Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus [Microbiology]

人分泌型IgA的第四纪结构对流感病毒【微生物学】中和关系

Secretory IgA (S-IgA) antibodies, the major contributors to humoral mucosal immunity to influenza virus infection, are polymeric Igs present in many external secretions. In the present study, the quaternary structures of human S-IgA induced in nasal mucosa after administration of intranasal inactivated influenza vaccines were characterized in relation to neutralization...

[详细]

  • PNAS
  • 5年前
  • Biological Sciences

Neurons selective to the number of visual items in the corvid songbird endbrain [Neuroscience]

神经元选择性对乌鸦的鸣禽端脑[神经]视觉项目数

It is unknown whether anatomical specializations in the endbrains of different vertebrates determine the neuronal code to represent numerical quantity. Therefore, we recorded single-neuron activity from the endbrain of crows trained to judge the number of items in displays. Many neurons were tuned for numerosities irrespective of the physical appearance...

[详细]

  • PNAS
  • 5年前
  • Biological Sciences

Establishing task- and modality-dependent dissociations between the semantic and default mode networks [Psychological and Cognitive Sciences]

建立任务和方式的依赖性解离的语义和默认模式网络[心理和认知科学之间的]

The default mode network (DMN) and semantic network (SN) are two of the most extensively studied systems, and both are increasingly used as clinical biomarkers in neurological studies. There are strong theoretical reasons to assume a relationship between the networks, as well as anatomical evidence that they might rely on...

[详细]

  • PNAS
  • 5年前
  • Biological Sciences

Statistical learning and selective inference [Statistics]

统计学习和选择性推理[统计]

We describe the problem of “selective inference.” This addresses the following challenge: Having mined a set of data to find potential associations, how do we properly assess the strength of these associations? The fact that we have “cherry-picked”—searched for the strongest associations—means that we must set a higher bar for...

[详细]

  • PNAS
  • 5年前
  • Physical Sciences

Random sampling of skewed distributions implies Taylor's power law of fluctuation scaling [Statistics]

偏斜分布的随机抽样意味着波动尺度[统计]泰勒幂法则

Taylor’s law (TL), a widely verified quantitative pattern in ecology and other sciences, describes the variance in a species’ population density (or other nonnegative quantity) as a power-law function of the mean density (or other nonnegative quantity): Approximately, variance = a(mean)b, a > 0. Multiple mechanisms have been proposed to...

[详细]

  • PNAS
  • 5年前
  • Biological Sciences

Kinetics of protein-ligand unbinding via smoothed potential molecular dynamics simulations

通过把潜在的分子动力学模拟蛋白质配体解离动力学

Drug discovery is expensive and high-risk. Its main reasons of failure are lack of efficacy and toxicity of a drug candidate. Binding affinity for the biological target has been usually considered one of the most relevant figures of merit to judge a drug candidate along with bioavailability, selectivity and metabolic properties, which could depend on off-target interactions. Nevertheless, affinity does not always satisfactorily correlate with in vivo drug efficacy. It is indeed becoming increasingly evident that the time a drug spends in contact with its target (aka residence time) can be a more reliable figure of merit. Experimental kinetic measurements are operatively limited by the cost and the time needed to synthesize compounds to be tested, to express and purify the target, and to setup the assays. We present here a simple and efficient molecular-dynamics-based computational approach to prioritize compounds according to their residence time. We devised a multiple-replica scaled molecular dynamics protocol with suitably defined harmonic restraints to accelerate the unbinding events while preserving the native fold. Ligands are ranked according to the mean observed scaled unbinding time. The approach, trivially parallel and easily implementable, was validated against experimental information available on biological systems of pharmacological relevance.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

A predictive machine learning approach for microstructure optimization and materials design

预测的机器学习方法和材料微观组织优化设计

This paper addresses an important materials engineering question: How can one identify the complete space (or as much of it as possible) of microstructures that are theoretically predicted to yield the desired combination of properties demanded by a selected application? We present a problem involving design of magnetoelastic Fe-Ga alloy microstructure for enhanced elastic, plastic and magnetostrictive properties. While theoretical models for computing properties given the microstructure are known for this alloy, inversion of these relationships to obtain microstructures that lead to desired properties is challenging, primarily due to the high dimensionality of microstructure space, multi-objective design requirement and non-uniqueness of solutions. These challenges render traditional search-based optimization methods incompetent in terms of both searching efficiency and result optimality. In this paper, a route to address these challenges using a machine learning methodology is proposed. A systematic framework consisting of random data generation, feature selection and classification algorithms is developed. Experiments with five design problems that involve identification of microstructures that satisfy both linear and nonlinear property constraints show that our framework outperforms traditional optimization methods with the average running time reduced by as much as 80% and with optimality that would not be achieved otherwise.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Temperature-induced shifts in hibernation behavior in experimental amphibian populations

