The complement system serves an important role in clearance of pathogens, immune complexes, and apoptotic cells present in the circulation. Complement fragments deposited on the particle surface ...serve as targets for complement receptors present on phagocytic cells. Although Kupffer cells, the liver resident macrophages, play a dominant role in clearing particles in circulation, complement receptors involved in this process have yet to be identified. Here we report the identification and characterization of a Complement Receptor of the Immunoglobulin superfamily, CRIg, that binds complement fragments C3b and iC3b. CRIg expression on Kupffer cells is required for efficient binding and phagocytosis of complement C3-opsonized particles. In turn, Kupffer cells from CRIg-deficient mice are unable to efficiently clear C3-opsonized pathogens in the circulation, resulting in increased infection and mortality of the host. CRIg therefore represents a dominant component of the phagocytic system responsible for rapid clearance of C3-opsonized particles from the circulation.
This epic history compares the empires built by Spain and Britain in the Americas, from Columbus's arrival in the New World to the end of Spanish colonial rule in the early nineteenth century. J. H. ...Elliott, one of the most distinguished and versatile historians working today, offers us history on a grand scale, contrasting the worlds built by Britain and by Spain on the ruins of the civilizations they encountered and destroyed in North and South America.Elliott identifies and explains both the similarities and differences in the two empires' processes of colonization, the character of their colonial societies, their distinctive styles of imperial government, and the independence movements mounted against them. Based on wide reading in the history of the two great Atlantic civilizations, the book sets the Spanish and British colonial empires in the context of their own times and offers us insights into aspects of this dual history that still influence the Americas.
Atlantic salmon Salmo salar, brown trout Salmo trutta (including the anadromous form, sea trout) and Arctic charr Salvelinus alpinus (including anadromous fish) provide important commercial and ...sports fisheries in Western Europe. As water temperature increases as a result of climate change, quantitative information on the thermal requirements of these three species is essential so that potential problems can be anticipated by those responsible for the conservation and sustainable management of the fisheries and the maintenance of biodiversity in freshwater ecosystems. Part I compares the temperature limits for survival, feeding and growth. Salmo salar has the highest temperature tolerance, followed by S. trutta and finally S. alpinus. For all three species, the temperature tolerance for alevins is slightly lower than that for parr and smolts, and the eggs have the lowest tolerance; this being the most vulnerable life stage to any temperature increase, especially for eggs of S. alpinus in shallow water. There was little evidence to support local thermal adaptation, except in very cold rivers (mean annual temperature <6·5° C). Part II illustrates the importance of developing predictive models, using data from a long‐term study (1967–2000) of a juvenile anadromous S. trutta population. Individual‐based models predicted the emergence period for the fry. Mean values over 34 years revealed a large variation in the timing of emergence with c. 2 months between extreme values. The emergence time correlated significantly with the North Atlantic Oscillation Index, indicating that interannual variations in emergence were linked to more general changes in climate. Mean stream temperatures increased significantly in winter and spring at a rate of 0·37° C per decade, but not in summer and autumn, and led to an increase in the mean mass of pre‐smolts. A growth model for S. trutta was validated by growth data from the long‐term study and predicted growth under possible future conditions. Small increases (<2·5° C) in winter and spring would be beneficial for growth with 1 year‐old smolts being more common. Water temperatures would have to increase by c. 4° C in winter and spring, and 3° C in summer and autumn before they had a marked negative effect on trout growth.
There is increasing evidence that recent changes in climate have had an effect on lake phytoplankton communities and it has been suggested that it is likely that Cyanobacteria will increase in ...relative abundance under the predicted future climate. However, testing such a qualitative prediction is challenging and usually requires some form of numerical computer model. Therefore, the lake modelling literature was reviewed for studies that examined the impact of climate change upon Cyanobacteria. These studies, taken collectively, generally show an increase in relative Cyanobacteria abundance with increasing water temperature, decreased flushing rate and increased nutrient loads. Furthermore, they suggest that whilst the direct effects of climate change on the lakes can change the timing of bloom events and Cyanobacteria abundance, the amount of phytoplankton biomass produced over a year is not enhanced directly by these changes. Also, warmer waters in the spring increased nutrient consumption by the phytoplankton community which in some lakes caused nitrogen limitation later in the year to the advantage of some nitrogen-fixing Cyanobacteria. Finally, it is also possible that an increase in Cyanobacteria dominance of the phytoplankton biomass will lead to poorer energy flow to higher trophic levels due to their relatively poor edibility for zooplankton.
