bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersion of air pollutants around buildings: A review of past studies and their methodologies
Authors: Xia Qian , Niu Jianlei , Liu Xiaoping
Published: October 2012

The review shows that on-site measurement has the benefit of obtaining real life data under real atmospheric boundary layer conditions, but it is too difficult to capture the real atmospheric conditions and too expensive to conduct such experiment as too many samplers and receptors are needed, particularly for investigating the air pollutant issues with regard to building arrays. This difficulty can be solved by physical-scale modelling, which can provide more controllable airflow boundary conditions, but accuracy is compromised by its inability to simulate real boundary layer turbulence conditions and buoyancy effects. Water channel is advantageous in buoyancy experiments but maintaining realistic viscosity and density properties of the medium could be challenging. Direct numerical simulation can provide accurate results; but it is impractical to simulate flows in large domains due to high computational requirements. Reynold-averaged Navier–Stokes numerical simulation is the most commonly used model for pollutant dispersion and infection control analysis but generally over-predicts surface concentrations at the leeward side of a building. Although large eddy simulation can over-predict the lateral pollutant concentration in the wake region of the building, flow unsteadiness and intermittency can be solved.
The impact of identity and economic cues on citizens’ EU support: An experimental study on the effects of party communication in the run-up to the 2009 European Parliament elections
Authors: Maier Michaela , Adam Silke , Maier Jürgen
Published: October 2012

In this article we seek to understand whether national parties have an impact on citizens’ EU support by publicly cueing Europe as a risk to or as an opportunity for the economy or identity. In order to answer this question, we have conducted a cross-country survey experiment (covering Austria, the Czech Republic, Germany, the United Kingdom, the Netherlands, Poland, Portugal, Spain and Sweden) relying on real-world stimuli from party campaign communication in the run-up to the 2009 European Parliament elections. By introducing this new methodology to cueing research we show substantial evidence for cueing effects even when thoroughly controlling for nuisance variables drawn from EU research as well as country contexts. We find support for the general cueing hypothesis in experimental groups that were exposed to negative economic messages while in two other groups partisanship works as a relevant moderator of the effects of persuasive messages. These findings are explained by distinguishing between consensual and conflicting issues and show in what circumstances campaign messages might reach beyond the particular partisan base.
Freedom, self-ownership, and equality in Steiner’s left-libertarianism
Authors: Shnayderman Ronen
Published: October 2012

Hillel Steiner’s left-libertarian theory of justice is the most serious recent attempt to reconcile the ideals of (luck-egalitarian) equality and freedom. This attempt consists in an argument that a universal right to equal freedom, which in Steiner’s view means also a universal right to maximal freedom, implies a universal right to self-ownership and to an egalitarian share of the world’s natural resources. In this article, I argue that this argument fails on Steiner’s own terms. I argue that, on Steiner’s conceptions of freedom, self-ownership, and an egalitarian share of the world’s natural resources, insofar as the right to equal freedom implies the right to self-ownership and to an egalitarian share of the world’s natural resources, it is incompatible with (luck-egalitarian) equality.
Professional perceptions of social work and potential impact on developing field
Authors: Gerritsen-McKane Ruth , Hunter Rosemarie , Ofori-Dua Kwadwo
Published: October 2012

In 2007, a collaborative project was initiated between Kwame Nkrumah University of Science and Technology’s (KNUST’s) Department of Sociology and Social Work (DSSW) and the University of Utah (U of U) College of Social Work (CSW) to establish a Bachelors of Social Work (BSW) Program in Kumasi, Ghana. As part of this initiative, there was a specific need to develop a field education component in the emerging BSW. To assist in establishment of an effective field education program, a research team from the U of U CSW returned to Kumasi, Ghana in 2008 to conduct a qualitative exploratory case study. This article presents initial research findings regarding perceptions of key community stakeholders about the role of social work in this developing country; and their perceptions regarding the necessity of practica for preparing students to practice social work. From evidence sources, themes about professionalism, gender/role of women and community structures emerged concerning perceptions of the role of social work. Themes specific to exposure to vulnerable populations, skill development, understanding the roles and perceptions of social workers in Ghana, and the importance of field education will be presented and implications for future international collaborations will be examined.
Firm Survival in Professional Sports
Authors: Oberhofer Harald , Philippovich Tassilo , Winner Hannes
Published: October 2012

This article investigates firm survival in professional football, arguing that the relegation and promotion system in football leagues is very similar to firm exits and entries in traditional goods and service markets. Empirically, we use a data set containing information on how long football teams have participated in the German Premier League over the playing seasons 1981-1982 to 2009-2010. Controlling for club- and market-specific characteristics, such as a team’s budget or its squad composition, our findings suggest that younger firms are systematically exposed to higher risks of market exit in professional football, which is often referred to as liability of newness in organizational ecology.
Perceived Importance of Five Different Health Issues for Gay and Bisexual Men
Authors: Grov Christian , Ventuneac Ana , Rendina H. Jonathon , Jimenez Ruben H. , Parsons Jeffrey T.
Published: October 2012