温度诱导实验两栖动物冬眠行为的转变

Phenological shifts are primary responses of species to recent climate change. Such changes might lead to temporal mismatches in food webs and exacerbate species vulnerability. Yet insights into this phenomenon through experimental approaches are still scarce, especially in amphibians, which are particularly sensitive to changing thermal environments. Here, under controlled warming conditions, we report a critical, but poorly studied, life-cycle stage (i.e., hibernation) in frogs inhabiting subtropical latitudes. Using outdoor mesocosm experiments, we examined the effects of temperature (ambient vs. + ~2.2/2.4 °C of pre-/post-hibernation warming) and food availability (normal vs. 1/3 food) on the date of entrance into/emergence from hibernation in Pelophylax nigromaculatus. We found temperature was the major factor determining the hibernation period, which showed a significant shortening under experimental warming (6–8 days), with delays in autumn and advances in spring. Moreover, the timing of hibernation was not affected by food availability, whereas sex and, particularly, age were key factors in the species’ phenological responses. Specifically, male individuals emerged from hibernation earlier, while older individuals also entered and emerged from hibernation earlier. We believe that this study provides some of the first experimental evidence for the effect of climate warming on the timing of amphibian hibernation.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Evidence for horizontal transfer of mitochondrial DNA to the plastid genome in a bamboo genus

对线粒体DNA在竹属植物叶绿体基因组水平转移的证据

In flowering plants, three genomes (nuclear, mitochondrial, and plastid) coexist and intracellular horizontal transfer of DNA is prevalent, especially from the plastid to the mitochondrion genome. However, the plastid genomes are generally conserved in evolution and have long been considered immune to foreign DNA. Recently, the opposite direction of DNA transfer from the mitochondrial to the plastid genome has been reported in two eudicot lineages. Here we sequenced 6 plastid genomes of bamboos, three of which are neotropical woody species and three are herbaceous ones. Several unusual features were found, including the duplication of trnT-GGU and loss of one copy of rps19 due to contraction of inverted repeats (IRs). The most intriguing was the ~2.7 kb insertion in the plastid IR regions in the three herbaceous bamboos. Furthermore, the insertion was documented to be horizontally transferred from the mitochondrial to the plastid genome. Our study provided evidence of the mitochondrial-to-plastid DNA transfer in the monocots, demonstrating again that this rare event does occur in other angiosperm lineages. However, the mechanism underlying the transfer remains obscure, and more studies in other plants may elucidate it in the future.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Reassortment and distinct evolutionary dynamics of Rift Valley Fever virus genomic segments

重组和裂谷热病毒基因组片段的不同的进化动力学

Rift Valley Fever virus (RVFV) is a member of Bunyaviridae family that causes a febrile disease affecting mainly ruminants and occasionally humans in Africa, with symptoms that range from mid to severe. RVFV has a tri-segmented ssRNA genome that permits reassortment and could generate more virulent strains. In this study, we reveal the importance of reassortment for RVFV evolution using viral gene genealogy inference and phylodynamics. We uncovered seven events of reassortment that originated RVFV lineages with discordant origins among segments. Moreover, we also found that despite similar selection regimens, the three segments have distinct evolutionary dynamics; the longer segment L evolves at a significant lower rate. Episodes of discordance between population size estimates per segment also coincided with reassortment dating. Our results show that RVFV segments are decoupled enough to have distinct demographic histories and to evolve under different molecular rates.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Zeno dynamics in quantum open systems

