bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Stool DNA Integrity Method for Early Colorectal Cancer Diagnosis
Authors: Rengucci Claudia , De Maio Giulia , Menghi Maura , Scarpi Emanuela , Guglielmo Simona , Fusaroli Pietro , Caletti Giancarlo , Saragoni Luca , Gardini Andrea Casadei , Zoli Wainer , Falcini Fabio , Amadori Dino , Calistri Daniele
Published: August 2014

Background: DNA integrity analysis could represent an alternative approach to the early detection of colorectal cancer. Previously, fluorescence long DNA (FL-DNA) in stools was extracted using a manual approach and analyzed by capillary electrophoresis assay (CE FL-DNA). We aimed to improve diagnostic accuracy using a simpler and more standardized method [Real Time PCR FL-DNA (RT FL-DNA)] for the detection of early malignant lesions in a population undergoing colorectal cancer screening.

Methods: From 241 stool samples, DNA was extracted using manual and semiautomatic extraction systems and analyzed using FL-DNA tests by CE and RT assays. The RT FL-DNA approach showed slightly higher sensitivity and specificity compared with the CE FL-DNA method. Furthermore, we compared the RT FL-DNA approach with the iFOBT report.

Results: Nonparametric ranking statistics were used to analyze the relationship between the median values of RT FL-DNA and the clinicohistopathologic characteristics. The median values of both variables were significantly higher in patients with cancer than in patients with noncancerous lesions. According to the Fagan nomogram results, the iFOBT and FL-DNA methods provided more accurate diagnostic information and were able to identify subgroups at varying risks of cancer.

Conclusions: The combination of the semiautomatic extraction system and RT FL-DNA analysis improved the quality of DNA extracted from stool samples.

Impact: RT FL-DNA shows great potential for colorectal cancer diagnosis as it is a reliable and relatively easy analysis to perform on routinely processed stool samples in combination with iFOBT. Cancer Epidemiol Biomarkers Prev; 23(11); 2553–60. ©2014 AACR.
Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide–Endostatin Mimic–Kringle 5 Protein
Authors: Wang Houbin , Yang Zhigang , Gu Jun
Published: August 2014

Angiogenesis is required for tumor growth and metastasis, and targeting angiogenesis is a novel anticancer strategy. However, cancer development is a complex multistep process, and single antiangiogenic agents have limited therapeutic efficacy. Here, we report a triple fusion protein, namely CTT peptide–endostatin mimic–kringle 5 (AARP), consisting of MMP-2/9–selective inhibitory peptide (CTT peptide) and well-known endogenous antiangiogenic agents (endostatin mimic and kringle 5), which can simultaneously target matrix metalloproteinases (MMP) and endothelial cells, blocking their actions. AARP was bacterially expressed, and biologic activity of purified AARP was assessed. AARP could significantly inhibit the enzymatic activity of MMP-2/9, proliferation, migration, and tube formation of endothelial cells in vitro. The antitumor activity of AARP was shown in a concentration-dependent manner when injected i.p. into immunodeficient mice bearing multidrug-resistant human epidermoid carcinomas (KB), and AARP is superior to clinical grade endostatin in inhibiting KB xenograft growth. In mouse models of Lewis lung carcinoma (LLC) and hepatoma H22, when given as a single dose, AARP is highly effective for reducing tumor growth, angiogenesis, and metastasis, and increasing survival time. AARP possessed significantly greater antiangiogenic activity than endostatin mimic, CTT peptide–kringle 5 (RK5) both in vitro and in vivo. Compared with conventional chemotherapeutic agents (cyclophosphamide and paclitaxel), AARP is also effective. More importantly, AARP is cytocompatible and no tissue toxicity could be observed after large dose administration. Taken together, our findings suggest AARP is a highly effective, safe, and more potent antiangiogenic agent for blocking tumor angiogenesis and metastasis, and warrants further testing for clinical applications. Mol Cancer Ther; 13(11); 2674–87. ©2014 AACR.
Synergistic Loss of Prostate Cancer Cell Viability by Coinhibition of HDAC and PARP
Authors: Chao Olivia S. , Goodman Oscar B.
Published: August 2014

Tumors with BRCA germline mutations are defective in repairing DNA double-strand breaks (DSB) through homologous recombination (HR) pathways, making them sensitive to PARP inhibitors (PARPi). However, BRCA germline mutations are rare in prostate cancer limiting the ability to therapeutically target these pathways. This study investigates whether histone deacetylase (HDAC) inhibitors (HDACi), reported to modulate DSB repair pathways in sporadic cancers, can downregulate DSB repair pathways and sensitize prostate cancer cells to PARPi. Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index < 0.9), whereas normal prostatic cells did not. Similarly, clonogenicity was significantly decreased after cotreatment. Flow cytometric cell-cycle analysis and Annexin-V staining revealed significant apoptosis upon treatment with SAHA+olaparib. This coincided with increased DNA damage observed by immunofluorescence microscopy analysis of γH2AX foci, a marker of DSBs. In addition, immunoblot analysis showed a significant and persistent increase in nuclear γH2AX levels. Both SAHA and olaparib downregulated the expression of HR-related proteins, BRCA1 and RAD51, whereas SAHA + olaparib had an additive effect on RAD51. Silencing RAD51 sensitized prostate cancer cells to SAHA and olaparib alone. Collectively, cotreatment with HDACi and PARPi downregulated HR-related protein expression and concomitantly increased DNA damage, resulting in prostate cancer cell death.