This study assessed the perceived importance of five health issues for gay and bisexual men ( N = 660) using time-space sampling in gay bars/clubs and bathhouses in New York City: “HIV & STDs,” “Drugs & Alcohol,” “Body Image,” “Mental Health,” and “Smoking.” This study compared ratings based on demographic differences, recent substance use, recent sexual risk behavior, and whether or not participants owned a smart device (e.g., “smart” phone, iPad, iPod touch). Contrary to research indicating that gay and bisexual men may be experiencing HIV prevention fatigue, this study identified that HIV and STIs were perceived as most important. Drugs and alcohol and mental health were also rated high, suggesting that providers may be well served to include mental health and drugs and alcohol as part of their comprehensive approach to HIV prevention. A majority of participants (72%) owned a smart device. Smart device owners rated health issues similarly to those who did not, suggesting that such devices may be a useful platform to reach gay and bisexual men for health education and prevention.
Treatment burden among people with chronic illness: what are consumer health organizations saying?
Authors: Sav Adem , McMillan Sara S , Kelly Fiona , Kendall Elizabeth , Whitty Jennifer A , King Michelle A , Wheeler Amanda J
Published: October 2012

Objectives:

To explore the perspectives of consumer health organizations about the burden of chronic illness and multiple treatment regimens experienced by the consumers they represent.

Methods:

In-depth interviews (n = 15) were conducted with senior representatives from peak Australian consumer health organizations representing diabetes, asthma, cardiovascular disease, cancer, musculoskeletal illness and mental health.

Results:

Medication burden, which included aspects such as multiple medications, side effects, stigma and adverse events resulting from medication use, emerged as the most significant and prevalent theme. Carer burden and the negative impact of financial burden was widely discussed, particularly for low-income earners with claims that these consumers were forced to prioritise medications according to how effective they perceived them to be. Time taken to learn about treatment, administer, and monitor or travel to obtain treatment also emerged as being burdensome, however, difficulty accessing treatment was considered to be particularly burdensome. The disjointed nature of care among healthcare services was thought to create a sense of confusion and distress.

Discussion:

Many of the issues discussed by participants corroborated existing research, underscoring the complementary provider, and advocacy role of these organisations in mitigating treatment burden for people with chronic illness.
The Cultural Historical Complexity of Human Personality Adaptation
Authors: Wynn Melissa E. , Winston Cynthia E. , Freeman Kimberley E.
Published: October 2012

Research on implicit intelligence has conceptualized students’ beliefs about the nature of intelligence as either fixed or malleable. This research has largely not included African American adolescents, a group for whom beliefs about intelligence have a cultural historical complexity related to both scientific racism and master narratives of race and intelligence. The purpose of this study was to investigate the nature of implicit theories of intelligence for 63 African American adolescents who are seventh and eighth graders in a public charter school. The two-way ANOVA revealed that these adolescents held a malleable view of intelligence, which did not vary by gender or grade. Exploratory correlation analysis showed some consistent relationships with achievement motivation variables found in other studies. These findings may be explained by African American cultural values and the personality characteristic adaptations that they make living within a racialized society.
Understanding Organizational Reality
Authors: Owen Keith O. , Dietz A. Steven
Published: October 2012

To achieve their purposes, organizations must constantly learn, adapt, and grow, a process typically referred to as change. Research shows that only a relatively few change efforts achieve great success—most just get by while the majority fail to reach predefined performance goals and objectives. That the success of planned change is relatively rare led to the following questions: (a) What facilitates or inhibits the change process? (b) How do these facilitators and inhibitors evolve within an organization? and (c) What are the implications of understanding this evolutionary process relative to achieving a more sustainable level of performance? This article addresses these questions and presents a holistic model for creating an open, fully transparent environment in which the many differences of potential relevance to a change are put in the open for analysis. The approach, the Full Dimensional Systems Model, assumes there are multiple, interrelated domains of influence that affect change and that these must each be appreciated and addressed simultaneously to achieve sustainable performance improvement.
Regulation of multiple DNA repair pathways by the Fanconi anemia protein SLX4
Authors: Kim Yonghwan , Spitz Gabriella S. , Veturi Uma , Lach Francis P. , Auerbach Arleen D. , Smogorzewska Agata
Published: October 2012

