bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotion, Emotion Regulation, and Conflict Resolution
Authors: Halperin Eran
Published: September 2013

The central role played by emotions in conflict has long been recognized by many of the scholars who study ethnic conflicts and conflict resolution. Yet recent developments in the psychological study of discrete emotions and of emotion regulation have yet to receive adequate attention by those who study and seek to promote conflict resolution. At the same time, scholars of emotion and emotion regulation have only rarely tested their core theories in the context of long-term conflicts, which constitute a unique and highly emotional environment. I argue that building bridges between these two communities would help us to form a better understanding of core processes in emotion and emotion regulation as well as greatly advance theory and practice in conflict resolution. To address that goal, a theoretical, appraisal-based model elucidating the way emotions operate in the context of conflict resolution processes is presented, followed by a review of recent empirical developments in the study of discrete emotions in conflict resolution processes. Next, I discuss various avenues of influence and provide preliminary data regarding the potential role of two types of emotion regulation processes (i.e., direct and indirect) in conflict resolution efforts. Finally, I describe the future challenges in integrating these two bodies of knowledge, at both the theoretical and the applied levels.
Blastocystis, an unrecognized parasite: an overview of pathogenesis and diagnosis
Authors: Wawrzyniak Ivan , Poirier Philippe , Viscogliosi Eric , Dionigia Meloni , Texier Catherine , Delbac Frédéric , Alaoui Hicham El
Published: September 2013

Blastocystis sp. is among the few enteric parasites with a prevalence that often exceeds 5% in the general population of industrialized countries and can reach 30–60% in developing countries. This parasite is frequently found in people who are immunocompromised (patients with human immunodeficiency virus/acquired immunodeficiency syndrome or cancer) and a higher risk of Blastocystis sp. infection has been found in people with close animal contact. Such prevalence in the human population and the zoonotic potential naturally raise questions about the impact of these parasites on public health and has increased interest in this area. Recent in vitro and in vivo studies have shed new light on the pathogenic power of this parasite, suggesting that Blastocystis sp. infection is associated with a variety of gastrointestinal disorders, may play a significant role in irritable bowel syndrome, and may be linked with cutaneous lesions (urticaria). Despite recent significant advances in the knowledge of the extensive genetic diversity of this species, the identification of extracellular proteases as virulence factors and the publication of one isolate genome, many aspects of the biology of Blastocystis sp. remain poorly investigated. In this review, we investigate several biological aspects of Blastocystis sp. (diversity and epidemiology, diagnosis tools and pathophysiology). These data pave the way for the following challenges concerning Blastocystis sp. research: deciphering key biological mechanisms and pathways of this parasite and clarification of its clinical impact in humans.
Review on Supply Chain Management Research—An Indian Perspective
Authors: Gurumurthy Anand , Soni Gunjan , Prakash Surya , Badhotiya Gaurav Kumar
Published: September 2013

In India, Supply Chain Management (SCM) has gained significant importance due to opening up of domestic economy as a result of globalization. However, a review of literature revealed that not many papers are available which attempt to document and understand the importance of SCM within the Indian business context. Hence, the purpose of this research is to fill in this research gap by analyzing the contributions of academicians and practitioners addressing various supply chain issues—specifically from an Indian perspective. Papers focusing on SCM scenario in India were collected from multiple sources by following the established methodologies available in the literature for carrying out such reviews. Furthermore, a new taxonomy was proposed on the basis of content and research methodology utilized. Based on this taxonomy, significant trends were observed and some unique inferences were drawn, apart from identifying the directions for future research. It is hoped that this work would add value by offering a unique contribution to the body of knowledge on SCM, as there is no article available in the literature, which has attempted to summarize the works from India related to SCM.
DNA methylation of Runx1 regulatory regions correlates with transition from primitive to definitive hematopoietic potential in vitro and in vivo
Authors: Webber Beau R. , Iacovino Michelina , Choi Si Ho , Tolar Jakub , Kyba Michael , Blazar Bruce R.
Published: September 2013

Key Points

DNA methylation profile of Runx1 locus correlates with transcriptional activity and promoter usage during blood development. Distal promoter hypomethylation is a novel signature of definitive hematopoiesis and is promoted in vitro by direct interaction with HoxB4.
Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study
Authors: Cruz Conrad Russell Y. , Micklethwaite Kenneth P. , Savoldo Barbara , Ramos Carlos A. , Lam Sharon , Ku Stephanie , Diouf Oumar , Liu Enli , Barrett A. John , Ito Sawa , Shpall Elizabeth J. , Krance Robert A. , Kamble Rammurti T. , Carrum George , Hosing Chitra M. , Gee Adrian P. , Mei Zhuyong , Grilley Bambi J. , Heslop Helen E. , Rooney Cliona M. , Brenner Malcolm K. , Bollard Catherine M. , Dotti Gianpietro
Published: September 2013

Key Points

Allogeneic CD19-CAR VSTs are well tolerated by patients with relapsed B-cell malignancies post-HSCT. At periods of CD19-CAR VST persistence, these cells demonstrate antitumor activity.
Myosin VI contributes to maintaining epithelial barrier function
Authors: Liao Yu-Wei , Wu Xing-Mao , Jia Jia , Wu Xiao-Lei , Hong Tao , Meng Ling-Xin , Wu Xiu-Ying
Published: September 2013

Background

Epithelial barrier dysfunction is associated with the pathogenesis of a number of immune inflammations; the etiology is not fully understood. The fusion of endosome/lysosome is a critical process in the degradation of endocytic antigens in epithelial cells. Recent reports indicate that myosin VI (myo6) is involved in the activities of endosomes. The present study aims to investigate the role of myo6 in epithelial barrier dysfunction.

