Magnetic particle imaging is an emerging tomographic technique with the potential for simultaneous high-resolution, high-sensitivity, and real-time imaging. Magnetic particle imaging is based on the ...unique behavior of superparamagnetic iron oxide nanoparticles modeled by the Langevin theory, with the ability to track and quantify nanoparticle concentrations without tissue background noise. It is a promising new imaging technique for multiple applications, including vascular and perfusion imaging, oncology imaging, cell tracking, inflammation imaging, and trauma imaging. In particular, many neuroimaging applications may be enabled and enhanced with magnetic particle imaging. In this review, we will provide an overview of magnetic particle imaging principles and implementation, current applications, promising neuroimaging applications, and practical considerations.
1000 dams down and counting O'Connor, J. E.; Duda, J. J.; Grant, G. E.
Science (American Association for the Advancement of Science),
05/2015, Letnik:
348, Številka:
6234
Journal Article
Recenzirano
Dam removals are reconnecting rivers in the United States
Forty years ago, the demolition of large dams was mostly fiction, notably plotted in Edward Abbey's novel
The Monkey Wrench Gang.
Its 1975 ...publication roughly coincided with the end of large-dam construction in the United States. Since then, dams have been taken down in increasing numbers as they have filled with sediment, become unsafe or inefficient, or otherwise outlived their usefulness (
1
) (see the figure, panel A). Last year's removals of the 64-m-high Glines Canyon Dam and the 32-m-high Elwha Dam in northwestern Washington State were among the largest yet, releasing over 10 million cubic meters of stored sediment. Published studies conducted in conjunction with about 100 U.S. dam removals and at least 26 removals outside the United States are now providing detailed insights into how rivers respond (
2
,
3
).
Abstract
Over 130 brain diseases are caused by mutations that disrupt genes encoding the proteome of excitatory synapses. These include neurological and psychiatric disorders with early and late ...onset such as autism, schizophrenia and depression and many other rarer conditions. The proteome of synapses is highly complex with over 1000 conserved proteins which are differentially expressed generating a vast, potentially unlimited, number of synapse types. The diversity of synapses and their location in the brain are described by the synaptome. A recent study has mapped the synaptome across the mouse brain, revealing that synapse diversity is distributed into an anatomical architecture observed at scales from individual dendrites to the whole systems level. The synaptome architecture is built from the hierarchical expression and assembly of proteins into complexes and supercomplexes which are distributed into different synapses. Mutations in synapse proteins change the synaptome architecture leading to behavioral phenotypes. Mutations in the mechanisms regulating the hierarchical assembly of the synaptome, including transcription and proteostasis, may also change synapse diversity and synaptome architecture. The logic of synaptome hierarchical assembly provides a mechanistic framework that explains how diverse genetic disorders can converge on synapses in different brain circuits to produce behavioral phenotypes.
The mechanism of CF2 transfer from TMSCF3 (1), mediated by TBAT (2–12 mol %) or by NaI (5–20 mol %), has been investigated by in situ/stopped-flow 19F NMR spectroscopic analysis of the kinetics of ...alkene difluorocyclopropanation and competing TFE/c-C3F6/homologous perfluoroanion generation, 13C/2H KIEs, LFERs, CF2 transfer efficiency and selectivity, the effect of inhibitors, and density functional theory (DFT) calculations. The reactions evolve with profoundly different kinetics, undergoing autoinhibition (TBAT) or quasi-stochastic autoacceleration (NaI) and cogenerating perfluoroalkene side products. An overarching mechanism involving direct and indirect fluoride transfer from a CF3 anionoid to TMSCF3 (1) has been elucidated. It allows rationalization of why the NaI-mediated process is more effective for less-reactive alkenes and alkynes, why a large excess of TMSCF3 (1) is required in all cases, and why slow-addition protocols can be of benefit. Issues relating to exothermicity, toxicity, and scale-up are also noted.