在量子开放系统的芝诺动力学

Quantum Zeno effect shows that frequent observations can slow down or even stop the unitary time evolution of an unstable quantum system. This effect can also be regarded as a physical consequence of the statistical indistinguishability of neighboring quantum states. The accessibility of quantum Zeno dynamics under unitary time evolution can be quantitatively estimated by quantum Zeno time in terms of Fisher information. In this work, we investigate the accessibility of quantum Zeno dynamics in quantum open systems by calculating noisy Fisher information when a trace preserving and completely positive map is assumed. We firstly study the consequences of non-Markovian noise on quantum Zeno effect and give the exact forms of the dissipative Fisher information and the quantum Zeno time. Then, for the operator-sum representation, an achievable upper bound of the quantum Zeno time is given with the help of the results in noisy quantum metrology. It is of significance that the noise reducing the accuracy in the entanglement-enhanced parameter estimation can conversely be favorable for the accessibility of quantum Zeno dynamics of entangled states.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Three-dimensional printing models improve understanding of spinal fracture—A randomized controlled study in China

三三维打印模型进一步了解脊柱骨折的随机对照研究在中国

Three-dimensional printing (3Dp) is being increasingly used in medical education. Although the use of such lifelike models is beneficial, well-powered, randomized studies supporting this statement are scarce. Two spinal fracture simulation models were generated by 3Dp. Altogether, 120 medical students (54.2% females) were randomized into three teaching module groups [two-dimensional computed tomography images (CT), 3D, or 3Dp] and asked to answer 10 key anatomical and 4 evaluative questions. Students in the 3Dp or 3D group performed significantly better than those in the CT group, although males in the 3D group scored higher than females. Students in the 3Dp group were the first to answer all questions, and there were no sex-related differences. Pleasure, assistance, effect, and confidence were more predominant in students in the 3Dp group than in those in the 3D and CT groups. This randomized study revealed that the 3Dp model markedly improved the identification of complex spinal fracture anatomy by medical students and was equally appreciated and comprehended by both sexes. Therefore, the lifelike fracture model made by 3Dp technology should be used as a means of premedical education.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Constructal thermodynamics combined with infrared experiments to evaluate temperature differences in cells

构造热力学结合红外实验评价细胞的温度差异

The aim of this work was to evaluate differences in energy flows between normal and immortalized cells when these distinct biological systems are exposed to environmental stimulation. These differences were considered using a constructal thermodynamic approach, and were subsequently verified experimentally. The application of constructal law to cell analysis led to the conclusion that temperature differences between cells with distinct behaviour can be amplified by interaction between cells and external fields. Experimental validation of the principle was carried out on two cellular models exposed to electromagnetic fields. By infrared thermography we were able to assess small changes in heat dissipation measured as a variation in cell internal energy. The experimental data thus obtained are in agreement with the theoretical calculation, because they show a different thermal dispersion pattern when normal and immortalized cells are exposed to electromagnetic fields. By using two methods that support and validate each other, we have demonstrated that the cell/environment interaction can be exploited to enhance cell behavior differences, in particular heat dissipation. We propose infrared thermography as a technique effective in discriminating distinct patterns of thermal dispersion and therefore able to distinguish a normal phenotype from a transformed one.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Phosphorylation of Pex11p does not regulate peroxisomal fission in the yeast Hansenula polymorpha

磷酸化的pex11p不规范的多形汉逊酵母中的过氧化物酶体分裂

Pex11p plays a crucial role in peroxisomal fission. Studies in Saccharomyces cerevisiae and Pichia pastoris indicated that Pex11p is activated by phosphorylation, which results in enhanced peroxisome proliferation. In S. cerevisiae but not in P. pastoris, Pex11p phosphorylation was shown to regulate the protein’s trafficking to peroxisomes. However, phosphorylation of PpPex11p was proposed to influence its interaction with Fis1p, another component of the organellar fission machinery. Here, we have examined the role of Pex11p phosphorylation in the yeast Hansenula polymorpha. Employing mass spectrometry, we demonstrate that HpPex11p is also phosphorylated on a Serine residue present at a similar position to that of ScPex11p and PpPex11p. Furthermore, through the use of mutants designed to mimic both phosphorylated and unphosphorylated forms of HpPex11p, we have investigated the role of this post-translational modification. Our data demonstrate that mutations to the phosphorylation site do not disturb the function of Pex11p in peroxisomal fission, nor do they alter the localization of Pex11p. Also, no effect on peroxisome inheritance was observed. Taken together, these data lead us to conclude that peroxisomal fission in H. polymorpha is not modulated by phosphorylation of Pex11p.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Quantifying the Number of Discriminable Coincident Dendritic Input Patterns through Dendritic Tree Morphology

