bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of active immunization against GnRH on testosterone concentration, libido and sperm quality in mature AI boars
Authors: Bilskis Ronaldas , Sutkeviciene Neringa , Riskeviciene Vita , Januskauskas Aloyzas , Zilinskas Henrikas
Published: May 2012

Background

The aim of the present study was to investigate the efficacy of the Improvac on testosterone concentration in blood serum, sexual behavior and sperm quality in matured AI boars. A total of nine Danish Landrace AI boars were included in the analysis.

Methods

The trial period lasted for 15 weeks and was divided into four periods: Control period: three weeks before vaccination; Period I – four weeks after first vaccination; Period II – four weeks after second vaccination, Period III – four weeks after third vaccination. Blood and sperm samples were collected at weekly intervals. Freshly collected sperm samples were analyzed.

Results

Testosterone concentration correlated with libido (r = 0.531; p < 0.001), volume of ejaculate (r = 0.324; p < 0.001) and the percentage of morphologically normal spermatozoa (r = 0.207; p < 0.05). Testosterone concentration rised significantly (p < 0.05) in 5–6 week of trial, e. i. after the first dose of Improvac and after this peak the level of testosterone further progressively decreased (p < 0.05).

Conclusions

Results from this study indicate that active immunization of sexually matured boars against GnRH has negative impact on testosterone concentration, sexual behavior, volume of ejaculate and total number of normal spermatozoa in ejaculate.
MicroRNA profiling of a CD133+spheroid-forming subpopulation of the OVCAR3 human ovarian cancer cell line
Authors: Nam Eun Ji , Lee Maria , Yim Ga Won , Kim Jae Hoon , Kim Sunghoon , Kim Sang Wun , Kim Young Tae
Published: May 2012

Background

Cancer stem cells (CSCs) are thought to be a source of tumor recurrence due to their stem cell-like properties. MicroRNAs (miRNAs) regulate both normal stem cells and CSCs, and dysregulation of miRNAs has an important role in tumorigenesis. Cluster of differentiation (CD) 133+and spheroid formation have been reported to be one of the main features of ovarian CSCs. Therefore, we determined the miRNA expression profile of a CD133+spheroid-forming subpopulation of the OVCAR3 human ovarian cancer cell line.

Methods

Initially, we confirmed the enrichment of the OVCAR3 CD133 subpopulation by evaluatingin vitroanchorage-independent growth. After obtaining a subpopulation of CD133+OVCAR3 cells with > 98% purity via cell sorting, miRNA microarray and real-time reverse transcription-polymerase chain reaction (RT-PCR) were performed to evaluate its miRNA profile.

Results

We found 37 differentially expressed miRNAs in the CD133+spheroid-forming subpopulation of OVCAR3 cells, 34 of which were significantly up-regulated, includingmiR-205, miR-146a, miR-200a, miR-200b, andmiR-3,and 3 of which were significantly down-regulated, includingmiR-1202andmiR-1181.

Conclusions

Our results indicate that dysregulation of miRNA may play a role in the stem cell-like properties of ovarian CSCs.
A shot in the genome: how accurately do shotgun 454 sequences represent a genome?
Authors: Meglécz Emese , Pech Nicolas , Gilles André , Martin Jean-François , Gardner Michael G
Published: May 2012

Background

Next generation sequencing (NGS) provides a valuable method to quickly obtain sequence information from non-model organisms at a genomic scale. In principle, if sequencing is not targeted for a genomic region or sequence type (e.g. coding region, microsatellites) NGS reads can be used as a genome snapshot and provide information on the different types of sequences in the genome. However, no study has ascertained if a typical 454 dataset of low coverage (1/4-1/8 of a PicoTiter plate leading to generally less than 0.1x of coverage) represents all parts of genomes equally.

Findings

Partial genome shotgun sequencing of total DNA (without enrichment) on a 454 NGS platform was used to obtain reads of Apis mellifera (454 reads hereafter). These 454 reads were compared to the assembled chromosomes of this species in three different aspects: (i) dimer and trimer compositions, (ii) the distribution of mapped 454 sequences along the chromosomes and (iii) the numbers of different classes of microsatellites. Highly significant chi-square tests for all three types of analyses indicated that the 454 data is not a perfect random sample of the genome. Only the number of 454 reads mapped to each of the 16 chromosomes and the number of microsatellites pooled by motif (repeat unit) length was not significantly different from the expected values. However, a very strong correlation (correlation coefficients greater than 0.97) was observed between most of the 454 variables (the number of different dimers and trimers, the number of 454 reads mapped to each chromosome fragments of one Mb, the number of 454 reads mapped to each chromosome, the number of microsatellites of each class) and their corresponding genomic variables.