Implications: These findings provide a strong rationale for supporting the use of combined HDAC and PARP inhibition in treating advanced prostate cancer. Mol Cancer Res; 12(12); 1755–66. ©2014 AACR.
Lack of Angiopoietin‐Like‐2 Expression Limits the Metabolic Stress Induced by a High‐Fat Diet and Maintains Endothelial Function in Mice
Authors: Yu Carol , Luo Xiaoyan , Farhat Nada , Daneault Caroline , Duquette Natacha , Martel Cécile , Lambert Jean , Thorin‐Trescases Nathalie , Rosiers Christine Des , Thorin Éric
Published: August 2014

Background

Angiopoietin‐like‐2 (angptl2) is produced by several cell types including endothelial cells, adipocytes and macrophages, and contributes to the inflammatory process in cardiovascular diseases. We hypothesized that angptl2 impairs endothelial function, and that lowering angptl2 levels protects the endothelium against high‐fat diet (
HFD
)‐induced fat accumulation and hypercholesterolemia.

Methods and Results

Acute recombinant angptl2 reduced (
P
<0.05) acetylcholine‐mediated vasodilation of isolated wild‐type (
WT
) mouse femoral artery, an effect reversed (
P
<0.05) by the antioxidant
N
‐acetylcysteine. Accordingly, in angptl2 knockdown (
KD
) mice,
AC
h‐mediated endothelium‐dependent vasodilation was greater (
P
<0.05) than in
WT
mice. In arteries from
KD
mice, prostacyclin contributed to the overall dilation unlike in
WT
mice. After a 3‐month
HFD
, overall vasodilation was not altered, but dissecting out the endothelial intrinsic pathways revealed that
NO
production was reduced in arteries isolated from
HFD
‐fed
WT
mice (
P
<0.05), while
NO
release was maintained in
KD
mice. Similarly, endothelium‐derived hyperpolarizing factor (
EDHF
) was preserved in mesenteric arteries from
HFD
‐fed
KD
mice but not in those from
WT
mice. Finally, the
HFD
increased (
P
<0.05) total cholesterol–to–high‐density lipoprotein ratios, low‐density lipoprotein–to–high‐density lipoprotein ratios, and leptin levels in
WT
mice only, while glycemia remained similar in the 2 strains.
KD
mice displayed less triglyceride accumulation in the liver (
P
<0.05 versus
WT
), and adipocyte diameters in mesenteric and epididymal white adipose tissues were smaller (
P
<0.05) in
KD
than in
WT
fed an
HFD
, while inflammatory gene expression increased (
P
<0.05) in the fat of
WT
mice only.

Conclusions

Lack of angptl2 expression limits the metabolic stress induced by an
HFD
and maintains endothelial function in mice.
Erik Erikson and His Problematic Identity
Authors: Wallerstein Robert S.
Published: August 2014

In his psychohistorical biographies of Luther and Gandhi, Erik Erikson proposed that great issues of a particular time and place, as experienced by sensitive and creative individuals who are working to resolve their inner conflicts within these contexts, could find solutions that transcend themselves and yield conceptualizations that transform the world. Although Erikson was able to create a conceptualization of the adolescent task of establishing a coherent identity, one that gave voice to the aspirations and frustrations of the rebellious student movements of the 1960s, he was never able, over his lifetime, to resolve his own identity issues. Was he Dane or German, American or Scandinavian, Jew or Christian or both? His lifelong back-and-forths on this struggle are chronicled.
The relationships between insomnia, sleep apnoea and depression: Findings from the American National Health and Nutrition Examination Survey, 2005–2008
Authors: Hayley Amie C , Williams Lana J , Venugopal Kamalesh , Kennedy Gerard A , Berk Michael , Pasco Julie A
Published: August 2014

Objective:

To determine the association between insomnia, obstructive sleep apnoea (OSA), and comorbid insomnia-OSA and depression, while controlling for relevant lifestyle and health factors, among a large population-based sample of US adults.

Method:

We examined a sample of 11,329 adults (≥18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2005–2008. Insomnia was classified via a combination of self-reported positive physician diagnosis and high-frequency ‘trouble falling asleep’, ‘waking during the night’, ‘waking too early’, and ‘feeling unrested during the day’. OSA was classified as a combination of a positive response to a physician-diagnosed condition, in addition to a high frequency of self-reported nocturnal ‘snoring’, ‘snorting/stopping breathing’ and ‘feeling overly sleepy during the day’. Comorbid insomnia-OSA was further assessed by combining a positive response to either insomnia (all), or sleep apnoea (all), as classified above. Depressive symptomology was assessed by the Patient Health Questionnaire-9 (PHQ-9), with scores of >9 used to indicate depression. Odds ratios (ORs) and 95% confidence intervals (CIs) for sleep disorders and depression were attained from logistic regression modelling adjusted for sex, age, poverty level, smoking status and body mass index (BMI).

