bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal correlates of impaired habituation in response to repeated trigemino-nociceptive but not to olfactory input in migraineurs: An fMRI study
Authors: Stankewitz A , Schulz E , May A
Published: December 2012

Introduction:

Using functional magnetic resonance imaging (fMRI), we aimed to explore the habituation behaviour to trigemino-nociceptive as well as olfactory stimuli in migraine patients. We exclusively focussed on intrasessional behavioural rating patterns and the related blood oxygen level dependent (BOLD) signal changes.

Findings:

We observed that groups significantly differ in the time course of pain intensity ratings during the stimulation session: whereas interictal migraineurs sensitized (increasing pain ratings), control subjects habituated (decreasing pain ratings). Pain ratings of ictal patients remained unchanged. This behaviour is accompanied by a similar time course of neuronal activity in the bilateral anterior insula, in the middle cingulate cortex and in the thalamus. In these areas, the brain activity increased in migraineurs but decreased in the control group during the session. In contrast to these findings, the rating patterns for the olfactory stimuli (rose odour) did not differ between patients and controls and a gradual decrease of perceived stimulus intensity was found in all three groups. This stimulus specific response may occur because the olfactory system is the only sensory system not passing the thalamus.

Conclusion:

Our data suggest that impaired habituation in functional brain systems in migraine is fundamental only to specific modalities including the trigemino-nociceptive, but, at least, excluding the olfactory system. Our findings further suggest that there is no single neuronal modulator responsible for the altered rating pattern in migraineurs.
Effect of different methods of cutting fluid application on turning of a difficult-to-machine steel (SAE EV-8)
Authors: Sanchez Luiz Eduardo de Angelo , Palma Geraldo L , Marinescu Ioan , Modolo Delson L , Nalon Luis J , Santos Alex E
Published: December 2012

In this study, different methods of cutting fluid application are used in turning of a difficult-to-machine steel (SAE EV-8). Initially, a semisynthetic cutting fluid was applied using a conventional method (i.e. overhead flood cooling), minimum quantity of cutting fluid, and pulverization. A lubricant of vegetable oil (minimum quantity of lubricant) was also applied using the minimum quantity method. Thereafter, a cutting fluid jet under high pressure (3.0 MPa) was singly applied in the following regions: chip–tool interface, top surface of the chip (between workpiece and chip) and tool–workpiece contact. Moreover, two other methods were used: an interflow between conventional application and chip–tool interface jet (combined method) and, finally, three jets simultaneously applied. In order to carry out these tests, it was necessary to set up a high-pressure system using a piston pump for generating a cutting fluid jet, a venturi for fluid application (minimum quantity of cutting fluid and minimum quantity of lubricant) and a nozzle for cutting fluid pulverization. The output variables analyzed included tool life, surface roughness, cutting tool temperature, cutting force, chip form, chip compression rate and machined specimen microstructure. Among the results, it can be observed that the tool life increases and the cutting force decreases with the application of cutting fluid jet, mainly when it is directed to the chip–tool interface. Excluding the methods involving jet fluid, the conventional method seems to be more efficient than other methods of low pressure, such as minimum quantity of volume and pulverization, when considering just the cutting tool wear.
Formability evaluation by novel specimen designs in sheet metal forming with two-step strain paths
Authors: Chen Yen-Ju , Lee Rong-Shean , Gau Jenn-Terng
Published: December 2012

Limit dome height test is commonly used for evaluating the formability of sheet material. Through altering the geometry of specimens, different strain paths could be obtained to establish forming limit diagram of the material. By incorporating finite element analysis with ductile energy criteria, engineers can also predict the formability of material. The forming limit diagram or constants in ductile energy criteria are usually determined by experiments with linear strain path. However, the predictions may lose their accuracy when evaluating products with complex strain paths, which is commonly seen in sheet forming processes. Therefore, a better method for evaluating formability of material under complex strain path should be developed. In this study, novel specimen designs for limit dome height test are applied to generate different strain paths with two-step strain effect on the specimens. Different geometric parameters of the novel specimen design can alter the slope of strain paths and create different strain paths similar to the two-step deformation conditions occurred in actual sheet forming processes. Three different two-step strain path conditions are created experimentally, and the changes in strain path are verified with simulations. From the results, the predictions of forming limit based on linear strain path forming limit diagram could be overestimated or underestimated under two-step strain path conditions. Thus, the formability of material under two-step strain path conditions can be determined by corresponding experiments using novel specimen designs, instead of predictions made by linear strain path conditions.
Exploration of the stiffness profiles of modern cars in pedestrian impacts
Authors: Davies Huw C
Published: December 2012