Conclusions

The results of chi square tests suggest that 454 shotgun reads cannot be regarded as a perfect representation of the genome especially if the comparison is done on a finer scale (e.g. chromosome fragments instead of whole chromosomes). However, the high correlation between 454 and genome variables tested indicate that a high proportion of the variability of 454 variables is explained by their genomic counterparts. Therefore, we conclude that using 454 data to obtain information on the genome is biologically meaningful.
Oncolytic adenovirus armed with IL-24 Inhibits the growth of breast cancer in vitro and in vivo
Authors: Zhu Wei , Wei Lai , Zhang Hongwei , Chen Junxue , Qin Xinyu
Published: May 2012

Background

Interleukin-24 (IL-24) is a cytokine that belongs to the IL-10 family. It can selectively induce cancer cell apoptosis which has been utilized as a cancer gene therapy strategy.

Methods

A recombinant type five adenovirus containing IL-24 gene (designated CNHK600-IL24) was constructed, whose replication is activated only in tumor cells. The replication of CNHK600-IL24 in breast tumor cells and fibroblasts were assessed by TCID50 and MTT assay; the secretion of IL-24 was measured by ELISA and western blotting. The in vivo anti-tumor effect of CNHK600-IL24 was investigated in nude mice carrying orthotopic or metastatic breast tumor.

Results

We observed that CNHK600-IL24 could replicate efficiently and resulted in high level IL-24 expression and massive cell death in human breast cancer cell MDA-MB-231 but not in normal fibroblast cell MRC-5. In addition, orthotopic breast tumor growth in the nude mice model was significantly suppressed when CNHK600-IL24 was administered. In the metastatic model generated by tail vein injection, CNHK600-IL24 virotherapy significantly improved survival compared with the same virus expressing EGFP (median survival CNHK600-IL24, 55 days vs. CNHK600-EGFP, 41 day, p < 0.05 Mantal-Cox test). A similar phenomenon was observed in the metastatic model achieved by left ventricular injection as suggested by in vivo luminescence imaging of tumor growth.

Conclusion

The oncolytic adenovirus armed with IL-24, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of breast cancer.
Overview of ultrasound usage trends in orthopedic and sports physiotherapy
Authors: de Brito Vieira Wouber Herickson , Aguiar Kardec Alecxandro , da Silva Kimberly Moreira , Canela Pablo Miranda , da Silva Flávio Santos , Abreu Bento João
Published: May 2012

Background

The purpose of this study is to examine current beliefs about the use, the clinical importance, the theoretical fundamentals and the utilization criteria of therapeutic ultrasound (TUS) among physical therapists on the clinical practice in orthopedic and sports physiotherapy in Brazil.

Methods

A brief survey was developed based on previous studies and was sent to 55 physical therapists with advanced competency in orthopedics and sports physiotherapy. The questions addressed general topics about the professional profile and ultrasound usage and dosage.

Results

Our data show the wide availability and frequent use of TUS in this sample of physical therapists. TUS is used in distinct musculoskeletal injuries and/or disorders in both acute and chronic conditions. Muscles, tendons and ligaments represented the major structures where TUS is used. Questions on the basic theory of TUS demonstrated a lack of knowledge of the ultrasound physiological effects as well as its interaction with biological tissues and TUS absolute contraindication.

Conclusion

A Brazilian profile about the US usage and dosage in orthopedic and sports physiotherapy is presented and highlights the need for a continuous upgrading process and further research into its effects.
The 1027th target candidate in stroke: Will NADPH oxidase hold up?
Authors: Radermacher Kim A , Wingler Kirstin , Kleikers Pamela , Altenhöfer Sebastian , JR Hermans Johannes , Kleinschnitz Christoph , HHW Schmidt Harald
Published: May 2012

As recently reviewed, 1026 neuroprotective drug candidates in stroke research have all failed on their road towards validation and clinical translation, reasons being quality issues in preclinical research and publication bias. Quality control guidelines for preclinical stroke studies have now been established. However, sufficient understanding of the underlying mechanisms of neuronal death after stroke that could be possibly translated into new therapies is lacking. One exception is the hypothesis that cellular death is mediated by oxidative stress. Oxidative stress is defined as an excess of reactive oxygen species (ROS) derived from different possible enzymatic sources. Among these, NADPH oxidases (NOX1-5) stand out as they represent the only known enzyme family that has no other function than to produce ROS. Based on data from different NOX knockout mouse models in ischemic stroke, the most relevant isoform appears to be NOX4. Here we discuss the state-of-the-art of this target with respect to stroke and open questions that need to be addressed on the path towards clinical translation.
Drug therapy in patients with Parkinson’s disease
Authors: Müller Thomas
Published: May 2012

Parkinson`s disease (PD) is a progressive, disabling neurodegenerative disorder with onset of motor and non-motor features. Both reduce quality of life of PD patients and cause caregiver burden. This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other. MAO-B-Inhibitors, NMDA antagonists, dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD. This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms. These PD features predominantly result from non dopaminergic neurodegeneration. Autonomic features, such as seborrhea, hyperhidrosis, orthostatic syndrome, salivation, bladder dysfunction, gastrointestinal disturbances, and neuropsychiatric symptoms, such as depression, sleep disorders, psychosis, cognitive dysfunction with impaired execution and impulse control may appear. Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions, - side effects, and altered pharmacokinetic behaviour of applied compounds. Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms. This complicates the differentiation from the disease process itself and influences therapeutic options, which are often limited because of additional morbidity with necessary concomitant drug therapy.
Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
Authors: Moore Brenda D , Chakrabarty Paramita , Levites Yona , Kukar Tom L , Baine Ann-Marie , Moroni Tina , Ladd Thomas B , Das Pritam , Dickson Dennis W , Golde Todd E
Published: May 2012