量化判别一致的树突输入模式数通过树突树形态

Current developments in neuronal physiology are unveiling novel roles for dendrites. Experiments have shown mechanisms of non-linear synaptic NMDA dependent activations, able to discriminate input patterns through the waveforms of the excitatory postsynaptic potentials. Contextually, the synaptic clustering of inputs is the principal cellular strategy to separate groups of common correlated inputs. Dendritic branches appear to work as independent discriminating units of inputs potentially reflecting an extraordinary repertoire of pattern memories. However, it is unclear how these observations could impact our comprehension of the structural correlates of memory at the cellular level. This work investigates the discrimination capabilities of neurons through computational biophysical models to extract a predicting law for the dendritic input discrimination capability (M). By this rule we compared neurons from a neuron reconstruction repository (neuromorpho.org). Comparisons showed that primate neurons were not supported by an equivalent M preeminence and that M is not uniformly distributed among neuron types. Remarkably, neocortical neurons had substantially less memory capacity in comparison to those from non-cortical regions. In conclusion, the proposed rule predicts the inherent neuronal spatial memory gathering potentially relevant anatomical and evolutionary considerations about the brain cytoarchitecture.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

In-vivo detection of binary PKA network interactions upon activation of endogenous GPCRs

在二进制PKA网络互动对内源性GPCR激活体内检测

Membrane receptor-sensed input signals affect and modulate intracellular protein-protein interactions (PPIs). Consequent changes occur to the compositions of protein complexes, protein localization and intermolecular binding affinities. Alterations of compartmentalized PPIs emanating from certain deregulated kinases are implicated in the manifestation of diseases such as cancer. Here we describe the application of a genetically encoded Protein-fragment Complementation Assay (PCA) based on the Renilla Luciferase (Rluc) enzyme to compare binary PPIs of the spatially and temporally controlled protein kinase A (PKA) network in diverse eukaryotic model systems. The simplicity and sensitivity of this cell-based reporter allows for real-time recordings of mutually exclusive PPIs of PKA upon activation of selected endogenous G protein-coupled receptors (GPCRs) in cancer cells, xenografts of mice, budding yeast, and zebrafish embryos. This extends the application spectrum of Rluc PCA for the quantification of PPI-based receptor-effector relationships in physiological and pathological model systems.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

An integrated approach to reveal miRNAs’ impacts on the functional consequence of copy number alterations in cancer

一个综合的方法来揭示miRNA对肿瘤的拷贝数变化的功能性后果

Copy number alteration (CNA) is known to induce gene expression changes mainly through dosage effect, and therefore affect the initiation and progression of tumor. However, tumor samples exhibit heterogeneity in gene dosage sensitivity due to the complicated mechanisms of transcriptional regulation. Currently, no high-throughput method has been available for identifying the regulatory factors affecting the functional consequences of CNA, and determining their effects on cancer. In view of the important regulatory role of miRNA, we investigated the influence of miRNAs on the dosage sensitivities of genes within the CNA regions. By integrating copy number, mRNA expression, miRNA expression profiles of three kinds of cancer, we observed a tendency for high dosage-sensitivity genes to be more targeted by miRNAs in cancer, and identified the miRNAs regulating the dosage sensitivity of amplified/deleted target genes. The results show that miRNAs can modulate oncogenic biological functions by regulating the genes within the CNA regions, and thus play a role as a trigger or balancer in cancer, affecting cancer processes, even survival. This work provided a framework for analyzing the regulation of dosage effect, which will shed a light on understanding the oncogenic and tumor suppressive mechanisms of CNA. Besides, new cancer-related miRNAs were identified.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

dbEMT: an epithelial-mesenchymal transition associated gene resource

dbemt:上皮-间质转化相关基因资源

As a cellular process that changes epithelial cells to mesenchymal cells, Epithelial-mesenchymal transition (EMT) plays important roles in development and cancer metastasis. Recent studies on cancer metastasis have identified many new susceptibility genes that control this transition. However, there is no comprehensive resource for EMT by integrating various genetic studies and the relationship between EMT and the risk of complex diseases such as cancer are still unclear. To investigate the cellular complexity of EMT, we have constructed dbEMT (http://dbemt.bioinfo-minzhao.org/), the first literature-based gene resource for exploring EMT-related human genes. We manually curated 377 experimentally verified genes from literature. Functional analyses highlighted the prominent role of proteoglycans in tumor metastatic cascades. In addition, the disease enrichment analysis provides a clue for the potential transformation in affected tissues or cells in Alzheimer’s disease and Type 2 Diabetes. Moreover, the global mutation pattern of EMT-related genes across multiple cancers may reveal common cancer metastasis mechanisms. Our further reconstruction of the EMT-related protein-protein interaction network uncovered a highly modular structure. These results illustrate the importance of dbEMT to our understanding of cell development and cancer metastasis, and also highlight the utility of dbEMT for elucidating the functions of EMT-related genes.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Ionizing air affects influenza virus infectivity and prevents airborne-transmission

