Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.
Dendritic spines are the postsynaptic components of most excitatory synapses in the mammalian brain. Spines accumulate rapidly during early postnatal development and undergo a substantial loss as animals mature into adulthood. In past decades, studies have revealed that the number and size of dendritic spines are regulated by a variety of gene products and environmental factors, underscoring the dynamic nature of spines and their importance to brain plasticity. Recently, in vivo time-lapse imaging of dendritic spines in the cerebral cortex suggests that, although spines are highly plastic during development, they are remarkably stable in adulthood, and most of them last throughout life. Therefore, dendritic spines may provide a structural basis for lifelong information storage, in addition to their well-established role in brain plasticity. Because dendritic spines are the key elements for information acquisition and retention, understanding how spines are formed and maintained, particularly in the intact brain, will likely provide fundamental insights into how the brain possesses the extraordinary capacity to learn and to remember.
We use electrospinning to prepare chitosan–PVA nanofibers containing graphene. The nanofibers can be directly used in wound healing: graphene, as an antibacterial material, can be beneficial for this. A possible antibacterial mechanism for graphene is presented.
Current therapeutic windows for effective application of thrombolytic agents are within 3-6 h of stroke. Although treatment can improve outcome, it is unclear what happens to synaptic fine structure during this critical periodin vivo. The relationship between microcirculation and dendritic spine structure was determined in mouse somatosensory neurons during stroke. Spines were, on average, 13 μm from a capillary and were supplied by ∼100 red blood cells per second. Moderate ischemia (∼50% supply) did not significantly affect spines within 5 h; however, severe ischemia (<10% supply) caused a rapid loss of spine and dendrite structure within as little as 10 min. Surprisingly, if reperfusion occurred within 20-60 min, dendrite and spine structure was mostly restored. These data suggest that the basic dendritic wiring diagram remains mostly intact during moderate ischemia and that affected synapses could potentially contribute to functional recovery. With severe ischemia, markedly deformed dendritic structure can partially recover if reperfusion occurs early.
Stroke induces rapid activation and expansion of microglia, but the main source of microgliosis is controversial. Here we investigated the formation of microgliosis and infiltration of circulating cells in a photothrombosis stroke model by taking advantage of parabiosis and two-photon microscopy. We found that a small population of blood-derived CX3CR1GFP/+ cells infiltrated the cerebral parenchyma, but these cells did not proliferate and were phenotypically distinguishable from resident microglia. CX3CR1GFP/+ infiltrating cells also displayed different kinetics from reactive microglia. The number of CX3CR1GFP/+ infiltrating cells peaked on Day 5 after stroke and then decreased. The decline of these infiltrating cells was associated with an active apoptotic process. In contrast, reactive microglia were recruited to the ischaemic area continuously during the first week after stroke induction. Immunohistology and in vivo two-photon imaging revealed that cells involved in the process of microgliosis were mainly derived from proliferating resident microglia. Expansion of microglia exhibited a consistent pattern and our in vivo data demonstrated for the first time that microglia underwent active division in regions surrounding the ischaemic core. Together, these results indicated that CX3CR1GFP/+ infiltrating cells and reactive microglia represented two distinct populations of cells with different functions and therapeutic potentials for the treatment of stroke.
In vivo two-photon microscopy was used to image in real time dendrites and their spines in a mouse photothrombotic stroke model that reduced somatosensory cortex blood flow in discrete regions of cortical functional maps. This approach allowed us to define relationships between blood flow, cortical structure, and function on scales not previously achieved with macroscopic imaging techniques. Acute ischemic damage to dendrites was triggered within 30 min when blood flow over >0.2 mm2 of cortical surface was blocked. Rapid damage was not attributed to a subset of clotted or even leaking vessels (extravasation) alone. Assessment of stroke borders revealed a remarkably sharp transition between intact and damaged synaptic circuitry that occurred over tens of μm and was defined by a transition between flowing and blocked vessels. Although dendritic spines were normally ~13 μm from small flowing vessels, we show that intact dendritic structure can be maintained (in areas without flowing vessels) by blood flow from vessels that are on average 80 μm away. Functional imaging of intrinsic optical signals associated with activity-evoked hemodynamic responses in somatosensory cortex indicated that sensory-induced changes in signal were blocked in areas with damaged dendrites, but were present ~400 μm away from the border of dendritic damage. These results define the range of influence that blood flow can have on local cortical fine structure and function, as well as to demonstrate that peri-infarct tissues can be functional within the first few hours after stroke and well positioned to aid in poststroke recovery. The brain is critically dependent on an adequate supply of energy as it consumes up to 20% of the oxygen we breathe. Here we determine the distance scale over which interruptions in blood flow affect synaptic hard wiring and brain function. High-resolution microscopy of live mice was used to image cerebral cortex synapses (the sites of connections between neurons) in real time during targeted interruptions of cortical blood flow that model small survivable strokes. Under normal conditions, synapses were tightly coupled to small brain blood vessels, on average only 13 μm away. During targeted strokes, we find that normal synaptic structure can be maintained by flowing blood vessels at a much greater distance of 80 μm. In contrast to structure, brain function was more sensitive to interruption in blood flow and was only present 400 μm from the border of synaptic structural damage. The identification of intact brain structure in regions lacking function defines brain tissue in which restoration of normal blood flow restores function. Our results define the range of influence that blood flow has on cortical fine structure and function and are important for understanding both the pathology of stroke and how changes in blood flow alter the normal brain.