Cold Spring Harbor perspectives in biology最新文献

Astrocytes play an important role in controlling microvascular diameter and regulating local cerebral blood flow (CBF) in several physiological and pathological scenarios. Neurotransmitters released from active neurons evoke Ca²⁺ increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid (AA) from astrocyte endfeet. Synthesis of prostaglandin E₂ (PGE₂) and epoxyeicosatrienoic acids (EETs) dilate blood vessels while 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels. The release of K⁺ from astrocyte endfeet also contributes to vasodilation or constriction in a concentration-dependent manner. Whether astrocytes exert a vasodilation or vasoconstriction depends on the local microenvironment, including the metabolic status, the concentration of Ca²⁺ reached in the endfoot, and the resting vascular tone. Astrocytes also contribute to the generation of steady-state vascular tone. Tonic release of both 20-HETE and ATP from astrocytes constricts vascular smooth muscle cells, generating vessel tone, whereas tone-dependent elevations in endfoot Ca²⁺ produce tonic prostaglandin dilators to limit the degree of constriction. Under pathological conditions, including Alzheimer's disease, epilepsy, stroke, and diabetes, disruption of normal astrocyte physiology can compromise the regulation of blood flow, with negative consequences for neurological function.

Carbon dioxide (CO₂) is a major greenhouse gas contributing to changing climatic conditions, which is a grand challenge affecting the security of food, energy, and environment. Photosynthesis plays the central role in plant-based CO₂ reduction. Plants performing CAM (crassulacean acid metabolism) photosynthesis have a much higher water use efficiency than those performing C₃ or C₄ photosynthesis. Therefore, there is a great potential for engineering CAM in C₃ or C₄ crops to enhance food/biomass production and carbon sequestration on arid, semiarid, abandoned, or marginal lands. Recent progresses in CAM plant genomics and evolution research, along with new advances in plant biotechnology, have provided a solid foundation for bioengineering to convert C₃/C₄ plants into CAM plants. Here, we first discuss the potential strategies for CAM engineering based on our current understanding of CAM evolution. Then we describe the technical approaches for engineering CAM in C₃ and C₄ plants, with a focus on an iterative four-step pipeline: (1) designing gene modules, (2) building the gene modules and transforming them into target plants, (3) testing the engineered plants through an integration of molecular biology, biochemistry, metabolism, and physiological approaches, and (4) learning to inform the next round of CAM engineering. Finally, we discuss the challenges and future opportunities for fully realizing the potential of CAM engineering.

The synapse is the communication unit of the brain, linking billions of neurons through trillions of synaptic connections. The lipid landscape of the synaptic membrane underpins neurotransmitter release through the exocytic fusion of neurotransmitter-containing vesicles, endocytic recycling of these synaptic vesicles, and the postsynaptic response following binding of the neurotransmitter to specialized receptors. How the connected brain can learn and acquire memories through synaptic plasticity is unresolved. Phospholipases, and especially the phospholipase A1 isoform DDHD2, have recently been shown to play a critical role in memory acquisition through the generation of saturated free fatty acids such as myristic and palmitic acids. This emerging synaptic plasticity pathway suggests that phospholipases cannot only respond to synaptic activity by altering the phospholipid landscape but also contribute to the establishment of long-term memories in our brain.

The concept of "genetic coupling" in mate recognition systems arose in the 1960s as a potential mechanism to maintain coordination between signals and receivers during evolutionary divergence. At its most basic it proposed that the same genes might influence trait and preference, and therefore mutations could result in coordinated changes in both traits. Since then, the concept has expanded in scope and is often used to include linkage or genetic correlation between recognition system components. Here we review evidence for genetic coupling, concentrating on proposed examples of a common genetic basis for signals and preferences. Mapping studies have identified several examples of tight genetic linkage between genomic regions influencing signals and preferences, or assortative mating. Whether this extends as far as demonstrating pleiotropy remains a more open question. Some studies, notably of Drosophila, have identified genes in the sex determination pathway and in pheromonal communication where single loci can influence both signals and preferences. This may be based on isoform divergence, in which sex- and tissue-specific effects are facilitated by alternative spicing, or on regulatory divergence. Hence it is not clear that such examples provide compelling evidence of pleiotropy in the sense that "magic mutations" could maintain trait coordination. Rather, coevolution may be facilitated by regulatory divergence but require different mutations or coevolution across isoforms. Reconsidering the logic of genetic coupling, it may be that pleiotropy could actually be less effective than linkage if distinct but associated variants allow molecular coevolution to occur more readily than potentially "unbalanced" mutations in single genes. Genetic manipulation or studies of mutation order effects during divergence are challenging but perhaps the only way to disentangle the role of pleiotropy versus close linkage in coordinated trait divergence.