pro-inflammatory cytokines, danger molecules and growth factors, and fibroblast proliferation.

Conclusion

Our novel data indicate the presence and functional activation of the NLRP3 inflammasome by crystalline silica in human lung epithelial cells, which prolongs an inflammatory signal and affects fibroblast proliferation, mediating a cadre of lung diseases.
Effects of the breed, sex and age on cellular content and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel
Authors: Giraldo Carlos E , López Catalina , Álvarez María E , Samudio Ismael J , Prades Marta , Carmona Jorge U
Published: February 2013

Background

There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF) release from equine pure-platelet rich plasma (P-PRP) and pure-platelet rich gel (P-PRG). The objectives of this study were: 1) to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP); 2) to compare the concentration of transforming GF beta 1 (TGF-β1) and platelet derived GF isoform BB (PDGF-BB) between P-PRP treated with non-ionic detergent (P-PRP+NID), P-PRG (activated with calcium gluconate -CG-), PPP+NID, PPP gel (PPG), and plasma and; 3) to evaluate and to correlate the effect of the breed, gender and age on the cellular and GF concentration for each blood component. Forty adult horses, 20 Argentinean Creole Horses (ACH) and, 20 Colombian Creole Horses (CCH) were included. Data were analyzed by parametric (i.e.: t-test, one way ANOVA) and non parametric (Kruskal-Wallis test, Wilcoxon test) tests. Correlation analysis was also performed by using the Spearman and Pearson tests. A p ≤ 0.05 was set as significant for all tests. All the blood components were compared for platelet (PLT), leukocyte (WBC), TGF-β1and PDGF-BB concentrations. The effect of the breed, gender and age on these variables was analyzed. A P ≤ 0.05 was accepted as significant for all the tests.

Results

PLT counts were 1.8 and 0.6 times higher in P-PRP than in whole blood and PPP, respectively; WBC counts were 0.5 and 0.1 times lower in P-PRP, in comparison with whole blood and PPP, respectively. TGF-β1and PDGF-BB concentrations were 2.3 and 262 times higher, respectively, in P-PRG than in plasma, and 0.59 and 0.48 times higher, respectively, in P-PRG than in PPG. P-PRG derived from CCH females or young horses presented significantly (P < 0.001) higher PDGF-BB concentrations than P-PRG derived from ACH males or older horses.

Conclusions

Our results indicated that P-PRP obtained by a manual method was affected by intrinsic factors such as the breed, gender and age. Equine practitioners should be aware that cellular and GF release from P-PRP/P-PRG could change according with the intrinsic variables associated with a patient in particular.
Synthesis, antifungal and antibacterial activity for novel amide derivatives containing a triazole moiety
Authors: Tang Ruping , Jin Linhong , Mou Chengli , Yin Juan , Bai Song , Hu Deyu , Wu Jian , Yang Song , Song Baoan
Published: February 2013

Background

Plant fungi (e.g., Pellicularia sasakii, Gibberella zeae, Fusarium oxysporum, and Cytospora mandshurica and Phytophthora infestans) and bacteria (e.g., Ralstonia solanacearum) are extremely difficult to manage in agricultural production. The high incidence of plant mortality and the lack of effective control methods make P. sasakii and R. solanacearum two of the world’s most destructive plant pathogens. Pathogenic fungi and bacteria are responsible for billions of dollars in economic losses worldwide each year. Thus, we designed an active amide structure and synthesized a series of novel amide derivatives containing a triazole moiety to discover new bioactive molecules and pesticides that can act against fungi and bacteria.

Results

A series of amide derivatives containing a triazole moiety were synthesized. All the obtained compounds were characterized through proton and carbon nuclear magnetic resonance spectroscopy, infrared spectroscopy, and elemental analysis. Preliminary antifungal activity test showed that some of the synthesized compounds exhibited moderate antifungal activity against P. sasakii, G. azeae, F. oxysporum, C. mandshurica, and P. infestans at 50 mg/L. Compound 4u displayed more potent antifungal activity against P. sasakii and G. azeae than hymexazol. Preliminary antibacterial activity results showed that some of the synthesized compounds exhibited high anti-bacterial activity against R. solanacearum at 200 mg/L. Compounds 4m and 4q displayed high antibacterial activity against R. solanacearum, with 71% and 65% inhibitory rates, respectively.

