Narcolepsy: biogenic amine deficits in an animal model

Concentrations of biogenic amine metabolites in discrete brain areas differed significantly between dogs with genetically transmitted narcolepsy and age- and breed-matched controls. Dopamine and 3,4-dihydroxyphenylacetic acid were consistently elevated in the brains of narcoleptic animals, while homovanillic acid was not. Narcoleptic animals consistently exhibited lower utilization of dopamine and higher intraneuronal degradation of dopamine but no uniform decrease in serotonin utilization. Hence neuropathology appears to be associated with genetically transmitted canine narcolepsy. The data indicate a nonglobal depression of dopamine utilization or turnover or both.     

The chimpanzee as an animal model for investigating alcoholism

Young chimpanzees (Pan troglodytes) will accept ethanol in quantities sufficient to produce symptoms of withdrawal when ethanol is subsequently discontinued. Mild to severe symptoms of physical dependence, including grand mal seizures, are observed when ethanol is abruptly withdrawn after 6 to 10 weeks of chronic oral intake. In addition, the rate of disappearance of ethanol in blood increased during periods of chronic ingestion, an indication of developing metabolic tolerance. These results suggest that the young chimpanzee may be a suitable model for experimental studies of alcoholism.     

In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies

Infection with the obligate intracellular protozoan Leishmania is thought to be initiated by direct parasitization of macrophages, but the early events following transmission to the skin by vector sand flies have been difficult to examine directly. Using dynamic intravital microscopy and flow cytometry, we observed a rapid and sustained neutrophilic infiltrate at localized sand fly bite sites. Invading neutrophils efficiently captured Leishmania major (L.m.) parasites early after sand fly transmission or needle inoculation, but phagocytosed L.m. remained viable and infected neutrophils efficiently initiated infection. Furthermore, neutrophil depletion reduced, rather than enhanced, the ability of parasites to establish productive infections. Thus, L.m. appears to have evolved to both evade and exploit the innate host response to sand fly bite in order to establish and promote disease.     

Reticular stimulation and chlorpromazine: an animal model for schizophrenic overarousal

It has been postulated that certain schizophrenic patients are in a state of continual central excitation and that improvement in these patients after treatment with chlorpromazine is a result of the action of the drug in reducing this excitation. A model was developed to test this postulated state of central excitation. Rats were electrically stimulated in the mesencephalic reticular formation while performing a simple attention task. Stimulation or treatment with chlorpromazine impaired the performance of the animals; however, the two treatments together resulted in performance indistinguishable from that seen after injections of saline alone.     

Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment

The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.     

极度高甘油三脂高胆固醇血症动物模型的建立

建立高脂血症以及联合高脂血症和糖尿病的金黄地鼠模型,为深入研究高脂症在动脉粥样硬化和糖尿病合并动脉粥样硬化等疾病中的作用提供耗时短、效果稳定的动物模型。试验组金黄地鼠(90～110 g)连续3 d腹腔注射小剂量链脲佐菌素(STZ)(30 mg.kg-1)。于注射后9 d,检测空腹血糖,选择血糖大于200 mg.dL-1的个体,给予高脂饲料(HF),对照组同时给予普通饲料(chow)或高脂饲料(HF),检测4周血浆葡萄糖(Glu)、甘油三酯(TG)、总胆固醇(TC)等指标。结果表明,地鼠注射STZ后血糖升高并维持在300～400 mg·dL-1。在喂饲高脂饲料4周后,糖尿病高脂组血脂极度升高,TG达20 000 mg·dL-1,TC达4 500 mg·dL-1;不注射STZ组饲喂高脂饲料后TG和TC也明显升高至1 000 mg·dL-1左右。利用高脂饲喂或联合STZ注射的方法,可以成功制造出稳定的高脂血症以及联合糖尿病的金黄地鼠模型。     

The Chlamydomonas genome reveals the evolution of key animal and plant functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.     

Using Markov Decision Processes to define an adaptive strategy to control the spread of an animal disease

A strategy to control an animal disease within an area is often based on one or more actions systematically implemented. In this paper, we illustrate how to use a Markov Decision Process (MDP) to compute an adaptive strategy depending on the pathogen spread within a group of farmers with only one decision-maker for the group. The objective at the group level is to decrease the cost of the disease and its control. Status for each farm is assumed to be exactly known each year by the decision-maker. Possible actions each year are Doing nothing or Vaccinating. The computed MDP policy results in a non-systematic vaccination. Although the objective is only based on the total costs, the computed MDP policy reduces the prevalence, that is the amount of infected herds, compared to a systematically Doing nothing strategy.     

4D electron diffraction reveals correlated unidirectional behavior in zinc oxide nanowires

The confined electronic structure of nanoscale materials has increasingly been shown to induce behavior quite distinct from that of bulk analogs. Direct atomic-scale visualization of nanowires of zinc oxide was achieved through their unique pancake-type diffraction by using four-dimensional (4D) ultrafast electron crystallography. After electronic excitation of this wide-gap photonic material, the wires were found to exhibit colossal expansions, two orders of magnitude higher than that expected at thermal equilibrium; the expansion is highly anisotropic, a quasi-one-dimensional behavior, and is facilitated by the induced antibonding character. By reducing the density of nanowires, the expansions reach even larger values and occur at shorter times, suggesting a decrease of the structural constraint in transient atomic motions. This unanticipated ultrafast carrier-driven expansion highlights the optoelectronic consequences of nanoscale morphologies.     

