bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Modeling of Primal Emotional Affects (SEEKING, PANIC and PLAY): Gateways to the Development of New Treatments for Depression
Authors: Panksepp Jaak , Yovell Yoram
Published: October 2014

Mammalian brains contain at least 7 primal emotional systems - SEEKING, RAGE, FEAR, LUST, CARE, PANIC and PLAY (capitalization reflects a proposed primary-process terminology, to minimize semantic confusions and mereological fallacies). These systems help organisms feel affectively balanced (e.g. euthymic) and unbalanced (e.g. depressive, irritable, manic), providing novel insights for understanding human psychopathologies. Three systems are especially important for understanding depression: The separation distress (PANIC) system mediates the psychic pain of separation distress (i.e. excessive sadness and grief), which can be counteracted by minimizing PANIC arousals (as with low-dose opioids). Depressive dysphoria also arises from reduced brain reward-seeking and related play urges (namely diminished enthusiasm (SEEKING) and joyful exuberance (PLAY) which promote sustained amotivational states). We describe how an understanding of these fundamental emotional circuits can promote the development of novel antidepressive therapeutics - (i) low-dose buprenorphine to counteract depression and suicidal ideation emanating from too much psychic pain (PANIC overarousal), (ii) direct stimulation of the SEEKING system to counteract amotivational dysphoria, and (iii) the discovery and initial clinical testing of social-joy-promoting molecules derived from the analysis of the PLAY system.
Mechanisms of Unexplained Neurological Deterioration After Intravenous Thrombolysis
Authors: Tisserand Marie , Seners Pierre , Turc Guillaume , Legrand Laurence , Labeyrie Marc-Antoine , Charron Sylvain , Méder Jean-François , Mas Jean-Louis , Oppenheim Catherine , Baron Jean-Claude
Published: October 2014

Background and Purpose—

Unstable clinical course characterizes the first 24 hours after thrombolysis for anterior circulation stroke, including early neurological deterioration (END), a secondary complication consistently predictive of poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END remains unclear in the majority of cases (END
unexplained
). Based on the core/penumbra model, we tested the hypothesis that END
unexplained
is caused by infarct growth beyond the initial penumbra and assessed the associated vascular patterns.

Methods—

From our database of consecutive thrombolyzed patients (n=309), we identified 10 END
unexplained
cases who had undergone both admission and 24-hour MRI. Diffusion-weighted imaging lesion growth both within and beyond the acute penumbra (T
max
>6 seconds) was mapped voxelwise. These 10 cases were compared with 30 no-END controls extracted from the database blinded to 24-hour diffusion-weighted imaging to individually match cases (3/case) according to 4 previously identified clinical and imaging variables.

Results—

As predicted, lesion growth beyond initial penumbra was present in 9 of 10 END
unexplained
patients (substantial in 8) and its volume was significantly larger in cases than controls (2
P
=0.047). All END
unexplained
cases had proximal arterial occlusion initially, of which only 2 had recanalized at 24 hours.

Conclusions—

In this exploratory study, most instances of END
unexplained
were related to diffusion-weighted imaging growth beyond acute penumbra. Consistent presence of proximal occlusion at admission and lack of recanalization at 24 hours in most cases suggest that hemodynamic factors played a key role, via for instance systemic instability/collateral failure or secondary thromboembolic processes. Preventing END after tissue-type plasminogen activator using, eg, early antithrombotics may therefore be feasible.
Phenotypical variation and taxonomic correlates of five closely related Andean species of Poa (Poaceae) along geographic and climatic gradients
Authors: Scrivanti Lidia Raquel , Mestre Luciana , Anton Ana Maria
Published: October 2014

Poa anfamensis, P. jujuyensis, P.lilloi, P. parviceps and P. scaberula (Poaceae) are a group of morphologically similar species. These species inhabit cool grasslands and mesic puna. They are highly polymorphic and their circumscriptions are uncertain, especially the entities around P. scaberula. Univariate and multivariate analyses (PCA and DA) were conducted to evaluate the morphological variation among 150 herbarium specimens identified as P. anfamensis, P. jujuyensis, P. lilloi, P. parviceps and P. scaberula. Forty morphological characters were included and their patterns of variation were analyzed among specimens, together with their relationship with environmental variables, using correlation analysis. The relationships between morphological variation and geographical distance, and climatic variables among specimens, were compared with Mantel permutation tests. Taxa were delimited according to the observed clustering of specimens in the PCA plots and DA, and diagnostic characters were identified. The five taxa showed continuous morphological variation. Morphological variation is explained by geographical and climatic factors such as elevation, geographical distance, latitudinal and longitudinal gradients, temperature and precipitation in the different sites in the Andes. Altitudinal and geographical distance are apparently more decisive factors in phenotypic differentiation and could have played a large role in interspecific differentiation among Poa entities, as shown by the stronger and significant association between vegetative and reproductive phenotype and altitudinal distance, and between vegetative and reproductive phenotype and geographical distance. In addition, we observed uncoupling among vegetative and floral characters in Poa specimens that grow along environmental gradients; these characters are responding independently to different abiotic forces promoting genetic divergence and speciation. Based on the results, P. anfamensis and P. parviceps are synonymised with P. scaberula, and P. jujuyensis is synonymised with P. lilloi.
A revision of the genus Rhynchostegiella (Brachytheciaceae) in the Iberian Peninsula and Balearic Islands
Authors: Guerra Juan , Ríos Diana , Gallego María Teresa
Published: October 2014