Results

The endosome accumulation was observed in myo6-deficient Rmcs. More than 80% endosomes were fused with lysosomes in naïve Rmcs while less than 30% endosomes were fused with lysosomes in the myo6-deficient Rmcs. The myo6-deficient Rmc monolayers showed high permeability to a macromolecular antigen, ovalbumin, the latter still conserved the antigenicity, which induced strong T cell activation.

Conclusions

We conclude that myo6 plays a critical role in the fusion of endosome/lysosome in Rmc epithelial cells. Deficiency of myo6 compromises the epithelial barrier function.
An EM algorithm based on an internal list for estimating haplotype distributions of rare variants from pooled genotype data
Authors: Kuk Anthony YC , Li Xiang , Xu Jinfeng
Published: September 2013

Background

Pooling is a cost effective way to collect data for genetic association studies, particularly for rare genetic variants. It is of interest to estimate the haplotype frequencies, which contain more information than single locus statistics. By viewing the pooled genotype data as incomplete data, the expectation-maximization (EM) algorithm is the natural algorithm to use, but it is computationally intensive. A recent proposal to reduce the computational burden is to make use of database information to form a list of frequently occurring haplotypes, and to restrict the haplotypes to come from this list only in implementing the EM algorithm. There is, however, the danger of using an incorrect list, and there may not be enough database information to form a list externally in some applications.

Results

We investigate the possibility of creating an internal list from the data at hand. One way to form such a list is to collapse the observed total minor allele frequencies to “zero” or “at least one”, which is shown to have the desirable effect of amplifying the haplotype frequencies. To improve coverage, we propose ways to add and remove haplotypes from the list, and a benchmarking method to determine the frequency threshold for removing haplotypes. Simulation results show that the EM estimates based on a suitably augmented and trimmed collapsed data list (ATCDL) perform satisfactorily. In two scenarios involving 25 and 32 loci respectively, the EM-ATCDL estimates outperform the EM estimates based on other lists as well as the collapsed data maximum likelihood estimates.

Conclusions

The proposed augmented and trimmed CD list is a useful list for the EM algorithm to base upon in estimating the haplotype distributions of rare variants. It can handle more markers and larger pool size than existing methods, and the resulting EM-ATCDL estimates are more efficient than the EM estimates based on other lists.
Genome and transcriptome sequencing of the halophilic fungus Wallemia ichthyophaga: haloadaptations present and absent
Authors: Zajc Janja , Liu Yongfeng , Dai Wenkui , Yang Zhenyu , Hu Jingzhi , Gostinčar Cene , Gunde-Cimerman Nina
Published: September 2013

Background

The basidomycete Wallemia ichthyophaga from the phylogenetically distinct class Wallemiomycetes is the most halophilic fungus known to date. It requires at least 10% NaCl and thrives in saturated salt solution. To investigate the genomic basis of this exceptional phenotype, we obtained a de-novo genome sequence of the species type-strain and analysed its transcriptomic response to conditions close to the limits of its lower and upper salinity range.

Results

The unusually compact genome is 9.6 Mb large and contains 1.67% repetitive sequences. Only 4884 predicted protein coding genes cover almost three quarters of the sequence. Of 639 differentially expressed genes, two thirds are more expressed at lower salinity. Phylogenomic analysis based on the largest dataset used to date (whole proteomes) positions Wallemiomycetes as a 250-million-year-old sister group of Agaricomycotina. Contrary to the closely related species Wallemia sebi, W. ichthyophaga appears to have lost the ability for sexual reproduction. Several protein families are significantly expanded or contracted in the genome. Among these, there are the P-type ATPase cation transporters, but not the sodium/ hydrogen exchanger family. Transcription of all but three cation transporters is not salt dependent. The analysis also reveals a significant enrichment in hydrophobins, which are cell-wall proteins with multiple cellular functions. Half of these are differentially expressed, and most contain an unusually large number of acidic amino acids. This discovery is of particular interest due to the numerous applications of hydrophobines from other fungi in industry, pharmaceutics and medicine.

Conclusions

W. ichthyophaga is an extremophilic specialist that shows only low levels of adaptability and genetic recombination. This is reflected in the characteristics of its genome and its transcriptomic response to salt. No unusual traits were observed in common salt-tolerance mechanisms, such as transport of inorganic ions or synthesis of compatible solutes. Instead, various data indicate a role of the cell wall of W. ichthyophaga in its response to salt. Availability of the genomic sequence is expected to facilitate further research into this unique species, and shed more light on adaptations that allow it to thrive in conditions lethal to most other eukaryotes.
Derivation and assessment of risk prediction models using case-cohort data
Authors: Sanderson Jean , Thompson Simon G , White Ian R , Aspelund Thor , Pennells Lisa
Published: September 2013

Background

Case-cohort studies are increasingly used to quantify the association of novel factors with disease risk. Conventional measures of predictive ability need modification for this design. We show how Harrell’s C-index, Royston’s D, and the category-based and continuous versions of the net reclassification index (NRI) can be adapted.

