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Journal Cover   F1000Research
  [SJR: 0.219]   [H-I: 3]   [3 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Short-term effect of acute and repeated urinary bladder inflammation on
           thigmotactic behaviour in the laboratory rat [v1; indexed,
           http://f1000r.es/56e]

    • Authors: Rosemary H Morland, Amparo Novejarque, Wenlong Huang, Rachel Wodarski, Franziska Denk, John D Dawes, Tim Pheby, Stephen B McMahon, Andrew SC Rice
      Abstract: Understanding the non-sensory components of the pain experience is crucial to developing effective treatments for pain conditions. Chronic pain is associated with increased incidence of anxio-depressive disorders, and patients often report feelings of vulnerability which can decrease quality of life. In animal models of pain, observation of behaviours such as thigmotaxis can be used to detect such affective disturbances by exploiting the influence of nociceptive stimuli on the innate behavioural conflict between exploration of a novel space and predator avoidance behaviour. This study investigates whether acute and repeated bladder inflammation in adult female Wistar rats increases thigmotactic behaviour in the open field paradigm, and aims to determine whether this correlates with activation in the central amygdala, as measured by c-Fos immunoreactivity. Additionally, up-regulation of inflammatory mediators in the urinary bladder was measured using RT-qPCR array featuring 92 transcripts to examine how local mediators change under experimental conditions. We found acute but not repeated turpentine inflammation of the bladder increased thigmotactic behaviour (decreased frequency of entry to the inner zone) in the open field paradigm, a result that was also observed in the catheter-only instrumentation group. Decreases in locomotor activity were also observed in both models in turpentine and instrumentation groups. No differences were observed in c-Fos activation, although a general increased in activation along the rostro-caudal axis was seen. Inflammatory mediator up-regulation was greatest following acute inflammation, with CCL12, CCL7, and IL-1β significantly up-regulated in both conditions when compared to naïve tissue. These results suggest that acute catheterisation, with or without turpentine inflammation, induces affective alterations detectable in the open field paradigm accompanied by up-regulation of multiple inflammatory mediators.
      PubDate: 2015-05-08T09:19:46Z
      DOI: 10.12688/f1000research.6255.1
      Issue No: Vol. 4 (2015)
       
  • Early vascular unclamping reduces warm ischaemia time in robot-assisted
           laparoscopic partial nephrectomy [v1; indexed, http://f1000r.es/570]

    • Authors: Kevin Lah, Devang Desai, Charles Chabert, Christian Gericke, Troy Gianduzzo
      Abstract: Introduction: The aim of this study was to assess the outcomes of early vascular release in robot-assisted laparoscopic partial nephrectomy (RAPN) to reduce warm ischaemia time (WIT) and minimise renal dysfunction. RAPN is increasingly utilised in the management of small renal masses. To this end it is imperative that WIT is kept to a minimum to maintain renal function. Methods: RAPN was performed via a four-arm robotic transperitoneal approach. The renal artery and vein were individually clamped with robotic vascular bulldog clamps to allow cold scissor excision of the tumour. The cut surface was then sutured with one or two running 3-0 V-LocTM sutures, following which the vascular clamps were released. Specific bleeding vessels were then selectively oversewn and the collecting system repaired. Renorrhaphy was then completed using a running horizontal mattress 0-0 V-LocTM suture. Results: A total of 16 patients underwent RAPN with a median WIT of 15 minutes (range: 8-25), operative time 230 minutes (range: 180-280) and blood loss of 100 mL (range: 50-1000). There were no transfusions, secondary haemorrhages or urine leaks. There was one focal positive margin in a central 5.5 cm pT3a renal cell carcinomas (RCC). Long-term estimated glomerular filtration rate (eGFR) was not significantly different to pre-operative values. Conclusion: In this patient series, early vascular release effectively minimised WIT and maintained renal function without compromising perioperative safety.
      PubDate: 2015-05-06T14:29:42Z
      DOI: 10.12688/f1000research.6276.1
      Issue No: Vol. 4 (2015)
       
  • Challenges and opportunities for early-career Teaching-Focussed academics
           in the biosciences [v2; indexed, http://f1000r.es/5c2]

