bluuebunny/crossref_metadata_2025 huggingface dataset:
Vibration-based damage identification of reinforced concrete member using optical sensor array data
Authors: Chao Shu-Hsien , Loh Chin-Hsiung
Published: September 2013

To detect and locate the structural damage from direct measurements can be done only when the sensors are very closely located to the damage initiating point, which is generally impossible to predict, particularly for the reinforced concrete structures. With the availability of high-resolution distributed sensing, using optical tracker on light targets, the damage location as well as the level of damage can be identified. The objective of this article is to conduct structural system identification of a reinforced concrete frame by using the proposed structural integrity index (identify the element curvature and null-space damage index) and the estimation of finite element strain. Finally, a discussion on the identified time-varying system natural frequency and stiffness/strength degradation of the reinforced concrete structure from global measurement in relation to the calculated structural integrity index using optical sensing array data and element strain on the identification of damage location and damage severity are presented.
Migrants’ perception of the police: Should it be a cause for concern in Finland?
Authors: Stephen Egharevba , Perpetual Crentsil
Published: September 2013

Existing criminological research studies have premised that race/ethnicity is one of the most salient factors producing dissatisfaction with the police. As immigrants are bound to bring with them into new countries their past experiences, values and norms as well as opinions about the police. Newcomers’ past experiences with the police in their country of origin may form the basis of their misconceptions and could pose a challenge to policing ethnic minorities at the street level in their country of settlement. This paper discusses African migrants’ perceptions and the factors that influence these perceptions and attitudes towards the police in Finland. Some of the participants’ judgements have been influenced by their past experiences with the police both in Finland and in their countries of origin in Africa. The paper argues that if the police are to have the confidence of immigrants they need to proactively and meaningfully engage with immigrant groups in society. Data for this analysis are based on observations and interviews with 35 African immigrants in the Finnish city of Turku.
Motor Impairment Factors Related to Brain Injury Timing in Early Hemiparesis, Part I
Authors: Sukal-Moulton Theresa , Krosschell Kristin J. , Gaebler-Spira Deborah J. , Dewald Julius P. A.
Published: September 2013

Background. Extensive neuromotor development occurs early in human life, but the time that a brain injury occurs during development has not been rigorously studied when quantifying motor impairments. Objective. This study investigated the impact of timing of brain injury on the magnitude and distribution of weakness in the paretic arm of individuals with childhood-onset hemiparesis. Methods. A total of 24 individuals with hemiparesis were divided into time periods of injury before birth (PRE-natal, n = 8), around the time of birth (PERI-natal, n = 8), or after 6 months of age (POST-natal, n = 8). They, along with 8 typically developing peers, participated in maximal isometric shoulder, elbow, wrist, and finger torque generation tasks using a multiple-degree-of-freedom load cell to quantify torques in 10 directions. A mixed-model ANOVA was used to determine the effect of group and task on a calculated relative weakness ratio between arms. Results. There was a significant effect of both time of injury group ( P < .001) and joint torque direction ( P < .001) on the relative weakness of the paretic arm. Distal joints were more affected compared with proximal joints, especially in the POST-natal group. Conclusions. The distribution of weakness provides evidence for the relative preservation of ipsilateral corticospinal motor pathways to the paretic limb in those individuals injured earlier, whereas those who sustained later injury may rely more on indirect ipsilateral corticobulbospinal projections during the generation of torques with the paretic arm.
Can Early Careers Teachers Be Teacher Leaders? A Study of Second-year Trainees in the Teach First Alternative Certification Programme
Authors: Muijs Daniel , Chapman Chris , Armstrong Paul
Published: September 2013

The most recent decade has seen a major growth in interest in teacher leadership, but there is limited research on the extent to which early career teachers can take on teacher leadership roles. In this article we explore this question by looking at teachers prepared through the alternative certification programme Teach First (TF), which aims to have its teachers take on leadership roles. We used a mixed methods approach, employing a range of quantitative and qualitative methods including surveys of TF teachers and headteachers, and 16 case studies, which included interview of TF teachers, heads, middle managers and non-TF teachers. We found that the TF teachers were keen and able to exercise leadership. This was most strongly the case for informal leadership roles like leading initiatives in the school. School support was important; senior management needs to be committed to distributed leadership, and practical hands-on support is required at the departmental level. A context that is stable and employs consistent and coherent policies makes it easier for teachers to engage in leadership. It is argued that if schools are to tap into the leadership potential of early careers teachers, initial teacher education needs to prepare them for teacher leadership.
Post-traumatic stress disorder
Authors: Wright Joy , Robinson Ben
Published: September 2013

Post-traumatic stress disorder (PTSD) is common in primary care but studies have shown poor levels of knowledge about it among GPs. Diagnosis is often delayed, contributing to high levels of complications such as depression or alcohol misuse. There is good evidence that treatment with trauma-specific psychological therapies can be effective. Prompt diagnosis allows appropriate and timely treatment.
The key principles of cognitive behavioural therapy
Authors: Fenn Kristina , Byrne Majella
Published: September 2013

