3,528 research outputs found
Comparison of bacterioneuston and bacterioplankton dynamics during a phytoplankton bloom in a fjord mesocosm
The bacterioneuston is the community of Bacteria present in surface microlayers, the
thin surface film that forms the interface between aquatic environments and the
atmosphere. In this study we compared bacterial cell abundance and bacterial
community structure of the bacterioneuston and the bacterioplankton (from the
subsurface water column) during a phytoplankton bloom mesocosm experiment.
Bacterial cell abundance, determined by flow cytometry, followed a typical
bacterioplankton response to a phytoplankton bloom, with Synechococcus and high
nucleic acid (HNA) bacterial cell numbers initially falling, probably due to selective
protist grazing. Subsequently HNA and low nucleic acid (LNA) bacterial cells
increased in abundance but Synechococcus did not. There was no significant
difference between bacterioneuston and bacterioplankton cell abundances during the
experiment. Conversely, distinct and consistent differences between the
bacterioneuston and the bacterioplankton community structure were observed. This
was monitored simultaneously by Bacteria 16S rRNA gene terminal restriction
fragment length polymorphism (T-RFLP) and denaturing gradient gel electrophoresis
(DGGE). The conserved patterns of community structure observed in all of the
mesocosms indicate that the bacterioneuston is distinctive and non-random
Sonic hedgehog functions upstream of disrupted-in-schizophrenia 1 (disc1): implications for mental illness
DISRUPTED-IN-SCHIZOPHRENIA (DISC1) has been one of the most intensively studied genetic risk factors for mental illness since it was discovered through positional mapping of a translocation breakpoint in a large Scottish family where a balanced chromosomal translocation was found to segregate with schizophrenia and affective disorders. While the evidence for it being central to disease pathogenesis in the original Scottish family is compelling, recent genome-wide association studies have not found evidence for common variants at the DISC1 locus being associated with schizophrenia in the wider population. It may therefore be the case that DISC1 provides an indication of biological pathways that are central to mental health issues and functional studies have shown that it functions in multiple signalling pathways. However, there is little information regarding factors that function upstream of DISC1 to regulate its expression and function. We herein demonstrate that Sonic hedgehog (Shh) signalling promotes expression of disc1 in the zebrafish brain. Expression of disc1 is lost in smoothened mutants that have a complete loss of Shh signal transduction, and elevated in patched mutants which have constitutive activation of Shh signalling. We previously demonstrated that disc1 knockdown has a dramatic effect on the specification of oligodendrocyte precursor cells (OPC) in the hindbrain and Shh signalling is known to be essential for the specification of these cells. We show that disc1 is prominently expressed in olig2-positive midline progenitor cells that are absent in smo mutants, while cyclopamine treatment blocks disc1 expression in these cells and mimics the effect of disc1 knock down on OPC specification. Various features of a number of psychiatric conditions could potentially arise through aberrant Hedgehog signalling. We therefore suggest that altered Shh signalling may be an important neurodevelopmental factor in the pathobiology of mental illness
Application of the Ceditest FMDV type O and FMDV-NS enzyme-linked immunosorbent assays for detection of antibodies against Foot-and-mouth disease virus in selected livestock and wildlife species in Uganda
Diagnosis and control of Foot-and-mouth disease virus (FMDV) requires rapid and sensitive diagnostic tests. Two antibody enzyme-linked immunosorbent assay (ELISA) kits, Ceditest® FMDV-NS for the detection of antibodies against the nonstructural proteins of all FMDV serotypes and Ceditest® FMDV type O for the detection of antibodies against serotype O, were evaluated under African endemic conditions where the presence of multiple serotypes and the use of nonpurified vaccines complicate serological diagnosis. Serum samples from 218 African buffalo, 758 cattle, 304 goats, and 88 sheep were tested using both kits, and selected samples were tested not only in serotype-specific ELISAs for antibodies against primarily FMDV serotype O, but also against other serotypes. The FMDV-NS assay detected far more positive samples (93%) than the FMDV type O assay (30%) in buffalo (P < 0.05), with predominant antibodies against the South African Territories (SAT) serotypes, while the seroprevalence was generally comparable in cattle with antibodies against serotype O elicited by infection and/or vaccination. However, some districts had higher seroprevalence using the FMDV type O assay indicating vaccination without infection, while 1 cattle herd with antibodies against the SAT serotypes had far more positive samples (85%) using the FMDV-NS versus the FMDV type O (10%), consistent with the latter test\u27s lower sensitivity for antibodies against SAT serotypes. Based on the current investigation, the FMDV type O ELISA may be limited by the presence of SAT serotypes. The FMD NS assay worked well as a screening test for antibodies against all FMDV serotypes present in Uganda; however, as long as nonpurified vaccines are applied in the region, this test cannot be used to differentiate between vaccinated and infected animals
The role of Sox6 in zebrafish muscle fiber type specification
Background
The transcription factor Sox6 has been implicated in regulating muscle fiber type-specific gene expression in mammals. In zebrafish, loss of function of the transcription factor Prdm1a results in a slow to fast-twitch fiber type transformation presaged by ectopic expression of sox6 in slow-twitch progenitors. Morpholino-mediated Sox6 knockdown can suppress this transformation but causes ectopic expression of only one of three slow-twitch specific genes assayed. Here, we use gain and loss of function analysis to analyse further the role of Sox6 in zebrafish muscle fiber type specification.