Conclusions

A series of novel amide derivatives containing 1,2,4-triazole moiety were synthesized through the reaction of intermediate 3 with different acyl chlorides and anhydrous potassium carbonates in anhydrous tetrahydrofuran at 50°C, using 2,4-dichloroacetophenoneas as a starting material. The title compounds exhibited high inhibitory effects against P. sasakii, R. solanacearum, and G. azeae.
Semiempirical investigations on the stabilization energies and ionic hydrogen-bonded structures of F−(H2O)
n
and Cl−(H2O)
n
(n = 1–4) clusters
Authors: Wang Qi , Suzuki Kimichi , Nagashima Umpei , Tachikawa Masanori , Yan Shiwei
Published: February 2013

Several semiempirical methods were utilized to analyze the structures and stabilities of X
−(H2O)
n
(X = F, Cl; n = 1–4) clusters with respect to the number of water molecules through their comparison with ab initio molecular orbital calculations. Our results show that the recently developed PM6-DH+ semiempirical method can provide reasonable binding energies of hydrated fluoride and chloride ion clusters, which are consistent with the corresponding experimental results. For the optimized geometries of X = F, however, the semiempirical methods show that the global minima are close to HF(OH)−(H2O)
n−1 structures, which are different from the ab initio calculations. Meanwhile, the topological characteristics for the global minima of X = Cl obtained by semiempirical methods have the same symmetries with ab initio calculations. All calculation levels agree on the trend of decreasing ion-water interaction with the increasing number of water molecules. We also found a new structure of Cl−(H2O)4 with a second hydration shell as a complement of previous studies. Those are very important data for our near-future study of on-the-fly semiempirical molecular dynamics (MD) or path integral MD simulation.

PACS

36.40.Mr, 31.15.bu, 31.15.A-
Quality of Care for Comorbid Conditions During the Transition to Survivorship: Differences Between Cancer Survivors and Noncancer Controls
Authors: Snyder Claire F. , Frick Kevin D. , Herbert Robert J. , Blackford Amanda L. , Neville Bridget A. , Wolff Antonio C. , Carducci Michael A. , Earle Craig C.
Published: February 2013

Purpose

Building on previous research documenting differences in preventive care quality between cancer survivors and noncancer controls, this study examines comorbid condition care.

Methods

Using data from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database, we examined comorbid condition quality of care in patients with locoregional breast, prostate, or colorectal cancer diagnosed in 2004 who were age ≥ 66 years at diagnosis, who had survived ≥ 3 years, and who were enrolled in fee-for-service Medicare. Controls were frequency matched to cases on age, sex, race, and region. Quality of care was assessed from day 366 through day 1,095 postdiagnosis using published indicators of chronic (n = 10) and acute (n = 19) condition care. The proportion of eligible cancer survivors and controls who received recommended care was compared by using Fisher's exact tests. The chronic and acute indicators, respectively, were then combined into single logistic regression models for each cancer type to compare survivors' care receipt to that of controls, adjusting for clinical and sociodemographic variables and controlling for within-patient variation.

Results

The sample matched 8,661 cancer survivors to 17,322 controls (mean age, 75 years; 65% male; 85% white). Colorectal cancer survivors were less likely than controls to receive appropriate care on both the chronic (odds ratio [OR], 0.88; 95% CI, 0.81 to 0.95) and acute (OR, 0.72; 95% CI, 0.61 to 0.85) indicators. Prostate cancer survivors were more likely to receive appropriate chronic care (OR, 1.28; 95% CI, 1.19 to 1.38) but less likely to receive quality acute care (OR, 0.75; 95% CI, 0.65 to 0.87). Breast cancer survivors received care equivalent to controls on both the chronic (OR, 1.06; 95% CI, 0.96 to 1.17) and acute (OR, 0.92; 95% CI, 0.76 to 1.13) indicators.