Cognitive behavioural therapy (CBT) explores the links between thoughts, emotions and behaviour. It is a directive, time-limited, structured approach used to treat a variety of mental health disorders. It aims to alleviate distress by helping patients to develop more adaptive cognitions and behaviours. It is the most widely researched and empirically supported psychotherapeutic method. This strong evidence base is reflected in clinical guidelines, which recommend it as a treatment for many common mental health disorders.
What are consultation models for?
Authors: Denness Claire
Published: September 2013

In today’s busy world of primary care, constant demands for our attention come from many different directions. Not only must we formulate a differential diagnosis during our consultations, but we must also establish rapport, explore ideas, concerns and expectations and negotiate a management plan, bearing in mind limited resources, the omnipresent Quality and Outcomes Framework, information technology skills and the need for health promotion. We typically have just 10 minutes in which to achieve all that, as well as to manage our own emotions, agendas and uncertainty. At first glance, consultation models, some of which were derived decades ago, may seem irrelevant to modern general practice. This article will discuss some of the more common consultation models in use today and their relative advantages and disadvantages. It will also demonstrate to you why consultation models are relevant and how they can help trainees, GPs and patients.
Diabetic retinopathy: A GP’s role
Authors: Williamson Phoebe , Calladine Daniel
Published: September 2013

Diabetic retinopathy is the leading cause of visual impairment in the UK’s working-age population. It is a progressive disease in which chronic hyperglycaemia causes vascular injury, resulting in leakage and occlusion of small vessels in the eye. Despite the recent implementation of a national NHS diabetic eye screening programme, some patients still present in the later stages of retinopathy; this is more difficult to treat. To help prevent this it is important to empower patients through educating them about their condition and the importance of attending the screening programme, and it also vital to ensure ease of access to this service. By utilising intensive glycaemic control, which the UK Prospective Diabetes Study showed can significantly reduce the risk of progression of diabetic retinopathy, GPs can successfully help patients avoid serious visual impairment. This article is focused on the ocular manifestations of diabetes, specifically the disease progression, and how it should be managed in both the primary and secondary care setting.
Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants
Authors: Dubensky Thomas W. , Kanne David B. , Leong Meredith L.
Published: September 2013

A principal barrier to the development of effective vaccines is the availability of adjuvants and formulations that can elicit both effector and long-lived memory CD4 and CD8 T cells. Cellular immunity is the presumptive immune correlate of protection against intracellular pathogens: a group composed of bacteria, viruses and protozoans that is responsible for a staggering level of morbidity and mortality on a global scale. T-cell immunity is also correlated with clinical benefit in cancer, and the development of therapeutic strategies to harness the immune system to treat diverse malignancies is currently undergoing a renaissance. Cyclic dinucleotides (CDNs) are ubiquitous small molecule second messengers synthesized by bacteria that regulate diverse processes and are a relatively new class of adjuvants that have been shown to increase vaccine potency. CDNs activate innate immunity by directly binding the endoplasmic reticulum-resident receptor STING (stimulator of interferon genes), activating a signaling pathway that induces the expression of interferon-β (IFN-β) and also nuclear factor-κB (NF-κB) dependent inflammatory cytokines. The STING signaling pathway has emerged as a central Toll-like receptor (TLR) independent mediator of host innate defense in response to sensing cytosolic nucleic acids, either through direct binding of CDNs secreted by bacteria, or, as shown recently, through binding of a structurally distinct CDN produced by a host cell receptor in response to binding cytosolic double-stranded (ds)DNA. Although this relatively new class of adjuvants has to date only been evaluated in mice, newly available CDN-STING cocrystal structures will likely intensify efforts in this field towards further development and evaluation in human trials both in preventive vaccine and immunotherapy settings.
The Value of Laboratory Tests in Diagnosing Secondary Osteoporosis at a Fracture and Osteoporosis Outpatient Clinic
Authors: Klerk Gijs de , Hegeman J. Han , van der Velde Detlef , van der Palen Job , van Bergeijk Leo , Duis Henk J. ten
Published: September 2013

Background:

As more and more patients meeting the criteria for osteoporosis are referred to a fracture and osteoporosis outpatient clinic (FO clinic), the laboratory costs to screen for secondary osteoporosis also increases. This study was conducted to determine the value of screening on underlying diseases at an FO clinic by obtaining a standard set of laboratory tests.

Methods:

We included all 541 patients ≥50 years with a fracture referred to our FO clinic, during the period January 2005 to January 2007. The bone mineral density (BMD) was measured by dual energy x-ray absorptiometry and expressed as a T score. A standard set of laboratory tests was obtained to screen on underlying diseases.

Results:

Laboratory results were as often abnormal in patients with a normal BMD compared to patients with a low BMD. Underlying diseases were infrequently diagnosed. However, the prevalence of secondary osteoporosis in men was quite high, up to 18.2%. The costs to diagnose 1 patient with an underlying disease did vary between €92 and €972 depending on the group of patients described.