Results:

Those who reported insomnia, OSA or comorbid insomnia-OSA symptoms reported higher rates of depression (33.6%, 22.2%, 27.1%, respectively), and consistently reported poorer physical health outcomes than those who did not report sleep disorders. After adjusting for sex, age, poverty level, smoking status and BMI (kg/m2), insomnia (OR 6.57, 95% CI 3.89-11.11), OSA (OR 5.14, 95% CI 3.14–8.41) and comorbid insomnia-OSA (OR 6.67, 95% CI 4.44–10.00) were associated with an increased likelihood of reporting depression.

Conclusions:

Insomnia, OSA and comorbid insomnia-OSA are associated with significant depressive symptomology among this large population-based sample of adults.
Randomized controlled trial protocol feasibility: The Wheelchair Self-Efficacy Enhanced for Use (WheelSeeU)
Authors: Best Krista L. , Miller William C. , Eng Janice J. , Routhier François , Goldsmith Charles
Published: August 2014

Background.

Manual wheelchairs (MWCs) can improve mobility and social participation for individuals who experience difficulty walking; however, older adults receive little training for wheelchair use. The Wheelchair Self-Efficacy Enhanced for Use (WheelSeeU) research program provides peer-led training that may positively influence wheelchair use while reducing clinician burden.

Purpose.

The purpose of this study is to evaluate the feasibility and clinical outcomes of WheelSeeU.

Method.

A randomized control trial (RCT) recruits and randomly assigns 40 MWC users (55+ years). Feasibility indicators assessing process, resource, management, and treatment issues are measured, and clinical outcomes (wheelchair skills, safety, confidence, mobility, social participation, quality of life, health utility) are collected at three time points.

Implications.

WheelSeeU provides an innovative approach for teaching wheelchair skills to an aging population that may improve wheelchair use and decrease clinician burden. Since RCTs are expensive and challenging in rehabilitation, establishing feasibility prior to larger effectiveness trials is prudent.
Investigating affect in algorithmic composition systems
Authors: Williams Duncan , Kirke Alexis , Miranda Eduardo R , Roesch Etienne , Daly Ian , Nasuto Slawomir
Published: August 2014

There has been a significant amount of work implementing systems for algorithmic composition with the intention of targeting specific emotional responses in the listener, but a full review of this work is not currently available. This gap creates a shared obstacle to those entering the field. Our aim is thus to give an overview of progress in the area of these affectively driven systems for algorithmic composition. Performative and transformative systems are included and differentiated where appropriate, highlighting the challenges these systems now face if they are to be adapted to, or have already incorporated, some form of affective control. Possible real-time applications for such systems, utilizing affectively driven algorithmic composition and biophysical sensing to monitor and induce affective states in the listener are suggested.
Pilot Randomized Evaluation of Publically Available Concussion Education Materials
Authors: Kroshus Emily , Baugh Christine M. , Hawrilenko Matt , Daneshvar Daniel H.
Published: August 2014

Many states and sports leagues are instituting concussion policies aimed at reducing risk of morbidity and mortality; many include mandates about the provision of concussion education to youth athletes. However, there is limited evidence if educational materials provided under these typically vague mandates are in fact effective in changing concussion risk-related behavior or any cognition predictive of risk-related behavior. The purpose of this pilot randomized controlled study was to conduct a theory-driven evaluation of three publically available concussion education materials: two videos and one informational handout. Participants were 256 late adolescent males from 12 teams in a single league of ice hockey competition in the United States. Randomization of educational condition occurred at the team level. Written surveys assessing postimpact symptom reporting behavior, concussion knowledge, and concussion reporting cognitions were completed by participants immediately before receiving their educational intervention, 1 day after, and 1 month after. Results indicated no change in any measure over any time interval, with the exception of perceived underreporting norms. In one of the video conditions, perceived underreporting norms increased significantly 1 day after viewing the video. Possible content and viewing environment-related reasons for this increase are discussed. Across all conditions, perceived underreporting norms increased 1 month after intervention receipt, raising the possibility that late in the competitive season underreporting may be perceived as normative. The need for the development of theory-driven concussion education materials, drawing on best practices from health behavior scholars, is discussed.
Workplace predictors of secondary school teachers’ intention to leave
Authors: You Sukkyung , Conley Sharon
Published: August 2014

The subject of teachers’ intentions to leave has recently captured the attention of researchers and practitioners. This paper reports on a study that examined the workplace predictors of teachers’ intentions to leave for teachers in different career stages. Structural equation modeling was used to assess the plausibility of a conceptual model specifying hypothesized linkages among secondary school teachers’ perceptions of workplace predictors, satisfaction and commitment, and teachers’ intent to leave. Using the USA Schools and Staffing Survey (SASS) data set, two mediational models were tested, one reflecting partial mediation and the second representing full mediation. Results indicated that the workplace variables had significant meaningful indirect effects on teachers’ intent to leave through three mediators: job satisfaction, work commitment, and career commitment. Furthermore, the effect of administrative support on work and career commitment was uniform and significant for teachers in the three career groups. Some differences across the three teacher career groups were discussed.
Personality and resilience characteristics of Greek primary school principals
Authors: Lazaridou Angeliki , Beka Apostolia
Published: August 2014