Conclusion

Because we found differences by cancer type, research exploring factors associated with these differences in care quality is needed.
Treating Patients With EGFR-Sensitizing Mutations: First Line or Second Line—Is There a Difference?
Authors: Mok Tony , Yang Jin-Ji , Lam Kwok-Chi
Published: February 2013

First-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is a standard treatment for patients with activating EGFR mutations. Six randomized studies have demonstrated consistent improvement in tumor response rate and progression-free survival over platinum-based combination chemotherapy. The only reason to consider EGFR TKI as second-line therapy is that none of the six comparative studies has shown improvement in overall survival, which can be explained by the high proportion of patients from the chemotherapy arm crossing over to the EGFR TKI arm on progression. It is true that patients with EGFR mutations may benefit from second-line EGFR TKI therapy, but we cannot conclude that the benefit is either equal to or inferior to first-line EGFR TKI therapy. To date, there are no direct comparative data between first- and second-line EGFR TKI in patients with activating EGFR mutations. Tumor response rates to second-line EGFR TKI have been inconsistent, which could potentially be explained by the impact of first-line chemotherapy on the abundance of tumor cells with activating EGFR mutations. However, numerous arguments, including assurance on drug exposure, improvement in quality of life, better tolerance by patients with poor performance status, and deferral of whole-brain radiation therapy for patients with brain metastasis, support the general application of first-line EGFR TKI.
Computed Tomography Screening for Lung Cancer: Has It Finally Arrived? Implications of the National Lung Screening Trial
Authors: Aberle Denise R. , Abtin Fereidoun , Brown Kathleen
Published: February 2013

The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer–specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.
Autologous and Allogeneic Stem-Cell Transplantation for Transformed Follicular Lymphoma: A Report of the Canadian Blood and Marrow Transplant Group
Authors: Villa Diego , Crump Michael , Panzarella Tony , Savage Kerry J. , Toze Cynthia L. , Stewart Douglas A. , MacDonald David A. , Buckstein Rena , Lee Christina , Alzahrani Mohsen , Rubinger Morel , Foley Ronan , Xenocostas Anargyros , Sabloff Mitchell , Muccilli Alexandra , Chua Neil , Couture Felix , Larouche Jean-François , Cohen Sandra , Connors Joseph M. , Ambler Kimberley , Al-Tourah Abdulwahab , Ramadan Khaled M. , Kuruvilla John
Published: February 2013

Purpose

To determine whether autologous (auto) or allogeneic (allo) stem-cell transplantation (SCT) improves outcome in patients with transformed follicular lymphoma compared with rituximab-containing chemotherapy alone.

Patients and Methods

This was a multicenter cohort study of patients with follicular lymphoma and subsequent biopsy-proven aggressive histology transformation. Patient, treatment, and outcome data were collected from each transplantation center and combined for analysis. A separate control group was composed of patients with transformation treated with rituximab-containing chemotherapy but not SCT. The primary end point was overall survival (OS) after transformation.

Results

One hundred seventy-two patients were identified: 22 (13%) treated with alloSCT, 97 (56%) with autoSCT, and 53 (31%) with rituximab-containing chemotherapy. Five-year OS after transformation was 46% for patients treated with alloSCT, 65% with autoSCT, and 61% with rituximab-containing chemotherapy (P = .24). Five-year progression-free survival (PFS) after transformation was 46% for those treated with alloSCT, 55% with autoSCT, and 40% with rituximab-containing chemotherapy (P = .12). In multivariate analysis, patients treated with autoSCT had improved OS compared with those who received rituximab-containing chemotherapy (hazard ratio [HR], 0.13; 95% CI, 0.05 to 0.34; P < .001). On the other hand, there was no OS difference between those treated with alloSCT and rituximab-containing chemotherapy (HR, 0.44; 95% CI, 0.16 to 1.24; P = .12). OS and PFS after SCT were similar between those treated with autoSCT and alloSCT. Five-year transplantation-related mortality was 23% for those treated with alloSCT and 5% for autoSCT.

Conclusion

Patients undergoing autoSCT had better outcomes than those treated with rituximab-containing chemotherapy alone. AlloSCT did not improve outcome compared with rituximab-containing chemotherapy and was associated with clinically significant toxicity.
ALK in Lung Cancer: Past, Present, and Future
Authors: Shaw Alice T. , Engelman Jeffrey A.
Published: February 2013

In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non–small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers.
Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies
Authors: Li Tianhong , Kung Hsing-Jien , Mack Philip C. , Gandara David R.
Published: February 2013