Methods

We simulated full cohort and case-cohort data, with sampling fractions ranging from 1% to 90%, using covariates from a cohort study of coronary heart disease, and two incidence rates. We then compared the accuracy and precision of the proposed risk prediction metrics.

Results

The C-index and D must be weighted in order to obtain unbiased results. The NRI does not need modification, provided that the relevant non-subcohort cases are excluded from the calculation. The empirical standard errors across simulations were consistent with analytical standard errors for the C-index and D but not for the NRI. Good relative efficiency of the prediction metrics was observed in our examples, provided the sampling fraction was above 40% for the C-index, 60% for D, or 30% for the NRI. Stata code is made available.

Conclusions

Case-cohort designs can be used to provide unbiased estimates of the C-index, D measure and NRI.
Mycobacterium tuberculosisis the causative agent of tuberculosis in the southern ecological zones of Cameroon, as shown by genetic analysis
Authors: Assam Jean Paul Assam , Beng Véronique Penlap , Cho-Ngwa Fidelis , Toukam Michel , Ngoh Ane-Anyangwe Irene , Kitavi Mercy , Nzuki Inoster , Nyonka Juliette N , Tata Emilienne , Tedom Jean Claude , Skilton Robert A , Pelle Roger , Titanji Vincent P K
Published: September 2013

Background

Tuberculosis (TB) is a major cause of mortality and suffering worldwide, with over 95% of TB deaths occurring in low- and middle-income countries. In recent years, molecular typing methods have been widely used in epidemiological studies to aid the control of TB, but this usage has not been the case with many African countries, including Cameroon. The aims of the present investigation were to identify and evaluate the diversity of the Mycobacterium tuberculosis complex (MTBC) isolates circulating in two ecological zones of Cameroon, seven years after the last studies in the West Region, and after the re-organization of the National TB Control Program (NTBCP). These were expected to shed light also on the transmission of TB in the country. The study was conducted from February to July 2009. During this period, 169 patients with symptomatic disease and with sputum cultures that were positive for MTBC were randomly selected for the study from amongst 964 suspected patients in the savannah mosaic zone (West and North West regions) and the tropical rainforest zone (Central region). After culture and diagnosis, DNA was extracted from each of the MTBC isolates and transported to the BecA-ILRI Hub in Nairobi, Kenya for molecular analysis.

Methods

Genetic characterization was done by mycobacterial interspersed repetitive unit–variable number tandem repeat typing (MIRU-VNTR) and Spoligotyping.

Results

Molecular analysis showed that all TB cases reported in this study were caused by infections with Mycobacterium tuberculosis (98.8%) and Mycobacterium africanum (M. africanum) (1.2%) respectively. We did not detect any M. bovis. Comparative analyses using spoligotyping revealed that the majority of isolates belong to major clades of M. tuberculosis: Haarlem (7.6%), Latin American-Mediterranean (34.4%) and T clade (26.7%); the remaining isolates (31.3%) where distributed among the minor clades. The predominant group of isolates (34.4%) corresponded to spoligotype 61, previously described as the “Cameroon family. Further analysis based on MIRU-VNTR profiles had greater resolving power than spoligotyping and defined additional genotypes in the same spoligotype cluster.

Conclusion

The molecular characterization of MTBC strains from humans in two ecological regions of Cameroon has shown that M. tuberculosis sensu stricto is the predominant agent of TB cases in the zones. Three decades ago, TB was reported to be caused by M. africanum in 56.0% of cases. The present findings are consistent with a major shift in the prevalence of M. tuberculosis in Cameroon.
A new mutation in the gene encoding mitochondrial seryl-tRNA synthetase as a cause of HUPRA syndrome
Authors: Rivera Henry , Martín-Hernández Elena , Delmiro Aitor , García-Silva María Teresa , Quijada-Fraile Pilar , Muley Rafael , Arenas Joaquín , Martín Miguel A , Martínez-Azorín Francisco
Published: September 2013

Background

HUPRA syndrome is a rare mitochondrial disease characterized by hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis. This syndrome was previously described in three patients with a homozygous mutation c.1169A > G (p.D390G) in SARS2, encoding the mitochondrial seryl-tRNA synthetase.

Case presentation

Here we report the clinical and genetic findings in a girl and her brother. Both patients were clinically diagnosed with the HUPRA syndrome. Analysis of the pedigree identified a new homozygous mutation c.1205G > A (p.R402H) in SARS2 gene. This mutation is very rare in the population and it is located at the C-terminal globular domain of the homodimeric enzyme very close to p.D390G.