Consumer and regulatory tests for improvement in pedestrian protection are now firmly established. A change in the vehicle frontal stiffness profiles as a result of these tests is less well established. The purpose of this paper is to contribute to the knowledge base on the vehicle frontal stiffness in pedestrian impacts. Using data recorded as part of the European New Car Assessment Programme, a series of 139 impact tests using headform and legform impactors were used to calculate the vehicle frontal stiffness profile of eight cars manufactured between 2006 and 2010. To account for one of the limitations of the legform as a device for measuring the stiffness of a surface, a methodology for determining a correction factor using the multi-body modelling software MADYMO is presented. Comparison with previous published work showed that the stiffness of the windscreen was unchanged, but that the stiffnesses of the bonnet and front bumper were reduced.
Implementing an Inpatient Social Early Warning System for Child Maltreatment
Authors: Atabaki Armita , Heddaeus Daniela , Metzner Franka , Schulz Holger , Siefert Sönke , Pawils Silke
Published: December 2012

Objectives:

The current article describes the process evaluation of a social early warning system (SEWS) for the prevention of child maltreatment in the federal state of Hamburg. This prevention initiative targets expectant mothers and their partners including an initial screening of risk factors for child maltreatment, a subsequent structured clearing interview further exploring risks and identifying protective factors and an optional referral to the regional health and social care system.

Method:

The process evaluation was conducted by examining the flow of participants through the different stages of the SEWS as well as asking social education workers, parents, and regional institutions about their satisfaction with the process of the SEWS.

Results:

The participation rate throughout the SEWS as well as the satisfaction rates were high.

Conclusions:

The SEWS is a secondary prevention initiative with a substantial difference to other early prevention initiatives, as it aims to facilitate intervention rather than providing it.
Non-local elasto-viscoplastic models with dislocations in finite elasto-plasticity. Part I: Constitutive framework
Authors: Cleja-Ţigoiu Sanda
Published: December 2012

In the first part of the paper we elaborate on a theoretical framework for elasto-plastic materials, based on the decomposition of the second-order deformation, associated with the motion, into its elastic and plastic second-order components, and applied to solids with lattice defects at the micro-structure level. Only the dislocations have been considered as possible lattice defects, which are modelled through the non-zero torsion of the plastic connection as a tensorial measure of the dislocations and through the scalar dislocation density and its gradient. The non-local evolution equations for the scalar dislocation density as well as for the plastic distortion have been derived to be compatible with the principle of the imbalance of the free energy. A coupling term dependent on the gradient of the scalar dislocation density influences the evolution of the plastic distortion. The internal power included the power dissipated by micro-forces, which consist from micro-stress and micro-momenta satisfying their own balance equations and being related not only with the plastic distortion but also with the scalar dislocation density. The free energy is defined to be dependent on the elastic strain and on the second-order plastic deformation, as well as on the scalar dislocation density and its gradient. Different constitutive non-local dissipative models have been derived and compared with the already existing ones.
The Effect of the Public Exercise Environment on the Physical Activity for the Active Ageing of the Elderly
Authors: An Somi , Lee Yeunsook , Kim Jeong Tai
Published: December 2012

Recent medical studies have revealed that the physical activity for active ageing is very important for health and well-being of elderly’s life. This study aims to identify the current situation of public exercise environments where the elderly in urban areas exercise daily, and to research how public exercise environments could influence the physical activities for the active ageing of the elderly. The site of this study is an underprivileged urban area where the low-income elderly population is dominant. Through field observations, and through direct interviews using questionnaire form for 180 subjects over a period in October to November 2011, data on the elderly’s physical activity were collected. The result of this study revealed that the elderly in underprivileged urban areas were using the public exercise environment regardless of their perceived health, and that the older residents would undertake less vigorous physical activities. The regular users of these public facilities would tend to be more active than those who do not. The research illustrates the significance of public exercise environments which should have a role in health promotion. Therefore, availability of public places, such as small neighbourhood gardens and parks, should be part of a nation’s strategy to encourage active ageing for the elderly, particular in low-income areas.
Leadership Matters
Authors: Jarvis Carol , Gulati Anita , McCririck Virginia , Simpson Peter
Published: December 2012

The Problem

This article explores some of the tensions that required careful management in the design and delivery of a leadership development program. This discussion draws particularly upon a formal evaluation of two cohorts, each comprising approximately 20 senior managers working in adult social care. Complexity theory, notably Complex Responsive Processes of Relating, is used to make visible, explore and articulate the need to hold in tension apparently contradictory forces and requirements. The program was established at a critical time in the U.K. government’s public services reform agenda, which was unfolding during a period of increasing resource constraint. This included a requirement upon commissioners to demonstrate impact and return on investment (ROI) in development programs. However, complexity theory explains why a direct causal relationship between inputs and outcomes is not amenable to demonstration by evaluation.

The Solution

Consequently, the approach to demonstrating ROI explored the microprocesses underpinning the development of the participants’ thinking and practice through formative real time and post hoc evaluation. This comprised a range of qualitative techniques: extended observations provided an “ethnographic” overview of the program; participant and stakeholder interviews gave insight into critical incidents and key learning points; and guided conversations placed greater emphasis on the everyday experience of participants in applying their learning. It is argued that such an approach to evaluation is both a research intervention and a contribution to the development process.