Conclusion:

Screening all patients, referred to an FO clinic, for underlying diseases by obtaining a standard set of laboratory tests is probably not useful since laboratory tests are as often abnormal in patients with a normal BMD compared to patients with a low BMD. Moreover, the prevalence of secondary osteoporosis is low, while laboratory costs are substantial.
rhIGF-1 Therapy for Growth Failure and IGF-1 Deficiency in Congenital Disorder of Glycosylation Ia (PMM2 Deficiency)
Authors: Miller Bradley S. , Duffy Meghann M. , Addo O. Yaw , Sarafoglou Kyriakie
Published: September 2013

Background. Congenital disorders of glycosylation (CDG) are a group of rare disorders in which glycosylation required for proper protein-protein interactions and protein stability is disrupted, manifesting clinically with multiple system involvement and growth failure. The insulin-like growth factor (IGF) system plays an important role in childhood growth and has been shown to be dysfunctional with low IGF-1 levels in children with CDG type Ia ( PMM2 deficiency). Case report. A 3-year-old Caucasian male with failure to thrive was diagnosed with PMM2-CDG at 5 months of age. Initially, his length and weight were less than −2 standard deviation score, IGF-1 <25 ng/mL (normal 55-327 ng/mL), IGFBP-3 1.0 µg/mL (normal 0.7-3.6 ng/mL), and acid-labile subunit 1.3 mg/L (normal 0.7-7.9 mg/L). Despite aggressive feeding, he continued to show poor linear growth and weight gain. At 17 months, he underwent an IGF-1 generation test with growth hormone (0.1 mg/kg/d) for 7 days; baseline IGF-1of 27 ng/mL (normal 55-327 ng/mL) stimulated to only 33 ng/mL. Recombinant human IGF-1 (rhIGF-1) therapy (up to 130 µg/kg/dose twice daily) was initiated at 21 months of age resulting in an excellent linear growth response with height increasing from −2.73 to −1.39 standard deviation score over 22 months. IGF-1 and IGFBP-3 levels also increased. Conclusion. This is the first case report of rhIGF-1 therapy in a patient with PMM2-CDG. The child had an excellent linear growth response. These results provide additional in vivo evidence for IGF dysfunction in PMM2-CDG and suggest that rhIGF-1 may be a novel treatment for growth failure in PMM2-CDG.
A Magnetic Resonance Imaging Study of the Significance of the Distal Femoral Physis During Medial Patellofemoral Ligament Reconstruction
Authors: Greenrod William , Cox James , Astori Ivan , Baulch Justin , Williams John
Published: September 2013

Background:

Medial patellofemoral ligament (MPFL) reconstruction in adults often utilizes screw fixation in the distal femur. The aim was to define the safety of similar fixation in young patients, with respect to their open physis.

Purpose:

To define the age-related relationship between the femoral insertion of the MPFL and the medial aspect of the distal femoral physis on magnetic resonance imaging (MRI) scans. The study investigates whether screw fixation at this point is safe with respect to patient age and screw inclination.

Study Design:

Cross-sectional study.

Methods:

Retrospective review of the MRI scans of 159 skeletally immature patients. The femoral insertion of the MPFL was defined with respect to the distal femoral physis. The predicted paths of 2-cm screw fixation were simulated both parallel to the joint line and 45° distally oblique; physeal and joint penetration were noted when present. Results are plotted against age and compared as quartile ranges.

Results:

The femoral insertion of the MPFL was found to be distal to the distal femoral physis in all patients by an average of 10 mm (range, 2-16 mm). The mean distance increases slightly with age in a nonlinear relationship ( r = 0.51, P < .001) from 9 mm at age 10 years to 12 mm by age 16 years. For the classic, parallel screw, the risk of physeal breach is high for all age groups (mean, 64%). For the novel, oblique screw, joint penetration and physeal breach were less prevalent (mean, 13%), and importantly, the vast majority of these breaches were in younger children (age <9 years 9 months). With oblique screws, older children were at significantly lower risk than younger children (<3% vs 48%; P < .001).

Conclusion:

This study accurately defines the relationship between the femoral insertion of the MPFL and the distal femoral physis in children and adolescents. A high risk of potentially poor outcomes was found during anatomic reconstruction of the MPFL in children utilizing classic (parallel) screw fixation, irrespective of age. However, in children older than 10 years, a 20-mm screw, from the anatomic MPFL insertion and directed 45° distally oblique, should be safe in 98% of patients.
Establishing an Imaging Protocol for Detection of Vascularity within the Median Nerve Using Contrast-Enhanced Ultrasound
Authors: Evans Kevin D. , Volz Kevin R. , Roll Shawn C. , Hutmire Cristina M. , Pargeon Rachel L. , Buford John A. , Sommerich Carolyn M.
Published: September 2013