Substantial advances have been made in understanding critical molecular and cellular mechanisms driving tumor initiation, maintenance, and progression in non–small-cell lung cancer (NSCLC). Over the last decade, these findings have led to the discovery of a variety of novel drug targets and the development of new treatment strategies. Already, the standard of care for patients with advanced-stage NSCLC is shifting from selecting therapy empirically based on a patient's clinicopathologic features to using biomarker-driven treatment algorithms based on the molecular profile of a patient's tumor. This approach is currently best exemplified by treating patients with NSCLC with first-line tyrosine kinase inhibitors when their cancers harbor gain-of-function hotspot mutations in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. These genotype-based targeted therapies represent the first step toward personalizing NSCLC therapy. Recent technology advances in multiplex genotyping and high-throughput genomic profiling by next-generation sequencing technologies now offer the possibility of rapidly and comprehensively interrogating the cancer genome of individual patients from small tumor biopsies. This advance provides the basis for categorizing molecular-defined subsets of patients with NSCLC in whom a growing list of novel molecularly targeted therapeutics are clinically evaluable and additional novel drug targets can be discovered. Increasingly, practicing oncologists are facing the challenge of determining how to select, interpret, and apply these new genetic and genomic assays. This review summarizes the evolution, early success, current status, challenges, and opportunities for clinical application of genotyping and genomic tests in therapeutic decision making for NSCLC.
Harnessing the Immune System for the Treatment of Non–Small-Cell Lung Cancer
Authors: Brahmer Julie R.
Published: February 2013

Over the last several years, new therapeutic targets have emerged in immunotherapy, particularly the immune checkpoint pathways. Blocking inhibitory pathways via monoclonal antibodies, such as the anti–cytotoxic T-lymphocyte antigen-4 antibody (ipilimumab), anti–programmed cell death-1 antibody (BMS-936558), and anti–programmed cell death-1 ligand antibody (BMS-936559), has the ability to break down the shield that tumors co-opt for their defense. Vaccines are able to help the immune system develop immune memory that can have long-lasting, tumor-specific effects. Newer vaccines, particularly the tumor cell vaccine, belagenpumatucel-L, and the antigen-specific vaccines, melanoma-associated antigen-A3, liposomal BLP-25, TG4010, and recombinant human epidermal growth factor, are being evaluated in some of the largest trials ever attempted in lung cancer therapy. These therapies alone or in combination may hold the key to making immunotherapy a reality in the treatment of lung cancer.
Specialized progenitors and regeneration
Authors: Reddien Peter W.
Published: February 2013

Planarians are flatworms capable of regenerating all body parts. Planarian regeneration requires neoblasts, a population of dividing cells that has been studied for over a century. Neoblast progeny generate new cells of blastemas, which are the regenerative outgrowths at wounds. If the neoblasts comprise a uniform population of cells during regeneration (e.g. they are all uncommitted and pluripotent), then specialization of new cell types should occur in multipotent, non-dividing neoblast progeny cells. By contrast, recent data indicate that some neoblasts express lineage-specific transcription factors during regeneration and in uninjured animals. These observations raise the possibility that an important early step in planarian regeneration is the specialization of neoblasts to produce specified rather than naïve blastema cells.
Functional dissection of the paired domain of Pax6 reveals molecular mechanisms of coordinating neurogenesis and proliferation
Authors: Walcher Tessa , Xie Qing , Sun Jian , Irmler Martin , Beckers Johannes , Öztürk Timucin , Niessing Dierk , Stoykova Anastassia , Cvekl Ales , Ninkovic Jovica , Götz Magdalena
Published: February 2013

To achieve adequate organ development and size, cell proliferation and differentiation have to be tightly regulated and coordinated. The transcription factor Pax6 regulates patterning, neurogenesis and proliferation in forebrain development. The molecular basis of this regulation is not well understood. As the bipartite DNA-binding paired domain of Pax6 regulates forebrain development, we examined mice with point mutations in its individual DNA-binding subdomains PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C). This revealed distinct roles in regulating proliferation in the developing cerebral cortex, with the PAI and RED subdomain mutations reducing and increasing, respectively, the number of mitoses. Conversely, neurogenesis was affected only by the PAI subdomain mutation, phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression profiling identified molecularly discrete signatures of Pax6Leca4 and Pax6Leca2 mutations. Comparison to Pax6 targets identified by chromatin immunoprecipitation led to the identification and functional characterization of distinct DNA motifs in the promoters of target genes dysregulated in the Pax6Leca2 or Pax6Leca4 mutants, further supporting the distinct regulatory functions of the DNA-binding subdomains. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing particular subdomains to coordinate patterning, neurogenesis and proliferation simultaneously.
Spectrum of neurological manifestations in dengue virus infection in Northwest India
Authors: Koshy Jency Maria , Joseph Deepa Mary , John Mary , Mani Anna , Malhotra Nitin , Abraham George M , Pandian Jeyaraj
Published: February 2013