Conclusion

Several data support that p.R402H mutation in SARS2 is a new cause of HUPRA syndrome.
Evaluation of the immune factors in the tumor environment before and after the treatment of cetuximab combined with chemotherapy
Authors: Zhu Yanyun , Li Jie , Jing Fangfang , Ji Tiefeng , Guo Xiaoqin , Yang Junlan , Jiao Shunchang
Published: September 2013

Background

The effect of chemotherapy combined with monoclonal antibodies (mAbs) on the immune state of the tumor environment remains unclear and controversial. The aim of this study is to examine the effect of chemotherapy combined with cetuximab (C225, an anti-EGFR mAb) on the immune state of tumor environment, and the correlation of that effect and the clinical efficacy.

Methods

Twelve patients with colorectal cancer, who received the treatment of chemotherapy combined with C225, were enrolled in this study. The tumor specimen of the primary colorectal cancer before and after treatment was obtained. The expression of a series of immune factors (TGF-β1, CD8, IL-2, TNF-α, and VEGF) was measured by immunochemistry. The expression of these immune factors before and after treatment was compared by the Wilcoxon signed-rank test. The correlation of the change of immune parameter expression after treatment and clinical efficacy was examined by chi-square tests. The correlation of the expression of immune factors, clinical efficacy, and treatment number was examined by the Spearman’s correlation analysis.

Results

There was no significant difference between the expression of TGF-β1 before and after the treatment (P >0.05). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (P = 0.05). As for CD8, IL-2, VEGF, and TNF-α, there were no significant differences between the expression before and after the treatment (P >0.05), and the change of expression after treatment also did not correlate significantly with clinical efficacy (P >0.05). The change of IL-2 expression after treatment significantly correlated negatively with treatment number (correlation coefficient = -0.585, P = 0.046). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (correlation coefficient = -0.684, P = 0.014). Before treatment, the expression of TNF-α significantly correlated positively with the expression of IL-2 (correlation coefficient = 0.629, P = 0.028). After treatment, the expression of TGF-β1 significantly correlated negatively with the expression of CD8 (correlation coefficient = -0.664, P = 0.019).

Conclusions

These results suggested that, in the tumor environment, the change of immune factors after treatment of cetuximab combined with chemotherapy may be associated with clinical efficacy.
rAAV-mediated overexpression of TGF-β stably restructures human osteoarthritic articular cartilage in situ
Authors: Venkatesan Jagadeesh K , Rey-Rico Ana , Schmitt Gertrud , Wezel Anna , Madry Henning , Cucchiarini Magali
Published: September 2013

Background

Therapeutic gene transfer is of significant value to elaborate efficient, durable treatments against human osteoarthritis (OA), a slow, progressive, and irreversible disorder for which there is no cure to date.

Methods

Here, we directly applied a recombinant adeno-associated virus (rAAV) vector carrying a human transforming growth factor beta (TGF-β) gene sequence to primary human normal and OA chondrocytesin vitroand cartilage explantsin situto monitor the stability of transgene expression and the effects of the candidate pleiotropic factor upon the regenerative cellular activities over time.

Results

Efficient, prolonged expression of TGF-β achieved via rAAV gene transfer enhanced both the proliferative, survival, and anabolic activities of cells over extended periods of time in all the systems evaluated (at least for 21 daysin vitroand for up to 90 daysin situ) compared with control (reporter) vector delivery, especiallyin situwhere rAAV-hTGF-β allowed for a durable remodeling of OA cartilage. Notably, sustained rAAV production of TGF-β in OA cartilage advantageously reduced the expression of key OA-associated markers of chondrocyte hypertrophic and terminal differentiation (type-X collagen, MMP-13, PTHrP, β-catenin) while increasing that of protective TIMPs and of the TGF-β receptor I in a manner that restored a favorable ALK1/ALK5 balance. Of note, the levels of activities in TGF-β-treated OA cartilage were higher than those of normal cartilage, suggesting that further optimization of the candidate treatment (dose, duration, localization, presence of modulating co-factors) will most likely be necessary to reproduce an original cartilage surface in relevant models of experimental OAin vivowithout triggering potentially adverse effects.

Conclusions

The present findings show the ability of rAAV-mediated TGF-β gene transfer to directly remodel human OA cartilage by activating the biological, reparative activities and by regulating hypertrophy and terminal differentiation in damaged chondrocytes as a potential treatment for OA or for other disorders of the cartilage that may require transplantation of engineered cells.
New microarchitectures of (Er,Yb):Lu2O3 nanocrystals embedded in PMMA: synthesis, structural characterization, and luminescent properties
Authors: Galceran Montserrat , Pujol Maria Cinta , Carvajal Joan Josep , Mateos Xavier , Formentín Pilar , Pallarès Josep , Marsal Lluis Francesc , Park Kyung Ho , Rotermund Fabian , Kim Kihong , Aguiló Magdalena , Díaz Francesc
Published: September 2013

We report the formation of two-dimensional disordered arrays of poly(methyl)methacrylate (PMMA) microcolumns with embedded single size distribution of Lu0.990Er0.520Yb0.490 nanocrystals, (Er,Yb):Lu2O3, using a disordered porous silicon template. The cubic (Er,Yb):Lu2O3 nanocrystals, which crystallize into the cubic system with