电离空气对流感病毒感染和防止空气传播

By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (>97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m3 room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Effect of papain-based gel on type I collagen - spectroscopy applied for microstructural analysis

影响木瓜蛋白酶基凝胶对I型胶原-光谱应用于微观结构分析

Considering the improvement of biomaterials that facilitate atraumatic restorative techniques in dentistry, a papain-based gel can be used in the chemomechanical removal of decayed dental tissue. However, there is no information regarding the influence of this gel on the structure of sound collagen. The aim of the present study was to investigate the adsorption of a papain-based gel (PapacarieTM) to collagen and determine collagen integrity after treatment. A pilot study was first performed with 10 samples of type I collagen membrane obtained from bovine Achilles deep tendon to compare the influence of hydration (Milli-Q water) on infrared bands of collagen. In a further experiment, 10 samples of type I collagen membrane were used to evaluate the effects of PapacarieTM on the collagen microstructure. All analyses were performed using the attenuated total reflectance technique of Fourier transform infrared (ATR-FTIR). The results demonstrated that the application of PapacarieTM does not lead to the degradation of collagen and this product can be safely used in minimally invasive dentistry. As the integrity of sound collagen is preserved after the application of the papain-based gel, this product is indicated for the selective removal of infected dentin, leaving the affected dentin intact and capable of re-mineralization.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Unsupervised segmentation of low-contrast multichannel images: discrimination of tissue components in microscopic images of unstained specimens

低对比度的多通道图像分割:在未染色标本的显微图像的组织成分的歧视

Low-contrast images, such as color microscopic images of unstained histological specimens, are composed of objects with highly correlated spectral profiles. Such images are very hard to segment. Here, we present a method that nonlinearly maps low-contrast color image into an image with an increased number of non-physical channels and a decreased correlation between spectral profiles. The method is a proof-of-concept validated on the unsupervised segmentation of color images of unstained specimens, in which case the tissue components appear colorless when viewed under the light microscope. Specimens of human hepatocellular carcinoma, human liver with metastasis from colon and gastric cancer and mouse fatty liver were used for validation. The average correlation between the spectral profiles of the tissue components was greater than 0.9985, and the worst case correlation was greater than 0.9997. The proposed method can potentially be applied to the segmentation of low-contrast multichannel images with high spatial resolution that arise in other imaging modalities.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

RNA metabolism: Methyladenosine promotes translation

翻译:甲基腺苷促进RNA代谢

N6-methyladenosine (m6A) is the most common eukaryotic internal mRNA modification. Wang et al. show that the m6A reader YTHDF1 promotes the translation of methylated mRNAs in human cells. Transcriptome-wide analyses indicated that YTHDF1 recognizes m6A on

[详细]

  • Nature Reviews Molecular Cell Biology 16, 390 (2015)
  • 5年前
  • Research Highlight

Splicing: Unmasking exitrons

拼接:揭露exitrons

Kalyna and colleagues characterized protein-coding exonic sequences that can undergo alternative splicing, which they termed exonic introns (exitrons; previously termed cryptic introns). They defined >1,000 exitrons in >3% of Arabidopsis thaliana coding genes, including in many genes annotated as intron-less, and found that they

[详细]

  • Nature Reviews Molecular Cell Biology 16, 390 (2015)
  • 5年前
  • Research Highlight

Techniques: microRNA switches to isolate specific cells

技术:microRNA开关隔离特定的细胞

For many cell types, no specific cell-surface markers that would facilitate their isolation have been identified. In this study, Miki et al. describe a method to isolate specific cell types on the basis of their endogenous microRNA (miRNA) activity. The authors designed 'miRNA switches',

[详细]

  • Nature Reviews Molecular Cell Biology 16, 391 (2015)
  • 5年前
  • Research Highlight