SLX4, the newly identified Fanconi anemia protein, FANCP, is implicated in repairing DNA damage induced by DNA interstrand cross-linking (ICL) agents, topoisomerase I (TOP1) inhibitors, and in Holliday junction resolution. It interacts with and enhances the activity of XPF-ERCC1, MUS81-EME1, and SLX1 nucleases, but the requirement for the specific nucleases in SLX4 function is unclear. Here, by complementing a null FA-P Fanconi anemia cell line with SLX4 mutants that specifically lack the interaction with each of the nucleases, we show that the SLX4-dependent XPF-ERCC1 activity is essential for ICL repair but is dispensable for repairing TOP1 inhibitor-induced DNA lesions. Conversely, MUS81-SLX4 interaction is critical for resistance to TOP1 inhibitors but is less important for ICL repair. Mutation of SLX4 that abrogates interaction with SLX1 results in partial resistance to both cross-linking agents and TOP1 inhibitors. These results demonstrate that SLX4 modulates multiple DNA repair pathways by regulating appropriate nucleases.
Some properties concerning close-to-convexity of certain analytic functions
Authors: Nunokawa Mamoru , Aydog̃an Melike , Kuroki Kazuo , Yildiz Ismet , Owa Shigeyoshi
Published: October 2012

Let

f
(
z
)

be an analytic function in the open unit disk

D

normalized with

f
(
0
)
=
0

and

f
′

(
0
)
=
1

. With the help of subordinations, for convex functions

f
(
z
)

in

D

, the order of close-to-convexity for

f
(
z
)

is discussed with some example.

MSC:30C45.
3D-FISH analysis of embryonic nuclei in mouse highlights several abrupt changes of nuclear organization during preimplantation development
Authors: Aguirre-Lavin Tiphaine , Adenot Pierre , Bonnet-Garnier Amélie , Lehmann Gaétan , Fleurot Renaud , Boulesteix Claire , Debey Pascale , Beaujean Nathalie
Published: October 2012

Background

Embryonic development proceeds through finely tuned reprogramming of the parental genomes to form a totipotent embryo. Cells within this embryo will then differentiate and give rise to all the tissues of a new individual. Early embryonic development thus offers a particularly interesting system in which to analyze functional nuclear organization. When the organization of higher-order chromatin structures, such as pericentromeric heterochromatin, was first analyzed in mouse embryos, specific nuclear rearrangements were observed that correlated with embryonic genome activation at the 2-cell stage. However, most existing analyses have been conducted by visual observation of fluorescent images, in two dimensions or on z-stack sections/projections, but only rarely in three dimensions (3D).

Results

In the present study, we used DNA fluorescent in situ hybridization (FISH) to localize centromeric (minor satellites), pericentromeric (major satellites), and telomeric genomic sequences throughout the preimplantation period in naturally fertilized mouse embryos (from the 1-cell to blastocyst stage). Their distribution was then analyzed in 3D on confocal image stacks, focusing on the nucleolar precursor bodies and nucleoli known to evolve rapidly throughout the first developmental stages. We used computational imaging to quantify various nuclear parameters in the 3D-FISH images, to analyze the organization of compartments of interest, and to measure physical distances between these compartments.

Conclusions

The results highlight differences in nuclear organization between the two parental inherited genomes at the 1-cell stage, i.e. just after fertilization. We also found that the reprogramming of the embryonic genome, which starts at the 2-cell stage, undergoes other remarkable changes during preimplantation development, particularly at the 4-cell stage.
High yield derivation of enriched glutamatergic neurons from suspension-cultured mouse ESCs for neurotoxicology research
Authors: Hubbard Kyle S , Gut Ian M , Lyman Megan E , Tuznik Kaylie M , Mesngon Mariano T , McNutt Patrick M
Published: October 2012

Background

Recently, there has been a strong emphasis on identifying an in vitro model for neurotoxicity research that combines the biological relevance of primary neurons with the scalability, reproducibility and genetic tractability of continuous cell lines. Derived neurons should be homotypic, exhibit neuron-specific gene expression and morphology, form functioning synapses and consistently respond to neurotoxins in a fashion indistinguishable from primary neurons. However, efficient methods to produce neuronal populations that are suitable alternatives to primary neurons have not been available.

Methods

With the objective of developing a more facile, robust and efficient method to generate enriched glutamatergic neuronal cultures, we evaluated the neurogenic capacity of three mouse embryonic stem cell (ESC) lines (R1, C57BL/6 and D3) adapted to feeder-independent suspension culture. Neurogenesis and neuronal maturation were characterized as a function of time in culture using immunological, genomic, morphological and functional metrics. The functional responses of ESNs to neurotropic toxins with distinctly different targets and mechanisms of toxicity, such as glutamate, α-latrotoxin (LTX), and botulinum neurotoxin (BoNT), were also evaluated.

Results

Suspension-adapted ESCs expressed markers of pluripotency through at least 30 passages, and differentiation produced 97×106 neural progenitor cells (NPCs) per 10-cm dish. Greater than 99% of embryonic stem cell-derived neurons (ESNs) expressed neuron-specific markers by 96 h after plating and rapidly developed complex axodendritic arbors and appropriate compartmentalization of neurotypic proteins. Expression profiling demonstrated the presence of transcripts necessary for neuronal function and confirmed that ESN populations were predominantly glutamatergic. Furthermore, ESNs were functionally receptive to all toxins with sensitivities and responses consistent with primary neurons.