Ia

3
¯

space group, were synthesized using the modified Pechini method. Electronic microscopic techniques were used to study the distribution of the nanocrystals in the PMMA columns. Cathodoluminescence was used to observe the visible luminescence of the particles. Red emission attributed to 4 F9/2 → 4I15/2 erbium transition is predominant in these new composites.
The Anopheles community and the role of Anopheles minimus on malaria transmission on the China-Myanmar border
Authors: Yu Guo , Yan Guiyun , Zhang Naixin , Zhong Daibin , Wang Ying , He Zhengbo , Yan Zhentian , Fu Wenbo , Yang Feilong , Chen Bin
Published: September 2013

Background

Malaria around the China-Myanmar border is a serious health problem in the countries of South-East Asia. An. minimus is a principle malaria vector with a wide geographic distribution in this area. Malaria is endemic along the boundary between Yunnan province in China and the Kachin State of Myanmar where the local Anopheles community (species composition) and the malaria transmission vectors have never been clarified.

Methods

Adult Anopheles specimens were collected using CDC light traps in four villages along the border of China and Myanmar from May 2012 to April 2013. Morphological and molecular identification of mosquito adults confirmed the species of Anopheles. Blood-meal identification using the female abdomens was conducted using multiplex PCR. For sporozoite detection in An. minimus, sets of 10 female salivary glands were pooled and identified with SSU rDNA using nested PCR. Monthly abundance of An. minimus populations during the year was documented. The diversity of Anopheles and the role of An. minimus on malaria transmission in this border area were analyzed.

Results

4,833 adult mosquitoes in the genus Anopheles were collected and morphologically identified to species or species complex. The Anopheles community is comprised of 13 species, and 78.83% of our total specimens belonged to An. minimus s.l., followed by An. maculatus (5.55%) and the An. culicifacies complex (4.03%). The quantity of trapped An. minimus in the rainy season of malaria transmission was greater than during the non-malarial dry season, and a peak was found in May 2012. An. minimus fed on the blood of four animals: humans (79.8%), cattle (10.6%), pigs (5.8%) and dogs (3.8%). 1,500 females of An. minimus were pooled into 150 samples and tested for sporozoites: only 1 pooled sample was found to have sporozoites of Plasmodium vivax.

Conclusion

Anopheles is abundant with An. minimus being the dominant species and having a high human blood index along the China-Myanmar border. The sporozoites in An. minimus were determined to be Plasmodium vivax with a 0.07-0.7% infection rate.
Optimal multiobjective design of digital filters using spiral optimization technique
Authors: Ouadi Abderrahmane , Bentarzi Hamid , Recioui Abdelmadjid
Published: September 2013

The multiobjective design of digital filters using spiral optimization technique is considered in this paper. This new optimization tool is a metaheuristic technique inspired by the dynamics of spirals. It is characterized by its robustness, immunity to local optima trapping, relative fast convergence and ease of implementation. The objectives of filter design include matching some desired frequency response while having minimum linear phase; hence, reducing the time response. The results demonstrate that the proposed problem solving approach blended with the use of the spiral optimization technique produced filters which fulfill the desired characteristics and are of practical use.
Interleukin-1 beta and tumor necrosis factor alpha inhibit migration activity of chondrogenic progenitor cells from non-fibrillated osteoarthritic cartilage
Authors: Joos Helga , Wildner Anja , Hogrefe Cathrin , Reichel Heiko , Brenner Rolf E
Published: September 2013

Introduction

The repair capability of traumatized articular cartilage is highly limited so that joint injuries often lead to osteoarthritis. Migratory chondrogenic progenitor cells (CPC) might represent a target cell population for in situ regeneration. This study aims to clarify, whether 1) CPC are present in regions of macroscopically intact cartilage from human osteoarthritic joints, 2) CPC migration is stimulated by single growth factors and the cocktail of factors released from traumatized cartilage and 3) CPC migration is influenced by cytokines present in traumatized joints.

Methods

We characterized the cells growing out from macroscopically intact human osteoarthritic cartilage using a panel of positive and negative surface markers and analyzed their differentiation capacity. The migratory response to platelet-derived growth factor (PDGF)-BB, insulin-like growth factor 1 (IGF-1), supernatants obtained from in vitro traumatized cartilage and interleukin-1 beta (IL-1β) as well as tumor necrosis factor alpha (TNF-α) were tested with a modified Boyden chamber assay. The influence of IL-1β and TNF-α was additionally examined by scratch assays and outgrowth experiments.

Results

A comparison of 25 quadruplicate marker combinations in CPC and bone-marrow derived mesenchymal stromal cells showed a similar expression profile. CPC cultures had the potential for adipogenic, osteogenic and chondrogenic differentiation. PDGF-BB and IGF-1, such as the supernatant from traumatized cartilage, induced a significant site-directed migratory response. IL-1β and TNF-α significantly reduced basal cell migration and abrogated the stimulative effect of the growth factors and the trauma supernatant. Both cytokines also inhibited cell migration in the scratch assay and primary outgrowth of CPC from cartilage tissue. In contrast, the cytokine IL-6, which is present in trauma supernatant, did not affect growth factor induced migration of CPC.