The research reported here investigated the personality traits and resilience that a sample of Greek school principals displayed. It probed also for differences associated with sex, age and years of service in the current leadership position, as well as relationships between personality characteristics and resilience strengths. To investigate these matters we used the “The Big Five Inventory” and the “Leader Resilience Profile”. The survey involved almost all school principals in the Magnesia regional government unit in central Greece. Only some of the findings echoed information found in the extant literature; indeed, our results suggest that understandings about school principals that have been developed elsewhere should not be generalized to Greece without considerable caution.
A critical analysis of the National Norms and Standards for School Funding policy
Authors: Mestry Raj
Published: August 2014

Assessment of the legacy of apartheid at the end of the apartheid era in South Africa highlighted major inequalities between white and black, urban and rural areas, and several departments of education. Eighteen years into democracy, the country needs to distinguish between the initiatives taken by the government to address the apartheid legacy, the actual changes made in education and the results thereof, and the continuities and discontinuities in education. Historically disadvantaged schools now receive larger state funding (no-fee schools) and school fee exemptions are granted to lower income or unemployed parents who find difficulty in paying school fees for their children, regardless of race. The public schooling system, especially township schools, is still characterized by low pass rates, low teacher and learner morale, a resurgence of violence amongst learners, ineffective leadership by school managers, poor governance by school governing boards and generally declining school quality, efficiency and effectiveness. The purpose of this paper is to interrogate the National Norms and Standards for School Funding (NNSSF) policy, in order to assess whether this post-apartheid government policy has succeeded in addressing social justice and equity in public primary and secondary education
A cross-sectional analysis of the relationship between uric acid and coronary atherosclerosis in patients with suspected coronary artery disease in China
Authors: Sun Yujiao , Yu Xin , Zhi Ying , Geng Song , Li Hua , Liu Ting , Xu Ke , Chen Ling , Wu Chunwei , Qi Guoxian
Published: August 2014

Background

Although many studies have examined the relationship between uric acid (UA) and coronary artery disease (CAD), whether UA is an independent risk factor contributing to progression of CAD is still controversial. Whether UA plays a different role in different sexes is also unclear.

Methods

A total of 1116 individuals with suspected CAD were stratified into four groups according to their serum UA quartiles in total (men and women combined), in men, and in women. The association of UA with coronary atherosclerosis was assessed by univariable and multivariable logistic regression.

Results

In total and in women, the prevalence of any plaques and significant/severe stenosis was significantly increased with an increase in quartiles of UA (all P < 0.05). The proportion of triple-vessel disease and left main artery lesion was highest in the fourth quartile (both p < 0.05). Increasing quartiles of UA were significantly associated with a coronary artery calcium score (CACS) >10 (all P < 0.01). As UA levels increased in women, the incidence of double-vessel lesions (p = 0.017) and the proportion of mixed plaques (p = 0.022) were significantly increased. The proportion of a CACS of 0 in total, in men and women was highest in the first quartile (all P < 0.01). UA was the strongest predictor of significant stenosis, multivessel disease, and mixed plaques in women (all p < 0.05). UA was the only risk factor for mixed plaques in total (P = 0.046).

Conclusion

The level of UA was significantly associated with coronary atherosclerosis in women, but not men.
Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross-sectional study of 619 consecutive patients with chronic hepatitis B
Authors: Liu Yu-rui , Lin Bin-bin , Zeng Da-wu , Zhu Yue-yong , Chen Jing , Zheng Qi , Dong Jing , Jiang Jia-ji
Published: August 2014

Background

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. This study aimed to investigate the relationship between serum alpha-fetoprotein (AFP) levels and pathological stages of liver biopsy in patients with chronic hepatitis B (CHB).

Methods

The study included 619 patients who were diagnosed with CHB from March 2005 to December 2011. AFP levels were measured by electrochemiluminescence. Liver biopsy samples were classified into five levels of inflammation (G) and fibrosis (S) stages, according to the Chinese guidelines for prevention and treatment of viral hepatitis. Two multivariable ordinal regression models were performed to determine associations between AFP, GGT, and APRI (AST/PLT ratio) and stages of inflammation and fibrosis.

Results

Significant positive and moderate correlations were shown between AFP levels and inflammation stages and between AFP levels and fibrosis stages (ρ = 0.436 and 0.404, p < 0.001). Median values of AFP at liver fibrosis stages S0-1, S2, S3, and S4 were 3.0, 3.4, 5.4, and 11.3 ng/ml, respectively, and median APRI (AST/PLT ratio) was 0.41. Receiver operating characteristic (ROC) curve analyses revealed that the areas under the curves (AUCs) were 0.685, 0.727, and 0.755 (all p <0.001) for judging inflammation stages of G ≥ 2, G ≥ 3, G = 4 by AFP; and 0.691, 0.717, and 0.718 (all p <0.001) for judging fibrosis stages of S ≥ 2, S ≥ 3, and S = 4 by AFP. APRI levels showed significant positive and moderate correlations with inflammation stages (ρ = 0.445, p < 0.001). AST, GGT, and APRI levels showed significant positive but very weak to weak correlations with fibrosis stages (ρ = 0.137, 0.237, 0.281, p < 0.001).