Conclusions

These findings demonstrate a cost-effective, scalable and flexible method to produce a highly enriched glutamatergic neuron population. The functional characterization of pathophysiological responses to neurotropic toxins and the compatibility with multi-well plating formats were used to demonstrate the suitability of ESNs as a discovery platform for molecular mechanisms of action, moderate-throughput analytical approaches and diagnostic screening. Furthermore, for the first time we demonstrate a cell-based model that is sensitive to all seven BoNT serotypes with EC50 values comparable to those reported in primary neuron populations. These data providing compelling evidence that ESNs offer a neuromimetic platform suitable for the evaluation of molecular mechanisms of neurotoxicity.
Does the variable-stiffness colonoscope makes colonoscopy easier? A meta-analysis of the efficacy of the variable stiffness colonoscope compared with the standard adult colonoscope
Authors: Xie Qin , Chen Bin , Liu Liu , Gan Huatian
Published: October 2012

Background

The variable-stiffness colonoscope (VSC) appears to have advantages over the standard adult colonoscope (SAC), although data are conflicting. To provide a comprehensive up-to-date review, we conducted a meta-analysis to compare the efficacies of the VSC and SAC.

Methods

Electronic databases, including PubMed, EMBASE, the Cochrane library and the Science Citation Index, were searched to retrieve relevant trials. In addition, meeting abstracts and the reference lists of retrieved articles were reviewed for further relevant studies.

Results

Eight randomized controlled trials (RCTs), enrolling a total of 2033 patients, were included in the meta-analysis. There was no significant heterogeneity among these studies. The cecal intubation rate was higher with the use of VSC (RR = 1.03, 95% CI 1.01 to 1.06, 8 RCTs). The VSC was also associated with fewer position changes made during colonoscopy. Time to cecal intubation was similar with VSC and SAC (WMD −0.54, 95% CI −1.40 to 0.32) but shorter in subgroup analysis with the use of VSC (WMD = −1.36, 95% CI −2.29 to −0.43). Sedation dose used with the two types of instruments showed no evidence of differences either. For all trials, only patients were blinded because of the nature of the interventions.

Conclusion

Use of the VSC significantly improved the cecal intubation rate and reduced ancillary maneuvers made during the procedure. Cecal intubation time was similar for the two colonoscope types over all trials, whereas a shortened time with the use of the adult VSC was seen in subgroup analysis.
SOXs in human prostate cancer: implication as progression and prognosis factors
Authors: Zhong Wei-de , Qin Guo-qiang , Dai Qi-shan , Han Zhao-dong , Chen Shan-ming , Ling Xiao-hui , Fu Xin , Cai Chao , Chen Jia-hong , Chen Xi-bin , Lin Zhuo-yuan , Deng Ye-han , Wu Shu-lin , He Hui-chan , Wu Chin-lee
Published: October 2012

Background

SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa).

Methods

The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa.

Results

The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance.

Conclusions

Our data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.
Possible relation between maternal consumption of added sugar and sugar-sweetened beverages and birth weight – time trends in a population
Authors: Grundt Jacob Holter , Nakling Jakob , Eide Geir Egil , Markestad Trond
Published: October 2012

Background

High birth weight (BW) is a risk factor for later obesity. In Norway, mean BW and proportion of large newborns increased from 1989 to 2000 and subsequently decreased to the 1989 level by 2010. The purpose of the study was to explore causes of this temporary increase.

Methods

From a regional prospective database pregnancy and newborn data were extracted for all 33088 singleton pregnancies resulting in live infants born at term without malformations during 1989–2010. Trends in BW, ponderal index and proportion of large newborns were related to individual prenatal exposures, including pre-pregnancy body mass index (PP-BMI) and gestational weight gain (GWG) for the years 2001–2010, and thereafter related ecologically to national population data on consumption of nutrients and physical activity.

Results

For the regional cohort mean (standard deviation) BW increased from 3580 (453) grams in 1989/90 to 3633 (493) grams in 2001/02 (p<0.001), and decreased to 3583 (481) grams in 2009/10 (p<0.001). The proportion with BW>4500 grams increased from 2.6% to 4.8% (p<0.001) and subsequently decreased to 3.3% (p=0.002). The trends remained after adjustment for relevant exposures. For the years 2001/02 to 2009/10 (n= 15240) mean (SD) PP-BMI increased from 24.36 (4.44) to 24.85 (5.02) kg/m2 (p<0.001) while GWG decreased from 14.79 (5.85) to 13.86 (5.79) kg (p<0.001). The estimated net effect of changes in PP-BMI, GWG and other known exposures was a 6 grams reduction in BW from 2001/02 to 2009/10, leaving 44 grams reduction unexplained. National consumption of major nutrients did not change, but consumption of sucrose, in large part as sugar-sweetened beverages (SSB) changed in parallel to the BW trends.

