Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
7,122
result(s) for
"Lin, John"
Sort by:
Irritant-evoked activation and calcium modulation of the TRPA1 receptor
The transient receptor potential ion channel TRPA1 is expressed by primary afferent nerve fibres, in which it functions as a low-threshold sensor for structurally diverse electrophilic irritants, including small volatile environmental toxicants and endogenous algogenic lipids
1
. TRPA1 is also a ‘receptor-operated’ channel whose activation downstream of metabotropic receptors elicits inflammatory pain or itch, making it an attractive target for novel analgesic therapies
2
. However, the mechanisms by which TRPA1 recognizes and responds to electrophiles or cytoplasmic second messengers remain unknown. Here we use strutural studies and electrophysiology to show that electrophiles act through a two-step process in which modification of a highly reactive cysteine residue (C621) promotes reorientation of a cytoplasmic loop to enhance nucleophilicity and modification of a nearby cysteine (C665), thereby stabilizing the loop in an activating configuration. These actions modulate two restrictions controlling ion permeation, including widening of the selectivity filter to enhance calcium permeability and opening of a canonical gate at the cytoplasmic end of the pore. We propose a model to explain functional coupling between electrophile action and these control points. We also characterize a calcium-binding pocket that is highly conserved across TRP channel subtypes and accounts for all aspects of calcium-dependent TRPA1 regulation, including potentiation, desensitization and activation by metabotropic receptors. These findings provide a structural framework for understanding how a broad-spectrum irritant receptor is controlled by endogenous and exogenous agents that elicit or exacerbate pain and itch.
Electrophiles activate the transient receptor potential ion channel TRPA1 by a two-step cysteine modification mechanism, which stabilizes a cytoplasmic loop that controls gating and calcium permeability.
Journal Article
Synthesis and evaluation of polyamine carbon quantum dots (CQDs) in Litopenaeus vannamei as a therapeutic agent against WSSV
White spot syndrome virus (WSSV) is the causative agent of white spot syndrome (WSS), a disease that has led to severe mortality rates in cultured shrimp all over the world. The WSSV is a large, ellipsoid, enveloped double-stranded DNA virus with a wide host range among crustaceans. Currently, the main antiviral method is to block the receptor of the host cell membrane using recombinant viral proteins or virus antiserum. In addition to interference with the ligand-receptor binding, disrupting the structure of the virus envelope may also be a means to combat the viral infection. Carbon quantum dots (CQDs) are carbonaceous nanoparticles that have many advantageous characteristics, including small size, low cytotoxicity, cheap, and ease of production and modification. Polyamine-modified CQDs (polyamine CQDs) with strong antibacterial ability have been identified, previously. In this study, polyamine CQDs are shown to attach to the WSSV envelope and inhibit the virus infection, with a dose-dependent effect. The results also show that polyamine CQDs can upregulate several immune genes in shrimp and reduce the mortality upon WSSV infection. This is first study to identify that polyamine CQDs could against the virus. These results, indeed, provide a direction to develop effective antiviral strategies or therapeutic methods using polyamine CQDs in aquaculture.
Journal Article
He Gan Bobo qu you he
Mr. Gumpy accepts more and more riders on his boat until the inevitable occurs.
BOOK
ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation
In this technical report, the authors describe a new, red-shifted variant of channelrhodopsin (called red-activatable channelrhodopsin or ReaChR) that shows faster kinetics and greater photocurrents than currently available red-shifted probes. In addition, they show that ReaChR can be activated in awake mice through the intact skull.
Channelrhodopsins (ChRs) are used to optogenetically depolarize neurons. We engineered a variant of ChR, denoted red-activatable ChR (ReaChR), that is optimally excited with orange to red light (
λ
∼590–630 nm) and offers improved membrane trafficking, higher photocurrents and faster kinetics compared to existing red-shifted ChRs. Red light is less scattered by tissue and is absorbed less by blood than the blue to green wavelengths that are required by other ChR variants. We used ReaChR expressed in the vibrissa motor cortex to drive spiking and vibrissa motion in awake mice when excited with red light through intact skull. Precise vibrissa movements were evoked by expressing ReaChR in the facial motor nucleus in the brainstem and illumination with red light through the external auditory canal. Thus, ReaChR enables transcranial optical activation of neurons in deep brain structures without the need to surgically thin the skull, form a transcranial window or implant optical fibers.
Journal Article
He Gan bobo qu dou feng
Mr. Gumpy's human and animal friends squash into his old car and go for a drive-- until it starts to rain.
BOOK
Space-based quantification of per capita CO2 emissions from cities
Urban areas are currently responsible for ∼70% of the global energy-related carbon dioxide (CO2) emissions, and rapid ongoing global urbanization is increasing the number and size of cities. Thus, understanding city-scale CO2 emissions and how they vary between cities with different urban densities is a critical task. While the relationship between CO2 emissions and population density has been explored widely in prior studies, their conclusions were sensitive to inconsistent definitions of urban boundaries and the reliance upon CO2 emission inventories that implicitly assumed population relationships. Here we provide the first independent estimates of direct per capita CO2 emissions (Epc) from spaceborne atmospheric CO2 measurements from the Orbiting Carbon Observatory-2 (OCO-2) for a total 20 cities across multiple continents. The analysis accounts for the influence of meteorology on the satellite observations with an atmospheric model. The resultant upwind source region sampled by the satellite serves as an objective urban extent for aggregating emissions and population densities. Thus, we are able to detect emission 'hotspots' on a per capita basis from a few cities, subject to sampling restrictions from OCO-2. Our results suggest that Epc declines as population densities increase, albeit the decrease in Epc is partially limited by the positive correlation between Epc and per capita gross domestic product. As additional CO2-observing satellites are launched in the coming years, our space-based approach to understanding CO2 emissions from cities has significant potential in tracking and evaluating the future trajectory of urban growth and informing the effects of carbon reduction plans.
Journal Article
Designing the rural : a global countryside in flux
The rural is not what it used to be. No longer simply a site for agricultural production for the city, the relationship between the rural and urban has become much more complex. Established categories such as rural/urban and village/city no longer hold true. Rural and urban conditions have become increasingly blurred, so how can we identify and distinguish their specific characteristics? This book investigates how architects and researchers are critically engaging with the rural as an experimental field of exploration.
Book
PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis
Glioblastoma is a universally lethal form of brain cancer that exhibits an array of pathophysiological phenotypes, many of which are mediated by interactions with the neuronal microenvironment
1
,
2
. Recent studies have shown that increases in neuronal activity have an important role in the proliferation and progression of glioblastoma
3
,
4
. Whether there is reciprocal crosstalk between glioblastoma and neurons remains poorly defined, as the mechanisms that underlie how these tumours remodel the neuronal milieu towards increased activity are unknown. Here, using a native mouse model of glioblastoma, we develop a high-throughput in vivo screening platform and discover several driver variants of PIK3CA. We show that tumours driven by these variants have divergent molecular properties that manifest in selective initiation of brain hyperexcitability and remodelling of the synaptic constituency. Furthermore, secreted members of the glypican (GPC) family are selectively expressed in these tumours, and GPC3 drives gliomagenesis and hyperexcitability. Together, our studies illustrate the importance of functionally interrogating diverse tumour phenotypes driven by individual, yet related, variants and reveal how glioblastoma alters the neuronal microenvironment.
Glioblastoma tumours expressing oncogenic PIK3CA variants secrete the glycan GPC3, which promotes the formation of neural synapses, brain synaptic hyperexcitability and gliomagenesis.
Journal Article