Introduction

A hallmark of Alzheimer's disease (AD) is the presence of senile plaques composed of aggregated amyloid β (Aβ) peptides. Pathological aging (PA) is a postmortem classification that has been used to describe brains with plaque pathology similar in extent to AD, minimal cortical tau pathology, and no accompanying history of cognitive decline in the brain donor prior to death. PA may represent either a prodromal phase of AD, a benign form of Aβ accumulation, or inherent individual resistance to the toxic effects of Aβ accumulation. To attempt to distinguish between these possibilities we have systematically characterized Aβ peptides in a postmortem series of PA, AD and non-demented control (NDC) brains.

Methods

Aβ was sequentially extracted with tris buffered saline (TBS), radioimmunoprecipitation buffer (RIPA), 2% sodium dodecyl sulfate (SDS) and 70% formic acid (FA) from the pre-frontal cortex of 16 AD, eight PA, and six NDC patients. These extracts were analyzed by 1) a panel of Aβ sandwich ELISAs, 2) immunoprecipitation followed by mass spectrometry (IP/MS) and 3) western blotting. These studies enabled us to asses Aβ levels and solubility, peptide profiles and oligomeric assemblies.

Results

In almost all extracts (TBS, RIPA, 2% SDS and 70% FA) the average levels of Aβ1-40, Aβ1-42, Aβ total, and Aβx-42 were greatest in AD. On average, levels were slightly lower in PA, and there was extensive overlap between Aβ levels in individual PA and AD cases. The profiles of Aβ peptides detected using IP/MS techniques also showed extensive similarity between the PA and AD brain extracts. In select AD brain extracts, we detected more amino-terminally truncated Aβ peptides compared to PA patients, but these peptides represented a minor portion of the Aβ observed. No consistent differences in the Aβ assemblies were observed by western blotting in the PA and AD groups.

Conclusions

We found extensive overlap with only subtle quantitative differences between Aβ levels, peptide profiles, solubility, and SDS-stable oligomeric assemblies in the PA and AD brains. These cross-sectional data indicate that Aβ accumulation in PA and AD is remarkably similar. Such data would be consistent with PA representing a prodromal stage of AD or a resistance to the toxic effects of Aβ.
Can erosions on MRI of the sacroiliac joints be reliably detected in patients with ankylosing spondylitis? - A cross-sectional study
Authors: Weber Ulrich , Pedersen Susanne J , Østergaard Mikkel , Rufibach Kaspar , Lambert Robert GW , Maksymowych Walter P
Published: May 2012

Introduction

Erosions of the sacroiliac joints (SIJ) on pelvic radiographs of patients with ankylosing spondylitis (AS) are an important feature of the modified New York classification criteria. However, radiographic SIJ erosions are often difficult to identify. Recent studies have shown that erosions can be detected also on magnetic resonance imaging (MRI) of the SIJ early in the disease course before they can be seen on radiography. The goals of this study were to assess the reproducibility of erosion and related features, namely, extended erosion (EE) and backfill (BF) of excavated erosion, in the SIJ using a standardized MRI methodology.

Methods

Four readers independently assessed T1-weighted and short tau inversion recovery sequence (STIR) images of the SIJ from 30 AS patients and 30 controls (15 patients with non-specific back pain and 15 healthy volunteers) ≤45 years old. Erosions, EE, and BF were recorded according to standardized definitions. Reproducibility was assessed by percentage concordance among six possible reader pairs, kappa statistics (erosion as binary variable) and intraclass correlation coefficient (ICC) (erosion as sum score) for all readers jointly.

Results

SIJ erosions were detected in all AS patients and six controls by ≥2 readers. The median number of SIJ quadrants affected by erosion recorded by four readers in 30 AS patients was 8.6 in the iliac and 2.1 in the sacral joint portion (P < 0.0001). For all 60 subjects and for all four readers, the kappa value for erosion was 0.72, 0.73 for EE, and 0.63 for BF. ICC for erosion was 0.79, 0.72 for EE, and 0.55 for BF, respectively. For comparison, the kappa and ICC values for bone marrow edema were 0.61 and 0.93, respectively.

Conclusions

Erosions can be detected on MRI to a comparable degree of reliability as bone marrow edema despite the significant heterogeneity of their appearance on MRI.
Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis
Authors: Gonzalo Elena , Toldos Oscar , Martínez-Vidal María P , Ordoñez María C , Santiago Begoña , Fernández-Nebro Antonio , Loza Estíbaliz , García Isabel , León Myriam , Pablos José L , Galindo María
Published: May 2012

Introduction

Microthrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN.

Methods

Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data.

Results

Microthrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome.