The objective of this study was to study the spectrum of neurological manifestations in patients with dengue infection. This was a prospective study undertaken at the Departments of Medicine and Neurology, Christian Medical College, Ludhiana, India. All patients diagnosed with dengue fever during an epidemic (1 September 2010–31 December 2010) were screened for neurological manifestations. There were a total of 799 patients with dengue infection. Neurological manifestations were present in 21 (2.63%),19 of whom were men with a mean age of 33.7 ± 13.9 years. The neurological diagnoses were hypokalaemia with: quadriparesis (7); myositis (4); encephalopathy (4); Guillain–Barre syndrome (2); acute disseminated encephalomyelitis (2); lumbosacral plexopathy (1); and intracranial haemorrhage (1). Three of these patients died. Clinicians should be aware that neurological manifestations in dengue fever are not uncommon.
Noninvasive assessment of hypoxia with 3-[18F]-fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO): a PET study in two experimental models of human glioma
Authors: Corroyer-Dulmont Aurélien , Pérès Elodie A. , Petit Edwige , Durand Lucile , Marteau Léna , Toutain Jérôme , Divoux Didier , Roussel Simon , MacKenzie Eric T. , Barré Louisa , Bernaudin Myriam , Valable Samuel
Published: February 2013

Despite multiple advances in cancer therapies, patients with glioblastoma (GBM) still have a poor prognosis. Numerous glioma models are used not only for the development of innovative therapies but also to optimize conventional ones. Given the significance of hypoxia in drug and radiation resistance and that hypoxia is widely observed among GBM, the establishment of a reliable method to map hypoxia in preclinical human models may contribute to the discovery and translation of future and more targeted therapies. The aim of this study was to compare the hypoxic status of two commonly used human orthotopic glioma models (U87 and U251) developed in rats and studied by noninvasive hypoxia imaging with 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol-micro-positron emission tomography ([18F]-FMISO-μPET). In parallel, because of the relationships between angiogenesis and hypoxia, we used magnetic resonance imaging (MRI), histology, and immunohistochemistry to characterize the tumoral vasculature. Although all tumors were detectable in T2-weighted MRI and 2-deoxy-2-[18F]fluoro-d-glucose-μPET, only the U251 model exhibited [18F]-FMISO uptake. Additionally, the U251 tumors were less densely vascularized than U87 tumors. Our study demonstrates the benefits of noninvasive imaging of hypoxia in preclinical models to define the most reliable one for translation of future therapies to clinic based on the importance of intratumoral oxygen tension for the efficacy of chemotherapy and radiotherapy.
Optimum CNT Concentration and Bath Temperature for Maximum Heat Transfer Rate during Quenching in CNT Nanofluids
Authors: Babu K. , Prasanna Kumar T. S.
Published: February 2013

This paper utilizes the experimental and numerical results obtained during quenching of stainless steel (SS) probes in carbon nanotube (CNT) nanofluids to arrive at an optimum CNT concentration and bath temperature for maximum quenching heat transfer rate. The individual effect of CNT concentration and bath temperature on the quenching heat transfer rate has recently been published by the authors. The objective of this work is to study the combined effect of CNT concentration and bath temperature on the heat transfer rate during quenching. For this purpose, CNT nanofluids were prepared by suspending chemically treated CNTs in de-ionized (DI) water without any surfactant at 0.50 and 0.75 wt. % of CNTs. Cylindrical quench probes made of SS 304L with a diameter of 20 mm and an aspect ratio of 2.5 were quenched in the CNT nanofluids by maintaining at 30, 40, and 50°C using an external water bath. The recorded time-temperature data during quenching were used as input and the heat flux and temperature at the quenched surface were estimated based on the inverse heat conduction (IHC) method. The computed boiling curves during quenching were used in conjunction with the boiling curves published in literature to arrive at an optimum CNT concentration and bath temperature for maximum heat transfer rates. The computational results showed that the peak heat flux during quenching of SS probes in CNT nanofluids increased when the CNT nanofluid was maintained at 40 than at 30°C and it started decreasing with further increase in the bath temperature irrespective of the CNT concentration. The enhanced heat transfer performance of CNT nanofluid at a slightly higher temperature during quenching is attributed to the enhanced Brownian motion of CNTs in nanofluid.
Preparation and Characterization of Surfactant Coated Ce-Zr Nanoparticles and Nanofuel
Authors: Sharma Rajiv , Kanagaraj S.
Published: February 2013

