Short Term Interactions with Long Term Consequences: Modulation of Chimeric Vessels by Neural Progenitors

Vessels are a critical and necessary component of most tissues, and there has been substantial research investigating vessel formation and stabilization. Several groups have investigated coculturing endothelial cells with a second cell type to promote formation and stabilization of vessels. Some have noted that long-term vessels derived from implanted cocultures are often chimeric consisting of both host and donor cells. The questions arise as to whether the coculture cell might impact the chimeric nature of the microvessels and can modulate the density of donor cells over time. If long-term engineered microvessels are primarily of host origin, any impairment of the host''s angiogenic ability has significant implications for the long-term success of the implant. If one can modulate the host versus donor response, one may be able to overcome a host''s angiogenic impairment. Furthermore, if one can modulate the donor contribution, one may be able to engineer microvascular networks to deliver molecules a patient lacks systemically for long times. To investigate the impact of the cocultured cell on the host versus donor contributions of endothelial cells in engineered microvascular networks, we varied the ratio of the neural progenitors to endothelial cells in subcutaneously implanted poly(ethylene glycol)/poly-L-lysine hydrogels. We found that the coculture of neural progenitors with endothelial cells led to the formation of chimeric host-donor vessels, and the ratio of neural progenitors has a significant impact on the long term residence of donor endothelial cells in engineered microvascular networks in vivo even though the neural progenitors are only present transiently in the system. We attribute this to the short term paracrine signaling between the two cell types. This suggests that one can modulate the host versus donor contributions using short-term paracrine signaling which has broad implications for the application of engineered microvascular networks and cellular therapy more broadly.     

乳酸影响记忆的神经机制

乳酸在以往的研究中一直被认为是糖酵解的产物,是不受欢迎的代谢副产品。近30年的研究证明乳酸可以作为能量底物,也可以通过影响信号通路影响神经活动。乳酸对空间记忆、恐惧记忆,成瘾记忆均能够发挥作用。星形胶质细胞和少突胶质细胞中产生的乳酸,转运到神经元中为神经元提供能量进而影响记忆。乳酸可以直接作用于乳酸受体,也可以间接通过促进神经发生、增强N-甲基-D-天冬氨酸受体（N-methyl-D-aspartic acid receptor,NMDAR）的活性促进突触可塑性和即刻早期基因的表达、诱导脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）的表达进而影响记忆。乳酸还是与记忆有关的神经系统性疾病的潜在治疗靶点,例如阿尔茨海默病（Alzheimer’s disease,AD）。本文综述了乳酸产生对不同记忆的影响、不同神经递质调控乳酸的产生对记忆的影响、乳酸影响记忆的神经机制、乳酸在与记忆有关神经性退行疾病中的作用。通过上述方面的梳理,希望进一步为乳酸在记忆中作用和乳酸在神经系统中作用的研究提供新的思路。     

小鸡早期记忆形成的神经机制

小鸡是研究早期记忆形成机制的理想动物模型.一日龄小鸡在一次性被动回避实验（one-trial-passive-avoidance-test）后,与记忆形成相关脑区的神经元在时间和空间上发生了一系列复杂的生理生化反应.综述了小鸡记忆形成过程的最新研究进展,分析了与记忆形成相关的神经回路、细胞和分子机制.     

Neural Substrates Related to Motor Memory with Multiple Timescales in Sensorimotor Adaptation

Recent computational and behavioral studies suggest that motor adaptation results from the update of multiple memories with different timescales. Here, we designed a model-based functional magnetic resonance imaging (fMRI) experiment in which subjects adapted to two opposing visuomotor rotations. A computational model of motor adaptation with multiple memories was fitted to the behavioral data to generate time-varying regressors of brain activity. We identified regional specificity to timescales: in particular, the activity in the inferior parietal region and in the anterior-medial cerebellum was associated with memories for intermediate and long timescales, respectively. A sparse singular value decomposition analysis of variability in specificities to timescales over the brain identified four components, two fast, one middle, and one slow, each associated with different brain networks. Finally, a multivariate decoding analysis showed that activity patterns in the anterior-medial cerebellum progressively represented the two rotations. Our results support the existence of brain regions associated with multiple timescales in adaptation and a role of the cerebellum in storing multiple internal models.     

Mechanism of Short Term Fe Reduction by Roots : Evidence against the Role of Secreted Reductants

The hypothesized role of secreted reducing compounds in Fe^III reduction has been examined with Fe-deficient peanuts (Arachis hypogaea L. cv A124B). Experiments involved the exposure of roots to (a) different gas mixtures, (b) carbonyl cyanide m-chlorophenylhydrazone (CCCP), and (c) agents which impair membrane integrity.