Conclusion

The temporary increase in BW and large babies in the regional cohort was identical to that reported for Norway. Individual level data on known pregnancy related predictors for BW could not explain these changes, but the parallel time trend in national consumption of sucrose, in particular as SSB, may lend support to a hypothesis that intake of sugar may have a direct effect on BW and infant body proportions independent of effects through PP-BMI and GWG.
Neonatal sepsis at Muhimbili National Hospital, Dar es Salaam, Tanzania; aetiology, antimicrobial sensitivity pattern and clinical outcome
Authors: Mhada Tumaini V , Fredrick Francis , Matee Mecky I , Massawe Augustine
Published: October 2012

Background

Neonatal sepsis contributes significantly to morbidity and mortality among young infants. The aetiological agents as well as their susceptibility to antimicrobial agents are dynamic. This study determined aetiology, antimicrobial susceptibility and clinical outcome of neonatal sepsis at Muhimbili National Hospital.

Methods

Three hundred and thirty neonates admitted at the Muhimbili National Hospital neonatal ward between October, 2009 and January, 2010 were recruited. Standardized questionnaires were used to obtain demographic and clinical information. Blood and pus samples were cultured on MacConkey, blood and chocolate agars and bacteria were identified based on characteristic morphology, gram stain appearance and standard commercially prepared biochemical tests. Antimicrobial sensitivity testing was performed for ampicillin, cloxacillin, gentamicin, amikacin, cefuroxime and ceftriaxone on Mueller Hinton agar using the Kirby Bauer diffusion method.

Results

Culture proven sepsis was noted in 24% (74/330) of the study participants. Isolated bacterial pathogens were predominantly Staphylococcus aureus, Klebsiella spp and Escherichia coli. Klebsiella spp 32.7% (17/52) was the predominant blood culture isolate in neonates aged below seven days while Staphylococcus aureus 54.5% (12/22) was commonest among those aged above seven days. Staphylococcus aureus was the predominant pus swabs isolate for both neonates aged 0–6 days 42.2% (98/232) and 7–28 days 52.3% (34/65). Resistance of blood culture isolates was high to ampicillin 81.1% (60/74) and cloxacillin 78.4% (58/74), moderate to ceftriaxone 14.9% (11/74) and cefuroxime 18.9% (14/74), and low to amikacin 1.3% (1/74). Isolates from swabs had high resistance to ampicillin 89.9% (267/297) and cloxacillin 85.2 (253/297), moderate resistance to ceftriaxone 38.0% (113/297) and cefuroxime 36.0% (107/297), and low resistance to amikacin 4.7% (14/297). Sepsis was higher in neonates with fever and hypothermia (p=0.02), skin pustules (p<0.001), umbilical pus discharge and abdominal wall hyperemia (p=0.04). Presence of skin pustules was an independent predictor of sepsis OR 0.26, 95% CI (0.10-0.66) p=0.004. The overall death rate was 13.9% (46/330), being higher in neonates with sepsis 24.3% (18/74) than those without 10.9% (28/256), p=0.003.

Conclusions

Staphylococcus aureus was predominant isolate followed by Klebsiella and Escherichia coli. There was high resistance to ampicillin and cloxacillin. Mortality rate due to neonatal sepsis was high in our setting. Routine antimicrobial surveillance should guide the choice of antibiotics for empirical treatment of neonatal sepsis.
Transcriptional profiling of Saccharomyces cerevisiae exposed to propolis
Authors: de Castro Patrícia Alves , Savoldi Marcela , Bonatto Diego , Malavazi Iran , Goldman Maria Helena S , Berretta Andresa A , Goldman Gustavo Henrique
Published: October 2012

Background

Propolis is a natural product of plant resins collected by honeybees (Apis mellifera) from various plant sources. Our previous studies indicated that propolis sensitivity is dependent on the mitochondrial function and that vacuolar acidification and autophagy are important for yeast cell death caused by propolis. Here, we extended our understanding of propolis-mediated cell death in the yeastSaccharomyces cerevisiaeby applying systems biology tools to analyze the transcriptional profiling of cells exposed to propolis.

Methods

We have used transcriptional profiling ofS. cerevisiaeexposed to propolis. We validated our findings by using real-time PCR of selected genes. Systems biology tools (physical protein-protein interaction [PPPI] network) were applied to analyse the propolis-induced transcriptional bevavior, aiming to identify which pathways are modulated by propolis inS. cerevisiaeand potentially influencing cell death.

