Covering up to January 2016
Cannabis sativa
L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids. The ...modular nature of the pathways that merge into the phytocannabinoid chemotype translates in differences in the nature of the resorcinyl side-chain and the degree of oligomerization of the isoprenyl residue, making the definition of phytocannabinoid elusive from a structural standpoint. A biogenetic definition is therefore proposed, splitting the phytocannabinoid chemotype into an alkyl- and a β-aralklyl version, and discussing the relationships between phytocannabinoids from different sources (higher plants, liverworts, fungi). The startling diversity of cannabis phytocannabinoids might be, at least in part, the result of non-enzymatic transformations induced by heat, light, and atmospheric oxygen on a limited set of major constituents (CBG, CBD, Δ
9
-THC and CBC and their corresponding acidic versions), whose degradation is detailed to emphasize this possibility. The diversity of metabotropic (cannabinoid receptors), ionotropic (thermos-TRPs), and transcription factors (PPARs) targeted by phytocannabinoids is discussed. The integrated inventory of these compounds and their biological macromolecular end-points highlights the opportunities that phytocannabinoids offer to access desirable drug-like space beyond the one associated to the narcotic target CB
1
.
Cannabis sativa
L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids.
The multidimensional character and inherent conflict with categorisation of interdisciplinarity makes its mapping and evaluation a challenging task. We propose a conceptual framework that aims to ...capture interdisciplinarity in the wider sense of knowledge integration, by exploring the concepts of diversity and coherence. Disciplinary diversity indicators are developed to describe the heterogeneity of a bibliometric set viewed from predefined categories, i.e. using a top-down approach that locates the set on the global map of science. Network coherence indicators are constructed to measure the intensity of similarity relations within a bibliometric set, i.e. using a bottom-up approach, which reveals the structural consistency of the publications network. We carry out case studies on individual articles in bionanoscience to illustrate how these two perspectives identify different aspects of interdisciplinarity: disciplinary diversity indicates the large-scale breadth of the knowledge base of a publication; network coherence reflects the novelty of its knowledge integration. We suggest that the combination of these two approaches may be useful for comparative studies of emergent scientific and technological fields, where new and controversial categorisations are accompanied by equally contested claims of novelty and interdisciplinarity.
In this trial involving patients after out-of-hospital cardiac arrest, fever prevention for 36 or 72 hours did not result in different percentages of patients dying or having severe disability or ...coma.
Regulation of myelination by oligodendrocytes in the CNS has important consequences for higher-order nervous system function (e.g., 1–4), and there is growing consensus that neuronal activity ...regulates CNS myelination (e.g., 5–9) through local axon-oligodendrocyte synaptic-vesicle-release-mediated signaling 10–12. Recent analyses have indicated that myelination along axons of distinct neuronal subtypes can differ 13, 14, but it is not known whether regulation of myelination by activity is common to all neuronal subtypes or only some. This limits insight into how specific neurons regulate their own conduction. Here, we use a novel fluorescent fusion protein reporter to study myelination along the axons of distinct neuronal subtypes over time in zebrafish. We find that the axons of reticulospinal and commissural primary ascending (CoPA) neurons are among the first myelinated in the zebrafish CNS. To investigate how activity regulates myelination by different neuronal subtypes, we express tetanus toxin (TeNT) in individual reticulospinal or CoPA neurons to prevent synaptic vesicle release. We find that the axons of individual tetanus toxin expressing reticulospinal neurons have fewer myelin sheaths than controls and that their myelin sheaths are 50% shorter than controls. In stark contrast, myelination along tetanus-toxin-expressing CoPA neuron axons is entirely normal. These results indicate that while some neuronal subtypes modulate myelination by synaptic vesicle release to a striking degree in vivo, others do not. These data have implications for our understanding of how different neurons regulate myelination and thus their own function within specific neuronal circuits.
•Live imaging of myelin sheath dynamics along single axons over time in zebrafish•Vesicular release from reticulospinal axons required for normal myelination•Vesicular release from CoPA axons not required for myelination•Evidence of neuronal subtype diversity of activity-regulated myelination
Neuronal activity can regulate myelination, which in turn affects nervous system function. Koudelka et al. use zebrafish to image myelination over time along individual axons in vivo. They find that while some neuronal subtypes regulate myelination by vesicular release, others do not, indicating striking diversity in activity-regulated myelination.