Methods
The GAL4 binary misexpression system was used to express Sox6 ectopically in zebrafish embryos. Cis-regulatory elements were characterized using transgenic fish. Zinc finger nuclease mediated targeted mutagenesis was used to analyse the effects of loss of Sox6 function in embryonic, larval and adult zebrafish. Zebrafish transgenic for the GCaMP3 Calcium reporter were used to assay Ca2+ transients in wild-type and mutant muscle fibres.
Results
Ectopic Sox6 expression is sufficient to downregulate slow-twitch specific gene expression in zebrafish embryos. Cis-regulatory elements upstream of the slow myosin heavy chain 1 (smyhc1) and slow troponin c (tnnc1b) genes contain putative Sox6 binding sites required for repression of the former but not the latter. Embryos homozygous for sox6 null alleles expressed tnnc1b throughout the fast-twitch muscle whereas other slow-specific muscle genes, including smyhc1, were expressed ectopically in only a subset of fast-twitch fibers. Ca2+ transients in sox6 mutant fast-twitch fibers were intermediate in their speed and amplitude between those of wild-type slow- and fast-twitch fibers. sox6 homozygotes survived to adulthood and exhibited continued misexpression of tnnc1b as well as smaller slow-twitch fibers. They also exhibited a striking curvature of the spine.
Conclusions
The Sox6 transcription factor is a key regulator of fast-twitch muscle fiber differentiation in the zebrafish, a role similar to that ascribed to its murine ortholog
New zebrafish models of neurodegeneration
In modern biomedicine, the increasing need to develop experimental models to further our understanding of disease conditions and delineate innovative treatments has found in the zebrafish (Danio rerio) an experimental model, and indeed a valuable asset, to close the gap between in vitro and in vivo assays. Translation of ideas at a faster pace is vital in the field of neurodegeneration, with the attempt to slow or prevent the dramatic impact on the society's welfare being an essential priority. Our research group has pioneered the use of zebrafish to contribute to the quest for faster and improved understanding and treatment of neurodegeneration in concert with, and inspired by, many others who have primed the study of the zebrafish to understand and search for a cure for disorders of the nervous system. Aware of the many advantages this vertebrate model holds, here, we present an update on the recent zebrafish models available to study neurodegeneration with the goal of stimulating further interest and increasing the number of diseases and applications for which they can be exploited. We shall do so by citing and commenting on recent breakthroughs made possible via zebrafish, highlighting their benefits for the testing of therapeutics and dissecting of disease mechanisms
The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)
Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed
system whereby the intervention is the only causal force acting upon the experimental group and absent in the
control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems
where factors relating to context, resources, interpretation and actions of individuals will affect implementation and
effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in
multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may
affect implementation and impact on the intervention.
Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from
mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and
ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using
observation, individual and multi-disciplinary group interviews with staff.
Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation
protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 %
of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior
nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based
on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning
readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse
availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and
inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision.