The moss genus Rhynchostegiella (Brachytheciaceae) is taxonomically revised for the Iberian Peninsula and Balearic Islands based on morphological data. After a thorough revision of both herbarium material and our own recent collections from the area, we recognize five Iberian species of the genus. A key, descriptions, illustrations and distribution data are provided for the species. The record for Rhynchostegiella bourgaeana in Europe, in Cadiz, Spain, is confirmed.
Five new species of Hypseloecus Reuter (Hemiptera: Miridae) on hemiparasitic Santalales from India
Authors: YESHWANTH H. M.
Published: October 2014

Five new species of Hypseloecus viz., Hypseloecus acutus sp. nov., Hypseloecus articulatus sp. nov., Hypseloecus belli sp. nov., Hypseloecus orientale sp. nov. and Hypseloecus spinosus sp. nov. are described from India. The genus is recorded for the first time from India collected on hemiparasitic plants of the genera Dendrophthoe and Viscum (Santalales). A key to identification of the five species has been provided with descriptions of the male genital structures, digital microscopic images and also photographic images of live individuals.
The identification of effective thermal conductivity for fibrous reinforcement composite by inverse method
Authors: Saad Aouatif , Echchelh Adil , Hattabi Mohamed , El Ganaoui Mohammed
Published: October 2014

In the present work, the thermal conductivity of a composite material is determined by inverse analysis of the heat conduction phenomenon in resin transfer molding process. The Gauss–Newton–Levenberg–Marquardt method was utilized to identify the thermal conductivities of fibrous reinforcement. Knowing the boundary conditions, the thermal conductivity can be deduced from the temperature values at some given positions through the part. Starting from an initial estimate of thermal conductivity, the inverse method begins by solving the direct problem, i.e. the heat equation. The solution gives the temperature field everywhere in the composite sample. Calculated temperatures are then compared with analytical temperatures based on a criterion. Conductivity is modified iteratively so as to minimize this criterion until the desired accuracy is achieved. The identified thermal conductivity by the inverse methodology was validated with experimental results of epoxy composites with carbon nanotube and chopped carbon fibers. Satisfactory agreement was obtained. Furthermore, this method offer the possibility to determinate conductivity of several part of composite at the same time, and could be generalized for bio composite, so it can be considered as accurate and economically efficient technique in the prediction of thermal conductivity of composite.
“Teaching” the therapeutic alliance: on peeling a banana with a knife and fork
Authors: Chazan Lynette
Published: October 2014

Objective:

This paper discusses the implications for training of the centrality of the therapeutic alliance to the practice of psychiatry.

Conclusion:

Recent research highlights the centrality of the therapeutic alliance, not only to positive outcomes across the psychotherapies but in all psychiatric practice. This understanding, along with a cultural shift toward psychological-mindedness, suggests that we teach relational as well as intellectual skills and implement a broader role for psychotherapy training. A subsequent article will address the question of whether and how such skills can be developed.
Distributed leadership and contract relations
Authors: Özdemir Murat , Demircioğlu Ebru
Published: October 2014

In recent years educational organizations have begun to be administered by more sharing, participation and democratic principles. The school-based management approach accelerated during the decentralization period in education is also seen as a cause for spread of leadership throughout the school. This trend is reflected in the educational leadership literature, which began to describe as distributed leadership (DL), the process/approach of spreading leadership organization-wide. However, the extent to which leadership in educational organizations is distributed cannot be easily delineated, particularly in countries such as Turkey where the system was established and managed centrally. Yet, DL attracts researchers’ attention in terms of the organizational behaviours. It ascribes to teachers, such as their commitment and associated psychological contracts (PCs). In this study of Turkish schools that are centrally organized, we consider the relationship between DL and teachers’ perceptions of their PC levels. As the research variables are multilevel, the data collected from 466 teachers working in 34 different schools were analysed by hierarchical linear modelling. The analyses indicated that the distribution of leadership among school managers was a significant predictor of the PCs of the teachers. However, the observed variance in the PC was determined to be explained by the service periods of teachers.
Mallet fingers with bone avulsion and DIP joint subluxation
Authors: Wada T. , Oda T.
Published: October 2014

One-third of all mallet fingers are associated with a fracture. Mallet fractures associated with large fracture fragments may result in volar subluxation of the distal phalanx. The management of mallet fractures varies based on injury pattern and surgeon preference. These treatment options include splinting regimens, closed reduction and percutaneous pinning and open reduction and internal fixation. Although numerous surgical techniques have been described, there is little clear consensus on operative treatment. Moreover, there is insufficient evidence to support operative over nonoperative treatment for mallet fractures.