Conclusion

These results indicate that traumatized cartilage releases chemoattractive factors for CPC but IL-1β and TNF-α inhibit their migratory activity which might contribute to the low regenerative potential of cartilage in vivo.
Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-κB inhibition
Authors: Whipple Rebecca A , Vitolo Michele I , Boggs Amanda E , Charpentier Monica S , Thompson Keyata , Martin Stuart S
Published: September 2013

Introduction

Detyrosinated tubulin, a post-translational modification of α-tubulin and a hallmark of stable microtubules, has gained recent attention given its association with tumor progression, invasiveness, and chemoresistance. We also recently reported that epithelial-to-mesenchymal transition (EMT) promotes tubulin detyrosination through tubulin tyrosine ligase (TTL) suppression. Furthermore, detyrosinated tubulin-enriched membrane protrusions, termed microtentacles (McTN), facilitate tumor cell reattachment to endothelial layers. Given the induction of EMT associated with inflammation and cancer progression, we tested anti-inflammatory nuclear factor-kappaB (NF-κB) inhibitors on a panel of human breast carcinoma cells to examine their effects on detyrosinated tubulin to identify more specific tubulin-directed anti-cancer treatments.

Methods

Using metastatic human breast carcinoma cells MDA-MB-157, MDA-MB-436, and Bt-549, we measured the impact of NF-κB inhibitors parthenolide, costunolide, and resveratrol on detyrosinated tubulin using protein expression analysis and immunofluorescence. A luciferase reporter assay and a viability screen were performed to determine if the effects were associated with their NF-κB inhibitory properties or were a result of apoptosis. Real-time monitoring of cell-substratum attachment was measured utilizing electrical impedance across microelectronic sensor arrays. We compared the selectivity of the NF-κB inhibitors to specifically target detyrosinated tubulin with traditional tubulin-targeted therapeutics, paclitaxel and colchicine, throughout the study.

Results

Sesquiterpene lactones, parthenolide and costunolide, selectively decrease detyrosinated tubulin independent of their inhibition of NF-κB. Live-cell scoring of suspended cells treated with parthenolide and costunolide show reduction in the frequency of microtentacles and inhibition of reattachment. Structural analysis shows that parthenolide and costunolide can decrease detyrosinated microtubules without significantly disrupting the overall microtubule network or cell viability. Paclitaxel and colchicine display indiscriminate disruption of the microtubule network.

Conclusions

Our data demonstrate that selective targeting of detyrosinated tubulin with parthenolide and costunolide can reduce McTN frequency and inhibit tumor cell reattachment. These actions are independent of their effects on NF-κB inhibition presenting a novel anti-cancer property and therapeutic opportunity to selectively target a stable subset of microtubules in circulating tumor cells to reduce metastatic potential with less toxicity in breast cancer patients.
Reducing assembly complexity of microbial genomes with single-molecule sequencing
Authors: Koren Sergey , Harhay Gregory P , Smith Timothy PL , Bono James L , Harhay Dayna M , Mcvey Scott D , Radune Diana , Bergman Nicholas H , Phillippy Adam M
Published: September 2013

Background

The short reads output by first- and second-generation DNA sequencing instruments cannot completely reconstruct microbial chromosomes. Therefore, most genomes have been left unfinished due to the significant resources required to manually close gaps in draft assemblies. Third-generation, single-molecule sequencing addresses this problem by greatly increasing sequencing read length, which simplifies the assembly problem.

Results

To measure the benefit of single-molecule sequencing on microbial genome assembly, we sequenced and assembled the genomes of six bacteria and analyzed the repeat complexity of 2,267 complete bacteria and archaea. Our results indicate that the majority of known bacterial and archaeal genomes can be assembled without gaps, at finished-grade quality, using a single PacBio RS sequencing library. These single-library assemblies are also more accurate than typical short-read assemblies and hybrid assemblies of short and long reads.

Conclusions

Automated assembly of long, single-molecule sequencing data reduces the cost of microbial finishing to $1,000 for most genomes, and future advances in this technology are expected to drive the cost lower. This is expected to increase the number of completed genomes, improve the quality of microbial genome databases, and enable high-fidelity, population-scale studies of pan-genomes and chromosomal organization.
Sensitivity of the spectral induced polarization method to microbial enhanced oil recovery processes
Authors: Heenan Jeffrey , Porter Abigail , Ntarlagiannis Dimitrios , Young Lily Y. , Werkema Dale D. , Slater Lee D.
Published: September 2013

The demand for more efficient and economic oil recovery techniques has driven research into novel extraction approaches, including microbial enhanced methods. Microbial enhanced oil recovery (MEOR) is an underutilized technology that could significantly enhance tertiary oil recovery. Previous research has shown the spectral induced polarization (SIP) method to be sensitive to microbial degradation of hydrocarbons, so the method should therefore be sensitive to MEOR treatments. To test this hypothesis, heavy-oil-containing sands were monitored for a period of approximately six months while undergoing MEOR treatment. SIP monitoring showed significant sensitivity to biodegradation induced changes. Increases in phase and imaginary conductivity, with a polarization peak centered on approximately 3–8 Hz, were observed for the two MEOR active columns. Similarly, the normalized chargeability, an integrated parameter of a Debye decomposition analysis of the spectra, showed a linear increase in time. Chromatographic methods confirmed oil biodegradation in the active columns. The SIP responses are likely the result of microbial processes and the changes they promote to oil properties, such as altering wettability, or possibly the effect of organic acid production. The results of this experiment indicate that SIP may be a viable method of monitoring MEOR processes.
Impact of patient involvement in mental health research: longitudinal study
Authors: Ennis Liam , Wykes Til
Published: September 2013

Background

It is deemed good practice to involve patients routinely in research but no study has investigated the practical benefits, particularly to successful recruitment.