Results

We were able to observe 1,339 genes modulated in at least one time point when compared to the reference time (propolis untreated samples) (t-test,p-value 0.01). Enrichment analysis performed by Gene Ontology (GO) Term finder tool showed enrichment for several biological categories among the genes up-regulated in the microarray hybridization such as transport and transmembrane transport and response to stress. Real-time RT-PCR analysis of selected genes showed by our microarray hybridization approach was capable of providing information aboutS. cerevisiaegene expression modulation with a considerably high level of confidence. Finally, a physical protein-protein (PPPI) network design and global topological analysis stressed the importance of these pathways in response ofS. cerevisiaeto propolis and were correlated with the transcriptional data obtained thorough the microarray analysis.

Conclusions

In summary, our data indicate that propolis is largely affecting several pathways in the eukaryotic cell. However, the most prominent pathways are related to oxidative stress, mitochondrial electron transport chain, vacuolar acidification, regulation of macroautophagy associated with protein target to vacuole, cellular response to starvation, and negative regulation of transcription from RNA polymerase II promoter. Our work emphasizes again the importance ofS. cerevisiaeas a model system to understand at molecular level the mechanism whereby propolis causes cell death in this organism at the concentration herein tested. Our study is the first one that investigates systematically by using functional genomics how propolis influences and modulates the mRNA abundance of an organism and may stimulate further work on the propolis-mediated cell death mechanisms in fungi.
Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines
Authors: Almanaa Taghreed N , Geusz Michael E , Jamasbi Roudabeh J
Published: October 2012

Background

Many cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized.

Methods

Cell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20–80 μM curcumin for 30 hrs. Cell lines surviving 40 or 60 μM curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-κB were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 μM curcumin to determine whether their sensitivity was different from the original lines.

Results

The cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 μM curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-κB and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity to curcumin when compared with the original lines.

Conclusion

Our results suggest that curcumin not only eliminates cancer cells but also targets CSCs. Therefore, curcumin may be an effective compound for treating esophageal and possibly other cancers in which CSCs can cause tumor recurrence.
Construction of a two-parameter empirical model of left ventricle wall motion using cardiac tagged magnetic resonance imaging data
Authors: Shi Jack J , Alenezy Mohammed , Smirnova Irina V , Bilgen Mehmet
Published: October 2012

Background

A one-parameter model was previously proposed to characterize the short axis motion of the LV wall at the mid-ventricle level. The single parameter of this model was associated with the radial contraction of myocardium, but more comprehensive model was needed to account for the rotation at the apex and base levels. The current study developed such model and demonstrated its merits and limitations with examples.

Materials and methods

The hearts of five healthy individuals were visualized using cardiac tagged magnetic resonance imaging (tMRI) covering the contraction and relaxation phases. Based on the characteristics of the overall dynamics of the LV wall, its motion was represented by a combination of two components - radial and rotational. Each component was represented by a transformation matrix with a time-dependent variable α or β.

Image preprocessing step and model fitting algorithm were described and applied to estimate the temporal profiles of α and β within a cardiac cycle at the apex, mid-ventricle and base levels. During this process, the tagged lines of the acquired images served as landmark reference for comparing against the model prediction of the motion. Qualitative and quantitative analyses were performed for testing the performance of the model and thus its validation.

Results

The α and β estimates exhibited similarities in values and temporal trends once they were scaled by the radius of the epicardium (r

epi
)and plotted against the time scaled by the period of the cardiac cycle (T

cardiac
) of each heart measured during the data acquisition. α/r

epi
peaked at about Δt/T

cardiac
=0.4 and with values 0.34, 0.4 and 0.3 for the apex, mid-ventricle and base level, respectively. β/r

epi
similarly maximized in amplitude at about Δt/T

cardiac
=0.4, but read 0.2 for the apex and - 0.08 for the base level. The difference indicated that the apex twisted more than the base.

Conclusion

It is feasible to empirically model the spatial and temporal evolution of the LV wall motion using a two-parameter formulation in conjunction with tMRI-based visualization of the LV wall in the transverse planes of the apex, mid-ventricle and base. In healthy hearts, the analytical model will potentially allow deriving biomechanical entities, such as strain, strain rate or torsion, which are typically used as diagnostic, prognostic or predictive markers of cardiovascular diseases including diabetes.
Charge transfer magnetoexciton formation at vertically coupled quantum dots
Authors: Gutiérrez Willian , Marin Jairo H , Mikhailov Ilia D
Published: October 2012

A theoretical investigation is presented on the properties of charge transfer excitons at vertically coupled semiconductor quantum dots in the presence of electric and magnetic fields directed along the growth axis. Such excitons should have two interesting characteristics: an extremely long lifetime and a permanent dipole moment. We show that wave functions and the low-lying energies of charge transfer exciton can be found exactly for a special morphology of quantum dots that provides a parabolic confinement inside the layers. To take into account a difference between confinement potentials of an actual structure and of our exactly solvable model, we use the Galerkin method. The density of energy states is calculated for different InAs/GaAs quantum dots’ dimensions, the separation between layers, and the strength of the electric and magnetic fields. A possibility of a formation of a giant dipolar momentum under external electric field is predicted.
Naturally occurring mutations to HCV protease inhibitors in treatment-naïve patients
Authors: Paolucci Stefania , Fiorina Loretta , Piralla Antonio , Gulminetti Roberto , Novati Stefano , Barbarini Giorgio , Sacchi Paolo , Gatti Marta , Dossena Luca , Baldanti Fausto
Published: October 2012

Background

Protease inhibitors (PIs) to treat hepatitis C (HCV) virus infection have been approved and others are under development.