Level of evidence: Level V
Effects of discontinuing anticholinergic treatment on movement disorders, cognition and psychopathology in patients with schizophrenia
Authors: Desmarais Julie Eve , Beauclair Linda , Annable Lawrence , Bélanger Marie-Claire , Kolivakis Theodore T. , Margolese Howard C.
Published: October 2014

Background:

Physicians have prescribed anticholinergic agents such as benztropine, procyclidine, biperiden and trihexyphenidyl for treatment and prophylaxis of antipsychotic-induced extrapyramidal symptoms (EPS) for decades. Anticholinergic agents can however worsen tardive dyskinesia and cause many adverse effects, including cognitive impairment. Previous studies of anticholinergic discontinuation in patients with schizophrenia receiving antipsychotics have yielded a wide range of EPS relapse rates. Improvement in cognition after anticholinergic withdrawal was observed in some studies.

Objective:

This study evaluated the effect of anticholinergic discontinuation on movement disorders, cognition and general psychopathology after a 4-week taper in 20 outpatients with schizophrenia or schizoaffective disorder treated with antipsychotics.

Results:

Eighteen of twenty patients successfully discontinued their anticholinergic medication; two did not because of akathisia. Repeated measures analysis of variance did not show a significant effect of anticholinergic discontinuation on total Extrapyramidal Symptoms Rating Scale score or on the Parkinsonism, Akathisia, Dystonia or Tardive Dyskinesia subscales. However, significant improvement was found on the Brief Assessment of Cognition in Schizophrenia composite z score at weeks 6, 8 and 12 compared with baseline. Significant improvements were seen on the motor and the symbol-coding tasks. No significant effects were observed on the Positive and Negative Syndrome Scale, Clinical Global Impression – Severity and Clinical Global Impression – Improvement scales.

Conclusion:

In this 12-week study of anticholinergic discontinuation in 20 outpatients with schizophrenia or schizoaffective disorder, gradual decrease and discontinuation of anticholinergics led to a positive effect on cognition. There were no adverse consequences on general psychopathology and no significant differences for 18 of 20 subjects on movement disorders.
Opposing regulation of BIM and BCL2 controls glucocorticoid-induced apoptosis of pediatric acute lymphoblastic leukemia cells
Authors: Jing Duohui , Bhadri Vivek A. , Beck Dominik , Thoms Julie A. I. , Yakob Nurul A. , Wong Jason W. H. , Knezevic Kathy , Pimanda John E. , Lock Richard B.
Published: October 2014

Key Points

The glucocorticoid receptor coordinately regulates the antiapoptotic BCL2 and proapoptotic BIM genes in pediatric ALL cells in vivo. GR binding at a novel intronic region is associated with BIM transcription and dexamethasone sensitivity in pediatric ALL cells in vivo.
What are the impacts of urban agriculture programs on food security in low and middle-income countries: a systematic review
Authors: Korth Marcel , Stewart Ruth , Langer Laurenz , Madinga Nolizwe , Rebelo Da Silva Natalie , Zaranyika Hazel , van Rooyen Carina , de Wet Thea
Published: October 2014

Background

Urban Agriculture is considered to contribute to improved food security among the income poor in urban contexts across developing countries. Much literature exists on the topic assuming a positive relationship. The aim of this review was to collect and analyse available evidence on the impact of urban agriculture in low and middle-income countries.

Methods

We employed systematic review methods to identify all relevant and reliable research on UA’s impact on food security and nutrition. Only impact evaluations that set out to measure the effectiveness of UA interventions on food security, as compared to the effects of not engaging in UA, qualified for inclusion. Studies had to have a comparison group and at least two data points.

Results

Systematic searches resulted in 8142 hits, and screening of abstracts resulted in 198 full texts identified. No studies met the review’s inclusion criteria. Therefore, the review found no available evidence that supports or refutes the suggestion that urban agriculture positively impacts on individual or household food security in low and middle-income countries. The largest proportion of studies at full text stage was excluded based on study design, as they were not impact evaluations, i.e. they did not have a comparison group and at least data points. Two observations were made: Firstly, searches yielded a range of studies that consider associations between UA and certain aspects of food security. Secondly, there is a large pool of cross-sectional studies on UA’s potential to contribute to increased food security, particularly from west and east Africa.

Conclusions

The research currently available does not allow for any conclusions to be made on whether or not urban agriculture initiatives contribute to food security. The fact that impact evaluations are absent from the current evidence-base calls for increased efforts to measure the impact of urban agriculture on food security in low and middle-income countries through rigorous impact evaluations. With regard to systematic review methodology, this review alludes to the value of compiling a systematic map prior to engaging in a full systematic review.
Computational approaches to interpreting genomic sequence variation
Authors: Ritchie Graham RS , Flicek Paul
Published: October 2014