When two selection environments operate upon each other, mutual shaping in a co-evolution along a particular trajectory is one possible outcome. When three selection environments are involved, more ...complex dynamics can be expected as a result of interactions involving bi-lateral and tri-lateral relations. Three selection environments are specified in the Triple Helix model: (1) wealth generation (industry), (2) novelty production (academia), and (3) public control (government). Furthermore, this model somewhat reduces the complexity by using university-industry-government relations for the specification of the historical conditions of the non-linear dynamics. Whereas the historical analysis informs us about how institutions and institutional arrangements carry certain functions, the evolutionary analysis focuses on the functions of selection environments in terms of outputs. One can no longer expect a one-to-one correspondence between institutions and functions; a statistics is needed for the evaluation of how, for how long, and to what extent institutional arrangements enhance synergies among different selection environments. The empirical contributions to this Triple Helix issue point in the direction of "rich ecologies": the construction of careful balances between differentiation and integration among the three functions. PUBLICATION ABSTRACT
How features of the visual scene are encoded in the population activity of retinal ganglion cells (RGCs) targeting specific regions of the brain is not well understood. To address this, we have used ...a genetically encoded reporter of presynaptic function (SyGCaMP3) to record visually evoked activity in the population of RGC axons innervating the zebrafish tectum. Using unbiased voxel-wise analysis of SyGCaMP3 signals, we identify three subtypes of direction-selective and two subtypes of orientation-selective retinal input. Composite parametric functional maps generated across many larvae show laminar segregation of direction- and orientation-selective responses and unexpected retinotopic biases in the distribution of functional subtypes. These findings provide a systematic description of the form, organization, and dimensionality of visual inputs to the brain and will serve as a platform for understanding emergent properties in tectal circuits associated with visually driven behavior.
► Fine-scale functional imaging of retinotectal inputs at the population level ► Voxel-wise analysis reveals direction- and orientation-selective retinotectal inputs ► Direction- and orientation-selective inputs segregate into distinct laminae ► Composite maps show retinotopic biases in directional and orientational inputs
The functional organization of sensory terminals within the brain is insufficiently characterized. Nikolaou et al. provide maps of retinal inputs to the zebrafish tectum that reveal segregation according to functional class. Their approach illustrates the strength of examining inputs en masse.
Abstract
Background
Resuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose at admission are at high risk of morbidity and mortality. This has been attributed to the ...post-cardiac arrest syndrome (PCAS) which encompasses multiple interacting components, including systemic inflammation. Elevated levels of circulating interleukin-6 (IL-6), a pro-inflammatory cytokine, is associated with worse outcomes in OHCA patients, including higher vasopressor requirements and higher mortality rates. In this study, we aim to reduce systemic inflammation after OHCA by administering a single infusion of tocilizumab, an IL-6 receptor antibody approved for use for other indications.
Methods
Investigator-initiated, double-blinded, placebo-controlled, single-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Brief inclusion criteria: OHCA of presumed cardiac cause, persistent unconsciousness, age ≥ 18 years. Intervention: 80 patients will be randomized in a 1:1 ratio to a single 1-h intravenous infusion of either tocilizumab or placebo (NaCl). During the study period, patients will receive standard of care, including sedation and targeted temperature management of 36 ° for at least 24 h, vasopressors and/or inotropes as/if needed, prophylactic antibiotics, and any additional treatment at the discretion of the treating physician. Blood samples are drawn for measurements of biomarkers included in the primary and secondary endpoints during the initial 72 h. Primary endpoint: reduction in C-reactive protein (CRP). Secondary endpoints (abbreviated): cytokine levels, markers of brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, adverse events, and follow-up assessment of cerebral function and mortality.
Discussion
We hypothesize that reducing the effect of circulating IL-6 by administering an IL-6 receptor antibody will mitigate the systemic inflammatory response and thereby modify the severity of PCAS, in turn leading to lessened vasopressor use, more normal hemodynamics, and better organ function. This will be assessed by primarily focusing on hemodynamics and biomarkers of organ damage during the initial 72 h.
In addition, pro-inflammatory and anti-inflammatory cytokines will be measured to assess if cytokine patterns are modulated by IL-6 receptor blockage.
Trial registration
ClinicalTrials.gov
Identifier:
NCT03863015
; submitted February 22, 2019, first posted March 5, 2019.
EudraCT: 2018-002686-19; date study was authorized to proceed: November 7, 2018.
This trial showed no significant difference in the percentage of patients who died or had severe disability or coma when higher or lower blood-pressure targets were used after an out-of-hospital ...cardiac arrest.
Oxygen Targets in Comatose Survivors of Cardiac Arrest Schmidt, Henrik; Kjaergaard, Jesper; Hassager, Christian ...
New England journal of medicine/The New England journal of medicine,
10/2022, Letnik:
387, Številka:
16
Journal Article
Recenzirano
Odprti dostop
In comatose patients after out-of-hospital cardiac arrest, the incidence of death or severe disability was similar regardless of whether a restrictive or a liberal oxygenation strategy was used.
This paper explores the relationship between scientific publication and patenting activity. More specifically, it examines for the field of nano-science and nano-technology whether researchers who ...both publish and patent are more productive and more highly cited than their peers who concentrate on scholarly publication in communicating their research results. This study is based on an analysis of the nano-science publications and nano-technology patents of a small set of European countries. While only a very few nano-scientists appear to hold patents in nano-technology, many nano-inventors seem to be actively publishing nano-science research. Overall, the patenting scientists appear to outperform their solely publishing (non-inventing) peers in terms of publication counts and citation frequency. However, a closer examination of the highly active and highly cited nano-authors points to a slightly different situation. While still over-represented among the highly cited authors, inventor-authors appear not to be among the most highly cited authors in that category, with a single notable exception. One policy implication is that, generally speaking, patenting activity does not appear to have an adverse impact on the publication and citation performance of researchers. PUBLICATION ABSTRACT
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