This preclinical study was conducted to develop discrete sonographic instrumentation settings and also safe contrast dosing that would consistently demonstrate perineural vascularity along the median nerve. This set of imaging studies was conducted with a convenience cohort of young adult female monkeys ( Macaca fascicularis). Sonographic equipment settings and dosing were refined throughout the imaging series to ensure consistent contrast-enhanced ultrasound imaging. A mechanical index of 0.13 was consistently used for imaging. Perineural vessels were imaged with a suspension solution of 0.04 mL Definity/0.96 mL saline introduced over 5 minutes for a total dose of 0.8 mL of contrast solution. Blinded studies of high and low dose contrast, along with saline injections, were correctly identified by two experienced sonographers. This preclinical study established adequate equipment settings and dosing that allowed for a valid demonstration of vascularity surrounding the median nerve.
Mobile Learning
Authors: Wilson Michelle , Bolliger Doris U.
Published: September 2013

As younger generations continue to grow and mature with mobile devices weaved into their lives, an expectation has formed to include these in as many ways as possible into all their activities. This demand has readily been felt in education. A learning evolution is occurring all over the world in environments from elementary settings to higher education. The public in general is thriving in a much larger universe, where education is no longer bound by walls or location. Instruction no longer needs to be performed in the present but rather at the fingertips of willing students equipped with tools that can access knowledge when they want it, where they want it, and with a critical openness to how much they want. Recently, there has been a strong desire to tap into this ubiquitous idea of learning in context, but where does one start? This article was written with the intent of expanding ideas on what mobile learning is, the possibilities that it holds to influence education both inside and outside the classroom, and how allied health educators may be able to incorporate mobile learning into their curricula.
NETosis: how vital is it?
Authors: Yipp Bryan G. , Kubes Paul
Published: September 2013

In this review, we examine the evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity. We summarize how NETs are formed in response to various stimuli and provide evidence that NETosis is not universally a cell death pathway. Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. We also evaluate the evidence for NETs in catching and killing pathogens. Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release.
Sexual activity increases resistance against Pseudomonas entomophila in male Drosophila melanogaster
Authors: Gupta Vanika , Ali Zeeshan S , Prasad Nagaraj G
Published: September 2013

Background

Maintenance and deployment cost of immunity is high, therefore, it is expected to trade-off with other high cost traits like sexual activity. Previous studies with Drosophila melanogaster show that male’s ability to clear bacteria decreases with increase in sexual activity. We subjected this idea to test using two pathogens (Pseudomonas entomophila and Staphylococcus succinus) and three different populations of Drosophila melanogaster.

Results

We found that sexual activity enhanced male survivorship in a pathogen specific manner. Sexually active males show higher resistance than virgins upon infection with Pseudomonas entomophila. Interestingly, the beneficial effects of sexual activity increased with time of co-habitation with females and declined when access to females was restricted. We observed no change in male survivorship upon experimentally varying the number of sexual interactions.

Conclusion

Our results show that the sexual activity-immunity trade-off in males cannot be generalised. The trade-off is potentially mediated through complex interactions between the host, pathogen and the environment experienced by the host.
Whirlin, a cytoskeletal scaffolding protein, stabilizes the paranodal region and axonal cytoskeleton in myelinated axons
Authors: Green James A , Yang Jun , Grati M’hamed , Kachar Bechara , Bhat Manzoor A
Published: September 2013

Background

Myelinated axons are organized into distinct subcellular and molecular regions. Without proper organization, electrical nerve conduction is delayed, resulting in detrimental physiological outcomes. One such region is the paranode where axo-glial septate junctions act as a molecular fence to separate the sodium (Na+) channel-enriched node from the potassium (K+) channel-enriched juxtaparanode. A significant lack of knowledge remains as to cytoskeletal proteins which stabilize paranodal domains and underlying cytoskeleton. Whirlin (Whrn) is a PDZ domain-containing cytoskeletal scaffold whose absence in humans results in Usher Syndromes or variable deafness-blindness syndromes. Mutant Whirlin (Whrn) mouse model studies have linked such behavioral deficits to improper localization of critical transmembrane protein complexes in the ear and eye. Until now, no reports exist about the function of Whrn in myelinated axons.

Results

RT-PCR and immunoblot analyses revealed expression of Whrn mRNA and Whrn full-length protein, respectively, in several stages of central and peripheral nervous system development. Comparing wild-type mice to Whrn knockout (Whrn

−/−
) mice, we observed no significant differences in the expression of standard axonal domain markers by immunoblot analysis but observed and quantified a novel paranodal compaction phenotype in 4 to 8 week-old Whrn

−/−
nerves. The paranodal compaction phenotype and associated cytoskeletal disruption was observed in Whrn

−/−
mutant sciatic nerves and spinal cord fibers from early (2 week-old) to late (1 year-old) stages of development. Light and electron microscopic analyses of Whrn knockout mice reveal bead-like swellings in cerebellar Purkinje axons containing mitochondria and vesicles by both. These data suggest that Whrn plays a role in proper cytoskeletal organization in myelinated axons.