Identifying sequence variants that play a mechanistic role in human disease and other phenotypes is a fundamental goal in human genetics and will be important in translating the results of variation studies. Experimental validation to confirm that a variant causes the biochemical changes responsible for a given disease or phenotype is considered the gold standard, but this cannot currently be applied to the 3 million or so variants expected in an individual genome. This has prompted the development of a wide variety of computational approaches that use several different sources of information to identify functional variation. Here, we review and assess the limitations of computational techniques for categorizing variants according to functional classes, prioritizing variants for experimental follow-up and generating hypotheses about the possible molecular mechanisms to inform downstream experiments. We discuss the main current bioinformatics approaches to identifying functional variation, including widely used algorithms for coding variation such as SIFT and PolyPhen and also novel techniques for interpreting variation across the genome.
Specialized Subpopulations of Kisspeptin Neurons Communicate With GnRH Neurons in Female Mice
Authors: Kumar Devesh , Candlish Michael , Periasamy Vinod , Avcu Nergiz , Mayer Christian , Boehm Ulrich
Published: October 2014

The neuropeptide kisspeptin is a potent stimulator of GnRH neurons and has been implicated as a major regulator of the hypothalamus-pituitary-gonadal axis. There are mainly two anatomically segregated populations of neurons that express kisspeptin in the female hypothalamus: one in the anteroventral periventricular nucleus (AVPV) and the other in the arcuate nucleus (ARC). Distinct roles have been proposed for AVPV and ARC kisspeptin neurons during reproductive maturation and in mediating estrogen feedback on the hypothalamus-pituitary-gonadal axis in adults. Despite their pivotal role in the regulation of reproductive physiology, little is known about kisspeptin neuron connectivity. Although previous data suggest heterogeneity within the AVPV and ARC kisspeptin neuron populations, how many and which of these potential kisspeptin neuron subpopulations are actually communicating with GnRH neurons is not known. Here we used a combinatorial genetic transsynaptic tracing strategy to start to analyze the connectivity of individual kisspeptin neurons with the GnRH neuron population in female mice with a single-cell resolution. We find that only subsets of AVPV and ARC kisspeptin neurons are synaptically connected with GnRH neurons. We demonstrate that the majority of kisspeptin neurons within the AVPV and ARC does not communicate with GnRH neurons. Furthermore, we show that all kisspeptin neurons within the AVPV connected to GnRH neurons are estrogen sensitive and that most of these express tyrosine hydroxylase. Our data demonstrate functional specialization within the two kisspeptin neuron populations.
Impact of Extent of Surgery on Survival for Papillary Thyroid Cancer Patients Younger Than 45 Years
Authors: Abdelgadir Adam Mohamed , Pura John , Goffredo Paolo , Dinan Michaela A. , Hyslop Terry , Reed Shelby D. , Scheri Randall P. , Roman Sanziana A. , Sosa Julie A.
Published: October 2014

Context:

Papillary thyroid cancer (PTC) patients <45 years old are considered to have an excellent prognosis; however, current guidelines recommend total thyroidectomy for PTC tumors >1.0 cm, regardless of age.

Objective:

Our objective was to examine the impact of extent of surgery on overall survival (OS) in patients <45 years old with stage I PTC of 1.1 to 4.0 cm.

Design, Setting, and Patients:

Adult patients <45 years of age undergoing surgery for stage I PTC were identified from the National Cancer Data Base (NCDB, 1998–2006) and the Surveillance, Epidemiology, and End Results dataset (SEER, 1988–2006).

Main Outcome Measure:

Multivariable modeling was used to compare OS for patients undergoing total thyroidectomy vs lobectomy.

Results:

In total, 29 522 patients in NCDB (3151 lobectomy, 26 371 total thyroidectomy) and 13 510 in SEER (1379 lobectomy, 12 131 total thyroidectomy) were included. Compared with patients undergoing lobectomy, patients having total thyroidectomy more often had extrathyroidal and lymph node disease. At 14 years, unadjusted OS was equivalent between total thyroidectomy and lobectomy in both databases. After adjustment, OS was similar for total thyroidectomy compared with lobectomy across all patients with tumors of 1.1 to 4.0 cm (NCDB: hazard ratio = 1.45 [confidence interval = 0.88–2.51], P = 0.19; SEER: 0.95 (0.70–1.29), P = 0.75) and when stratified by tumor size: 1.1 to 2.0 cm (NCDB: 1.12 [0.50–2.51], P = 0.78; SEER: 0.95 [0.56–1.62], P = 0.86) and 2.1 to 4.0 cm (NCDB: 1.93 [0.88–4.23], P = 0.10; SEER: 0.94 [0.60–1.49], P = 0.80).

Conclusions:

After adjusting for patient and clinical characteristics, total thyroidectomy compared with thyroid lobectomy was not associated with improved survival for patients <45 years of age with stage I PTC of 1.1 to 4.0 cm. Additional clinical and pathologic factors should be considered when choosing extent of resection.
“Division Is Common”
Authors: Martel James
Published: October 2014

In this essay, I engage with Jodi Dean’s idea from The Communist Horizon (2012) that “division is common; we must seize it.” I argue that this is a critical insight that helps us think both about the kinds of political subjectivity that we find in Marxist philosophy as well as the actual practices of communism. Looking to Marx’s Capital, and especially his writing about the development of a community of laborers, I argue that readings of the proletariat as a monolith and as the teleological expression of class more generally are not supported in this volume. The story that Marx tells here is, rather, one of division, internal tension, and contingency. What is produced from this history then is a dynamic and complex form of identity that must be recognized to avoid reproducing old class hierarchies in new guises. Turning next to the idea of “seizing,” I argue that this moment of radical transformation is equivalent to the community of laborers recognizing itself as divided and internally contested. The “species being” that emerges from this history can be a vehicle for self-transformation only if all of that contingency and dynamism are allowed to be expressed, only if the subject itself is seen as plural and internally complex.
A fat body-derived apical extracellular matrix enzyme is transported to the tracheal lumen and is required for tube morphogenesis in Drosophila
Authors: Dong Bo , Miao Guangxia , Hayashi Shigeo
Published: October 2014