► Lake modelling studies of climate change impacts on Cyanobacteria (Cb) were reviewed. ► Cb dominance was enhanced by temperature especially in nutrient rich lakes. ► Warmer Spring time caused an increase in nitrogen-fixing Cb later in the year. ► Increased Cb could lead to poor energy flow to higher trophic levels.
We quantify the impact of the Wuhan Covid-19 lockdown on concentrations of four air pollutants using a two-step approach. First, we use machine learning to remove the confounding effects of weather ...conditions on pollution concentrations. Second, we use a new augmented synthetic control method (Ben-Michael et al. in The augmented synthetic control method. University of California Berkeley, Mimeo,
2019
.
https://arxiv.org/pdf/1811.04170.pdf
) to estimate the impact of the lockdown on weather normalised pollution relative to a control group of cities that were not in lockdown. We find NO
2
concentrations fell by as much as 24
μ
g/m
3
during the lockdown (a reduction of 63% from the pre-lockdown level), while PM10 concentrations fell by a similar amount but for a shorter period. The lockdown had no discernible impact on concentrations of SO
2
or CO. We calculate that the reduction of NO
2
concentrations could have prevented as many as 496 deaths in Wuhan city, 3368 deaths in Hubei province and 10,822 deaths in China as a whole.
The electro-optical Pockels effect is an essential nonlinear effect used in many applications. The ultrafast modulation of the refractive index is, for example, crucial to optical modulators in ...photonic circuits. Silicon has emerged as a platform for integrating such compact circuits, but a strong Pockels effect is not available on silicon platforms. Here, we demonstrate a large electro-optical response in silicon photonic devices using barium titanate. We verify the Pockels effect to be the physical origin of the response, with r
= 923 pm V
, by confirming key signatures of the Pockels effect in ferroelectrics: the electro-optic response exhibits a crystalline anisotropy, remains strong at high frequencies, and shows hysteresis on changing the electric field. We prove that the Pockels effect remains strong even in nanoscale devices, and show as a practical example data modulation up to 50 Gbit s
. We foresee that our work will enable novel device concepts with an application area largely extending beyond communication technologies.
Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the entire blood system. We generated a highly specific transgenic reporter of HSPCs in zebrafish. This allowed us to ...perform high-resolution live imaging on endogenous HSPCs not currently possible in mammalian bone marrow. Using this system, we have uncovered distinct interactions between single HSPCs and their niche. When an HSPC arrives in the perivascular niche, a group of endothelial cells remodel to form a surrounding pocket. This structure appears conserved in mouse fetal liver. Correlative light and electron microscopy revealed that endothelial cells surround a single HSPC attached to a single mesenchymal stromal cell. Live imaging showed that mesenchymal stromal cells anchor HSPCs and orient their divisions. A chemical genetic screen found that the compound lycorine promotes HSPC-niche interactions during development and ultimately expands the stem cell pool into adulthood. Our studies provide evidence for dynamic niche interactions upon stem cell colonization.
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•Direct observation of endogenous blood stem cells using highly specific transgenics•Perivascular lodgement of blood stem cells triggers active remodeling of the niche•Correlative light and electron microscopy reveals high-resolution niche architecture•Chemical treatment of the embryo increases the size of the stem cell pool in adults
Live imaging reveals that hematopoietic stem cell lodgement in the perivascular niche triggers remodeling of endothelial cells into a surrounding pocket. The stem cell becomes anchored to a single mesenchymal stromal cell that orients its division plane.
We engineered light-gated channelrhodopsins (ChRs) whose current strength and light sensitivity enable minimally invasive neuronal circuit interrogation. Current ChR tools applied to the mammalian ...brain require intracranial surgery for transgene delivery and implantation of fiber-optic cables to produce light-dependent activation of a small volume of tissue. To facilitate expansive optogenetics without the need for invasive implants, our engineering approach leverages the substantial literature of ChR variants to train statistical models for the design of high-performance ChRs. With Gaussian process models trained on a limited experimental set of 102 functionally characterized ChRs, we designed high-photocurrent ChRs with high light sensitivity. Three of these, ChRger1-3, enable optogenetic activation of the nervous system via systemic transgene delivery. ChRger2 enables light-induced neuronal excitation without fiber-optic implantation; that is, this opsin enables transcranial optogenetics.
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