Results

The aims of this study were to illustrate natural polymorphisms in the HCV protease and measure the frequency of PI resistance mutations in different HCV genotypes from PI-naïve patients.

Direct sequencing of HCV NS3/4A protease was performed in 156 HCV patients naïve to PIs who were infected with genotype 1a (n = 31), 1b (n = 39), 2 (n = 30), 3 (n = 33) and 4 (n = 23).

Amino acid (aa) substitutions associated with HCV PI resistance were found in 17/156 (10.8%) sequences. Mutations V36L, T54S, V55A/I, and Q80K/L were observed in 29% of patients with genotype 1a, and V55F, Q80L/N and M175L in 10% of patients with genotype 1b. The mutation V158M was found in 3% of patients with genotype 2, D168Q was present in 100% of patients with genotype 3 and D168E was observed in 13% of patients with genotype 4. In addition, multiple aa polymorphisms not associated with PI resistance were detected in patients with genotypes 1a, 1b and 4.

Conclusions

Although major PI resistance mutations were not detected, other resistance mutations conferring low level resistance to PIs together with a number of natural polymorphisms were observed in proteases of PI naïve HCV patients. A more extensive analysis is needed to better evaluate the impact of baseline resistance and compensatory mutations in the efficacy of HCV PI treatment.
RETRACTED ARTICLE: Assessment of the influence of whole body vibration on Cochlear function
Authors: Moussavi-Najarkola Seyyed-Ali , Khavanin Ali , Mirzaei Ramazan , Salehnia Mojdeh , Akbari Mehdi
Published: October 2012

Background

Whole body vibration (WBV) is a potentially harmful consequence resulting from the dissipation of energy by industrial machineries. The result of WBV exposure on the auditory system remains unknown. The objective of the present research was to evaluate the influence of WBV on cochlear function, in particular outer hair cell function. It is hypothesized that WBV impairs cochlear function resulting in decreased Distortion Product Otoacoustic Emission (DPOAE) levels (Ldp) in rabbits subjected to WBV.

Methods

Twelve rabbits were equally divided into vibration and control groups. Animals in vibration group were exposed to 1.0 ms-2 r.m.s vertical WBV at 4–8 Hz for 8 h/day during 5 consecutive days. Outer hair cell function was assessed by comparing repeated-measurements of DPOAE levels (Ldp) across a range of f2 frequencies in rabbits both exposed and unexposed to WBV. DPOAE level shifts (LSdp) were compared across ears, frequencies, groups, and times.

Results

No differences were seen over time in DPOAE levels in the non-exposed rabbits (p = 0.082). Post-exposure Ldp in rabbits exposed to WBV were significantly increased at all test frequencies in both ears compared to baseline measures (p = 0.021). The greatest increase in Ldp following exposure was seen at 5888.5 Hz (mean shift = 13.25 dB). Post-exposure Ldp in rabbits exposed to WBV were not significantly different between the right and left ears (p = 0.083).

Conclusion

WBV impairs cochlear function resulting in increased DPOAE responses in rabbits exposed to WBV. DPOAE level shifts occurred over a wide range of frequencies following prolonged WBV in rabbits.
Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP
Authors: Aulas Anaïs , Stabile Stéphanie , Vande Velde Christine
Published: October 2012

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, a cell type that is intrinsically more vulnerable than other cell types to exogenous stress. The interplay between genetic susceptibility and environmental exposures to toxins has long been thought to be relevant to ALS. One cellular mechanism to overcome stress is the formation of small dense cytoplasmic domains called stress granules (SG) which contain translationally arrested mRNAs. TDP-43 (encoded by TARDBP) is an ALS-causative gene that we have previously implicated in the regulation of the core stress granule proteins G3BP and TIA-1. TIA-1 and G3BP localize to SG under nearly all stress conditions and are considered essential to SG formation. Here, we report that TDP-43 is required for proper SG dynamics, especially SG assembly as marked by the secondary aggregation of TIA-1. We also show that SG assembly, but not initiation, requires G3BP. Furthermore, G3BP can rescue defective SG assembly in cells depleted of endogenous TDP-43. We also demonstrate that endogenous TDP-43 and FUS do not have overlapping functions in this cellular process as SG initiation and assembly occur normally in the absence of FUS. Lastly, we observe that SG assembly is a contributing factor in the survival of neuronal-like cells responding to acute oxidative stress. These data raise the possibility that disruptions of normal stress granule dynamics by loss of nuclear TDP-43 function may contribute to neuronal vulnerability in ALS.
Directed evolution of bright mutants of an oxygen-independent flavin-binding fluorescent protein from Pseudomonas putida
Authors: Mukherjee Arnab , Weyant Kevin B , Walker Joshua , Schroeder Charles M
Published: October 2012