The apical extracellular matrix plays a central role in epithelial tube morphogenesis. In the Drosophila tracheal system, Serpentine (Serp), a secreted chitin deacetylase expressed by the tracheal cells plays a key role in regulating tube length. Here, we show that the fly fat body, which is functionally equivalent to the mammalian liver, also contributes to tracheal morphogenesis. Serp was expressed by the fat body, and the secreted Serp was taken up by the tracheal cells and translocated to the lumen to functionally support normal tracheal development. This process was defective in rab9 and shrub/vps32 mutants and in wild-type embryos treated with a secretory pathway inhibitor, leading to an abundant accumulation of Serp in the fat body. We demonstrated that fat body-derived Serp reached the tracheal lumen after establishment of epithelial barrier function and was retained in the lumen in a chitin synthase-dependent manner. Our results thus reveal that the fat body, a mesodermal organ, actively contributes to tracheal development.
Tissue-specific genome editing in Ciona embryos by CRISPR/Cas9
Authors: Stolfi Alberto , Gandhi Shashank , Salek Farhana , Christiaen Lionel
Published: October 2014

The CRISPR/Cas9 system has ushered in a new era of targeted genetic manipulations. Here, we report the use of CRISPR/Cas9 to induce double-stranded breaks in the genome of the sea squirt Ciona intestinalis. We use electroporation to deliver CRISPR/Cas9 components for tissue-specific disruption of the Ebf (Collier/Olf/EBF) gene in hundreds of synchronized Ciona embryos. Phenotyping of transfected embryos in the ‘F0’ generation revealed that endogenous Ebf function is required for specification of Islet-expressing motor ganglion neurons and atrial siphon muscles. We demonstrate that CRISPR/Cas9 is sufficiently effective and specific to generate large numbers of embryos carrying mutations in a targeted gene of interest, which should allow for rapid screening of gene function in Ciona.
The TRAF-interacting protein (TRAIP) is a regulator of the spindle assembly checkpoint
Authors: Chapard Christophe , Meraldi Patrick , Gleich Tobias , Bachmann Daniel , Hohl Daniel , Huber Marcel
Published: October 2014

Accurate chromosome segregation during mitosis is temporally and spatially coordinated by fidelity-monitoring checkpoint systems. Deficiencies in these checkpoint systems can lead to chromosome segregation errors and aneuploidy and promote tumorigenesis. We report that the TRAF-interacting protein (TRAIP), a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation, was localized close to mitotic chromosomes. Its functional inactivation in HeLa cells by siRNAs decreased the time of early mitosis progression from nuclear envelope breakdown to anaphase onset and increased the percentages of chromosome alignment defects in metaphase and lagging chromosomes in anaphase compared to control cells. The decrease in progression time was corrected by the expression of wild-type but not by an ubiquitin ligase deficient form of TRAIP. TRAIP-depleted cells by-passed taxol-induced mitotic arrest, and significantly reduced kinetochore levels of MAD2 but not of other spindle checkpoint proteins in the presence of nocodazole. These results imply that TRAIP regulates the spindle assembly checkpoint, MAD2 abundance at kinetochores and the accurate cellular distribution of chromosomes. The TRAIP ubiquitin ligase activity is functionally required for the spindle assembly checkpoint control.
The synaptic cell adhesion molecules SynCAMs are involved in sensory axon pathfinding by regulating axon-axon contacts
Authors: Frei Jeannine A. , Andermatt Irwin , Gesemann Matthias , Stoeckli Esther T.
Published: October 2014

SynCAMs (Synaptic Cell Adhesion Molecules) are crucial for synapse formation and plasticity. However, we demonstrated that SynCAMs were also required during earlier stages of neural circuit formation, as SynCAM1 and SynCAM2 were shown to be important for the guidance of post-crossing commissural axons. In contrast to the exclusively homophilic cis-interactions reported by previous studies, our in vivo results suggested the existence of heterophilic cis-interactions between SynCAM1 and SynCAM2. Indeed, as we show here, the presence of homo- and heterophilic cis-interactions modulates the interaction of SynCAMs with trans-binding partners, as observed previously for other immunoglobulin superfamily cell adhesion molecules. These in vitro findings are in agreement with results from in vivo studies, which demonstrate a role for SynCAMs in the formation of sensory neural circuits in the chicken embryo. In the absence of SynCAMs selective axon-axon interactions are perturbed resulting in aberrant pathfinding of sensory afferents.
Ciliopathy proteins establish a bipartite signaling compartment in aC. elegansthermosensory neuron
Authors: Nguyen Phuong Anh T. , Liou Willisa , Hall David H. , Leroux Michel R.
Published: October 2014