Aims

To identify whether patient involvement is associated with study success.

Method

All studies listed on the Mental Health Research Network (MHRN) portfolio database (n = 374) were interrogated using logistic regression, ANOVA and Pearson's correlation to identify associations with study characteristics, funding bodies and recruitment success.

Results

Patient involvement increased over time although in some areas of research it was limited. Some funders, especially the National Institute for Health Research (NIHR), had more associated patient involvement than others. Studies that involved patients to a greater extent were more likely to have achieved recruitment targets (χ2 = 4.58, P<0.05), defined as reaching at least 90% of the target.

Conclusions

This is the first time associations with study success have been identified for patient involvement. Researchers might now consider ways to involve patients more comprehensively as this is associated with study success. Further research is needed to explore this finding.
Developing a reporting guideline for social and psychological intervention trials
Authors: Mayo-Wilson Evan , Montgomery Paul , Hopewell Sally , Macdonald Geraldine , Moher David , Grant Sean
Published: September 2013

Social and psychological interventions are often complex. Understanding randomised controlled trials (RCTs) of these complex interventions requires a detailed description of the interventions tested and the methods used to evaluate them. However, RCT reports often omit, or inadequately report, this information. Incomplete and inaccurate reporting hinders the optimal use of research, wastes resources and fails to meet ethical obligations to research participants and consumers. In this paper, we explain how reporting guidelines have improved the quality of reports in medicine, and describe the ongoing development of a new reporting guideline for RCTs: CONSORT-SPI (an extension for social and psychological interventions). We invite readers to participate in the project by visiting our website, in order to help us reach the best-informed consensus on these guidelines (http://tinyurl.com/CONSORT-study).
Completely Humanizing Prolactin Rescues Infertility in Prolactin Knockout Mice and Leads to Human Prolactin Expression in Extrapituitary Mouse Tissues
Authors: Christensen Heather R. , Murawsky Michael K. , Horseman Nelson D. , Willson Tara A. , Gregerson Karen A.
Published: September 2013

A variety of fundamental differences have evolved in the physiology of the human and rodent prolactin (PRL) systems. The PRL gene in humans and other primates contains an alternative promoter, 5.8 kbp upstream of the pituitary transcription start site, which drives expression of PRL in “extrapituitary” tissues, where PRL is believed to exert local, or paracrine, actions. Several of these extrapituitary PRL tissues serve a reproductive function (eg, mammary gland, decidua, prostate, etc), consistent with the hypothesis that local PRL production may be involved in, and required for, normal reproductive physiology in primates. Rodent research models have generated significant findings regarding the role of PRL in reproduction. Specifically, disruption (knockout) of either the PRL gene or its receptor causes profound female reproductive defects at several levels (ovaries, preimplantation endometrium, mammary glands). However, the rodent PRL gene differs significantly from the human, most notably lacking the alternative promoter. Understanding of the physiological regulation and function of extrapituitary PRL has been limited by the absence of a readily accessible experimental model, because the rodent PRL gene does not contain the alternative promoter. To overcome these limitations, we have generated mice that have been “humanized” with regard to the structural gene and tissue expression of PRL. Here, we present the characterization of these animals, demonstrating that the human PRL transgene is responsive to known physiological regulators both in vitro and in vivo. More importantly, the expression of the human PRL transgene is able to rescue the reproductive defects observed in mouse PRL knockout (mPRL−) females, validating their usefulness in studying the function or regulation of this hormone in a manner that is relevant to human physiology.
Effects of Antenatal Synthetic Glucocorticoid on Glucocorticoid Receptor Binding, DNA Methylation, and Genome-Wide mRNA Levels in the Fetal Male Hippocampus
Authors: Crudo Ariann , Petropoulos Sophie , Suderman Matthew , Moisiadis Vasilis G. , Kostaki Alisa , Hallett Michael , Szyf Moshe , Matthews Stephen G.
Published: September 2013