Conclusions

Microthrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series.
Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy
Authors: Caudle Abigail S , Yu Tse-Kuan , Tucker Susan L , Bedrosian Isabelle , Litton Jennifer K , Gonzalez-Angulo Ana M , Hoffman Karen , Meric-Bernstam Funda , Hunt Kelly K , Buchholz Thomas A , Mittendorf Elizabeth A
Published: May 2012

Introduction

Breast cancers of different molecular subtypes have different survival rates. The goal of this study was to identify patients at high risk for local-regional recurrence according to response to neoadjuvant chemotherapy and surrogate markers of molecular subtypes in patients undergoing breast conserving therapy (BCT).

Methods

Clinicopathologic data from 595 breast cancer patients who received neoadjuvant chemotherapy and BCT from 1997 to 2005 were identified. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression determined by immunohistochemistry were used to construct the following subtypes: ER+ or PR+ and HER2- (hormone receptor (HR)+/HER2-; 52%), ER+ or PR+ and HER2+ (HR+/HER2+; 9%), ER- and PR- and HER2+ (HR-/HER2+; 7%) and ER- and PR- and HER2- (HR-/HER2-; 32%). Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used for multivariate analysis (MVA).

Results

After a median follow-up of 64 months, the five-year local-regional recurrence (LRR)-free survival rate for all patients was 93.8%. The five-year LRR-free survival rates varied by subtype: HR+/HER2- 97.0%, HR+/HER2+ 95.9%, HR-/HER2+ 86.5% and HR-/HER2- 89.5% (P = 0.001). In addition to subtype, clinical stage III disease (90% vs. 95% for I/II, P = 0.05), high nuclear grade (92% vs. 97% with low/intermediate grade, P = 0.03), presence of lymphovascular invasion (LVI) (89% vs. 95% in those without LVI, P = 0.02) and four or more positive lymph nodes on pathologic examination (87% vs. 95% with zero to three positive lymph nodes, P = 0.03) were associated with lower five-year LRR-free survival on univariate analysis. On MVA, HR-/HER2+ and HR-/HER2- subtypes and disease in four or more lymph nodes were associated with decreased LRR-free survival. A pathologic complete response (pCR) was associated with improved LRR-free survival.

Conclusions

Patients with HR+/HER2- and HR+/HER2+ subtypes had excellent LRR-free survival regardless of tumor response to neoadjuvant chemotherapy. Patients with HR-/HER2+ and HR-/HER2- subtypes with poor response to neoadjuvant chemotherapy had worse LRR-free survival after BCT. Additional study is needed to determine the impact of trastuzumab on local-regional control in HER2+ tumors. Our data suggest that patients with HR-/HER2- subtype tumors not achieving pCR may benefit from novel strategies to improve local-regional control.
A new approach for detecting low-level mutations in next-generation sequence data
Authors: Li Mingkun , Stoneking Mark
Published: May 2012

We propose a new method that incorporates population re-sequencing data, distribution of reads, and strand bias in detecting low-level mutations. The method can accurately identify low-level mutations down to a level of 2.3%, with an average coverage of 500×, and with a false discovery rate of less than 1%. In addition, we also discuss other problems in detecting low-level mutations, including chimeric reads and sample cross-contamination, and provide possible solutions to them.
A whole genome association study of mother-to-child transmission of HIV in Malawi
Authors: Joubert Bonnie R , Lange Ethan M , Franceschini Nora , Mwapasa Victor , North Kari E , Meshnick Steven R ,   the NIAID Center for HIV/AIDS Vaccine Immunology
Published: May 2012

Background

More than 300,000 children are newly infected with HIV each year, predominantly through mother-to-child transmission (HIV MTCT). Identification of host genetic traits associated with transmission may more clearly explain the mechanisms of HIV MTCT and further the development of a vaccine to protect infants from infection. Associations between transmission and a selection of genes or single nucleotide polymorphisms (SNP)s may give an incomplete picture of HIV MTCT etiology. Thus, this study employed a genome-wide association approach to identify novel variants associated with HIV MTCT.

Methods

We conducted a nested case-control study of HIV MTCT using infants of HIV(+) mothers, drawn from a cohort study of malaria and HIV in pregnancy in Blantyre, Malawi. Whole genome scans (650,000 SNPs genotyped using Illumina genotyping assays) were obtained for each infant. Logistic regression was used to evaluate the association between each SNP and HIV MTCT.

Results

Genotype results were available for 100 HIV(+) infants (at birth, 6, or 12 weeks) and 126 HIV(-) infants (at birth, 6, and 12 weeks). We identified 9 SNPs within 6 genes with a P-value < 5 × 10-5 associated with the risk of transmission, in either unadjusted or adjusted by maternal HIV viral load analyses. Carriers of the rs8069770 variant allele were associated with a lower risk of HIV MTCT (odds ratio = 0.27, 95% confidence interval = 0.14, 0.51), where rs8069770 is located within HS3ST3A1, a gene involved in heparan sulfate biosynthesis. Interesting associations for SNPs located within or near genes involved in pregnancy and development, innate immunological response, or HIV protein interactions were also observed.