Conclusions

Domain organization in myelinated axons remains a complex developmental process. Here we demonstrate that loss of Whrn disrupts proper axonal domain organization. Whrn likely contributes to the stabilization of paranodal myelin loops and axonal cytoskeleton through yet unconfirmed cytoskeletal proteins. Paranodal abnormalities are consistently observed throughout development (2 wk-1 yr) and similar between central and peripheral nervous systems. In conclusion, our observations suggest that Whrn is not required for the organization of axonal domains, but once organized, Whrn acts as a cytoskeletal linker to ensure proper paranodal compaction and stabilization of the axonal cytoskeleton in myelinated axons.
Anticonvulsant activity of bone marrow cells in electroconvulsive seizures in mice
Authors: Ferrazoli Enéas Galdini , Blanco Miriam Marcela , Bittencourt Simone , Bachi André Luis Lacerda , Bahia Luciana , Soares Milena Botelho Pereira , Ribeiro-dos-Santos Ricardo , Mello Luiz Eugênio , Longo Beatriz Monteiro
Published: September 2013

Background

Bone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells. To assess the anticonvulsant effects of bone marrow cell transplantation, we measured the frequency and duration of tonic seizure, the mortality rate, the microglial expression and the blood levels of cytokine IL-1, IL-6, IL-10 and TNF-α after MES induction. We hypothesized that these behavioral and inflammatory responses to a strong stimulus such as a convulsive seizure could be modified by the transplantation of bone marrow cells.

Results

Bone marrow transplanted cells altered the convulsive threshold and showed anticonvulsant effect by protecting from tonic seizures. Bone marrow cells modified the microglial expression in the analyzed brain areas, increased the IL-10 and attenuate IL-6 levels.

Conclusions

Bone marrow cells exert protective effects by blocking the course of electroconvulsive seizures. Additionally, electroconvulsive seizures induced acute inflammatory responses by altering the pattern of microglia expression, as well as in IL-6 and IL-10 levels. Our findings also indicated that the anticonvulsant effects of these cells can be tested with the MES model following the same paradigm used for drug testing in pharmacological screening. Studies on the inflammatory reaction in response to acute seizures in the presence of transplanted bone marrow cells might open a wide range of discussions on the mechanisms relevant to the pathophysiology of epilepsies.
High-risk human papillomavirus infection is associated with premature rupture of membranes
Authors: Cho GeumJoon , Min Kyung-Jin , Hong Hye-Ri , Kim SuhngWook , Hong Jin-Hwa , Lee Jae-Kwan , Oh Min-Jeong , Kim HaiJoong
Published: September 2013

Background

Human papillomavirus (HPV) is known to be more prevalent in spontaneous abortions than in elective terminations of pregnancy. More recently, placental infection with HPV was shown to be associated with spontaneous preterm delivery. However, no study has evaluated the prevalence of HPV infection in pregnant Korean females and its association with adverse pregnancy outcomes.

Methods

We conducted a cross-sectional study of 311 females who gave birth at Korea University Medical Center. Our sample included 45 preterm deliveries, 50 cases of premature rupture of the membranes (PROM), 21 preeclampsia cases, and 8 gestational diabetes mellitus (GDM) patients. We used the Hybrid Capture II system to detect high-risk (HR)-HPV infection at six weeks postpartum.

Results

The prevalence of HR-HPV infection was 14.1%. Women with HR-HPV infection had a higher incidence of PROM than those without HR-HPV. HR-HPV infection was associated with an increased risk of PROM (OR, 2.380; 95% CI, 1.103-5.134). The prevalence of preterm delivery, preeclampsia, or GDM was not different between the two groups.

Conclusions

We observed a high prevalence of HR-HPV infection in pregnant women. Moreover, HR-HPV infection was associated with a risk of PROM at term. Further studies are needed to evaluate mechanisms by which HR-HPV infection induces PROM.
Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer
Authors: Liang Xing-Hua , Li Ling-ling , Wu Geng-Gang , Xie Yi-Cheng , Zhang Guang-Xian , Chen Wei , Yang Hai-Feng , Liu Qi-Long , Li Wen-Hong , He Wen-guang , Huang Yan-Nian , Zeng Xian-Cheng
Published: September 2013

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood.

Methods

In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells.

Results

Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1.

Conclusions

Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics.
A multilectin affinity approach for comparative glycoprotein profiling of rheumatoid arthritis and spondyloarthropathy
Authors: Bhattacharjee Mitali , Sharma Rakesh , Goel Renu , Balakrishnan Lavanya , Renuse Santosh , Advani Jayshree , Gupta Shantal Tankala , Verma Renu , Pinto Sneha M , Sekhar Nirujogi Raja , Nair Bipin , Prasad T S Keshava , Harsha H C , Jois Ramesh , Shankar Subramanian , Pandey Akhilesh
Published: September 2013

Background

Arthritis refers to inflammation of joints and includes common disorders such as rheumatoid arthritis (RA) and spondyloarthropathies (SpAs). These diseases differ mainly in terms of their clinical manifestations and the underlying pathogenesis. Glycoproteins in synovial fluid might reflect the disease activity status in the joints affected by arthritis; yet they have not been systematically studied previously. Although markers have been described for assisting in the diagnosis of RA, there are currently no known biomarkers for SpA.