The Stakeholders

Our article will be of particular relevance to human resource professionals, leadership development practitioners, commissioners, business schools and evaluators facing the challenge of finding meaningful measures of “ROI” for individual and organizational development.
Schmallenberg virus challenge models in cattle: infectious serum or culture-grown virus?
Authors: Wernike Kerstin , Eschbaumer Michael , Breithaupt Angele , Hoffmann Bernd , Beer Martin
Published: December 2012

Schmallenberg virus (SBV), discovered in Europe in 2011, causes mild transient disease in adult ruminants, but fetal infection can lead to severe malformation in cattle, sheep and goats.

To elucidate the pathogenesis of this novel orthobunyavirus, considerable efforts are required. A reliable and standardized infection model is essential for in vivo studies. In the present study, two groups of four cattle were inoculated with either serum passaged in cattle only or cell culture-grown virus. The replication of culture-grown SBV in cattle was reduced compared to virus inoculated via infectious serum. In a second experiment, the infectious serum was titrated in calves; the tested batch contained 102.83 infectious doses per mL. Hence, serum-borne virus that was only passaged in the natural host is a suitable option for a standardized SBV infection model.
Structure and evolution of barley powdery mildew effector candidates
Authors: Pedersen Carsten , van Themaat Emiel Ver Loren , McGuffin Liam J , Abbott James C , Burgis Timothy A , Barton Geraint , Bindschedler Laurence V , Lu Xunli , Maekawa Takaki , Weßling Ralf , Cramer Rainer , Thordal-Christensen Hans , Panstruga Ralph , Spanu Pietro D
Published: December 2012

Background

Protein effectors of pathogenicity are instrumental in modulating host immunity and disease resistance. The powdery mildew pathogen of grasses Blumeria graminis causes one of the most important diseases of cereal crops. B. graminis is an obligate biotrophic pathogen and as such has an absolute requirement to suppress or avoid host immunity if it is to survive and cause disease.

Results

Here we characterise a superfamily predicted to be the full complement of Candidates for Secreted Effector Proteins (CSEPs) in the fungal barley powdery mildew parasite B. graminis f.sp. hordei. The 491 genes encoding these proteins constitute over 7% of this pathogen’s annotated genes and most were grouped into 72 families of up to 59 members. They were predominantly expressed in the intracellular feeding structures called haustoria, and proteins specifically associated with the haustoria were identified by large-scale mass spectrometry-based proteomics. There are two major types of effector families: one comprises shorter proteins (100–150 amino acids), with a high relative expression level in the haustoria and evidence of extensive diversifying selection between paralogs; the second type consists of longer proteins (300–400 amino acids), with lower levels of differential expression and evidence of purifying selection between paralogs. An analysis of the predicted protein structures underscores their overall similarity to known fungal effectors, but also highlights unexpected structural affinities to ribonucleases throughout the entire effector super-family. Candidate effector genes belonging to the same family are loosely clustered in the genome and are associated with repetitive DNA derived from retro-transposons.

Conclusions

We employed the full complement of genomic, transcriptomic and proteomic analyses as well as structural prediction methods to identify and characterize the members of the CSEPs superfamily in B. graminis f.sp. hordei. Based on relative intron position and the distribution of CSEPs with a ribonuclease-like domain in the phylogenetic tree we hypothesize that the associated genes originated from an ancestral gene, encoding a secreted ribonuclease, duplicated successively by repetitive DNA-driven processes and diversified during the evolution of the grass and cereal powdery mildew lineage.
Transcriptome response analysis of Arabidopsis thaliana to leafminer (Liriomyza huidobrensis)
Authors: Zhang Sufang , Zhang Zhen , Kang Le
Published: December 2012

Background

Plants have evolved a complicated resistance system and exhibit a variety of defense patterns in response to different attackers. Previous studies have shown that responses of plants to chewing insects and phloem-feeding insects are significantly different. Less is known, however, regarding molecular responses to leafminer insects. To investigate plant transcriptome response to leafminers, we selected the leafminer Liriomyza huidobrensis, which has a special feeding pattern more similar to pathogen damage than that of chewing insects, as a model insect, and Arabidopsis thaliana as a response plant.

Results

We first investigated local and systemic responses of A. thaliana to leafminer feeding using an Affymetrix ATH1 genome array. Genes related to metabolic processes and stimulus responses were highly regulated. Most systemically-induced genes formed a subset of the local response genes. We then downloaded gene expression data from online databases and used hierarchical clustering to explore relationships among gene expression patterns in A. thaliana damaged by different attackers.

Conclusions

Our results demonstrate that plant response patterns are strongly coupled to damage patterns of attackers.
Endo-(1,4)-β-Glucanase gene families in the grasses: temporal and spatial Co-transcription of orthologous genes1
Authors: Buchanan Margaret , Burton Rachel A , Dhugga Kanwarpal S , Rafalski Antoni J , Tingey Scott V , Shirley Neil J , Fincher Geoffrey B
Published: December 2012

Background

Endo-(1,4)-β-glucanase (cellulase) glycosyl hydrolase GH9 enzymes have been implicated in several aspects of cell wall metabolism in higher plants, including cellulose biosynthesis and degradation, modification of other wall polysaccharides that contain contiguous (1,4)-β-glucosyl residues, and wall loosening during cell elongation.