Conclusions

This study used a genome-wide approach to identify novel variants associated with the risk of HIV MTCT in order to gain new insights into HIV MTCT etiology. Replication of this work using a larger sample size will help us to differentiate true positive findings.
H3K4me3 inversely correlates with DNA methylation at a large class of non-CpG-island-containing start sites
Authors: Balasubramanian Dheepa , Akhtar-Zaidi Batool , Song Lingyun , Bartels Cynthia F , Veigl Martina , Beard Lydia , Myeroff Lois , Guda Kishore , Lutterbaugh James , Willis Joseph , Crawford Gregory E , Markowitz Sanford D , Scacheri Peter C
Published: May 2012

Background

In addition to mutations, epigenetic silencing of genes has been recognized as a fundamental mechanism that promotes human carcinogenesis. To date, characterization of epigenetic gene silencing has largely focused on genes in which silencing is mediated by hypermethylation of promoter-associated CpG islands, associated with loss of the H3K4me3 chromatin mark. Far less is known about promoters lacking CpG-islands or genes that are repressed by alternative mechanisms.

Methods

We performed integrative ChIP-chip, DNase-seq, and global gene expression analyses in colon cancer cells and normal colon mucosa to characterize chromatin features of both CpG-rich and CpG-poor promoters of genes that undergo silencing in colon cancer.

Results

Epigenetically repressed genes in colon cancer separate into two classes based on retention or loss of H3K4me3 at transcription start sites. Quantitatively, of transcriptionally repressed genes that lose H3K4me3 in colon cancer (K4-dependent genes), a large fraction actually lacks CpG islands. Nonetheless, similar to CpG-island containing genes, cytosines located near the start sites of K4-dependent genes become DNA hypermethylated, and repressed K4-dependent genes can be reactivated with 5-azacytidine. Moreover, we also show that when the H3K4me3 mark is retained, silencing of CpG island-associated genes can proceed through an alternative mechanism in which repressive chromatin marks are recruited.

Conclusions

H3K4me3 equally protects from DNA methylation at both CpG-island and non-CpG island start sites in colon cancer. Moreover, the results suggest that CpG-rich genes repressed by loss of H3K4me3 and DNA methylation represent special instances of a more general epigenetic mechanism of gene silencing, one in which gene silencing is mediated by loss of H3K4me3 and methylation of non-CpG island promoter-associated cytosines.
ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially
Authors: Vantaggiato Chiara , Formentini Ivan , Bondanza Attilio , Bonini Chiara , Naldini Luigi , Brambilla Riccardo
Published: May 2012

Background

The mitogen-activated protein (MAP) kinases p44ERK1 and p42ERK2 are crucial components of the regulatory machinery underlying normal and malignant cell proliferation. A currently accepted model maintains that ERK1 and ERK2 are regulated similarly and contribute to intracellular signaling by phosphorylating a largely common subset of substrates, both in the cytosol and in the nucleus.

Results

Here, we show that ablation of ERK1 in mouse embryo fibroblasts and NIH 3T3 cells by gene targeting and RNA interference results in an enhancement of ERK2-dependent signaling and in a significant growth advantage. By contrast, knockdown of ERK2 almost completely abolishes normal and Ras-dependent cell proliferation. Ectopic expression of ERK1 but not of ERK2 in NIH 3T3 cells inhibits oncogenic Ras-mediated proliferation and colony formation. These phenotypes are independent of the kinase activity of ERK1, as expression of a catalytically inactive form of ERK1 is equally effective. Finally, ectopic expression of ERK1 but not ERK2 is sufficient to attenuate Ras-dependent tumor formation in nude mice.

Conclusion

These results reveal an unexpected interplay between ERK1 and ERK2 in transducing Ras-dependent cell signaling and proliferation. Whereas ERK2 seems to have a positive role in controlling normal and Ras-dependent cell proliferation, ERK1 probably affects the overall signaling output of the cell by antagonizing ERK2 activity.
Editorial: (CD)40 winks to prevent CD8+ T cell lethargy
Authors: Bullock Timothy N J
Published: May 2012

Discussion of how CD40 stimulation of DC and/or CD8+ T cells affects primary and memory CD8+ T cell responses.
Timing of Voice Breaking in Males Associated with Growth and Weight Gain Across the Life Course
Authors: Ong Ken K. , Bann David , Wills Andrew K. , Ward Kate , Adams Judith E. , Hardy Rebecca , Kuh Diana ,   on behalf of the National Survey of Health and Development Scientific and Data Collection Team
Published: May 2012

Background:

In contrast to the many studies in females, there are few data in males on the relationships between childhood growth and weight gain and the timing of pubertal maturation and its relevance to adult body mass index (BMI) and body composition.

Methods:

A total of 2008 males in the 1946 British Birth Cohort Study had assessment of pubertal status including voice-breaking status (no change, starting, or complete) at age 14 yr. These responses were related to growth measurements at birth (weight only) and at 2, 4, 6, 7, 11, 14, 20, 26, 36, 43, 53, and 60–64 yr. Body composition was assessed by dual-energy x-ray absorptiometry at 60–64 yr.