How signaling domains form is an important, largely unexplored question. We show that ciliary proteins help establish two contiguous, yet distinct cGMP signaling compartments in C. elegans thermosensory AFD neurons. One compartment, a bona fide cilium, is delineated by Bardet-Biedl syndrome (BBS), Meckel syndrome and nephronophthis is associated proteins at its base, and requires Inversin/NPHP-2 to anchor a cGMP-gated ion channel within the proximal ciliary region. The other, a subcompartment with profuse microvilli and different lipid environment, is separated from the dendrite by a cellular junction and requires BBS-8 and DAF-25/Ankmy2 for correct localization of guanylyl cyclases needed for thermosensation. Consistent with a requirement for a membrane diffusion barrier at the subcompartment base, we reveal the unexpected presence of ciliary transition zone proteins where no canonical transition zone ultrastructure exists. We propose that differential compartmentalization of signal transduction components by ciliary proteins is important for the functions of ciliated sensory neurons.
Tet-Trap, a genetic approach to the identification of bacterial RNA thermometers: application to Pseudomonas aeruginosa
Authors: Delvillani Francesco , Sciandrone Barbara , Peano Clelia , Petiti Luca , Berens Christian , Georgi Christiane , Ferrara Silvia , Bertoni Giovanni , Pasini Maria Enrica , Dehò Gianni , Briani Federica
Published: October 2014

Modulation of mRNA translatability either by trans-acting factors (proteins or sRNAs) or by in cis-acting riboregulators is widespread in bacteria and controls relevant phenotypic traits. Unfortunately, global identification of post-transcriptionally regulated genes is complicated by poor structural and functional conservation of regulatory elements and by the limitations of proteomic approaches in protein quantification. We devised a genetic system for the identification of post-transcriptionally regulated genes and we applied this system to search for Pseudomonas aeruginosa RNA thermometers, a class of regulatory RNA that modulates gene translation in response to temperature changes. As P. aeruginosa is able to thrive in a broad range of environmental conditions, genes differentially expressed at 37°C versus lower temperatures may be involved in infection and survival in the human host. We prepared a plasmid vector library with translational fusions of P. aeruginosa DNA fragments (PaDNA) inserted upstream of TIP2, a short peptide able to inactivate the Tet repressor (TetR) upon expression. The library was assayed in a streptomycin-resistant merodiploid rpsL+/rpsL31 Escherichia coli strain in which the dominant rpsL+ allele, which confers streptomycin sensitivity, was repressed by TetR. PaDNA fragments conferring thermosensitive streptomycin resistance (i.e., expressing PaDNA–TIP2 fusions at 37°C, but not at 28°C) were sequenced. We identified four new putative thermosensors. Two of them were validated with conventional reporter systems in E. coli and P. aeruginosa. Interestingly, one regulates the expression of ptxS, a gene implicated in P. aeruginosa pathogenesis.
Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs
Authors: Zhang Yijun , Fan Miaomiao , Zhang Xue , Huang Feng , Wu Kang , Zhang Junsong , Liu Jun , Huang Zhuoqiong , Luo Haihua , Tao Liang , Zhang Hui
Published: October 2014

The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4+ T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1–encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression.
The capacity of target silencing by Drosophila PIWI and piRNAs
Authors: Post Christina , Clark Josef P. , Sytnikova Yuliya A. , Chirn Gung-Wei , Lau Nelson C.
Published: October 2014

Although Piwi proteins and Piwi-interacting RNAs (piRNAs) genetically repress transposable elements (TEs), it is unclear how the highly diverse piRNA populations direct Piwi proteins to silence TE targets without silencing the entire transcriptome. To determine the capacity of piRNA-mediated silencing, we introduced reporter genes into Drosophila OSS cells, which express microRNAs (miRNAs) and piRNAs, and compared the Piwi pathway to the Argonaute pathway in gene regulation. Reporter constructs containing several target sites that were robustly silenced by miRNAs were not silenced to the same degrees by piRNAs. However, another set of reporters we designed to enable a large number of both TE-directed and genic piRNAs to bind were robustly silenced by the PIWI/piRNA complex in OSS cells. These reporters show that a bulk of piRNAs are required to pair to the reporter's transcripts and not the reporter's DNA sequence to engage PIWI-mediated silencing. Following our genome-wide study of PIWI-regulated targets in OSS cells, we assessed candidate gene elements with our reporter platform. These results suggest TE sequences are the most direct of PIWI regulatory targets while coding genes are less directly affected by PIWI targeting. Finally, our study suggests that the PIWI transcriptional silencing mechanism triggers robust chromatin changes on targets with sufficient piRNA binding, and preferentially regulates TE transcripts because protein-coding transcripts lack a threshold of targeting by piRNA populations. This reporter platform will facilitate future dissections of the PIWI-targeting mechanism.
THE PRESENT AND FUTURE PROSPECTS OF FRICTION STIR WELDING IN AERONAUTICS
Authors: Sinka Viliam
Published: October 2014