Conclusions

Serum AFP levels increased as pathological levels of inflammation and fibrosis increased in CHB patients. Our data showed the clinical significance of serum AFP levels in diagnosing liver inflammation and fibrosis. Assessment of liver pathology may be improved by creating a predictive mathematical model by which AFP levels with other biomarkers.
Exponential replicate broadcasting mechanism for adaptive bandwidth allocation in mobile networks
Authors: Lin Chi-Kun , Horng Gwo-Jiun , Wang Chi-Hsuan , Yang Jar-Ferr
Published: August 2014

This paper proposes an exponential replicate broadcasting (ERB) algorithm for data dissemination to improve data access efficiency. The proposed ERB algorithm first constructs a broadcast tree to determine the broadcast frequency of each data and splits the broadcast tree into some broadcast wood to generate the broadcast program. In addition, this paper develops an analytical model to derive the mean access latency of the generated broadcast program. In light of the derived results, both the index channel's bandwidth and the data channel's bandwidth can be optimally allocated to maximize bandwidth utilization. This paper presents experiments to help evaluate the effectiveness of the proposed strategy. From the experimental results, it can be seen that the proposed mechanism is feasible in practice.
Interactions between planar cell polarity genes cause diverse neural tube defects
Authors: Murdoch Jennifer N. , Damrau Christine , Paudyal Anju , Bogani Debora , Wells Sara , Greene Nicholas D. E. , Stanier Philip , Copp Andrew J.
Published: August 2014

Neural tube defects (NTDs) are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP) pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in human patients are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in human patients. To determine the phenotypes produced in double heterozygotes we bred mice with all three pairwise combinations of Vangl2Lp, ScribCrc and Celsr1Crsh mutations, the most intensively studied PCP mutants. The majority of double mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double heterozygote combinations. Phenotypically, Celsr1Crsh; Vangl2Lp; ScribCrc triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double mutant phenotypes may be attributed to the nature of the protein disruption in each allele: while ScribCrc is a null mutant and produces no Scrib protein, Celsr1Crsh and Vangl2Lp homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic interactions are of direct relevance to human patients and emphasize the importance of performing comprehensive genetic screens in humans.
Histone acetylation in astrocytes suppresses GFAP and stimulates a re-organization of the intermediate filament network
Authors: Kanski R. , Sneeboer M. A. M. , van Bodegraven E. J. , Sluijs J. A. , Kropff W. , Vermunt M. W. , Creyghton M. P. , De Filippis L. , Vescovi A. , Aronica E. , van Tijn P. , van Strien M. E. , Hol E. M.
Published: August 2014

Glial Fibrillary Acidic Protein (GFAP) is the main intermediate filament in astrocytes and is regulated by epigenetic mechanisms during development. We demonstrate that histone acetylation controls GFAP expression also in mature astrocytes. Inhibition of histone deacetylases (HDACs) with Trichostatin-A or Sodium-butyrate reduced GFAP expression in primary human astrocytes and astrocytoma cells. Since splicing occurs co-transcriptional, we investigated whether histone acetylation changes the ratio between the canonical isoform GFAPα and the alternative GFAPδ splice-variant. We observed that decreased transcription of GFAP enhanced alternative isoform expression, as HDAC inhibition increased the GFAPδ/α ratio favouring GFAPδ. Expression of GFAPδ was dependent on the presence and binding of the splicing factors of the SR protein family. Inhibition of HDAC activity also resulted in aggregation of the GFAP network, reminiscent to our earlier findings of a GFAPδ-induced network collapse. Together, our data demonstrate that HDAC inhibition results in changes in transcription, splicing, and organization of GFAP. These data imply that a tight regulation of histone acetylation in astrocytes is essential, since dysregulation of gene expression causes aggregation of GFAP, a hallmark of human diseases like Alexander's disease.
Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons
Authors: Gärtner Annette , Fornasiero Eugenio F. , Valtorta Flavia , Dotti Carlos G.
Published: August 2014

Final morphological polarization of neurons, with the development of a distinct axon and of several dendrites, is preceded by phases of non-polarized architecture. The earliest of these phases is that of the round neuron arising from the last mitosis. A second non polarized stage corresponds to the bipolar neuron, with two morphologically identical neurites. Both phases have their distinctive relevance in the establishment of neuronal polarity. During the round cell stage a decision is made as to where from the cell periphery a first neurite will form, thus creating the first sign of asymmetry. At the bipolar stage a decision is made as to which of the two neurites becomes the axon in neurons polarizing in vitro and the leading edge in neurons in situ. In this study we analysed cytoskeletal and membrane dynamics in cells at these two “pre-polarity” stages. By mean of time lapse imaging in dissociated hippocampal neurons and ex vivo cortical slices we show that both stages are characterized by polarized intracellular arrangements, however with distinct temporal hierarchies: polarized actin dynamics marks the site of first polarization in round cells, whereas polarized membrane dynamics precedes asymmetric growth in the bipolar stage.
The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle
Authors: Wang Gang , Jiang Qing , Zhang Chuanmao
Published: August 2014