Results:

Males with more advanced voice-breaking status at age 14 yr had similar birth weights compared with other males; they showed faster weight gain from 0–2 yr and had higher mean weight and BMI at age 2 yr. Subsequently, they continued to accelerate in weight and BMI, and also in height, and maximum differences in body size were seen at age 14 yr. Adult height did not differ between groups, but males with advanced voice breaking had higher adult BMI and greater whole-body lean mass and greater android fat mass at 60–64 yr.

Conclusion:

Similar to females with earlier menarche, the trajectory to earlier sexual maturation in males is manifested by faster early postnatal growth and weight gain and leads to higher adult BMI. Timing of pubertal maturation has potential relevance to adult disease risks in males. We also describe conditional height difference in sd score as a proxy marker of pubertal timing in males.
Theater and Media before “New” Media
Authors: Harries Martin
Published: May 2012

Harries looks back at Samuel Beckett’s complex intermedial experiments to historicize the question of theater’s relationship to “new” media, and argue for a more nuanced theorization of theater’s exchanges with other media, and theater’s status as a medium in itself.
Theater Is Media
Authors: Bay-Cheng Sarah
Published: May 2012

In her essay-manifesto, Sarah Bay-Cheng outlines principles for a new historiography of performance taking into account the multiple layers of mediation that surround any experience of live art in the twenty-first century.
Gesamtkunstwerk and Glitch
Authors: Smith Matthew Wilson
Published: May 2012

Smith considers Robert Lepage’s recent high-tech production of Wagner’s Ring cycle at New York’s Metropolitan Opera, as a digital-age extension of the modernist aspiration—incited by Wagner—to create the total work of art.
Viral Performance
Authors: Felton-Dansky Miriam
Published: May 2012

Felton-Dansky proposes a new category of performance called “viral performance,” in which artists use new media and technology to stage politically provocative public hoaxes. These artists disseminate tantalizing fictions, then reveal the truths beneath them, as a strategy for “inoculating” the public against paranoia.
Autophagy and cell growth – the yin and yang of nutrient responses
Authors: Neufeld Thomas P.
Published: May 2012

As a response to nutrient deprivation and other cell stresses, autophagy is often induced in the context of reduced or arrested cell growth. A plethora of signaling molecules and pathways have been shown to have opposing effects on cell growth and autophagy, and results of recent functional screens on a genomic scale support the idea that these processes might represent mutually exclusive cell fates. Understanding the ways in which autophagy and cell growth relate to one another is becoming increasingly important, as new roles for autophagy in tumorigenesis and other growth-related phenomena are uncovered. This Commentary highlights recent findings that link autophagy and cell growth, and explores the mechanisms underlying these connections and their implications for cell physiology and survival. Autophagy and cell growth can inhibit one another through a variety of direct and indirect mechanisms, and can be independently regulated by common signaling pathways. The central role of the mammalian target of rapamycin (mTOR) pathway in regulating both autophagy and cell growth exemplifies one such mechanism. In addition, mTOR-independent signaling and other more direct connections between autophagy and cell growth will also be discussed.
Shear Relaxation of Water–Ionic Liquid Mixtures
Authors: Yamaguchi Tsuyoshi , Mikawa Ken-ichi , Koda Shinobu
Published: May 2012

The frequency-dependent shear viscosity of the mixtures of water with two ionic liquids, 1-butyl-3-methylimidazolium tetrafluoroborate and 1-hexyl-3-methylimidazolium tetrafluoroborate, is measured at frequencies between 5 and 205 MHz. In the cases of both mixtures, the normalized spectra at different water contents reduce to single curves when they are plotted against frequency multiplied with zero-frequency shear viscosity. It indicates that the addition of water into ionic liquids reduces their shear viscosity through the promotion of structural relaxation.
Identifying Addressable Impediments to Student Learning in an Introductory Statistics Course
Authors: Stevens Scott P. , Palocsay Susan W.
Published: May 2012

Using performance data on a common test instrument administered to more than 4,000 business statistics students studying under 16 different instructors over a period of 6.5 years, we identify areas of consistent student weakness. In addition to verifying difficulties found by earlier researchers, we document a fundamental problem in students' ability to reason with cumulative probabilities, a problem with implications for solving problems with both discrete and continuous distributions. Our performance data also suggest that it may be useful to view statistics problems using a taxonomy based more on solution procedure than on traditional statistics topics. We employ a new methodology based on cluster analysis to identify areas where the observed student difficulties may be particularly addressable. Finally, we offer some preliminary findings on how these problems may be addressed with practical teaching suggestions based on the approaches employed by our more successful instructors.
Enhanced Synaptic Integration of Adult-Born Neurons in the Olfactory Bulb of Lactating Mothers
Authors: Kopel Hagit , Schechtman Eitan , Groysman Maya , Mizrahi Adi
Published: May 2012