    • Authors: Katharine Hubbard, Sarah Gretton, Katherine Jones, Lucy Tallents
      Abstract: Twenty-seven percent of academics in UK Higher Education (HE) are in Teaching-Focussed positions, making major contributions to undergraduate programmes in an era of high student expectations when it comes to teaching quality. However, institutional support for Teaching-Focussed academics is often limited, both in terms of peer networking and opportunities for career development. As four early-career stage Teaching-Focussed academics working in a variety of institutions, we explore what motivated our choices to make teaching our primary academic activity, and the challenges that we have faced in doing so. In addition to highlighting the need for universities to fully recognise the achievements of teaching staff, we discuss the role that the various biosciences learned societies have in supporting Teaching-Focussed academics. We identify that there is a need for the learned societies to come together and pool their expertise in this area. The fragmented nature of the Teaching-Focussed academic community means that clear sources of national support are needed in order to best enable the next generation of bioscience educators to reach their full potential.
      PubDate: 2015-04-29T13:22:26Z
      DOI: 10.12688/f1000research.6227.2
      Issue No: Vol. 4 (2015)
       
  • How difficult is the validation of clinical biomarkers' [v1; indexed,
           http://f1000r.es/5al]

    • Authors: Jan Voskuil
      Abstract: Recent developments of introducing stratified medicine/personal health care have led to an increased demand for specific biomarkers. However, despite the myriads of biomarkers claimed to be fit for all sorts of diseases and applications, the scientific integrity of the claims and therefore their credibility is far from satisfactory. Biomarker databases are met with scepticism. The reasons for this lack of faith come from different directions: lack of integrity of the biospecimen and meta-analysis of data derived from biospecimen prepared in various ways cause incoherence and false indications. Although the trend for antibody-independent assays is on the rise, demand for consistent performance of antibodies (both in choice of antibody and how to apply it in the correct dilution where applicable) in immune assays remains unmet in too many cases. Quantitative assays suffer from a lack of world-wide accepted criteria when the immune assay is not ELISA-based. Finally, statistical analysis suffer from coherence both in the way software packages are being scrutinized for mistakes in the script and remaining invisible after small-scale analysis, and in the way appropriate queries are fed into the packages in search for output that is fit for the types of data put in. Wrong queries would lead to wrong statistical conclusions, for example when data from a cohort of patients with different backgrounds are being analysed, or when one seeks an answer from software that was not designed for such query.
      PubDate: 2015-04-28T14:18:12Z
      DOI: 10.12688/f1000research.6395.1
      Issue No: Vol. 4 (2015)
       
  • Assessing the bipotency of in vitro-derived neuromesodermal progenitors
           [v1; indexed, http://f1000r.es/58z]

    • Authors: Anestis Tsakiridis, Valerie Wilson
      Abstract: Retrospective clonal analysis in the mouse has demonstrated that the posterior spinal cord neurectoderm and paraxial mesoderm share a common bipotent progenitor. These neuromesodermal progenitors (NMPs) are the source of new axial structures during embryonic rostrocaudal axis elongation and are marked by the simultaneous co-expression of the transcription factors T(Brachyury) (T(Bra)) and Sox2. NMP-like cells have recently been derived from pluripotent stem cells in vitro following combined stimulation of Wnt and fibroblast growth factor (FGF) signaling. Under these conditions the majority of cultures consist of T(Bra)/Sox2 co-expressing cells after 48-72 hours of differentiation. Although the capacity of these cells to generate posterior neural and paraxial mesoderm derivatives has been demonstrated at the population level, it is unknown whether a single in vitro-derived NMP can give rise to both neural and mesodermal cells. Here we demonstrate that T(Bra) positive cells obtained from mouse epiblast stem cells (EpiSCs) after culture in NMP-inducing conditions can generate both neural and mesodermal clones. This finding suggests that, similar to their embryonic counterparts, in vitro-derived NMPs are truly bipotent and can thus be exploited as a model for studying the molecular basis of developmental cell fate decisions.
      PubDate: 2015-04-28T14:07:44Z
      DOI: 10.12688/f1000research.6345.1
      Issue No: Vol. 4 (2015)
       