Since its invention friction stir welding as a solid state joining method was considered primarily for aluminium alloys in the aerospace industry. Years of intense research and development were necessary to introduce the process for fabrication of aerospace components. It was necessary to accumulate sufficient information about process parameters, tooling and machinery for process specification, certification and design allowables. Friction stir welding was first used in space vehicles and in military aircraft, later it was used in civil aviation. Aircraft manufacturers such as Boeing, Airbus, and Embraer use this technique for components such as floor panels, fuselage panels, and wing ribs among others. This process allows for the introduction of new structural solutions in the same way that the development of advanced alloys also permits similar advances.
STUDY OF INFLUENCE OF pH VALUE ON REMOVING OF Cu2+ IONS FROM SOLUTION ONTO PERLITE
Authors: Plešingerová Beatrice , Dedinská Eva
Published: October 2014

The expanded perlite was studied as adsorbent for removing of Cu2+ ion from contaminated water. The test conditions were following: pH = 2 – 11; a perlite dosage 0,1 – 1 g; ratio solution: sorbent = 20 – 500 ml : 1 g; basic concentration of the Cu2+ ions 0,5 and 5 mg.1-1, laboratory temperature. The results showed that the perlite shifts the pH value of solutions which have the pH in region of 4 – 9 to neutral region 6 – 7. The pH value of solution was adjusted by HCl/NaOH and McIlvaine (citric acid/Na2HPO4); and Sőrensen (Na2HPO4/KH2PO4) buffer. Top-tests were carried out with solution adjusted by HCl/NaOH. The removing of Cu2+ ions from water relates with the basicity of aqueous solutions. If the ratio of perlite to solution with Cu2+ concentration of 5 mg.l-1 is 1 g : < 40 ml the removal of Cu2+ ions from solution rapidly increases in interval of pH from 4,5 to 5,5 and at pH ³ 6 achieves a maximum. The removal of the Cu2+ ions from initial solution (5 mg.1-1 of Cu2+) is 90 – 95 % at an exposition time of 180 min. and pH > 6. The values from desorption test were about 25 – 30 % lower. The purpose of this paper was to show the influence of phosphate and citrate anions in aqueous solutions on removing of Cu2+ ions from diluted water solution, too. The results confirmed that the citrate anions in the McIlvaine buffer inhibit sorption of Cu2+ on perlite while phosphate anions in Sőrensen buffer generate conditions for formation of Cu2+ precipitates.
MICROSTRUCTURE AND MECHANICAL PROPERTIES OF ULTRA-FINE GRAINED AZ31 ALLOY PROCESSED BY ECAP
Authors: Janeček Miloš , Stráská Jitka , Čížek Jakub
Published: October 2014

Commercial magnesium alloy AZ31 was processed by equal channel angular pressing preceded by hot extrusion (EX-ECAP). Microstructure evolution with strain due to ECAP was investigated by light and transmission electron microscopy. ECAP processing resulted in continuous grain fragmentation, significant grain refinement and the formation of dislocations. Dislocation structure changes in individual specimens after different number of ECAP passes were investigated by positron annihilation spectroscopy (PAS). Substantial increase of dislocation density occurred during the first two passes of ECAP and was followed by the decline manifesting the dynamic recovery at higher strains. The microstructure and defect structure evolution correlates well with mechanical properties as determined by a detail inspection of microhardness variations in individual ECAPed specimens.
Considerations for Digital PCR as an Accurate Molecular Diagnostic Tool
Authors: Huggett Jim F , Cowen Simon , Foy Carole A
Published: October 2014

BACKGROUND

Digital PCR (dPCR) is an increasingly popular manifestation of PCR that offers a number of unique advantages when applied to preclinical research, particularly when used to detect rare mutations and in the precise quantification of nucleic acids. As is common with many new research methods, the application of dPCR to potential clinical scenarios is also being increasingly described.

CONTENT

This review addresses some of the factors that need to be considered in the application of dPCR. Compared to real-time quantitative PCR (qPCR), dPCR clearly has the potential to offer more sensitive and considerably more reproducible clinical methods that could lend themselves to diagnostic, prognostic, and predictive tests. But for this to be realized the technology will need to be further developed to reduce cost and simplify application. Concomitantly the preclinical research will need be reported with a comprehensive understanding of the associated errors. dPCR benefits from a far more predictable variance than qPCR but is as susceptible to upstream errors associated with factors like sampling and extraction. dPCR can also suffer systematic bias, particularly leading to underestimation, and internal positive controls are likely to be as important for dPCR as they are for qPCR, especially when reporting the absence of a sequence.

In this review we highlight some of the considerations that may be needed when applying dPCR and discuss sources of error. The factors discussed here aim to assist in the translation of dPCR to diagnostic, predictive, or prognostic applications.
Circulating Tumor Cell Enumeration with a Combination of Epithelial Cell Adhesion Molecule– and Cell-Surface Vimentin–Based Methods for Monitoring Breast Cancer Therapeutic Response
Authors: Satelli Arun , Brownlee Zachary , Mitra Abhisek , Meng Qing H , Li Shulin
Published: October 2014

BACKGROUND

Detection, isolation, and enumeration of circulating tumor cells (CTCs) from cancer patients has become an important modality in clinical management of patients with breast cancer. Although CellSearch, an epithelial cell adhesion molecule (EpCAM)-based method that is used to isolate epithelial CTCs, has gained prominence, its inability to detect mesenchymal CTCs from breast cancer patients raises concerns regarding its utility in clinical management.