One of the most dramatic events during the life of adult mammals is the transition into motherhood. This transition is accompanied by specific maternal behaviors, displayed by the mother, that ensure the survival and the well-being of her offspring. The execution of these behaviors is most likely accompanied by plastic changes in specific neuronal circuits, but these are still poorly defined. In this work, we studied the mammalian olfactory bulb (OB), which has been shown to be an essential brain region for maternal behaviors in mice. In the OB, we focused on adult-born neurons, which are continuously incorporated into the circuit during adulthood, thus providing a potential substrate for heightened plasticity after parturition. We analyzed the dynamics and morphological characteristics of adult-born granule cells (abGCs), innervating the OB of primiparous lactating mothers, shortly after parturition as well as in naive females.In vivotime-lapse imaging of abGCs revealed that dendritic spines were significantly more stable in lactating mothers compared with naive virgins. In contrast, spine stability of resident GCs remained unchanged after parturition. In addition, while spine size distribution of abGCs was approximately similar between mothers and naive virgins, the spine density of abGCs was lower in lactating mothers and the density of their presynaptic components was higher. These structural features are indicative of enhanced integration of adult-born neurons into the bulbar circuitry of lactating mothers. This enhanced integration may serve as a cellular mechanism, supporting changes in olfactory coding of new mothers during their first days following parturition.
Comparing Enhancer Action in Cis and in Trans
Authors: Bateman Jack R , Johnson Justine E , Locke Melissa N
Published: May 2012

Studies from diverse systems have shown that distinct interchromosomal interactions are a central component of nuclear organization. In some cases, these interactions allow an enhancer to act in trans, modulating the expression of a gene encoded on a separate chromosome held in close proximity. Despite recent advances in uncovering such phenomena, our understanding of how a regulatory element acts on another chromosome remains incomplete. Here, we describe a transgenic approach to better understand enhancer action in trans in Drosophila melanogaster. Using phiC31-based recombinase-mediated cassette exchange (RMCE), we placed transgenes carrying combinations of the simple enhancer GMR, a minimal promoter, and different fluorescent reporters at equivalent positions on homologous chromosomes so that they would pair via the endogenous somatic pairing machinery of Drosophila. Our data demonstrate that the enhancer GMR is capable of activating a promoter in trans and does so in a variegated pattern, suggesting stochastic interactions between the enhancer and the promoter when they are carried on separate chromosomes. Furthermore, we quantitatively assessed the impact of two concurrent promoter targets in cis and in trans to GMR, demonstrating that each promoter is capable of competing for the enhancer’s activity, with the presence of one negatively affecting expression from the other. Finally, the single-cell resolution afforded by our approach allowed us to show that promoters in cis and in trans to GMR can both be activated in the same nucleus, implying that a single enhancer can share its activity between multiple promoter targets carried on separate chromosomes.
Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions
Authors: Sivagurunathan Senthilkumar , Schnittker Robert R , Razafsky David S , Nandini Swaran , Plamann Michael D , King Stephen J
Published: May 2012

Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies.
Caracterização de larvas de trematódeos emergentes de moluscos gastrópodes coletados em Mariana, Minas Gerais, Brasil
Authors: Souza Marco A. A. , Melo Alan L.
Published: May 2012

Em levantamento malacológico realizado no município de Mariana, estado de Minas Gerais, Brasil, entre abril de 2003 e fevereiro de 2004 foram encontrados moluscos Biomphalaria glabrata (Say, 1818) e Physa marmorata Guilding, 1828 albergando larvas de trematódeos digenéticos. Em B. glabrata foram observadas além de cercária de Schistosoma mansoni Sambon, 1907, estrigeocercária, dois tipos de xifidiocercária, cercária ocelífera e dois tipos de gimnocéfala, enquanto em P. marmorata a única forma larvar emergente foi a cercária equinóstoma. Algumas das cercárias encontradas diferem daquelas descritas na literatura.
Estratégias ótimas de irrigação do feijão‑caupi para produção de grãos verdes
Authors: Ramos Herbert Moraes Moreira , Bastos Edson Alves , Andrade Júnior Aderson Soares de , Marouelli Waldir Aparecido
Published: May 2012

O objetivo deste trabalho foi determinar estratégias ótimas de irrigação do feijão‑caupi (Vigna unguiculata) para a produção de grãos verdes, com a água como fator limitante da produção e diferentes valores de preço do produto. O experimento foi conduzido na Embrapa Meio‑Norte, em Teresina, PI, entre setembro e novembro de 2009. Foram avaliadas cinco lâminas de irrigação, estabelecidas com base em frações da evapotranspiração de referência (25, 50, 75, 100 e 125% da ETo), e as cultivares BRS Guariba e BRS Paraguaçu de feijão‑caupi. Aplicou-se a irrigação por sistema de aspersão convencional fixo. Utilizou-se o delineamento experimental de blocos ao acaso, com quatro repetições e parcelas subdivididas (cultivares). As lâminas de irrigação entre 290 e 325 mm (108 e 130% da ETo) (BRS Paraguaçu) e entre 325 e 363 mm (130 e 153% da ETo) (BRS Guariba) maximizam a receita líquida na faixa de variação de preço do produto entre US$ 0,75 e 2,00 kg‑1, para a cultivar BRS Paraguaçu, e entre US$ 0,50 e 2,00 kg‑1, para a BRS Guariba. A cultivar BRS Guariba apresenta melhor desempenho econômico que a BRS Paraguaçu.
Avaliação do estado nutricional do nitrogênio em batateira por meio de polifenóis e clorofila na folha
Authors: Coelho Fabrício Silva , Fontes Paulo Cezar Rezende , Finger Fernando Luiz , Cecon Paulo Roberto
Published: May 2012