Conclusions: We examined and identified contextual and organisational factors that may impact on the
implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning
broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to
evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors
we can more fully understand their impact on study outcomes
Responsible management: Engaging moral reflexive practice through threshold concepts
YesIn this conceptual paper we argue that, to date, principles of responsible management have not impacted practice as anticipated because of a disconnect between knowledge and practice. This disconnect means that an awareness of ethical concerns, by itself, does not help students take personal responsibility for their actions. We suggest that an abstract knowledge of principles has to be supplemented by an engaged understanding of the responsibility of managers and leaders to actively challenge irresponsible practices. We argue that a form of moral reflexive practice drawing on an understanding of threshold concepts is central to responsible management, and provides a gateway to transformative learning. Our conceptual argument leads to implications for management and professional education
Incidence of rotavirus gastroenteritis by age in African, Asian and European children: Relevance for timing of rotavirus vaccination
© 2016 The Author(s). Published with license by Taylor & Francis. © GSK Biologicals SA.Variability in rotavirus gastroenteritis (RVGE) epidemiology can influence the optimal vaccination schedule. We evaluated regional trends in the age of RVGE episodes in low- to middle- versus high-income countries in three continents. We undertook a post-hoc analysis based on efficacy trials of a human rotavirus vaccine (HRV; Rotarix™, GSK Vaccines), in which 1348, 1641, and 5250 healthy infants received a placebo in Europe (NCT00140686), Africa (NCT00241644), and Asia (NCT00197210, NCT00329745). Incidence of any/severe RVGE by age at onset was evaluated by active surveillance over the first two years of life. Severity of RVGE episodes was assessed using the Vesikari-scale. The incidence of any RVGE in Africa was higher than in Europe during the first year of life (≤2.78% vs. ≤2.03% per month), but much lower during the second one (≤0.86% versus ≤2.00% per month). The incidence of severe RVGE in Africa was slightly lower than in Europe during the first year of life. Nevertheless, temporal profiles for the incidence of severe RVGE in Africa and Europe during the first (≤1.00% and ≤1.23% per month) and second (≤0.53% and ≤1.13% per month) years of life were similar to those of any RVGE. Any/severe RVGE incidences peaked at younger ages in Africa vs. Europe. In high-income Asian regions, severe RVGE incidence (≤0.31% per month) remained low during the study. The burden of any RVGE was higher earlier in life in children from low- to middle- compared with high-income countries. Differing rotavirus vaccine schedules are likely warranted to maximize protection in different settings
Individual leader to interdependent leadership: A case study in leadership development and tripartite evaluation
This article is available open access through the publisher’s website at the link below. Copyright @ 2013 Sage Publications.The Problem - In this case study we see a move away from orthodox views of school leadership as “headship” to a more contemporary model of educational leadership wherein we note a departure from functional, curricula-based school leadership toward more human resource development (HRD) approaches. The aim of this study was to consider the effectiveness of an educational development program for middle leaders within an educational establishment.
The Solution - We examined the impact of a bespoke higher education leadership development intervention in Leadership (and Change) on the formation and cohesiveness of a newly formed innovative leadership structure.
The Stakeholders - The leadership development intervention was designed through a tripartite collaboration including a university, senior school leaders, and staff. The intervention was designed to shift leadership from individual leader agency to interdependent human leadership agency. Through tripartite evaluation we uncover leadership development praxis that transcends the boundaries of conventional educational leadership and reemphasizes the benefits of bridging the academic/practitioner divide and the application of theory to praxis
An assessment of the strength of knots and splices used as eye terminations in a sailing environment
Research into knots, splices and other methods of forming an eye termination has been limited, despite the fact that they are essential and strongly affect the performance of a rope. The aim of this study was to carry out a comprehensive initial assessment of the breaking strength of eye terminations commonly used in a sailing environment, thereby providing direction for further work in the field. Supports for use in a regular tensile testing machine were specially developed to allow individual testing of each sample and a realistic spread of statistical data to be obtained. Over 180 break tests were carried out on four knots (the bowline, double bowline, figure-of-eight loop and perfection loop) and two splices (three-strand eye splice and braid-on-braid splice). The factors affecting their strength were investigated. A statistical approach to the analysis of the results was adopted. The type of knot was found to have a significant effect on the strength. This same effect was seen in both types of rope construction (three-strand and braid-on-braid). Conclusions were also drawn as to the effect of splice length, eye size, manufacturer and rope diameter on the breaking strength of splices. Areas of development and further investigation were identified
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