Results

The endo-(1,4)-β-glucanase gene families from barley (Hordeum vulgare), maize (Zea mays), sorghum (Sorghum bicolor), rice (Oryza sativa) and Brachypodium (Brachypodium distachyon) range in size from 23 to 29 members. Phylogenetic analyses show variations in clade structure between the grasses and Arabidopsis, and indicate differential gene loss and gain during evolution. Map positions and comparative studies of gene structures allow orthologous genes in the five species to be identified and synteny between the grasses is found to be high. It is also possible to differentiate between homoeologues resulting from ancient polyploidizations of the maize genome. Transcript analyses using microarray, massively parallel signature sequencing and quantitative PCR data for barley, rice and maize indicate that certain members of the endo-(1,4)-β-glucanase gene family are transcribed across a wide range of tissues, while others are specifically transcribed in particular tissues. There are strong correlations between transcript levels of several members of the endo-(1,4)-β-glucanase family and the data suggest that evolutionary conservation of transcription exists between orthologues across the grass family. There are also strong correlations between certain members of the endo-(1,4)-β-glucanase family and other genes known to be involved in cell wall loosening and cell expansion, such as expansins and xyloglucan endotransglycosylases.

Conclusions

The identification of these groups of genes will now allow us to test hypotheses regarding their functions and joint participation in wall synthesis, re-modelling and degradation, together with their potential role in lignocellulose conversion during biofuel production from grasses and cereal crop residues.
Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma
Authors: Fairfax BP , Pratap S , Roberts ISD , Collier J , Kaplan R , Meade AM , Ritchie AW , Eisen T , Macaulay VM , Protheroe A
Published: December 2012

Background

Sorafenib is an orally available kinase inhibitor with activity at Raf, PDGFβ and VEGF receptors that is licensed for the treatment of advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Current evidence-based post-nephrectomy management of individuals with localized RCC consists of surveillance-based follow up. The SORCE trial is designed to investigate whether treatment with adjuvant sorafenib can reduce recurrence rates in this cohort.

Case presentation

Here we report an idiosyncratic reaction to sorafenib resulting in fatal hepatotoxicity and associated renal failure in a 62 year-old man treated with sorafenib within the SORCE trial.

Conclusion

This is the first reported case of sorafenib exposure associated fatal toxicity in the adjuvant setting and highlights the unpredictable adverse effects of novel adjuvant therapies.
Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression
Authors: Chen Junyi , Jiao Li , Xu Chuanliang , Yu Yongwei , Zhang Zhensheng , Chang Zheng , Deng Zhen , Sun Yinghao
Published: December 2012

Background

Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms.

Methods

First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues.

Results

Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion.

Conclusions

Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer.
Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3
Authors: Zhao Lei , He Li-Ru , Xi Mian , Cai Mu-Yan , Shen Jing-Xian , Li Qiao-Qiao , Liao Yi-Ji , Qian Dong , Feng Zi-Zhen , Zeng Yi-Xin , Xie Dan , Liu Meng-Zhong
Published: December 2012

Background

Epidermal growth factor receptor (EGFR) is suggested to predict the radiosensitivity and/or prognosis of human esophageal squamous cell carcinoma (ESCC). The objective of this study was to investigate the efficacy of Nimotuzumab (an anti-EGFR monoclonal antibody) on ESCC radiotherapy (RT) and underlying mechanisms.

Methods

Nimotuzumab was administrated to 2 ESCC cell lines KYSE30 and TE-1 treated with RT. Cell growth, colony formation and apoptosis were used to measure anti-proliferation effects. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3) in ESCC cells radiosensitivity treated with Nimotuzumab. In vivo effect of Nimotuzumab on ESCC radiotherapy was done using a mouse xenograft model.

Results

Nimotuzumab enhanced radiation response of KYSE30 cells (with high EGFR expression) in vitro, as evidenced by increased radiation-inhibited cell growth and colony formation and radiation-mediated apoptosis. Mechanism study revealed that Nimotuzumab inhibited phosphorylated EGFR (p-EGFR) induced by EGF in KYSE30 cells. In addition, knockdown of IGFBP-3 by short hairpin RNA significantly reduced KYSE30 cells radiosensitivity (P<0.05), and even after the administration of Nimotuzumab, the RT response of IGFBP-3 silenced KYSE30 cells was not enhanced (P>0.05). In KYSE30 cell xenografts, Nimotuzumab combined with radiation led to significant tumor growth delay, compared with that of radiation alone (P=0.029), and also with IGFBP-3 up-regulation in tumor tissue.