  • Funding source and primary outcome changes in clinical trials registered
           on ClinicalTrials.gov are associated with the reporting of a statistically
           significant primary outcome: a cross-sectional study [v2; indexed,
           http://f1000r.es/5bj]

    • Authors: Sreeram V Ramagopalan, Andrew P. Skingsley, Lahiru Handunnetthi, Daniel Magnus, Michelle Klingel, Julia Pakpoor, Ben Goldacre
      Abstract: Background: We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov. Methods: A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Findings: 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3%) had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome. Conclusions: Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov.
      PubDate: 2015-04-24T15:13:19Z
      DOI: 10.12688/f1000research.6312.2
      Issue No: Vol. 4 (2015)
       
  • The “NF-ĸB interacting long noncoding RNA” (NKILA)
           transcript is antisense to cancer-associated gene PMEPA1 [v1; indexed,
           http://f1000r.es/5aq]

    • Authors: Johannes M. Dijkstra, David B. Alexander
      Abstract: This correspondence concerns a recent publication in Cancer Cell by Liu et al.1 who analyzed a long noncoding RNA (lncRNA) that they designated “NKILA”. Liu et al. found that NKILA (1) is upregulated by immunostimulants, (2) has a promoter with an NF-ĸB binding motif, (3) can bind to the p65 protein of the NF-ĸB transcription factor and then interfere with phosphorylation of IĸBα, and (4) negatively affects functions that involve NF-ĸB pathways.  And, importantly, they found that (5) low NKILA expression in breast cancers is associated with poor patient prognosis.  However, they entirely failed to mention PMEPA1, a gene which runs antisense to NKILA, and the expression of which is associated with several tumors and which encodes a protein that participates in immune pathways. The PMEPA1 locus, including its promoter region, which Liu et al.1 only discuss in regard to NKILA, is highly conserved through evolution.  Our impression is that NKILA emerged only later in evolution, possibly as an additional means of PMEPA1 regulation.  Liu et al., however, only consider direct binding between NKILA and NF-ĸB as the mechanism for their in vivo observations of NKILA function, but do not provide solid evidence for their model.  If in vivo observations by Liu et al. could be explained by NKILA regulation of PMEPA1, it would contribute to the establishment of PMEPA1 as an important topic of cancer research.  We feel that the herein presented discussion is necessary for a correct interpretation of the Liu et al. article.
      PubDate: 2015-04-22T14:11:35Z
      DOI: 10.12688/f1000research.6400.1
      Issue No: Vol. 4 (2015)
       
  • Ocular disconjugacy cannot be measured without establishing a solid
           spatial reference [v2; indexed, http://f1000r.es/5as]

    • Authors: Jun Maruta
      Abstract: This correspondence points out a need for clarification concerning the methodology utilized in the study “Eye tracking detects disconjugate eye movements associated with structural traumatic brain injury and concussion”, recently published in Journal of Neurotrauma. The authors of the paper state that binocular eye movements were recorded using a single-camera video-oculography technique and that binocular disconjugate characteristics were analyzed without calibration of eye orientation. It is claimed that a variance-based disconjugacy metric was found to be sensitive to the severity of a concussive brain injury and to the status of recovery after the original injury. However, the reproducibility of the paper’s findings may be challenged simply by the paucity of details in the methodological description. More importantly, from the information supplied or cited in the paper, it is difficult to evaluate the validity of the potentially interesting conclusions of the paper.
      PubDate: 2015-04-22T09:53:19Z
      DOI: 10.12688/f1000research.6162.2
      Issue No: Vol. 4 (2015)
       
  • Blockade or deletion of transient receptor potential vanilloid 4 (TRPV4)
           is not protective in a murine model of sepsis [v1; indexed,
           http://f1000r.es/57n]