The centrosome acts as the major microtubule-organizing center (MTOC) for cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate cells. It duplicates only once per cell cycle in a highly spatiotemporally regulated manner. When the cell undergoes mitosis, the duplicated centrosomes separate to define spindle poles and monitor the assembly of the bipolar mitotic spindle for accurate chromosome separation and the maintenance of genomic stability. However, centrosome abnormalities occur frequently and often lead to monopolar or multipolar spindle formation, which results in chromosome instability and possibly tumorigenesis. A number of studies have begun to dissect the role of mitotic kinases, including NIMA-related kinases (Neks), cyclin-dependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in regulating centrosome duplication, separation and maturation and subsequent mitotic spindle assembly during cell cycle progression. In this Commentary, we review the recent research progress on how these mitotic kinases are coordinated to couple the centrosome cycle with the cell cycle, thus ensuring bipolar mitotic spindle fidelity. Understanding this process will help to delineate the relationship between centrosomal abnormalities and spindle defects.
Quantifying mRNA targeting to P bodies in living human cells reveals a dual role in mRNA decay and storage
Authors: Aizer Adva , Kalo Alon , Kafri Pinhas , Shraga Amit , Ben-Yishay Rakefet , Jacob Avi , Kinor Noa , Shav-Tal Yaron
Published: August 2014

The 5′→3′ mRNA degradation machinery localizes to cytoplasmic P bodies (PBs), which are non-membranous structures found in all eukaryotes. While PB function has been intensively studied in yeast, less is known in mammalian cells, such as whether PB enzymes are actively engaged in mRNA degradation or if PBs serve as mRNA storage depots, particularly during cellular stress. We examined the fate of mammalian mRNAs in PBs during translational stress, and show that mRNAs accumulate within PBs during amino acid starvation. The 5′ and 3′ ends of the transcripts residing in PBs could be identified, but polyA tails were not detected. Using the MS2 mRNA-tagging system for mRNA visualization in living cells, we found that a stationary mRNA population formed in PBs during translational stress, which cleared gradually after the stress was relieved. Dcp2 knockdown experiments showed that there is constant degradation of part of the PB-associated mRNA population. This analysis demonstrates the dual role of PBs as decay sites and storage areas under regular and stress conditions.
Turning a new page on nucleostemin and self-renewal
Authors: Tsai Robert Y. L.
Published: August 2014

A quintessential trait of stem cells is embedded in their ability to self-renew without incurring DNA damage as a result of genome replication. One key self-renewal factor is the nucleolar GTP-binding protein nucleostemin (also known as guanine-nucleotide-binding protein-like 3, GNL3, in invertebrate species). Several studies have recently pointed to an unexpected role of nucleostemin in safeguarding the genome integrity of stem and cancer cells. Since its discovery, the predominant presence of nucleostemin in the nucleolus has led to the notion that it might function in the card-carrying event of the nucleolus – the biogenesis of ribosomes. As tantalizing as this might be, a ribosomal role of nucleostemin is refuted by evidence from recent studies, which argues that nucleostemin depletion triggers a primary event of DNA damage in S phase cells that then leads to ribosomal perturbation. Furthermore, there have been conflicting reports regarding the p53 dependency of nucleostemin activity and the cell cycle arrest profile of nucleostemin-depleted cells. In this Commentary, I propose a model that explains how the many contradictory observations surrounding nucleostemin can be reconciled and suggest that this protein might not be as multi-tasking as has been previously perceived. The story of nucleostemin highlights the complexity of the underlying molecular events associated with the appearance of any cell biological phenotype and also signifies a new understanding of the genome maintenance program in stem cells.
Tetraspanins at a glance
Authors: Charrin Stéphanie , Jouannet Stéphanie , Boucheix Claude , Rubinstein Eric
Published: August 2014

Tetraspanins are a family of proteins with four transmembrane domains that play a role in many aspects of cell biology and physiology; they are also used by several pathogens for infection and regulate cancer progression. Many tetraspanins associate specifically and directly with a limited number of proteins, and also with other tetraspanins, thereby generating a hierarchical network of interactions. Through these interactions, tetraspanins are believed to have a role in cell and membrane compartmentalization. In this Cell Science at a Glance article and the accompanying poster, we describe the basic principles underlying tetraspanin-based assemblies and highlight examples of how tetraspanins regulate the trafficking and function of their partner proteins that are required for the normal development and function of several organs, including, in humans, the eye, the kidney and the immune system.
Traditional versus online newspapers: The perspective of news audiences in Botswana
Authors: Lesitaokana William , Akpabio Eno
Published: August 2014

Contemporary studies of journalism and new media indicate that news audiences prefer to read online newspapers because they are generally interactive, host multimedia content and report breaking news. However, the literature on the impact of digital media technologies on traditional
print publication consumption patterns in Botswana and the African continent is hard to come by. Thus, this study, using multistage cluster sampling and focus group discussions, sets out to explore how audience members in Botswana engage with online news vis-á-vis traditional newspapers.
It finds out that news audiences have a favorable attitude towards online newspapers but still prefer traditional newspapers, and that in Botswana specifically, access to online and traditional newspapers is influenced by factors such as cost and convenience. The study’s findings indicate
clearly that while new media technologies continue to influence new trends and practices in journalism globally, audiences’ experience with these technologies differ from country to country.
Accountability for College and Career Readiness: Developing a New Paradigm
Authors: Darling-Hammond Linda , Wilhoit Gene , Pittenger Linda
Published: August 2014