Materials and methods

We sought to determine the relative abundance of glycoproteins in RA and SpA by lectin affinity chromatography coupled to iTRAQ labeling and LC-MS/MS analysis. We also used ELISA to validate the overexpression of VCAM-1, one of the candidate proteins identified in this study, in synovial fluid from RA patients.

Results and discussion

We identified proteins that were previously reported to be overexpressed in RA including metalloproteinase inhibitor 1 (TIMP1), myeloperoxidase (MPO) and several S100 proteins. In addition, we discovered several novel candidates that were overexpressed in SpA including Apolipoproteins C-II and C-III and the SUN domain-containing protein 3 (SUN3). Novel molecules found overexpressed in RA included extracellular matrix protein 1 (ECM1) and lumican (LUM). We validated one of the candidate biomarkers, vascular cell adhesion molecule 1 (VCAM1), in 20 RA and SpA samples using ELISA and confirmed its overexpression in RA (p-value <0.01). Our quantitative glycoproteomic approach to study arthritic disorders should open up new avenues for additional proteomics-based discovery studies in rheumatological disorders.
The Oct1 homolog Nubbin is a repressor of NF-κB-dependent immune gene expression that increases the tolerance to gut microbiota
Authors: Dantoft Widad , Davis Monica M , Lindvall Jessica M , Tang Xiongzhuo , Uvell Hanna , Junell Anna , Beskow Anne , Engström Ylva
Published: September 2013

Background

Innate immune responses are evolutionarily conserved processes that provide crucial protection against invading organisms. Gene activation by potent NF-κB transcription factors is essential both in mammals and Drosophila during infection and stress challenges. If not strictly controlled, this potent defense system can activate autoimmune and inflammatory stress reactions, with deleterious consequences for the organism. Negative regulation to prevent gene activation in healthy organisms, in the presence of the commensal gut flora, is however not well understood.

Results

We show that the Drosophila homolog of mammalian Oct1/POU2F1 transcription factor, called Nubbin (Nub), is a repressor of NF-κB/Relish-driven antimicrobial peptide gene expression in flies. In nub

1
mutants, which lack Nub-PD protein, excessive expression of antimicrobial peptide genes occurs in the absence of infection, leading to a significant reduction of the numbers of cultivatable gut commensal bacteria. This aberrant immune gene expression was effectively blocked by expression of Nub from a transgene. We have identified an upstream regulatory region, containing a cluster of octamer sites, which is required for repression of antimicrobial peptide gene expression in healthy flies. Chromatin immunoprecipitation experiments demonstrated that Nub binds to octamer-containing promoter fragments of several immune genes. Gene expression profiling revealed that Drosophila Nub negatively regulates many genes that are involved in immune and stress responses, while it is a positive regulator of genes involved in differentiation and metabolism.

Conclusions

This study demonstrates that a large number of genes that are activated by NF-κB/Relish in response to infection are normally repressed by the evolutionarily conserved Oct/POU transcription factor Nub. This prevents uncontrolled gene activation and supports the existence of a normal gut flora. We suggest that Nub protein plays an ancient role, shared with mammalian Oct/POU transcription factors, to moderate responses to immune challenge, thereby increasing the tolerance to biotic stress.
The effect of periodontal therapy on C-reactive protein, endothelial function, lipids and proinflammatory biomarkers in patients with stable coronary artery disease: study protocol for a randomized controlled trial
Authors: Saffi Marco Aurélio Lumertz , Furtado Mariana Vargas , Montenegro Márlon Munhoz , Ribeiro Ingrid Webb Josephson , Kampits Cassio , Rabelo-Silva Eneida Rejane , Polanczyk Carisi Anne , Rösing Cassiano Kuchenbecker , Haas Alex Nogueira
Published: September 2013

Background

Scarce information exists regarding the preventive effect of periodontal treatment in the recurrence of cardiovascular events. Prevention may be achieved by targeting risk factors for recurrent coronary artery disease (CAD) in patients with previous history of cardiovascular events. The aim of this trial is to compare the effect of two periodontal treatment approaches on levels of C-reactive protein, lipids, flow-mediated dilation and serum concentrations of proinflammatory and endothelial markers in stable CAD patients with periodontitis over a period of 12 months.

Methods/design

This is a randomized, parallel design, examiner blinded, controlled clinical trial. Individuals from both genders, 35 years of age and older, with concomitant diagnosis of CAD and periodontitis will be included. CAD will be defined as the occurrence of at least one of the following events 6 months prior to entering the trial: documented history of myocardial infarction; surgical or percutaneous myocardial revascularization and lesion >50% in at least one coronary artery assessed by angiography; presence of angina and positive noninvasive testing of ischemia. Diagnosis of periodontitis will be defined using the CDC-AAP case definition (≥2 interproximal sites with clinical attachment loss ≥6 mm and ≥1 interproximal site with probing depth ≥5 mm). Individuals will have to present at least ten teeth present to be included. One hundred individuals will be allocated to test (intensive periodontal treatment comprised by scaling and root planing) or control (community periodontal treatment consisting of one session of supragingival plaque removal only) treatment groups. Full-mouth six sites per tooth periodontal examinations and subgingival biofilm samples will be conducted at baseline, 3, 6 and 12 months after treatment. The primary outcome of this study will be C-reactive protein changes over time. Secondary outcomes include levels of total cholesterol, LDL-C, HDL-C, triglycerides, IL-1β, IL-6, TNFα, fibrinogen, ICAM-1, VCAM-1 and E-selectin. These outcomes will be assessed at all time points over 12 months. Flow-mediated dilation will be assessed at baseline, 1, 3 and 6 months after periodontal therapy.

