Phagocytosis in the brain: homeostasis and disease

Microglia are resident macrophages of the central nervous system and significantly contribute to overall brain function by participating in phagocytosis during development, homeostasis, and diseased states. Phagocytosis is a highly complex process that is specialized for the uptake and removal of opsonized and non-opsonized targets, such as pathogens, apoptotic cells, and cellular debris. While the role of phagocytosis in mediating classical innate and adaptive immune responses has been known for decades, it is now appreciated that phagocytosis is also critical throughout early neural development, homeostasis, and initiating repair mechanisms. As such, modulating phagocytic processes has provided unexplored avenues with the intent of developing novel therapeutics that promote repair and regeneration in the CNS. Here, we review the functional consequences that phagocytosis plays in both the healthy and diseased CNS, and summarize how phagocytosis contributes to overall pathophysiological mechanisms involved in brain injury and repair

On modular decompositions of system signatures

Considering a semicoherent system made up of $n$ components having i.i.d. continuous lifetimes, Samaniego defined its structural signature as the $n$-tuple whose $k$-th coordinate is the probability that the $k$-th component failure causes the system to fail. This $n$-tuple, which depends only on the structure of the system and not on the distribution of the component lifetimes, is a very useful tool in the theoretical analysis of coherent systems. It was shown in two independent recent papers how the structural signature of a system partitioned into two disjoint modules can be computed from the signatures of these modules. In this work we consider the general case of a system partitioned into an arbitrary number of disjoint modules organized in an arbitrary way and we provide a general formula for the signature of the system in terms of the signatures of the modules. The concept of signature was recently extended to the general case of semicoherent systems whose components may have dependent lifetimes. The same definition for the $n$-tuple gives rise to the probability signature, which may depend on both the structure of the system and the probability distribution of the component lifetimes. In this general setting, we show how under a natural condition on the distribution of the lifetimes, the probability signature of the system can be expressed in terms of the probability signatures of the modules. We finally discuss a few situations where this condition holds in the non-i.i.d. and nonexchangeable cases and provide some applications of the main results

Evolutionary origins and development of saw-teeth on the sawfish and sawshark rostrum (Elasmobranchii; Chondrichthyes)

A well-known characteristic of chondrichthyans (e.g. sharks, rays) is their covering of external skin denticles (placoid scales), but less well understood is the wide morphological diversity that these skin denticles can show. Some of the more unusual of these are the tooth-like structures associated with the elongate cartilaginous rostrum ‘saw’ in three chondrichthyan groups: Pristiophoridae (sawsharks; Selachii), Pristidae (sawfish; Batoidea) and the fossil Sclerorhynchoidea (Batoidea). Comparative topographic and developmental studies of the ‘saw-teeth’ were undertaken in adults and embryos of these groups, by means of three-dimensional-rendered volumes from X-ray computed tomography. This provided data on development and relative arrangement in embryos, with regenerative replacement in adults. Saw-teeth are morphologically similar on the rostra of the Pristiophoridae and the Sclerorhynchoidea, with the same replacement modes, despite the lack of a close phylogenetic relationship. In both, tooth-like structures develop under the skin of the embryos, aligned with the rostrum surface, before rotating into lateral position and then attaching through a pedicel to the rostrum cartilage. As well, saw-teeth are replaced and added to as space becomes available. By contrast, saw-teeth in Pristidae insert into sockets in the rostrum cartilage, growing continuously and are not replaced. Despite superficial similarity to oral tooth developmental organization, saw-tooth spatial initiation arrangement is associated with rostrum growth. Replacement is space-dependent and more comparable to that of dermal skin denticles. We suggest these saw-teeth represent modified dermal denticles and lack the ‘many-for-one’ replacement characteristic of elasmobranch oral dentitions

Hydroxypyridine/Pyridone Interconversions within Ruthenium Complexes for their Catalytic Application in the Hydrogenation of CO2

Reaction of a new ligand 6-DiPPon {where 6-DiPPon = 6-diisopropylphosphino-2-pyridone} with half equivalent of [RuCl2(p-cymene)]2 resulted in the formation of a mixture of [RuCl2(p-cymene)(κ1-P-(6-DiPPon)]2 (1) and [RuCl(p-cymene)(κ2-P,N-(6-DiPPin)]Cl ([2]Cl) {where 6-DiPPin = 6-diisopropylphosphino-2-hydroxypyridine}. The ratio between the two products can be controlled by the nature of the solvent. The similar reaction between 6-DiPPon and [RuCl2(p-cymene)]2 in the presence of AgOTf or Na[BArF24] {where BArF24 = [{3,5-(CF3)2C6H3}4B]−} resulted in the formation of the complexes, [RuCl(p-cymene)(κ2-P,N-(6-DiPPin)]OTf, ([2]OTf) and [RuCl(p-cymene)(κ2-P,N-(6-DiPPin)]BArF24, ([2]BArF24), respectively. Reactions between the complexes [2]Cl, [2]OTf or [2]BArF24 with a base (either DBU or NaOMe) resulted in the deprotonation of hydroxyl functional group to form a novel neutral orange coloured dearomatised complex, 3. The identity of complex 3 was confirmed as [RuCl(p-cymene)(κ2-P,N-6-DiPPon*)], where 6-DiPPon* is the anionic species, [6-diisopropylphosphino-2-oxo-pyridinide], which contains the deprotonated moiety. The new 6-DiPPon ligand and its corresponding air stable half-sandwich derivative ruthenium complexes, 1, [2]OTf, [2]BArF24 and 3 were all isolated in good yields and fully characterized by spectroscopic and analytical methods. The interconversions between the neutral and anionic forms of the ligands 6-DiPPon, 6-DiPPin and 6-DiPPon* offer the potential for novel secondary sphere interactions and proton shuttling reactivity. The consequences for this have been explored in the activation of H2 and the subsequent catalytic hydrogenations of CO2 into formate-salts in the presence of a base

Constitutive changes in pigment concentrations: implications for estimating isoprene emissions using the photochemical reflectance index

The photochemical reflectance index (PRI), through its relationship with light use efficiency (LUE) and xanthophyll cycle activity, has recently been shown to hold potential for tracking isoprene emissions from vegetation. However, both PRI and isoprene emissions can also be influenced by changes in carotenoid pigment concentrations. Xanthophyll cycle activity and changes in carotenoid concentrations operate over different timescales but the importance of constitutive changes in pigment concentrations for accurately estimating isoprene emissions using PRI is unknown. To clarify the physiological mechanisms behind the PRI–isoprene relationship, the light environment of potted Salix viminalis (dwarf willow) trees was modified to induce acclimation in photosynthetic rates, phytopigments, isoprene emissions and PRI. Acclimation resulted in differences in pigment concentrations, isoprene emissions and PRI. Constitutive changes in carotenoid concentration were significantly correlated with both isoprene emissions and PRI, suggesting that the relationship between PRI and isoprene emissions is significantly influenced by constitutive pigment changes. Consequently knowledge regarding how isoprene emissions are affected by both longer term changes in total carotenoid concentrations and shorter term dynamic adjustments of LUE is required to facilitate interpretation of PRI for monitoring isoprene emissions