基于姿态估计的动物行为识别研究进展

为分析姿态估计在动物行为识别和动物福利研究中的应用和发展潜力,本文以基于深度学习的姿态估计方法为突破口,从二维和三维空间的角度综述了动物姿态估计研究进展和方向,并介绍常见数据集与评价指标;然后整合基于姿态估计的动物行为识别相关研究成果,重点介绍关键点检测和行为分类的算法及其特征选取方式。姿态估计为动作识别和行为分析等研究提供了骨架信息和运动特征,成为动物行为识别和异常信息预警的非接触式监测方法。但由于受到训练数据集较少的限制,相对于人体姿态估计,动物姿态估计研究和发展速度相对较慢。因此,近年来利用跨域学习的方式来进一步提升其性能成为一种新兴手段。本综述为动物智能行为识别、动物福利研究以及智慧养殖等相关研究者扩展研究思路和研究方法。     

雌性食蟹猴去卵巢(OVX)诱导骨质疏松动物模型建立及评价

为了探索建立食蟹猴骨质疏松模型的可行性并评价阿仑膦酸钠(ALN)的治疗效果,将12只成年雌性食蟹猴随机分为卵巢切除(OVX)模型组、OVX阳性组、假手术(Sham)组。造模1个月后,OVX模型组和Sham组口服生理盐水(10 mL/周),OVX阳性组口服ALN(5 mg/周)。结果表明:OVX术后1个月,血清雌二醇(E2)水平较术前下降。OVX模型组血清骨代谢物骨特异性碱性磷酸酶(sALP)、I型胶原羧基末端肽(CTx-I)明显高于OVX阳性组和Sham组(P0.01)。OVX模型组骨密度(BMD)明显低于OVX阳性组和Sham组(P0.01)。骨组织形态计量学分析显示OVX模型组骨体积分数、骨小梁厚度及骨小梁数量均减少,骨小梁分离度增大,与OVX阳性组和Sham组相比差异有统计学意义(P0.05)。OVX阳性组的松质骨骨强度参数明显低于OVX模型组(P0.05)。以上结果表明,雌性食蟹猴去卵巢后因雌激素降低导致的骨质疏松,与人类临床上绝经后女性骨质疏松的各项指标相符。本研究成功建立了雌性食蟹猴去卵巢(OVX)后诱导建立骨质疏松动物模型,并通过经阿仑膦酸钠治疗效果的评价验证。此模型为研究绝经后骨质疏松发病机理、评价药物疗效等提供重要的基础。     

Isolation of mutants of an animal virus in bacteria

Mutants of animal viruses can be isolated in bacteria by recombinant DNA methods. Since no viral functions are required for propagation of recombinants in bacteria, viral mutants with lethal changes in cis- or trans-acting elements can be isolated, as well as partially or conditionally defective mutants. In the cases of viruses with small DNA genomes, such as the tumorigenic simian virus 40 (SV40), the entire viral DNA can be inserted into the bacterial plasmid pBR322 and cloned in Escherichia coli. Recombinant plasmids with a single copy of SV40 DNA cause morphological transformation of mouse cells in culture with the same efficiency as SV40 DNA isolated from virus-infected monkey cells, but the recombinant DNA is noninfectious and replicates poorly in permissive cells. However, SV40 DNA excised from the plasmid replicates as well as authentic viral DNA and is fully infectious. SV40 mutants with small deletions or base substitutions have been isolated by in vitro site-specific or random local mutagenesis of recombinant DNA followed by cloning in E. coli. Many of the mutants thus isolated are defective in specific viral functions.     

Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of PTP1B

Endoplasmic reticulum-localized protein-tyrosine phosphatase PTP1B terminates growth factor signal transduction by dephosphorylation of receptor tyrosine kinases (RTKs). But how PTP1B allows for RTK signaling in the cytoplasm is unclear. In order to test whether PTP1B activity is spatially regulated, we developed a method based on F?rster resonant energy transfer for imaging enzyme-substrate (ES) intermediates in live cells. We observed the establishment of a steady-state ES gradient across the cell. This gradient exhibited robustness to cell-to-cell variability, growth factor activation, and RTK localization, which demonstrated spatial regulation of PTP1B activity. Such regulation may be important for generating distinct cellular environments that permit RTK signal transduction and that mediate its eventual termination.     

Thermochronometry reveals headward propagation of erosion in an alpine landscape

Glacial erosion of mountain ranges produces spectacular alpine landscapes and, by linking climate with tectonics, influences a broad array of geophysical phenomena. Although the resultant landforms are easily identified, the timing and spatial pattern of topographic adjustment to Pleistocene glaciations remain poorly known. We investigated topographic evolution in the archetypal glacial landscape of Fiordland, New Zealand, using (U-Th)/He thermochronometry. We find that erosion during the past 2 million years removed the entire pre-Pleistocene landscape and fundamentally reshaped the topography. Erosion focused on steep valley segments and propagated from trunk valleys toward the heads of drainage basins, a behavior expected if subglacial erosion rate depends on ice sliding velocity. The Fiordland landscape illustrates complex effects of climate on Earth's surface morphology.