The use of the oxygen storing capacity (OSC) of CeO2 to enhance the conditioning of engine exhaust is being explored as a means to reduce the harmful products of emission. A doping agent, Zr, is used to further improve ceria's OSC and thermal stability. In this study, a high OSC endowed cerium-zirconium mixed-oxide (Ce0.6Zr0.4O2) three-way catalyst (TWC) was synthesized using a surfactant assisted co-precipitation method, and a stable suspension of the mixed oxide in diesel was prepared. The characterization of the mixed oxide and nanofuel was done using different analytical techniques, and the formation of a solid solution of the mixed oxide was confirmed. A stable dispersion of mixed oxide nanoparticles in diesel was achieved with the use of a mixed alkyl chain length surfactant. The thermal conductivity of the nanofuel did not show any significant increase with an increase in TWC concentration, and the calorific value of the nanofuel decreased. It is concluded that the cerium-zirconium mixed-oxide has a much higher OSC than pure ceria and could be potentially be used for better combustion of fuel in engines.
Thermal Conductivity and Rheological Behaviour of Al-alloy Dispersed Ethylene Glycol Based Nanofluids
Authors: Paul Gayatri , Philip John , Raj Baldev , Das Prasanta Kumar , Manna Indranil
Published: February 2013

Al-alloy (Al-5 wt. %Zn and Al-5 wt. %Si) nanoparticle dispersed (0.01–2.00 vol. %) ethylene glycol based nanofluids are prepared by a two-step process. Prior to dispersing in ethylene glycol by magnetic stirring and ultrasonication the Al-alloy nanoparticles synthesized by mechanical alloying are characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area diffraction (SAD), and energy dispersive spectroscopy (EDS) to analyze the identity, size, shape, and purity of the powder. A maximum thermal conductivity enhancement of 16 % for Al-5 wt. %Zn and 13 % for Al-5 wt. %Si dispersed nanofluids are observed at 0.1 vol. % of nanoparticle concentrations. Rheological studies of nanofluids show interesting findings as the viscosity of both types of nanofluids are observed to exhibit values lower than that of base fluid at lower concentrations and higher at higher concentrations. Maximum enhancement of viscosity up to 180 % for Al-5 wt. %Si and 120 % for Al-5 wt. %Zn dispersed nanofluids are observed at 2.0 vol. % concentration.
Effect of Addition of Aluminum Nanoparticles on Cooling Performance and Quench Severity of Water during Immersion Quenching
Authors: Ramesh G. , Prabhu K. Narayan
Published: February 2013

In the present work, the effect of the addition of aluminum nano-particles in concentrations varying from 0.001 to 0.5 vol. % on the cooling performance and quench severity of water during immersion quenching is investigated. The results of cooling curve analyses show that an increase in nanoparticle concentration increased the cooling rates at critical temperatures up to 0.05 vol. % and decreased them thereafter. The transition from the vapor blanket stage to the nucleate boiling stage was also altered by quenching in nanofluids. A finite difference heat transfer program was employed to generate cooling curves at different values of heat transfer coefficient from thermo-physical properties of the quench probe material. A Grossmann H quench severity versus cooling rate curve was established, and from this curve, the H factors of prepared nanofluids were estimated. An increase in nanoparticle concentration up to 0.05 vol. % resulted in an increase of the H value of water from 63 m−1 to 93 m−1, and any further increase in the concentration of nanoparticles resulted in a decrease in H. The results suggest both the enhancement and the deterioration of the cooling performance of water by the addition of aluminum nanoparticles.
Genomic Prediction of Northern Corn Leaf Blight Resistance in Maize with Combined or Separated Training Sets for Heterotic Groups
Authors: Technow Frank , Bürger Anna , Melchinger Albrecht E
Published: February 2013