As schools across the country prepare for new standards under the Common Core, states are moving toward creating more aligned systems of assessment and accountability. This paper recommends an accountability approach that focuses on meaningful learning, enabled by professionally skilled and committed educators, and supported by adequate and appropriate resources, so that all students regardless of background are prepared for both college and career when they graduate from high school. Drawing on practices already established in other states and on the views of policymakers and school experts, this paper proposes principles for effective accountability systems and imagines what a new accountability system could look like in an imagined “51st state” in the United States. While considerable discussion and debate will be needed before a new approach can take shape, this paper’s objective is to get the conversation started so the nation can meet its aspirations for preparing college- and career-ready students.
Choice and pronunciation of words: Individual differences within a homogeneous group of speakers
Authors: Hanique Iris , Ernestus Mirjam , Boves Lou
Published: August 2014

This paper investigates whether individual speakers forming a homogeneous group differ in their choice and pronunciation of words when engaged in casual conversation, and if so, how they differ. More specifically, it examines whether the Balanced Winnow classifier is able to distinguish between the twenty speakers of the Ernestus Corpus of Spontaneous Dutch, who all have the same social background. To examine differences in choice and pronunciation of words, instead of characteristics of the speech signal itself, classification was based on lexical and pronunciation features extracted from hand-made orthographic and automatically generated broad phonetic transcriptions. The lexical features consisted of words and two-word combinations. The pronunciation features represented pronunciation variations at the word and phone level that are typical for casual speech. The best classifier achieved a performance of 79.9% and was based on the lexical features and on the pronunciation features representing single phones and triphones. The speakers must thus differ from each other in these features. Inspection of the relevant features indicated that, among other things, the words relevant for classification generally do not contain much semantic content, and that speakers differ not only from each other in the use of these words but also in their pronunciation.
BioMime – A Sirolimus-eluting Coronary Stent System for the Treatment of Patients with De Novo Coronary Lesions – meriT-1 Report
Authors:   Meril Life Sciences, Muktanand Marg, Chala, Vapi 396 191. Gujarat, India. E: clinical.trials@merillife.com
Published: August 2014

Background:Since the first reported use of percutaneous transluminal coronary angioplasty, advances in the interventional cardiology arena have been fast paced. Developers and clinicians are adapting from the learning curve awarded by the time-course of drug-eluting stent (DES) evolution. BioMime™ sirolimus-eluting stent (SES) is a step towards biomimicry. The stent is built on a strut of ultra-low thickness (65μm), a cobalt–chromium platform using an intelligent hybrid of closed and open cells allowing for morphology-mediated expansion. It employs a well-known antiproliferative – sirolimus – that elutes from a known biodegradable copolymer formulation within 30 days. The resultant stent demonstrates almost 100% endothelialisation at 30 days in preclinical models.Methods:The meriT-1 was a prospective, single-arm, single-centre trial to evaluate the safety and efficacy of BioMime SES in 30 patients with a single de novo lesion in native coronary arteries. The primary safety and efficacy end-points were major adverse cardiac events (MACE) at 30 days and in-stent late lumen loss at eight months, as measured using quantitative coronary angiographic (QCA) method. Secondary safety and efficacy end-points included MACE at one and two years and angiographic binary restenosis at eight-month angiographic follow-up. Other end-points included the occurrence of stent thrombosis at acute, subacute, late and very late periods and the percentage of diameter stenosis by QCA.Results:No MACE were observed and the median in-stent late luminal loss in 20 (67%) subjects studied by QCA was 0.15mm, with 0% binary restenosis at eight-month follow-up. No stent thrombosis was observed up to one-year follow-up.Conclusions:In comparison to currently available DES, BioMime SES appears to have a considerable scientific basis for prevention of neointimal proliferation, restenosis and associated clinical events.
Re-induction of desiccation tolerance after germination of Cedrela fissilis Vell. seeds
Authors: MASETTO TATHIANA E. , FARIA JOSE M. , FRAIZ ANA C.R.
Published: August 2014

This work aimed to characterize the re-induction of desiccation tolerance (DT) in germinated seeds, using polyethylene glycol (PEG 8000). Cell changes were investigated through cytological assays (cell viability and transmission electronic microscopy) as well as DNA integrity during loss and re-establishment of DT. The loss of DT was characterized by drying germinated seeds with different radicle lengths (1, 2, 3, 4 and 5 mm) in silica gel, decreasing the moisture content to ten percentage points intervals, followed by pre-humidification (100% RH / 24 h) and rehydration. To re-induce DT, germinated seeds were treated for 72 h with PEG (-2.04 MPa) and PEG (-2.04 MPa) + ABA (100 µM) before dehydration. Germinated seeds did not tolerate desiccation to 10% moisture content, irrespectively of the radicle length. However, when incubated in PEG, those with 1 and 2 mm long radicle attained 71% and 29% survival, respectively. The PEG+ABA treatment was efficient to re-establish DT in seeds with 1 mm long radicles (100% survival). The ultrastructural assays of the cells of germinated seeds with 2 and 5 mm length confirmed the obtained physiological results. Germinated seeds of C. fissilis constitute a useful tool for desiccation tolerance investigations.
Thyroid gland development in Rachycentron canadum during early life stages
Authors: OTERO ADRIANA P.S. , RODRIGUES RICARDO V. , SAMPAIO LUÍS A. , ROMANO LUIS A. , TESSER MARCELO B.
Published: August 2014