Conclusions

Nimotuzumab could enhance the RT effect of ESCC cells with a functional active EGFR pathway. In particular, the increased ESCC radiosensitivity by Nimotuzumab might be dependent on the up-regulation of IGFBP-3 through EGFR-dependent pathway.
A fixed point theorem for cyclic generalized contractions in metric spaces
Authors: Alghamdi Maryam A , Petruşel Adrian , Shahzad Naseer
Published: December 2012

In this paper, we extend a recent result of V. Pata (J. Fixed Point Theory Appl. 10:299-305, 2011) in the frame of a cyclic representation of a complete metric space.
Existence results for nonlocal boundary value problems of nonlinear fractional q-difference equations
Authors: Ahmad Bashir , Ntouyas Sotiris K , Purnaras Ioannis K
Published: December 2012

In this paper, we study a nonlinear fractional q-difference equation with nonlocal boundary conditions. The existence of solutions for the problem is shown by applying some well-known tools of fixed-point theory such as Banach’s contraction principle, Krasnoselskii’s fixed-point theorem, and the Leray-Schauder nonlinear alternative. Some illustrating examples are also discussed.

MSC:34A08, 39A05, 39A12, 39A13.
p42.3 gene expression in gastric cancer cell and its protein regulatory network analysis
Authors: Zhang Jianhua , Lu Chunlei , Shang Zhigang , Xing Rui , Shi Li , Lv Youyong
Published: December 2012

Background

To analyze the p42.3 gene expression in gastric cancer (GC) cell, find the relationship between protein structure and function, establish the regulatory network of p42.3 protein molecule and then to obtain the optimal regulatory pathway.

Methods

The expression of p42.3 gene was analyzed by RT-PCR, Western Blot and other biotechnologies. The relationship between the spatial conformation of p42.3 protein molecule and its function was analyzed using bioinformatics, MATLAB and related knowledge about protein structure and function. Furthermore, based on similarity algorithm of spatial layered spherical coordinate, we compared p42.3 molecule with several similar structured proteins which are known for the function, screened the characteristic nodes related to tumorigenesis and development, and established the multi variable relational model between p42.3 protein expression, cell cycle regulation and biological characteristics in the level of molecular regulatory networks. Finally, the optimal regulatory network was found by using Bayesian network.

Results

(1) The expression amount of p42.3 in G1 and M phase was higher than that in S and G2 phase; (2) The space coordinate systems of different structural domains of p42.3 protein were established in Matlab7.0 software; (3) The optimal pathway of p42.3 gene in protein regulatory network in gastric cancer is Ras protein, Raf-1 protein, MEK, MAPK kinase, MAPK, tubulin, spindle protein, centromere protein and tumor.

Conclusion

It is of vital significance for mechanism research to find out the action pathway of p42.3 in protein regulatory network, since p42.3 protein plays an important role in the generation and development of GC.
Chromosome mapping of repetitive sequences in Anostomidae species: implications for genomic and sex chromosome evolution
Authors: da Silva Edson Lourenço , de Borba Rafael Splendore , Parise-Maltempi Patrícia Pasquali
Published: December 2012

Background

Members of the Anostomidae family provide an interesting model system for the study of the influence of repetitive elements on genome composition, mainly because they possess numerous heterochromatic segments and a peculiar system of female heterogamety that is restricted to a few species of the Leporinus genus. The aim of this study was to isolate and identify important new repetitive DNA elements in Anostomidae through restriction enzyme digestion, followed by cloning, characterisation and chromosome mapping of this fragment. To identify repetitive elements in other Leporinus species and expand on studies of repetitive elements in Anostomidae, hybridisation experiments were also performed using previously described probes of LeSpe I repetitive elements.

Results

The 628-base pair (bp) LeSpe II fragment was hybridised to metaphase cells of L. elongatus individuals as well as those of L. macrocephalus, L. obtusidens, L. striatus, L. lacustris, L. friderici, Schizodon borellii and S. isognathus. In L. elongatus, both male and female cells contained small clusters of LeSpe II repetitive elements dispersed on all of the chromosomes, with enrichment near most of the terminal portions of the chromosomes. In the female sex chromosomes of L. elongatus (Z2,Z2/W1W2), however, this repeated element was absent. In the remaining species, a dispersed pattern of hybridisation was observed on all chromosomes irrespective of whether or not they were sex chromosomes. The repetitive element LeSpe I produced positive hybridisations signals only in L. elongatus, L. macrocephalus and L. obtusidens, i.e., species with differentiated sex chromosomes. In the remaining species, the LeSpe I element did not produce hybridisation signals.