Northern corn leaf blight (NCLB), a severe fungal disease causing yield losses worldwide, is most effectively controlled by resistant varieties. Genomic prediction could greatly aid resistance breeding efforts. However, the development of accurate prediction models requires large training sets of genotyped and phenotyped individuals. Maize hybrid breeding is based on distinct heterotic groups that maximize heterosis (the dent and flint groups in Central Europe). The resulting allocation of resources to parallel breeding programs challenges the establishment of sufficiently sized training sets within groups. Therefore, using training sets combining both heterotic groups might be a possibility of increasing training set sizes and thereby prediction accuracies. The objectives of our study were to assess the prospect of genomic prediction of NCLB resistance in maize and the benefit of a training set that combines two heterotic groups. Our data comprised 100 dent and 97 flint lines, phenotyped for NCLB resistance per se and genotyped with high-density single-nucleotide polymorphism marker data. A genomic BLUP model was used to predict genotypic values. Prediction accuracies reached a maximum of 0.706 (dent) and 0.690 (flint), and there was a strong positive response to increases in training set size. The use of combined training sets led to significantly greater prediction accuracies for both heterotic groups. Our results encourage the application of genomic prediction in NCLB-resistance breeding programs and the use of combined training sets.
Fine-Scale Mapping of the Nasonia Genome to Chromosomes Using a High-Density Genotyping Microarray
Authors: Desjardins Christopher A , Gadau Jürgen , Lopez Jacqueline A , Niehuis Oliver , Avery Amanda R , Loehlin David W , Richards Stephen , Colbourne John K , Werren John H
Published: February 2013

Nasonia, a genus of four closely related parasitoid insect species, is a model system for genetic research. Their haplodiploid genetics (haploid males and diploid females) and interfertile species are advantageous for the genetic analysis of complex traits and the genetic basis of species differences. A fine-scale genomic map is an important tool for advancing genetic studies in this system. We developed and used a hybrid genotyping microarray to generate a high-resolution genetic map that covers 79% of the sequenced genome of Nasonia vitripennis. The microarray is based on differential hybridization of species-specific oligos between N. vitripennis and Nasonia giraulti at more than 20,000 markers spanning the Nasonia genome. The map places 729 scaffolds onto the five linkage groups of Nasonia, including locating many smaller scaffolds that would be difficult to map by other means. The microarray was used to characterize 26 segmental introgression lines containing chromosomal regions from one species in the genetic background of another. These segmental introgression lines have been used for rapid screening and mapping of quantitative trait loci involved in species differences. Finally, the microarray is extended to bulk-segregant analysis and genotyping of other Nasonia species combinations. These resources should further expand the usefulness of Nasonia for studies of the genetic basis and architecture of complex traits and speciation.
Regulation of the S-Locus Receptor Kinase and Self-Incompatibility inArabidopsis thaliana
Authors: Strickler Susan R , Tantikanjana Titima , Nasrallah June B
Published: February 2013

Intraspecific mate selectivity often is enforced by self-incompatibility (SI), a barrier to self-pollination that inhibits productive pollen-pistil interactions. In the Brassicaceae, SI specificity is determined by two highly-polymorphic proteins: the stigmatic S-locus receptor kinase (SRK) and its pollen coat-localized ligand, the S-locus cysteine-rich protein (SCR). Arabidopsis thaliana is self fertile, but several of its accessions can be made to express SI, albeit to various degrees, by transformation with functional SRK-SCR gene pairs isolated from its close self-incompatible relative, Arabidopsis lyrata. Here, we use a newly identified induced mutation that suppresses the SI phenotype in stigmas of SRK-SCR transformants of the Col-0 accession to investigate the regulation of SI and the SRK transgene. This mutation disrupts NRPD1a, a gene that encodes a plant-specific nuclear RNA polymerase required for genomic methylation and production of some types of silencing RNAs. We show that NRPD1a, along with the RNA-dependent RNA polymerase RDR2, is required for SI in some A. thaliana accessions. We also show that Col-0 nrpd1a mutants exhibit decreased accumulation of SRK transcripts in stigmas, which is not, however, responsible for loss of SI in these plants. Together, our analysis of the nrpd1a mutation and of SRK promoter activity in various accessions reveals that the SRK transgene is subject to several levels of regulation, which vary substantially by tissue type and by accession. This study thus helps explain the well-documented differences in expression of SI exhibited by SRK-SCR transformants of different A. thaliana accessions.
Genetic and Physiological Characterization of Two Clusters of Quantitative Trait Loci Associated With Seed Dormancy and Plant Height in Rice
Authors: Ye Heng , Beighley Donn H , Feng Jiuhuan , Gu Xing-You
Published: February 2013