The endogenous glucocorticoid (GC) surge in late gestation plays a vital role in maturation of several organ systems. For this reason, pregnant women at risk of preterm labor are administered synthetic glucocorticoids (sGCs) to promote fetal lung development. Animal studies have shown that fetal sGC exposure can cause life-long changes in endocrine and metabolic function. We have previously shown that antenatal sGC treatment is associated with alterations in global DNA methylation and modifications to the hippocampal methylome and acetylome. In this study, we hypothesized that: 1) there are changes in the transcriptional landscape of the fetal hippocampus in late gestation, associated with the endogenous cortisol surge; 2) fetal sGC exposure alters genome-wide transcription in the hippocampus; and 3) these changes in transcription are associated with modified glucocorticoid receptor (GR) DNA binding and DNA methylation. sGC was administered as 2 courses on gestational days (GD) 40, 41, 50, and 51, and the hippocampi of fetal guinea pigs were examined before (GD52) and after (GD65) the endogenous cortisol surge (Term ∼GD67). We also analyzed fetal hippocampi 24 hours and 14 days following maternal sGC injections (n = 3–4/group). Genome-wide modification of transcription and GR DNA binding occurred in late gestation, in parallel with the normal GC surge. Further, sGC exposure had a substantial impact on the hippocampal transcriptome, GR-DNA binding, and DNA methylation at 24 hours and 14 days following the final sGC treatment. These data support the hypothesis that GC exposure in late gestation plays a significant role in modifying the transcriptional and epigenetic landscape of the developing fetal hippocampus and that substantial effects are evident for at least 2 weeks after sGC exposure.
Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biomechanical perspective
Authors: Namjoshi Dhananjay R. , Good Craig , Cheng Wai Hang , Panenka William , Richards Darrin , Cripton Peter A. , Wellington Cheryl L.
Published: September 2013

Traumatic brain injury (TBI) is a major worldwide healthcare problem. Despite promising outcomes from many preclinical studies, the failure of several clinical studies to identify effective therapeutic and pharmacological approaches for TBI suggests that methods to improve the translational potential of preclinical studies are highly desirable. Rodent models of TBI are increasingly in demand for preclinical research, particularly for closed head injury (CHI), which mimics the most common type of TBI observed clinically. Although seemingly simple to establish, CHI models are particularly prone to experimental variability. Promisingly, bioengineering-oriented research has advanced our understanding of the nature of the mechanical forces and resulting head and brain motion during TBI. However, many neuroscience-oriented laboratories lack guidance with respect to fundamental biomechanical principles of TBI. Here, we review key historical and current literature that is relevant to the investigation of TBI from clinical, physiological and biomechanical perspectives, and comment on how the current challenges associated with rodent TBI models, particularly those involving CHI, could be improved.
The pathophysiology of traumatic brain injury at a glance
Authors: Prins Mayumi , Greco Tiffany , Alexander Daya , Giza Christopher C.
Published: September 2013

Traumatic brain injury (TBI) is defined as an impact, penetration or rapid movement of the brain within the skull that results in altered mental state. TBI occurs more than any other disease, including breast cancer, AIDS, Parkinson’s disease and multiple sclerosis, and affects all age groups and both genders. In the US and Europe, the magnitude of this epidemic has drawn national attention owing to the publicity received by injured athletes and military personnel. This increased public awareness has uncovered a number of unanswered questions concerning TBI, and we are increasingly aware of the lack of treatment options for a crisis that affects millions. Although each case of TBI is unique and affected individuals display different degrees of injury, different regional patterns of injury and different recovery profiles, this review and accompanying poster aim to illustrate some of the common underlying neurochemical and metabolic responses to TBI. Recognition of these recurrent features could allow elucidation of potential therapeutic targets for early intervention.
Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism
Authors: Tiedemann Kerstin , Boraschi-Diaz Iris , Rajakumar Irina , Kaur Jasvir , Roughley Peter , Reinhardt Dieter P. , Komarova Svetlana V.
Published: September 2013

Mutations in the fibrillin-1 gene give rise to a number of heritable disorders, which are all characterized by various malformations of bone as well as manifestations in other tissues. However, the role of fibrillin-1 in the development and homeostasis of bone is not well understood. Here, we examined the role of fibrillin-1 in regulating osteoclast differentiation from primary bone-marrow-derived precursors and monocytic RAW 264.7 cells. The soluble N-terminal half of fibrillin-1 (rFBN1-N) strongly inhibited osteoclastogenesis, whereas the C-terminal half (rFBN1-C) did not. By contrast, when rFBN1-N was immobilized on calcium phosphate, it did not affect osteoclastogenesis but modulated osteoclast resorptive activity, which was evident by a larger number of smaller resorption pits. Using a panel of recombinant sub-fragments spanning rFBN1-N, we localized an osteoclast inhibitory activity to the 63 kDa subfragment rF23 comprising the N-terminal region of fibrillin-1. Osteoclastic resorption led to the generation of small fibrillin-1 fragments that were similar to those identified in human vertebral bone extracts. rF23, but not rFBN1-N, was found to inhibit the expression of cathepsin K, matrix metalloproteinase 9 and Dcstamp in differentiating osteoclasts. rFBN1-N, but not rF23, exhibited interaction with RANKL. Excess RANKL rescued the inhibition of osteoclastogenesis by rFBN1-N. By contrast, rF23 disrupted RANKL-induced Ca2+ signaling and activation of transcription factor NFATc1. These studies highlight a direct dual inhibitory role of N-terminal fibrillin-1 fragments in osteoclastogenesis, the sequestration of RANKL and the inhibition of NFATc1 signaling, demonstrating that osteoclastic degradation of fibrillin-1 provides a potent negative feedback that limits osteoclast formation and function.