Removing roots from solution and exposing them to air or N₂ for 10 minutes did not result in any accumulation in the free space of compounds capable of increasing rates of Fe^III reduction when roots were returned to solutions. On the contrary, exposing roots to N₂ decreased rates of Fe^III reduction. CCCP also decreased rates of Fe^III reduction.

Acetic acid and ethylenediaminetetraacetic acid (disodium salt) (EDTA) impaired the integrity and function of the plasma membranes of roots of Fe-deficient peanuts. That is, in the presence of acetic acid or EDTA, there was an efflux of K⁺ from the roots; K⁺ (⁸⁶Rb) uptake was also impaired. Acetic acid increased the efflux from the roots of compounds capable of reducing Fe^III. However, both acetic acid and EDTA caused rapid decreases in rates of Fe^III reduction by the roots. In addition to peanuts, acetic acid also decreased rates of Fe^III reduction by roots of Fe-deficient sunflowers (Helianthus annuus L. cv Sobrid) but not maize (Zea mays L. cv Garbo).

These results suggest that, at least in the short term, the enhanced Fe^III reduction by roots of Fe-deficient plants is not due to the secretion of reducing compounds.

     

CREB——长时记忆的介导因子

综述了CREB的研究进展和该领域中需深入研究和注意的问题.CREB作为一种转录因子参与短时记忆向长时记忆的转化,它具有激活型和抑制型两种形式,籍此可以更加精细地调节记忆的转化,这在不同种属动物中已经得到证实,且其基因序列存在着高度的保守性.     

A Short Term Quality Control Tool for Biodegradable Microspheres

Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C.     

A Portable Chemotaxis Platform for Short and Long Term Analysis

Flow-based microfluidic systems have been widely utilized for cell migration studies given their ability to generate versatile and precisely defined chemical gradients and to permit direct visualization of migrating cells. Nonetheless, the general need for bulky peripherals such as mechanical pumps and tubing and the complicated setup procedures significantly limit the widespread use of these microfluidic systems for cell migration studies. Here we present a simple method to power microfluidic devices for chemotaxis assays using the commercially available ALZET® osmotic pumps. Specifically, we developed a standalone chemotaxis platform that has the same footprint as a multiwell plate and can generate well-defined, stable chemical gradients continuously for up to 7 days. Using this platform, we validated the short-term (24 hours) and long-term (72 hours) concentration dependent PDGF-BB chemotaxis response of human bone marrow derived mesenchymal stem cells.     

情绪记忆权衡与拓宽效应及其认知神经机制

情绪图片能比中性图片产生更好的记忆效果。然而近年研究发现，对于复杂场景图片，情绪诱发的记忆增强并非单一的过程，而包含两个相反的现象：情绪信息既可能选择性地增强场景中具有情感色彩的中心记忆，并带来背景记忆的下降，诱发情绪记忆权衡效应；也可能同时增强中心和背景记忆，诱发情绪记忆拓宽效应。两种现象的发生取决于记忆信息特性（情绪效价、中心-背景联结程度）及记忆过程（编码、巩固和提取）相关的诸多因素，而其背后的机制仍未明晰。当前该领域存在情绪记忆权衡是否是一种不由注意所介导的自动化过程的争论，另有少数研究考察了与记忆权衡效应相关的脑网络，而针对记忆拓宽效应机制的研究仍较为匮乏。未来需从行为和神经层面，对比情绪诱发的记忆权衡与拓宽效应的发生机制，针对二者的自动化特性、涉及的记忆表征形式等问题深入研究，并将这些效应拓展至空间之外的维度，以系统揭示情绪信息选择性增强记忆现象背后的深层原因。     

Model for Short Term Movements in Stapelia variegata Linn

Recently it was demonstrated that holographic interferometry could be used to quantify minute displacements of a mature Stapelia variegata Linn. The previously unobtainable measurements revealed that the short term response of the stapelia was regular enough so that the dynamics could be evaluated through the use of a highly damped mass, spring, dashpot model. Such a model is derived explicitly and the relationship between movements of the entire plant and the dynamics of individual cells or groups of cells is shown.     