Seed dormancy and plant height have been well-studied in plant genetics, but their relatedness and shared regulatory mechanisms in natural variants remain unclear. The introgression of chromosomal segments from weedy into cultivated rice (Oryza sativa) prompted the detection of two clusters (qSD1-2/qPH1 and qSD7-2/qPH7) of quantitative trait loci both associated with seed dormancy and plant height. Together, these two clusters accounted for >96% of the variances for plant height and ~71% of the variances for germination rate in an isogenic background across two environments. On the initial introgression segments, qSD1-2/qPH1 was dissected genetically from OsVp1 for vivipary and qSD7-2/qPH7 separated from Sdr4 for seed dormancy. The narrowed qSD1-2/qPH1 region encompasses the semidwarf1 (sd1) locus for gibberellin (GA) biosynthesis. The qSD1-2/qPH1 allele from the cultivar reduced germination and stem elongation and the mutant effects were recovered by exogenous GA, suggesting that sd1 is a candidate gene of the cluster. In contrast, the effect-reducing allele at qSD7-2/qPH7 was derived from the weedy line; this allele was GA-insensitive and blocked GA responses of qSD1-2/qPH1, including the transcription of a GA-inducible α-amylase gene in imbibed endosperm, suggesting that qSD7-2/qPH7 may work downstream from qSD1-2/qPH1 in GA signaling. Thus, this research established the seed dormancy-plant height association that is likely mediated by GA biosynthesis and signaling pathways in natural populations. The detected association contributed to weed mimicry for the plant stature in the agro-ecosystem dominated by semidwarf cultivars and revealed the potential benefit of semidwarf genes in resistance to preharvest sprouting.
Genetic Control and Comparative Genomic Analysis of Flowering Time in Setaria (Poaceae)
Authors: Mauro-Herrera Margarita , Wang Xuewen , Barbier Hugues , Brutnell Thomas P , Devos Katrien M , Doust Andrew N
Published: February 2013

We report the first study on the genetic control of flowering in Setaria, a panicoid grass closely related to switchgrass, and in the same subfamily as maize and sorghum. A recombinant inbred line mapping population derived from a cross between domesticated Setaria italica (foxtail millet) and its wild relative Setaria viridis (green millet), was grown in eight trials with varying environmental conditions to identify a small number of quantitative trait loci (QTL) that control differences in flowering time. Many of the QTL across trials colocalize, suggesting that the genetic control of flowering in Setaria is robust across a range of photoperiod and other environmental factors. A detailed comparison of QTL for flowering in Setaria, sorghum, and maize indicates that several of the major QTL regions identified in maize and sorghum are syntenic orthologs with Setaria QTL, although the maize large effect QTL on chromosome 10 is not. Several Setaria QTL intervals had multiple LOD peaks and were composed of multiple syntenic blocks, suggesting that observed QTL represent multiple tightly linked loci. Candidate genes from flowering time pathways identified in rice and Arabidopsis were identified in Setaria QTL intervals, including those involved in the CONSTANS photoperiod pathway. However, only three of the approximately seven genes cloned for flowering time in maize colocalized with Setaria QTL. This suggests that variation in flowering time in separate grass lineages is controlled by a combination of conserved and lineage specific genes.
Origin and Evolution of Dishevelled
Authors: Dillman Adler R , Minor Paul J , Sternberg Paul W
Published: February 2013

Dishevelled (Dsh or Dvl) is an important signaling protein, playing a key role in Wnt signaling and relaying cellular information for several developmental pathways. Dsh is highly conserved among metazoans and has expanded into a multigene family in most bilaterian lineages, including vertebrates, planarians, and nematodes. These orthologs, where explored, are known to have considerable overlap in function, but evidence for functional specialization continues to mount. We performed a comparative analysis of Dsh across animals to explore protein architecture and identify conserved and divergent features that could provide insight into functional specialization with an emphasis on invertebrates, especially nematodes. We find evidence of dynamic evolution of Dsh, particularly among nematodes, with taxa varying in ortholog number from one to three. We identify a new domain specific to some nematode lineages and find an unexpected nuclear localization signal conserved in many Dsh orthologs. Our findings raise questions of protein evolution in general and provide clues as to how animals have dealt with the complex intricacies of having a protein, such as Dsh, act as a central messenger hub connected to many different and vitally important pathways. We discuss our findings in the context of functional specialization and bring many testable hypotheses to light.