Background

Fluorescent reporter proteins have revolutionized our understanding of cellular bioprocesses by enabling live cell imaging with exquisite spatio-temporal resolution. Existing fluorescent proteins are predominantly based on the green fluorescent protein (GFP) and related analogs. However, GFP-family proteins strictly require molecular oxygen for maturation of fluorescence, which precludes their application for investigating biological processes in low-oxygen environments. A new class of oxygen-independent fluorescent reporter proteins was recently reported based on flavin-binding photosensors from Bacillus subtilis and Pseudomonas putida. However, flavin-binding fluorescent proteins show very limited brightness, which restricts their utility as biological imaging probes.

Results

In this work, we report the discovery of bright mutants of a flavin-binding fluorescent protein from P. putida using directed evolution by site saturation mutagenesis. We discovered two mutations at a chromophore-proximal amino acid (F37S and F37T) that confer a twofold enhancement in brightness relative to the wild type fluorescent protein through improvements in quantum yield and holoprotein fraction. In addition, we observed that substitution with other aromatic amino acids at this residue (F37Y and F37W) severely diminishes fluorescence emission. Therefore, we identify F37 as a key amino acid residue in determining fluorescence.

Conclusions

To increase the scope and utility of flavin-binding fluorescent proteins as practical fluorescent reporters, there is a strong need for improved variants of the wild type protein. Our work reports on the application of site saturation mutagenesis to isolate brighter variants of a flavin-binding fluorescent protein, which is a first-of-its-kind approach. Overall, we anticipate that the improved variants will find pervasive use as fluorescent reporters for biological studies in low-oxygen environments.
Paradigmatic status of an endo- and exoglucanase and its effect on crystalline cellulose degradation
Authors: Moraïs Sarah , Barak Yoav , Lamed Raphael , Wilson David B , Xu Qi , Himmel Michael E , Bayer Edward A
Published: October 2012

Background

Microorganisms employ a multiplicity of enzymes to efficiently degrade the composite structure of plant cell wall cellulosic polysaccharides. These remarkable enzyme systems include glycoside hydrolases (cellulases, hemicellulases), polysaccharide lyases, and the carbohydrate esterases. To accomplish this challenging task, several strategies are commonly observed either separately or in combination. These include free enzyme systems, multifunctional enzymes, and multi-enzyme self-assembled designer cellulosome complexes.

Results

In order to compare these different paradigms, we employed a synthetic biology approach to convert two different cellulases from the free enzymatic system of the well-studied bacterium, Thermobifida fusca, into bifunctional enzymes with different modular architectures. We then examined their performance compared to those of the combined parental free-enzyme and equivalent designer-cellulosome systems. The results showed that the cellulolytic activity displayed by the different architectures of the bifunctional enzymes was somewhat inferior to that of the wild-type free enzyme system.

Conclusions

The activity exhibited by the designer cellulosome system was equal or superior to that of the free system, presumably reflecting the combined proximity of the enzymes and high flexibility of the designer cellulosome components, thus enabling efficient enzymatic activity of the catalytic modules.
Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults
Authors: Dixon Brian M , Barker Tyler , McKinnon Toni , Cuomo John , Frei Balz , Borregaard Niels , Gombart Adrian F
Published: October 2012

Background

Transcription of the cathelicidin antimicrobial peptide (CAMP) gene is induced by binding of the bioactive form of vitamin D, 1,25-dihydroxyvitamin D, to the vitamin D receptor. Significant levels of the protein hCAP18/LL-37 are found in the blood and may protect against infection and/or sepsis. We hypothesized that serum vitamin D levels may modulate the circulating levels of hCAP18. Only three studies have shown a positive correlation between circulating 25-hydroxyvitamin D and hCAP18 levels. Here we provide additional evidence for such a correlation in healthy, middle-aged adults.

Findings

Serum levels of 25-hydroxyvitamin D [25(OH)D] and plasma levels of hCAP18 were determined in 19 healthy middle-aged (mean of 50.1 years) adult men and women. Plasma hCAP18 concentrations correlated with serum 25(OH)D concentrations in subjects with 25(OH)D levels ≤ 32 ng/ml (r = 0.81, p < 0.005) but not in subjects with concentrations > 32 ng/ml (r = 0.19, p = 0.63).

Conclusions

We conclude that plasma hCAP18 levels correlate with serum 25(OH)D levels in subjects with concentrations of 25(OH)D ≤ 32 ng/ml as opposed to those with concentrations > 32 ng/ml and that vitamin D status may regulate systemic levels of hCAP18/LL-37.