Earth is heading towards a climate that last existed more than three million years ago (Ma) during the 'mid-Pliocene warm period'
, when atmospheric carbon dioxide concentrations were about 400 parts ...per million, global sea level oscillated in response to orbital forcing
and peak global-mean sea level (GMSL) may have reached about 20 metres above the present-day value
. For sea-level rise of this magnitude, extensive retreat or collapse of the Greenland, West Antarctic and marine-based sectors of the East Antarctic ice sheets is required. Yet the relative amplitude of sea-level variations within glacial-interglacial cycles remains poorly constrained. To address this, we calibrate a theoretical relationship between modern sediment transport by waves and water depth, and then apply the technique to grain size in a continuous 800-metre-thick Pliocene sequence of shallow-marine sediments from Whanganui Basin, New Zealand. Water-depth variations obtained in this way, after corrections for tectonic subsidence, yield cyclic relative sea-level (RSL) variations. Here we show that sea level varied on average by 13 ± 5 metres over glacial-interglacial cycles during the middle-to-late Pliocene (about 3.3-2.5 Ma). The resulting record is independent of the global ice volume proxy
(as derived from the deep-ocean oxygen isotope record) and sea-level cycles are in phase with 20-thousand-year (kyr) periodic changes in insolation over Antarctica, paced by eccentricity-modulated orbital precession
between 3.3 and 2.7 Ma. Thereafter, sea-level fluctuations are paced by the 41-kyr period of cycles in Earth's axial tilt as ice sheets stabilize on Antarctica and intensify in the Northern Hemisphere
. Strictly, we provide the amplitude of RSL change, rather than absolute GMSL change. However, simulations of RSL change based on glacio-isostatic adjustment show that our record approximates eustatic sea level, defined here as GMSL unregistered to the centre of the Earth. Nonetheless, under conservative assumptions, our estimates limit maximum Pliocene sea-level rise to less than 25 metres and provide new constraints on polar ice-volume variability under the climate conditions predicted for this century.
Objectives/Hypothesis
Concurrent chemoradiotherapy is the gold‐standard nonsurgical organ‐preservation treatment for advanced laryngeal carcinoma. Total laryngectomy (TL) is increasingly reserved for ...surgical salvage. Salvage surgery is associated with more complications than primary surgery. A systematic review and meta‐analysis was undertaken to establish the impact of organ preservation protocols on pharyngo‐cutaneous fistula incidence following TL, and to synthesize evidence on the role of “onlay” prophylactic tissue flaps in reducing this complication in salvage TL.
Data Sources
The English language literature (January 1, 2000, to September 1, 2013) was searched, using PUBMED and EMBASE databases, for the terms “laryngectomy” and “fistula.” Of 522 studies identified from database searches, 33 were included in the quantitative synthesis.
Review Methods
Studies reporting fistula incidence following primary TL (PTL), salvage TL (STL), and STL with “onlay” flap‐reinforced pharyngeal closure were included. Data were extracted by the first author (M.S.). Meta‐analysis of fistula incidence was performed.
Results
PTL fistula incidence is 14.3% (95% CI 11.7–17.0), STL 27.6% (23.4–31.8), and STL with flap‐reinforced closure 10.3% (4.6–15.9). Chemoradiotherapy is associated with a pooled fistula incidence of 34.1% (22.6–45.6), compared to 22.8% (18.3–27.4) for radiotherapy alone. Relative risk of fistula is 0.566 (0.374–0.856, P = 0.001) for STL with flap‐reinforced closure compared to STL alone. The number needed to treat (NNT) to prevent one fistula is 6.05.
Conclusion
Prophylactic flaps used in an “onlay” technique reduce fistula incidence in STL. Chemoradiotherapy increases fistula incidence more than radiotherapy alone. Prophylactic flaps should be offered in salvage cases after failed chemoradiation protocols.
Level of Evidence
3A.Laryngoscope, 124:1150–1163, 2014
The spacing of hair in mammals and feathers in birds is one of the most apparent morphological features of the skin. This pattern arises when uniform fields of progenitor cells diversify their ...molecular fate while adopting higher-order structure. Using the nascent skin of the developing chicken embryo as a model system, we find that morphological and molecular symmetries are simultaneously broken by an emergent process of cellular self-organization. The key initiators of heterogeneity are dermal progenitors, which spontaneously aggregate through contractility-driven cellular pulling. Concurrently, this dermal cell aggregation triggers the mechanosensitive activation of β-catenin in adjacent epidermal cells, initiating the follicle gene expression program. Taken together, this mechanism provides a means of integrating mechanical and molecular perspectives of organ formation.