    • Authors: Claire A. Sand, Anna Starr, Manasi Nandi, Andrew D. Grant
      Abstract: Sepsis is a systemic inflammatory response triggered by microbial infection that can cause cardiovascular collapse, insufficient tissue perfusion and multi-organ failure. The cation channel transient receptor potential vanilloid 4 (TRPV4) is expressed in vascular endothelium and causes vasodilatation, but excessive TRPV4 activation leads to profound hypotension and circulatory collapse - key features of sepsis pathogenesis. We hypothesised that loss of TRPV4 signaling would protect against cardiovascular dysfunction in a mouse model of sepsis (endotoxaemia). Multi-parameter monitoring of conscious systemic haemodynamics (by radiotelemetry probe), mesenteric microvascular blood flow (laser speckle contrast imaging) and blood biochemistry (iSTAT blood gas analysis) was carried out in wild type (WT) and TRPV4 knockout (KO) mice. Endotoxaemia was induced by a single intravenous injection of lipopolysaccharide (LPS; 12.5 mg/kg) and systemic haemodynamics monitored for 24 h. Blood flow recording was then conducted under terminal anaesthesia after which blood was obtained for haematological/biochemical analysis. No significant differences were observed in baseline haemodynamics or mesenteric blood flow. Naïve TRPV4 KO mice were significantly acidotic relative to WT counterparts. Following induction of sepsis, all mice became significantly hypotensive, though there was no significant difference in the degree of hypotension between TRPV4 WT and KO mice. TRPV4 KO mice exhibited a higher sepsis severity score. While septic WT mice became significantly hypernatraemic relative to the naïve state, this was not observed in septic KO mice. Mesenteric blood flow was inhibited by topical application of the TRPV4 agonist GSK1016790A in naïve WT mice, but enhanced 24 h following LPS injection. Contrary to the initial hypothesis, loss of TRPV4 signaling (either through gene deletion or pharmacological antagonism) did not attenuate sepsis-induced cardiovascular dysfunction: in fact, pathology appeared to be modestly exaggerated in mice lacking TRPV4. Local targeting of TRPV4 signalling may be more beneficial than global inhibition in sepsis treatment.
      PubDate: 2015-04-20T08:45:06Z
      DOI: 10.12688/f1000research.6298.1
      Issue No: Vol. 4 (2015)
       
  • Effect of the distal histidine on the peroxidatic activity of monomeric
           cytoglobin [v1; indexed, http://f1000r.es/4xg]

    • Authors: Penny Beckerson, Dimitri Svistunenko, Brandon Reeder
      Abstract: The reaction of hydrogen peroxide with ferric human cytoglobin and a number of distal histidine variants were studied. The peroxidase activity of the monomeric wildtype protein with an internal disulfide bond, likely to be the form of the protein in vivo, exhibits a high peroxidase-like activity above that of other globins such as myoglobin. Furthermore, the peroxidatic activity of wildtype cytoglobin shows increased resistance to radical-based degradation compared to myoglobin. The ferryl form of wildtype cytoglobin is unstable, but is able to readily oxidize substrates such as guaiacol. In contrast distal histidine mutants of cytoglobin (H81Y and H81V) show very low peroxidase activity but enhanced radical-induced degradation. Therefore, the weakly bound distal histidine appears to modulate ferryl stability and limit haem degradation. These data are consistent with a role of a peroxidase activity of cytoglobin in cell stress response mechanisms.
      PubDate: 2015-04-07T09:43:49Z
      DOI: 10.12688/f1000research.5971.1
      Issue No: Vol. 4 (2015)
       
  • Observations of membrane fusion in a liposome dispersion: the missing
           fusion intermediate' [v2; indexed, http://f1000r.es/56t]

    • Authors: Marianna Foldvari
      Abstract: Early intermediate structures of liposome-liposome fusion events were captured by freeze-fracture electron microscopic (EM) technique. The images show the morphology of the fusion interface at several different stages of the fusion event. One of the intermediates was captured at a serendipitous stage of two vesicles’ membranes (both leaflets) merging and their contents starting to intermix clearly showing the fusion interface with a previously unseen fusion rim. From the morphological information a hypothetical sequence of the fusion event and corresponding lipid structural arrangements are described.
      PubDate: 2015-03-18T16:48:48Z
      DOI: 10.12688/f1000research.6003.2
      Issue No: Vol. 4 (2015)
       