Conclusions

Results are discussed in terms of the effects of repetitive sequences on the differentiation of the Anostomidae genome, especially with respect to sex chromosome evolution. LeSpe II showed hybridisation patterns typical of Long Interspersed Elements (LINEs). The differential distribution of this element may be linked to sex chromosome differentiation in L. elongatus species. The relationship between sex chromosome specificity and the LeSpe I element is confirmed in the species L. elongatus, L. macrocephalus and L. obtusidens.
Protein expression in the midgut of sugar-fed Aedes albopictus females
Authors: Saboia-Vahia Leonardo , Borges-Veloso Andre , Cuervo Patricia , Junqueira Magno , Mesquita-Rodrigues Camila , Britto Constanca , Domont Gilberto Barbosa , De Jesus Jose Batista
Published: December 2012

Background

Aedes albopictus is a vector for several fatal arboviruses in tropical and sub-tropical regions of the world. The midgut of the mosquito is the first barrier that pathogens must overcome to establish infection and represents one of the main immunologically active sites of the insect. Nevertheless, little is known about the proteins involved in the defense against pathogens, and even in the processing of food, and the detoxification of metabolites. The identification of proteins exclusively expressed in the midgut is the first step in understanding the complex physiology of this tissue and can provide insight into the mechanisms of pathogen-vector interaction. However, identification of the locally expressed proteins presents a challenge because the Ae. albopictus genome has not been sequenced.

Methods

In this study, two-dimensional electrophoresis (2DE) was combined with liquid chromatography in line with tandem mass spectrometry (LC-MS/MS) and data mining to identify the major proteins in the midgut of sugar-fed Ae. albopictus females.

Results

Fifty-six proteins were identified by sequence similarity to entries from the Ae. aegypti genome. In addition, two hypothetical proteins were experimentally confirmed. According to the gene ontology analysis, the identified proteins were classified into 16 clusters of biological processes. Use of the STRING database to investigate protein functional associations revealed five functional networks among the identified proteins, including a network for carbohydrate and amino acid metabolism, a group associated with ATP production and a network of proteins that interact during detoxification of toxic free radicals, among others. This analysis allowed the assignment of a potential role for proteins with unknown function based on their functional association with other characterized proteins.

Conclusion

Our findings represent the first proteome map of the Ae. albopictus midgut and denotes the first steps towards the description of a comprehensive proteome map of this vector. In addition, the data contributes to the functional annotation of Aedes spp. genomes using mass spectrometry-based proteomics data combined with complementary gene prediction methods.
The way in which a physiotherapy service is structured can improve patient outcome from a surgical intensive care: a controlled clinical trial
Authors: Hanekom Susan D , Louw Quinette , Coetzee Andre
Published: December 2012

Introduction

The physiological basis of physiotherapeutic interventions used in intensive care has been established. We must determine the optimal service approach that will result in improved patient outcome. The aim of this article is to report on the estimated effect of providing a physiotherapy service consisting of an exclusively allocated physiotherapist providing evidence-based/protocol care, compared with usual care on patient outcomes.

Methods

An exploratory, controlled, pragmatic, sequential-time-block clinical trial was conducted in the surgical unit of a tertiary hospital in South Africa. Protocol care (3 weeks) and usual care (3 weeks) was provided consecutively for two 6-week intervention periods. Each intervention period was followed by a washout period. The physiotherapy care provided was based on the unit admission date. Data were analyzed with Statistica in consultation with a statistician. Where indicated, relative risks with 95% confidence intervals (CIs) are reported. Significant differences between groups or across time are reported at the alpha level of 0.05. All reported P values are two-sided.

Results

Data of 193 admissions were analyzed. No difference was noted between the two patient groups at baseline. Patients admitted to the unit during protocol care were less likely to be intubated after unit admission (RR, 0.16; 95% CI, 0.07 to 0.71; RRR, 0.84; NNT, 5.02; P = 0.005) or to fail an extubation (RR, 0.23; 95% CI, 0.05 to 0.98; RRR, 0.77; NNT, 6.95; P = 0.04). The mean difference in the cumulative daily unit TISS-28 score during the two intervention periods was 1.99 (95% CI, 0.65 to 3.35) TISS-28 units (P = 0.04). Protocol-care patients were discharged from the hospital 4 days earlier than usual-care patients (P = 0.05). A tendency noted for more patients to reach independence in the transfers (P = 0.07) and mobility (P = 0.09) categories of the Barthel Index.

Conclusions

A physiotherapy service approach that includes an exclusively allocated physiotherapist providing evidence-based/protocol care that addresses pulmonary dysfunction and promotes early mobility improves patient outcome. This could be a more cost-effective service approach to care than is usual care. This information can now be considered by administrators in the management of scarce physiotherapy resources and by researchers in the planning of a multicenter randomized controlled trial.

Trial registration

PACTR201206000389290
Monitoring mitochondrial inner membrane potential for detecting early changes in viability of bacterium-infected human bone marrow-derived mesenchymal stem cells
Authors: Pietilä Mika , Lähteenmäki Kaarina , Lehtonen Siri , Leskelä Hannu-Ville , Närhi Marko , Lönnroth Maarit , Mättö Jaana , Lehenkari Petri , Nordström Katrina
Published: December 2012

Introduction

One of the most challenging safety issues in the manufacture of cell based medicinal products is the control of microbial risk as cell-based products cannot undergo terminal sterilization. Accordingly, sensitive and reliable methods for detection of microbial contamination are called for. As mitochondrial function has been shown to correlate with the viability and functionality of human mesenchymal stem cells (hMSCs) we have studied the use of a mitochondrial inner membrane potential sensitive dye for detecting changes in the function of mitochondria following infection by bacteria.