Discussion

This trial will provide new evidence regarding the effect of periodontal treatment on risk markers for recurrence of cardiovascular events in stable coronary artery disease patients.

Trial registration number

ClinicalTrials.gov Identifier, NCT01609725
Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models
Authors: Capello Michela , Cappello Paola , Linty Federica Caterina , Chiarle Roberto , Sperduti Isabella , Novarino Anna , Salacone Paola , Mandili Giorgia , Naccarati Alessio , Sacerdote Carlotta , Beghelli Stefania , Bersani Samantha , Barbi Stefano , Bassi Claudio , Scarpa Aldo , Nisticò Paola , Giovarelli Mirella , Vineis Paolo , Milella Michele , Novelli Francesco
Published: September 2013

Background

Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy with only a 5% 5-year survival rate. Reliable biomarkers for early detection are still lacking. The goals of this study were (a) to identify early humoral responses in genetically engineered mice (GEM) spontaneously developing PDAC; and (b) to test their diagnostic/predictive value in newly diagnosed PDAC patients and in prediagnostic sera.

Methods and results

The serum reactivity of GEM from inception to invasive cancer, and in resectable or advanced human PDAC was tested by two-dimensional electrophoresis Western blot against proteins from murine and human PDAC cell lines, respectively. A common mouse-to-human autoantibody signature, directed against six antigens identified by MALDI-TOF mass spectrometry, was determined. Of the six antigens, Ezrin displayed the highest frequency of autoantibodies in GEM with early disease and in PDAC patients with resectable disease. The diagnostic value of Ezrin-autoantibodies to discriminate PDAC from controls was further shown by ELISA and ROC analyses (P < 0.0001). This observation was confirmed in prediagnostic sera from the EPIC prospective study in patients who eventually developed PDAC (with a mean time lag of 61.2 months between blood drawing and PDAC diagnosis). A combination of Ezrin-autoantibodies with CA19.9 serum levels and phosphorylated α-Enolase autoantibodies showed an overall diagnostic accuracy of 0.96 ± 0.02.

Conclusions

Autoantibodies against Ezrin are induced early in PDAC and their combination with other serological markers may provide a predictive and diagnostic signature.
The NPR1 ortholog PhaNPR1 is required for the induction of PhaPR1 in Phalaenopsis aphrodite
Authors: Chen Jen-Chih , Lu Hsiang-Chia , Chen Cheng-En , Hsu Hua-Fang , Chen Hong-Hwa , Yeh Hsin-Hung
Published: September 2013

Background

Systematic acquired resistance (SAR) is an effective broad-spectrum defense mechanism that confers long-lasting protection against biotrophic pathogens trough defense related salicylic acid (SA) signaling. Gene(s) involved in SAR have been extensively studied in dicot plants; however, remains largely unresolved in monocot plants. NPR1, an evolutionary conserved gene, plays a central role in SAR, and PR-1 is widely used as a marker for effective SA signaling.

Results

We identified NPR1 and PR-1 homologous genes, PhaNPR1 and PhaPR1, from an economically important orchid, Phalaenopsis aphrodite, and characterized their roles in SA signaling and Cymbidium mosaic virus (CymMV) resistance. A phylogenetic analysis of NPR1 homologs showed that these genes appear to have evolved before angiospermy. Similar to Arabidopsis NPR1, PhaNPR1 was only moderately induced upon SA treatment and CymMV infection. Although PhaPR1 shows only 36% identity with AtPR1, its promoter shared conserved elements with those of other PR-1 genes, and it was induced upon SA treatment and CymMV infection. After CymMV infection, silencing on PhaNPR1 also reduced PhaPR1 expression; however, CymMV accumulation was not affected.

Conclusions

In conclusion, after virus infection, PhaNPR1 is required for PhaPR1 induction, but plays little role in defense against CymMV.
Would you want to know? Public attitudes on early diagnostic testing for Alzheimer's disease
Authors: Wikler Elizabeth M , Blendon Robert J , Benson John M
Published: September 2013

Introduction

Research is underway to develop an early medical test for Alzheimer's disease (AD).

Methods

To evaluate potential demand for such a test, we conducted a cross-sectional telephone survey of 2,678 randomly selected adults across the United States and four European countries.