The aim of this study was to describe the ontogeny of thyroid follicles in cobia Rachycentron canadum. Larvae were sampled daily (n=15 - 20) from hatching until 15 dah (days after hatching). Following, larvae were sampled every two days by 28 dah; a new sample was taken at 53 dah. The samples were dehydrated, embedded in Paraplast, and sections of 3 µm were dewaxed, rehydrated and stained with HE and PAS. A single follicle was already present 1 dah and three follicles were found 8 dah. The number of follicles increased up to 19 on 53 dah. The diameter of follicles and follicular cell height were lower 1 dah (6.83 ± 1.00 and 4.6 ± 0.01 µm), but increased from 8 dah (24.03 ± 0.46 µm e 6.43 ± 0.46 µm). From 8 dah, the presence of reabsorption vesicles was observed in the colloid and from the 19 dah some follicles did not present colloid. The early thyroid follicle appearance in cobia larvae as well as the high quantity of follicles without colloid and/or with vesicles even after the metamorphosis, might be the explanation of the fast growth of the cobia.
The scientific literature on Limnoperna fortunei (Dunker 1857) from 1982 to 2012
Authors: BARBOSA FABIANA G.
Published: August 2014

Limnoperna fortunei (golden mussel) is a freshwater bivalve native to Southeast Asia, but is becoming an invasive species in several aquatic ecosystems in the world. In this study, a scientometric analysis was performed to identify the patterns, trends and gaps of knowledge for this invasive species. A survey of the published literature was conducted using the database of the Thomson Institute for Scientific Information (ISI). A total of 107 papers were surveyed that were published between 1982 and 2012 in 60 journals. The number of papers on L. fortunei over the years has increased, especially within the last eight years of the study period. Argentina, Brazil, and Japan are the countries that contributed the most papers to the literature on invasive bivalve. The majority of papers were field-observational studies. Among some important gaps that need to be addressed are the relatively small number and/or lack of studies conducted in the native countries and in countries invaded by L. fortunei, the lack of internationally collaborative publications in these countries, as well as a low number of internationally collaborative studies.
Magnetic Parkia pendula seed gum as matrix for Concanavalin A lectin immobilization and its application in affinity purification
Authors: RÊGO MOACYR J.B.M. , ALMEIDA SINARA M. , BEZERRA SÉRGIO A. , CARVALHO JÚNIOR LUIZ B. , BELTRÃO EDUARDO I.C.
Published: August 2014

The present work aimed to magnetize Parkia pendula seeds gum and use it as a matrix for Concanavalin A covalent immobilization. This composite was applied in affinity purification of glycoconjugates. Parkia pendula seeds were hydrated and the gum provenient from the supernatant was precipitated and washed with ethanol and dried. The gum was magnetized in co-precipitation using solutions of Fe+2 and Fe+3. Matrix activation was accomplished with NaIO4. Magnetized Parkia pendula seeds gum with covalently immobilized Concanavalin A was used as an affinity matrix for the recognition of bovine serum fetuin glycoprotein. Fetuin elution was carried out with a solution of glucose (300mM) and evaluated through SDS-PAGE. The efficiency of lectin immobilization and fetuin purification were 63% and 14%, respectively. These results indicate that the composite produced is a promising magnetic polysaccharide matrix for lectins immobilization. Thus, such system can be applied for affinity purification allowing an easy recovery by magnetic field.
Composição química, compostos bioativos e dissimilaridade genética entre cultivares de amoreira (Rubus spp.) cultivadas no Sul de Minas Gerais
Authors: Guedes Mayara Neves Santos , Maro Luana Aparecida Castilho , Abreu Celeste Maria Patto de , Pio Rafael , Patto Leonardo Silva
Published: August 2014

Frutos das cultivares Arapaho, Brazos, Caingangue, Cherokee, Choctaw, Comanche, Ébano, Guarani, Tupy e Xavante, e uma espécie de amoreira-vermelha (Rubus rosifolius Smith) foram avaliados quanto à composição química. Avaliou-se também a variação genética entre as cultivares de amoreira-preta e a espécie de amoreira-vermelha. Os resultados demonstraram variações na composição química dos frutos estudados. A amora- vermelha apresentou menor teor de umidade e maiores valores para os componentes cinzas, açúcares totais, açúcares redutores, açúcares näo redutores, pectina total, pectina solúvel, fenóis, flavonoides, licopeno, β-caroteno e vitamina A. Os teores de umidade e antocianinas, a porcentagem de solubilização e a atividade antioxidante foram maiores nos frutos da cultivar Ébano. Verificou-se que os frutos da amoreira-vermelha e da cultivar Ébano apresentaram o maior grau de divergência genética para as variáveis analisadas. Isto indica a possibilidade de uso das mesmas em programas de melhoramento que visem à melhoria da composição química.