We compared two genetically highly defined transgenic systems to identify parameters affecting reprogramming of somatic cells to a pluripotent state. Our results demonstrate that the level and ...stoichiometry of reprogramming factors during the reprogramming process strongly influence the resulting pluripotency of iPS cells. High expression of Oct4 and Klf4 combined with lower expression of c-Myc and Sox2 produced iPS cells that efficiently generated “all-iPSC mice” by tetraploid (4n) complementation, maintained normal imprinting at the
Dlk1-
Dio3 locus, and did not create mice with tumors. Loss of imprinting (LOI) at the
Dlk1-Dio3 locus did not strictly correlate with reduced pluripotency though the efficiency of generating “all-iPSC mice” was diminished. Our data indicate that stoichiometry of reprogramming factors can influence epigenetic and biological properties of iPS cells. This concept complicates efforts to define a “generic” epigenetic state of iPSCs and ESCs and should be considered when comparing different iPS and ES cell lines.
Display omitted
► Optimal reprogramming factor stoichiometry yields high-quality iPSCs ► Infrequent loss of imprinting (LOI) of Dlk1-Dio3 iPSCs seen in Col1a-OSKM mice ► Adult mice from Col1a1-OSKM iPSCs do not develop tumors ► Dlk1-Dio3 LOI is not an absolute marker for reduced pluripotency
The synapse in traumatic brain injury Jamjoom, Aimun A B; Rhodes, Jonathan; Andrews, Peter J D ...
Brain (London, England : 1878),
02/2021, Letnik:
144, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and is a risk factor for dementia later in life. Research into the pathophysiology of TBI has focused on the impact ...of injury on the neuron. However, recent advances have shown that TBI has a major impact on synapse structure and function through a combination of the immediate mechanical insult and the ensuing secondary injury processes, leading to synapse loss. In this review, we highlight the role of the synapse in TBI pathophysiology with a focus on the confluence of multiple secondary injury processes including excitotoxicity, inflammation and oxidative stress. The primary insult triggers a cascade of events in each of these secondary processes and we discuss the complex interplay that occurs at the synapse. We also examine how the synapse is impacted by traumatic axonal injury and the role it may play in the spread of tau after TBI. We propose that astrocytes play a crucial role by mediating both synapse loss and recovery. Finally, we highlight recent developments in the field including synapse molecular imaging, fluid biomarkers and therapeutics. In particular, we discuss advances in our understanding of synapse diversity and suggest that the new technology of synaptome mapping may prove useful in identifying synapses that are vulnerable or resistant to TBI.
Direct comparison of protein components from human and mouse excitatory synapses is important for determining the suitability of mice as models of human brain disease and to understand the evolution ...of the mammalian brain. The postsynaptic density is a highly complex set of proteins organized into molecular networks that play a central role in behavior and disease. We report the first direct comparison of the proteome of triplicate isolates of mouse and human cortical postsynaptic densities. The mouse postsynaptic density comprised 1556 proteins and the human one 1461. A large compositional overlap was observed; more than 70% of human postsynaptic density proteins were also observed in the mouse postsynaptic density. Quantitative analysis of postsynaptic density components in both species indicates a broadly similar profile of abundance but also shows that there is higher abundance variation between species than within species. Well known components of this synaptic structure are generally more abundant in the mouse postsynaptic density. Significant inter-species abundance differences exist in some families of key postsynaptic density proteins including glutamatergic neurotransmitter receptors and adaptor proteins. Furthermore, we have identified a closely interacting set of molecules enriched in the human postsynaptic density that could be involved in dendrite and spine structural plasticity. Understanding synapse proteome diversity within and between species will be important to further our understanding of brain complexity and disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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