O objetivo deste trabalho foi avaliar o efeito de doses de N sobre índices fisiológicos relacionados à nutrição nitrogenada e verificar a possibilidade de estimar indiretamente os teores foliares de N em batata. Foram avaliados os índices de flavonóis (IFLV), de clorofila (ICHL) e de balanço de N (IBN), e as estimativas dos teores foliares de N foram realizadas aos 21 e 42 dias após a emergência, por meio do medidor portátil Dualex. O experimento foi conduzido de novembro de 2010 a fevereiro de 2011, em delineamento de blocos ao acaso, e os tratamentos consistiram de cinco doses de N (0, 50, 100, 200 e 300 kg ha‑1 de N, na forma de ureia) aplicadas em pré‑plantio, com quatro repetições. Houve aumento no ICHL e no IBN e decréscimo no IFLV com o aumento das doses de N. Os índices determinados com o medidor Dualex correlacionaram-se com os teores de N e de clorofila extraível na quarta folha, bem como com o rendimento de tubérculos na safra. O Dualex pode ser utilizado para avaliar o estado nutricional de N em batateira e prognosticar a produtividade de tubérculos.
Compensador série de tensão em onda quadrada para mitigação de afundamentos de tensão
Authors: Pires Igor Amariz , Cardoso Filho Braz de Jesus , Silva Sidelmo Magalhães
Published: May 2012

Compensadores Série de Tensão (CST) são utilizados para mitigação de fenômenos de qualidade da energia elétrica relacionados a distúrbios na tensão. Os mais conhecidos en-TM tre os CSTs são o DVR (Dynamic Voltage Restorer) e o TM DySC (Dynamic Sag Corrector), utilizados para proteção de cargas elétricas sensíveis a afundamentos de tensão. A tensão injetada pelo restaurador é senoidal, sintetizada através de um inversor em ponte-H modulado em alta frequência por PWM (Pulse Width Modulation), em conjunto com um filtro de saída senoidal. Considerando a duração típica dos afundamentos da ordem de centenas de milisegundos, este artigo propõe a implementação de um CST com injeção de tensão em onda quadrada, sendo incluídos, ainda, aspectos relativos à estratégia de controle para injeção de tensão. Resultados experimentais mostram a eficácia da injeção em onda quadrada na proteção de cargas eletrônicas
Teste do degrau e teste da cadeira: comportamento das respostas metábolo-ventilatórias e cardiovasculares na DPOC
Authors: Pessoa Bruna Varanda , Jamami Mauricio , Basso Renata Pedrolongo , Regueiro Eloisa Maria Gatti , Di Lorenzo Valéria Amorim Pires , Costa Dirceu
Published: May 2012

OBJETIVOS: Verificar as respostas metabólicas, ventilatórias, cardiovasculares e de percepção de esforço entre o isotime de dois minutos do teste do degrau (TD2) e o teste do degrau de seis minutos (TD6) com o teste de sentar-se e levantar-se da cadeira de dois minutos (TSL) nos indivíduos com DPOC. MATERIAIS E MÉTODOS: Foram avaliados 11 homens com DPOC (71 ± 8 anos, VEF1 = 46,1 ± 15,2% previsto), clinicamente estáveis, por meio do TD6 e TSL associados à análise de gases e à coleta de lactato sanguíneo, realizadas em dias diferentes e não consecutivos. No TD2 e TD6, os indivíduos foram instruídos a subir e descer um degrau de 20 cm de altura o mais rápido possível. O mesmo foi recomendado no TSL, que foi realizado em uma cadeira de 46 cm de altura. RESULTADOS:Na análise intertestes não se observou diferença significativa nas variáveis metábolo-ventilatórias, cardiovasculares e Δdispneia no pico de ambos os testes, bem como no TD2. Quanto ao Δfrequκncia cardíaca e ao Δfadiga nos membros inferiores, constataram-se valores significantemente maiores para o TSL comparado ao TD2; e correlações positivas entre o consumo de oxigênio, Δfrequência cardíaca e os desempenhos no TD2 e TD6, entre os desempenhos no TD6 e TSL, e no TD2 com TSL. CONCLUSÃO:Os testes realizados apresentaram respostas metábolo-ventilatórias, cardiovasculares e dispneia similares; e o TD2 mostrou-se uma alternativa para avaliar as limitações funcionais dos indivíduos com DPOC de obstrução grave, proporcionando menor estresse cardiovascular e fadiga muscular se comparado ao TSL, pelas exigências metabólicas periféricas e ajustes posturais.