  • Non-contact radiofrequency-induced reduction of subcutaneous abdominal fat
           correlates with initial cardiovascular autonomic balance and fat tissue
           hormones: safety analysis [v1; indexed, http://f1000r.es/4pj]

    • Authors: Jiri Pumprla, Kinga Howorka, Zuzana Kolackova, Eliska Sovova
      Abstract: Background and objective: The non-invasive reduction of subcutaneous abdominal fat became popular in the last decade. Radiofrequency (RF), non-contact, selective-field device Vanquish® has been developed to selectively induce deep fat tissue heating to reduce waist circumference. Our analysis evaluates immediate and sustained effects of this treatment on cardiovascular autonomic function and on selected metabolic parameters. Study design/patients and methods: A retrospective proof-of-concept analysis of RF treatment effects was conducted in 20 individuals with metabolic syndrome, to reduce the subcutaneous abdominal fat. Four 30-minutes treatment sessions (manufacturer´s standard protocol) were performed in 1-week intervals. Vital signs, ECG, lab screening, body composition, subcutaneous fat thickness and spectral analysis of heart rate variability (HRV) have been examined before, after the 1st and 4th treatment, and at follow-up visits 1 month and 3 months after the treatment. Results: The RF treatment led to a significant reduction of abdominal circumference after the 4th session (p
      PubDate: 2015-02-20T16:16:54Z
      DOI: 10.12688/f1000research.5708.1
      Issue No: Vol. 4 (2015)
       
  • Antiviral therapies against Ebola and other emerging viral diseases using
           existing medicines that block virus entry [v2; indexed,
           http://f1000r.es/52g]

    • Authors: Jason Long, Edward Wright, Eleonora Molesti, Nigel Temperton, Wendy Barclay
      Abstract: Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.
      PubDate: 2015-02-10T16:13:30Z
      DOI: 10.12688/f1000research.6085.2
      Issue No: Vol. 4 (2015)
       
  • Dynamics of Ebola epidemics in West Africa 2014 [v2; indexed,
           http://f1000r.es/5fh]

    • Authors: Robin J. Evans, Musa Mammadov
      Abstract: This paper investigates the dynamics of Ebola virus transmission in West Africa during 2014. The reproduction numbers for the total period of epidemic and for different consequent time intervals are estimated based on a simple linear model. It contains one major parameter - the average infectious period that defines the dynamics of epidemics. Numerical implementations are carried out on data collected from three countries Guinea, Sierra Leone and Liberia as well as the total data collected worldwide. Predictions are provided by considering different scenarios involving the average times of infectiousness for the next few months and the end of the current epidemic is estimated according to each scenario.
      PubDate: 2015-05-26T13:02:20Z
      DOI: 10.12688/f1000research.5941.2
      Issue No: Vol. 3 (2015)
       
  • Case Report: Gollop-Wolfgang Complex in a 5 month old baby [v3; indexed,
           http://f1000r.es/53y]

    • Authors: Ihtesham A. Qureshi, Rohit Kumar Gudepu, Ravikanth Chava, Sravya Emmani, Syed Husain Asghar, Mohtashim A. Qureshi, Nimmathota Arlappa
      Abstract: Skeletal dysplasias are disorders associated with a generalized abnormality in the skeleton. The Gollop-Wolfgang complex (GWC) is a limb deficiency disorder and an unusual limb malformation with highly variable manifestations. Here we report an interesting case of a 5-month old male baby from India with Gollop-Wolfgang Complex showing bifurcation of the right femur, ectrodactyly of both feet, ectrodactyly of left hand, syndactyly of right hand and unusual presentation of bilateral fibular agenesis and caudal (Sacrococcygeal) agenesis. The etiology of GWC in this 5 month old male baby could possibly be attributed to spontaneous gene mutation. The clinical, radiographic findings and the unusual presentation are presented in detail.
      PubDate: 2015-02-24T10:35:50Z
      DOI: 10.12688/f1000research.5889.3
      Issue No: Vol. 3 (2015)
       
 
 
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