Methods

The effect of bacterial contamination on the viability of bone marrow-derived mesenchymal stem cells (BMMSCs) was studied. BMMSC lines were infected with three different bacterial species, namely two strains of Pseudomonas aeruginosa, three strains of Staphylococcus aureus, and three strains of Staphylococcus epidermidis. The changes in viability of the BMMSCs after bacterial infection were studied by staining with Trypan blue, by morphological analysis and by monitoring of the mitochondrial inner membrane potential.

Results

Microscopy and viability assessment by Trypan blue staining showed that even the lowest bacterial inocula caused total dissipation of BMMSCs within 24 hours of infection, similar to the effects seen with bacterial loads which were several magnitudes higher. The first significant signs of damage induced by the pathogens became evident after 6 hours of infection. Early changes in mitochondrial inner membrane potential of BMMSCs were evident after 4 hours of infection even though no visible changes in viability of the BMMSCs could be seen.

Conclusions

Even low levels of bacterial contamination can cause a significant change in the viability of BMMSCs. Moreover, monitoring the depolarization of the mitochondrial inner membrane potential may provide a rapid tool for early detection of cellular damage induced by microbial infection. Accordingly, mitochondrial analyses offer sensitive tools for quality control and monitoring of safety and efficacy of cellular therapy products.
Numerical simulation of ambient seismic wavefield modification caused by pore-fluid effects in an oil reservoir
Authors: Lambert Marc-André , Saenger Erik H. , Quintal Beatriz , Schmalholz Stefan M.
Published: December 2012

We have modeled numerically the seismic response of a poroelastic inclusion with properties applicable to an oil reservoir that interacts with an ambient wavefield. The model includes wave-induced fluid flow caused by pressure differences between mesoscopic-scale (i.e., in the order of centimeters to meters) heterogeneities. We used a viscoelastic approximation on the macroscopic scale to implement the attenuation and dispersion resulting from this mesoscopic-scale theory in numerical simulations of wave propagation on the kilometer scale. This upscaling method includes finite-element modeling of wave-induced fluid flow to determine effective seismic properties of the poroelastic media, such as attenuation of P- and S-waves. The fitted, equivalent, viscoelastic behavior is implemented in finite-difference wave propagation simulations. With this two-stage process, we model numerically the quasi-poroelastic wave-propagation on the kilometer scale and study the impact of fluid properties and fluid saturation on the modeled seismic amplitudes. In particular, we addressed the question of whether poroelastic effects within an oil reservoir may be a plausible explanation for low-frequency ambient wavefield modifications observed at oil fields in recent years. Our results indicate that ambient wavefield modification is expected to occur for oil reservoirs exhibiting high attenuation. Whether or not such modifications can be detected in surface recordings, however, will depend on acquisition design and noise mitigation processing as well as site-specific conditions, such as the geologic complexity of the subsurface, the nature of the ambient wavefield, and the amount of surface noise.
Elliptical moveout operator for data regularization in azimuthally anisotropic media
Authors: Shragge Jeffrey
Published: December 2012

Data regularization by azimuthal moveout (AMO) is an important seismic processing step applied to minimize the deleterious effects of irregular and incomplete acquisition in complex geology. Using isotropic AMO operators on data acquired over azimuthally anisotropic media, though, can lead to poor regularization results due to mixing of wavefield information from neighboring traces with azimuthally varying velocity profiles. An elliptical moveout operator (EMO), representing an extension of isotropic AMO to elliptical azimuthally anisotropic media, is sensitive to variations in the magnitude and the orientation of velocity ellipticity. AMO and EMO operators can be applied to regularize data by moving wavefield information from traces acquired at neighboring offsets and midpoints to infill existing data holes. Unlike AMO, though, EMO operators also can be used in a data conditioning procedure to interpolate energy between seismic traces where input and output velocity profiles are azimuthally elliptical and isotropic, respectively. Resulting processed data volumes are approximately free of elliptical azimuthal anisotropy, as can be shown by comparing analytical traveltimes and numerically calculated wavefield arrivals. EMO thus represents a one-step regularization/conditioning procedure for elliptically azimuthally anisotropic media that is more consistent with wave-equation physics and yields more accurate results than when compared with those from isotropic processing and elliptical residual moveout operator static corrections.
The Discovery of the Isoquant
Authors: Lloyd Peter
Published: December 2012