METHODS

To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma tumors. In the present study, we tested the sensitivity and specificity of detecting CTCs from blood collected at a random time during therapy from each of 58 patients with metastatic breast cancer by use of 84-1 (a monoclonal antibody against CSV to detect epithelial/mesenchymal-transition CTCs) and CellSearch methods. Additionally, we tested the possibility of improving the sensitivity and specificity of detection by use of additional parameters including nuclear EpCAM localization and epithelial mesenchymal ratios.

RESULTS

CTC counts with CSV were significant (P = 0.0053) in differentiating populations responsive and nonresponsive to treatment compared with CTC counts with CellSearch (P = 0.0564). The specificity of CTC detection was found to be highest when the sum of CTC counts from the 2 methods was above a threshold of 8 CTCs/7.5 mL.

CONCLUSIONS

The sum of CTC counts from the CellSearch and CSV methods appears to provide new insights for assessment of therapeutic response and thus provides a new approach to personalized medicine in breast cancer patients.
Governmental Financial Accounting and European Harmonisation: Case Study of Finland
Authors: Oulasvirta Lasse Olavi
Published: October 2014

The Finnish government accounting has developed from its own premises which used to emphasise the importance of budgetary accounting and prudence. Since the 1990s and the impact of New Public Financial Management, the Finnish government financial accounting has been accruals based. However, the Finnish application of accruals is based on the income statement approach, realisation principle and prudence. The International Public Sector Accounting Standards (IPSAS) based more on the balance sheet approach and fair value accounting are not suitable for the Finnish government accounting culture and practice. Furthermore, this means from the Finnish perspective that the EPSAS standards should not be based on IPSAS but on a conceptual framework especially developed for the European context.
Die frühkindliche Entwicklung sozialkognitiver und metakognitiver Fertigkeiten. Empirische Befunde, theoretische Kontroversen und Implikationen für die Ontogenese des Selbstbewusstseins
Authors: Paulus Markus
Published: October 2014

The present paper argues that the early development of social cognitive and metacognitive abilities informs the ongoing theoretical debate on the ontogenesis of the human self concept. To this end, the article provides first an overview on the early development of a self concept in the toddler years. Subsequently, it reviews central empirical findings and theoretical approaches on the early development of social-cognitive and metacognitive abilities from infancy to the preschool years. The paper concludes with a discussion of the implications of these findings and approaches for our understanding of the developmental origins of the human self concept.
Selective Elimination of Gametes during Pollen Storage at Low Temperature as a Way to Improve the Genetic Structure of Sporophytic Population for Cold Tolerance
Authors: Lyakh V. A. , Totsky I. V.
Published: October 2014

The genetic structure of F
An Innovative Dual Frequency PPP Model for Combined GPS/Galileo Observations
Authors: Afifi Akram , El-Rabbany Ahmed
Published: October 2014

This paper develops a new dual-frequency precise point positioning model, which combines GPS and Galileo observables. The addition of Galileo satellite system offers more visible satellites to the user, which is expected to enhance the satellite geometry and the overall PPP solution in comparison with GPS-only PPP solution. However, combining GPS and Galileo observables introduces additional biases, which require rigorous modelling, including the GPS to Galileo time offset, and Galileo satellite hardware delay. In this research, a GPS/Galileo ionosphere-free linear combination PPP model is developed. The additional biases of the GPS/Galileo combination are lumped and accounted for through the introduction of a new unknown parameter, inter-systems bias, in the PPP mathematical model. It is shown that a subdecimeter positioning accuracy level and 25% reduction in the solution convergence time can be achieved with the developed GPS/Galileo PPP model.
A facile method for generating Michael acceptor thin films via amine substituted poly(vinyl methyl ketone)
Authors: Bicak Niyazi
Published: October 2014

Alpha-morpholine substituted poly(vinyl methyl ketone) (PVMK) was determined to undergo rapid self-crosslinking by short-term vacuuming (i.e., 30–60 min) or curing at 70–100 °C. The chemical transformations involved were monitored by TGA, DSC, FT-IR, 1HNMR and solid-state 13C NMR techniques. These experiments revealed an “unzipping-like” mechanism yielding multi conjugated enone structure via consecutive deamination by β-hydrogen elimination and simultaneous Diels–Alder cyclization resulting in crosslinking. This chemistry was exploited for generating Michael acceptor thin film coatings on silica nanoparticles, in which the silica was impregnated with morpholine substituted poly(vinyl methyl ketone) and simply heated at 100 °C. The dense polyene functional films so formed were demonstrated to add amines and thiols at room temperature. The resulting silica nanoparticles were employed to form homogenous composite films using poly(butyl acrylate-stat-methylmethacrylate) as carrier matrix. Morpholine substituted poly(vinyl methyl ketone) (MSP) seems to be generally applicable for surface modification of different inorganic surfaces with organics.