Results

Most surveyed adults (67%) reported that they are "somewhat" or "very likely" to get an early medical test if one becomes available in the future. Interest was higher among those worried about developing AD, those with an immediate blood relative with AD, and those who have served as caregivers for AD patients. Older respondents and those living in Spain and Poland also exhibited greater interest in testing. Knowing AD is a fatal condition did not influence demand for testing, except among those with an immediate blood relative with the disease.

Conclusions

Potential demand for early medical testing for AD could be high. A predictive test could not only advance medical research, it could transform political and legal landscapes by creating a large constituency of asymptomatic, diagnosed adults.
Moho depth and sediment thickness estimation beneath the Red Sea derived from satellite and terrestrial gravity data
Authors: Salem Ahmed , Green Chris , Campbell Simon , Fairhead J. Derek , Cascone Lorenzo , Moorhead Lee
Published: September 2013

We sought to map the depth and density contrast of the Mohorovičić discontinuity (Moho) across the Red Sea area and to model sedimentary thickness from gravity data. The gravity data that are used are a combination of satellite and terrestrial gravity data processed into a Bouguer anomaly grid. A 200-km low-pass filter was used to separate this grid into regional and residual gravity grids. We inverted the regional gravity grid to a Moho depth map based on a density contrast map that is constrained by published seismic results. The interpreted Moho is shallowest ([Formula: see text]) along the axis of the central Red Sea, [Formula: see text] along the axis to the south, and [Formula: see text] in the northern Red Sea. The depth increased to [Formula: see text] at the coast and 35–40 km in the adjacent continents. The residual gravity data provided insights into the tectonic fabric along the whole rift and provided a good correlation with magnetic lineaments where these are available. We used the complete Bouguer anomaly to model sedimentary thicknesses constrained by wells and the interpreted Moho. The modeling results are consistent with the presence of large-scale, ridge parallel tilted fault blocks forming subbasins with a maximum depth of about 6–7 km. Our models suggest that the northern Red Sea has an asymmetric basement surface with the western side deeper than the eastern side. The results indicate the presence of oceanic crust in the central and southern parts of the Red Sea, but not in the north. The very thin crust and interpreted oceanic crustal density in the central Red Sea suggest that this area is fully oceanic—although possibly quite young.
Multisource waveform inversion of marine streamer data using normalized wavefield
Authors: Choi Yunseok , Alkhalifah Tariq
Published: September 2013

Multisource full-waveform inversion based on the [Formula: see text]- and [Formula: see text]-norm objective functions cannot be applied to marine streamer data because it does not take into account the unmatched acquisition geometries between the observed and modeled data. To apply multisource full-waveform inversion to marine streamer data, we construct the [Formula: see text]- and [Formula: see text]-norm objective functions using the normalized wavefield. The new residual seismograms obtained from the [Formula: see text]- and [Formula: see text]-norms using the normalized wavefield mitigate the problem of unmatched acquisition geometries, which enables multisource full-waveform inversion to work with marine streamer data. In the new approaches using the normalized wavefield, we used the back-propagation algorithm based on the adjoint-state technique to efficiently calculate the gradients of the objective functions. Numerical examples showed that multisource full-waveform inversion using the normalized wavefield yields much better convergence for marine streamer data than conventional approaches.
Qualitative geophysical interpretation of the Sudbury Structure
Authors: Olaniyan Oladele , Smith Richard S. , Morris Bill
Published: September 2013

The Sudbury Structure is one of the most studied geologic structures in the world due to its enigmatic nature and mineral wealth. The available geologic work from the literature and mining industry operations accumulated for more than a century was recently assessed and compiled into a bedrock geologic map. Most regional geophysical investigations of the Sudbury Structure have been quantitative — modeling and depth estimation without a clear definition of surface control. Airborne total magnetic intensity data over the Sudbury Structure were compiled, processed, and interpreted, to define magnetic stratigraphy boundaries and near-surface lineaments. Traditional directional and normalized derivatives were computed to enhance the high-frequency information in the magnetic field. Available airborne frequency-domain electromagnetic (EM) data were also interactively interpreted along profiles and in a gridded format to isolate conductive structures. On-screen geographic information system-based information extraction from multiple derivatives was used to interpret the magnetic contacts, dykes, and lineaments. The magnetic interpretation was compared with published bedrock maps of the Sudbury Structure. Magnetic contacts based on the qualitative classification of the magnetic texture did not always correspond to the geologic boundaries on the existing maps. Some magnetic lineaments corresponded with well-defined geologic structures, some were further extensions of partially mapped structures, and others are newly identified linear structures. Conductive locations identified from the EM profiles were probably due to responses from conductive ore bodies, faults, dykes, lithological contacts, and cultural objects.
Thoughts and observations on interpreting depth-imaged data
Authors: Herron Donald A.
Published: September 2013

Interpreting depth-imaged data requires attention to elements of uncertainty different from those associated with time-imaged data. In particular, an interpreter must visualize how the migration velocity model affects focusing and positioning of reflections in final images and, consequently, interpretation of the geology contained in those images. The availability of several versions of depth imaging based on a single velocity model but with different migration algorithms complicates interpretation in that the interpreter must decide which version provides the most accurate representation of the true geology.