Colocalization of Multiple DNA Loci: A Physical Mechanism

A variety of important cellular processes require, for functional purposes, the colocalization of multiple DNA loci at specific time points. In most cases, the physical mechanisms responsible for bringing them in close proximity are still elusive. Here we show that the interaction of DNA loci with a concentration of diffusing molecular factors can induce spontaneously their colocalization, through a mechanism based on a thermodynamic phase transition. We consider up to four DNA loci and different valencies for diffusing molecular factors. In particular, our analysis illustrates that a variety of nontrivial stable spatial configurations is allowed in the system, depending on the details of the molecular factor/DNA binding-sites interaction. Finally, we discuss as a case study an application of our model to the pairing of X chromosome at X inactivation, one of the best-known examples of DNA colocalization. We also speculate on the possible links between X colocalization and inactivation.     

Having and Holding: Storage, Memory, Knowledge, and Social Relations

Starting from Giddens's concept of mutual knowledge, in this article I argue for an expanded definition of storage as a situated practice through which groups construct identity, remember, and control knowledge as part of a moral economy. Drawing on ethnographic and archaeological examples from a range of societies, including those of the Trobriand Islands, Neolithic Europe, and Mesoamerica, I consider the spatial and social meaning of utilitarian, household storage. Many of the social meanings embodied in utilitarian storage are found to also inform other kinds of storage, especially those categorized as burials and votive offerings, or caches, [storage, mutual knowledge, social memory, inalienable wealth, Mesoamerica]     

A Novel Whole-Cell Mechanism for Long-Term Memory Enhancement

Olfactory-discrimination learning was shown to induce a profound long-lasting enhancement in the strength of excitatory and inhibitory synapses of pyramidal neurons in the piriform cortex. Notably, such enhancement was mostly pronounced in a sub-group of neurons, entailing about a quarter of the cell population. Here we first show that the prominent enhancement in the subset of cells is due to a process in which all excitatory synapses doubled their strength and that this increase was mediated by a single process in which the AMPA channel conductance was doubled. Moreover, using a neuronal-network model, we show how such a multiplicative whole-cell synaptic strengthening in a sub-group of cells that form a memory pattern, sub-serves a profound selective enhancement of this memory. Network modeling further predicts that synaptic inhibition should be modified by complex learning in a manner that much resembles synaptic excitation. Indeed, in a subset of neurons all GABA_A-receptors mediated inhibitory synapses also doubled their strength after learning. Like synaptic excitation, Synaptic inhibition is also enhanced by two-fold increase of the single channel conductance. These findings suggest that crucial learning induces a multiplicative increase in strength of all excitatory and inhibitory synapses in a subset of cells, and that such an increase can serve as a long-term whole-cell mechanism to profoundly enhance an existing Hebbian-type memory. This mechanism does not act as synaptic plasticity mechanism that underlies memory formation but rather enhances the response of already existing memory. This mechanism is cell-specific rather than synapse-specific; it modifies the channel conductance rather than the number of channels and thus has the potential to be readily induced and un-induced by whole-cell transduction mechanisms.     

Short Term Morphine Exposure In Vitro Alters Proliferation and Differentiation of Neural Progenitor Cells and Promotes Apoptosis via Mu Receptors

Background

Chronic morphine treatment inhibits neural progenitor cell (NPC) progression and negatively effects hippocampal neurogenesis. However, the effect of acute opioid treatment on cell development and its influence on NPC differentiation and proliferation in vitro is unknown. We aim to investigate the effect of a single, short term exposure of morphine on the proliferation, differentiation and apoptosis of NPCs and the mechanism involved.

Methods

Cell cultures from 14-day mouse embryos were exposed to different concentrations of morphine and its antagonist naloxone for 24 hours and proliferation, differentiation and apoptosis were studied. Proliferating cells were labeled with bromodeoxyuridine (BrdU) and cell fate was studied with immunocytochemistry.

Results

Cells treated with morphine demonstrated decreased BrdU expression with increased morphine concentrations. Analysis of double-labeled cells showed a decrease in cells co-stained for BrdU with nestin and an increase in cells co-stained with BrdU and neuron-specific class III β-tubuline (TUJ1) in a dose dependent manner. Furthermore, a significant increase in caspase-3 activity was observed in the nestin- positive cells. Addition of naloxone to morphine-treated NPCs reversed the anti-proliferative and pro-apoptotic effects of morphine.

Conclusions

Short term morphine exposure induced inhibition of NPC proliferation and increased active caspase-3 expression in a dose dependent manner. Morphine induces neuronal and glial differentiation and decreases the expression of nestin- positive cells. These effects were reversed with the addition of the opioid antagonist naloxone. Our results demonstrate the effects of short term morphine administration on the proliferation and differentiation of NPCs and imply a mu-receptor mechanism in the regulation of NPC survival.