This article examines the first appearances of the isoquant, a concept that is central to production and supply theory. It appears to have been discovered independently by Bowley, Frisch, Cobb, and Lerner, in that order. Frisch coined the term isoquant. It is possible but not likely that Frisch took the concept from Bowley, and Lerner may have taken it from R. G. D. Allen. The article also discusses why the discovery of the isoquant was not made until more than forty years after that of the indifference curve, when to a modern analyst the isoquant appears isomorphic to the indifference curve and could have been copied straight from utility theory.
On Adam Smith’s Ambiguities on Value and Wealth
Authors: Meacci Ferdinando
Published: December 2012

David Ricardo’s criticisms of Adam Smith on value and wealth have been rather ignored in the recent revival of Ricardian economics. This essay intends to fill the gap by revisiting Smith’s link between value and wealth in the light of Ricardo’s criticisms. This is done in two steps. The first step is provided in section 1. This deals with Ricardo’s criticisms both of Say’s and Lauderdale’s criticisms of Smith and of Smith’s and Malthus’s arguments on the related issues of rent and the “annual produce of the land and labour of a country.” The second step is provided in section 2. The aim of this section is to dissolve Smith’s terminological inaccuracies or contradictions on the issue of value and wealth. This is done by highlighting the distinctions between the two points of view (of an individual and of society) and between the two aspects of labor (as work done and work to be done) that underlie Smith’s own system of thought. The article closes with a reappraisal of the principle of value as command of labor as work to be done in the economy as a whole and of Smith’s vision of a permanent increase in the natural price of labor (in Smith’s rather than in Ricardo’s sense) resulting from a continuous process of accumulation.
14-3-3 proteins interact with neurofilament protein-L and regulate dynamic assembly of neurofilaments
Authors: Miao Linqing , Teng Junlin , Lin Jiqiang , Liao Xianzhi , Chen Jianguo
Published: December 2012

Neurofilament protein-L (NF-L) is the core component of neurofilaments. Recent studies indicate that the NF-L mutations reported in human Charcot–Marie–Tooth (CMT) disease lead to the formation of NF-L aggregates and result in axon degeneration of motor and sensory neurons, which are thought to be the cause of CMT disease type 2E. In the present study, we investigated the dynamic regulation of NF-L assembly and the mechanism of aggregate formation of CMT NF-L mutants. We report that 14-3-3 proteins interact with NF-L in a phosphorylation-dependent manner. Investigation of mutations of phospho-serine sites at the head domain of NF-L revealed that several phosphorylation sites, particularly Ser43 and Ser55, were important for 14-3-3 binding. 14-3-3 overexpression resulted in a significant increase in the dynamic exchange rate of NF-L subunits and induced striking disassembly of neurofilaments. CMT NF-L mutants, particularly those with mutations in the Pro8 and Pro22 sites of the NF-L head domain, led to substantially diminished interaction between 14-3-3 and NF-L, which resulted in the formation of NF-L aggregates and the disruption of the neurofilament co-assembly of NF-L and NF-M. However, aggregate formation in CMT NF-L mutants was downregulated by 14-3-3 overexpression. Taken together, these results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. Thus, the 14-3-3 proteins are a possible molecular target for CMT disease therapy.
Cytoplasmic mislocalization of p27 and CDK2 mediates the anti-migratory and anti-proliferative effects of Nodal in human trophoblast cells
Authors: Nadeem Lubna , Brkic Jelena , Chen Yangchun Frank , Bui Tung , Munir Sadia , Peng Chun
Published: December 2012

p27Kip1, a cyclin-dependent kinase (CDK) inhibitor, is a multi-functional protein that regulates various cellular activities. Trophoblast proliferation, migration and invasion are some of the key processes of placental development. We have recently reported that Nodal, a member of the transforming growth factor-β (TGF-β) superfamily, inhibits human trophoblast cell proliferation, migration and invasion. In the present study, we investigated the mechanism by which Nodal regulates trophoblast activities. We found that Nodal increased p27 mRNA and protein levels by enhancing their stability. Interestingly, Nodal signaling also induced nuclear export of p27 and CDK2. Cytoplasmic translocation of p27 induced by Nodal requires p27 phosphorylation at S10. In addition, Nodal enhanced the association of p27 with CDK2, CDK5 and a microtubule-destabilizing protein, stathmin, and induced stathmin phosphorylation at S25 and S38. Furthermore, Nodal increased tubulin stability as revealed by immunofluorescent staining of acetylated tubulin. Finally, silencing of p27 reversed the inhibitory effect of Nodal on trophoblast cell proliferation, migration and invasion. Taken together, our findings revealed a novel function of simultaneous p27 and CDK2 cytoplasmic mislocalization in mediating growth-factor-regulated cell proliferation, migration and invasion.
An Endocrine Cause of Acute Post-partum Hypertension
Authors: Bretherton Ingrid , Pattison David , Pattison Sarah , Varadarajan Suresh
Published: December 2012

This is a case of acute peri-partum hypertension secondary to Conn's syndrome. The timing of presentation offers a rare insight into the hormonal physiology of pregnancy and its impact on blood pressure regulation. This case highlights the challenges of diagnosing primary hyperaldosteronism in the peripartum period and the high index of suspicion required by the obstetric physician.