42 research outputs found

    Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.

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    Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability

    MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

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    MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGF , and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed

    MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

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    MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed

    Retrieval of Phytoplankton Pigment Composition from Their In Vivo Absorption Spectra

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    Algal pigment composition is an indicator of phytoplankton community structure that can be estimated from optical observations. Assessing the potential capability to retrieve different types of pigments from phytoplankton absorption is critical for further applications. This study investigated the performance of three models and the utility of hyperspectral in vivo phytoplankton absorption spectra for retrieving pigment composition using a large database (n = 1392). Models based on chlorophyll-a (Chl-a model), Gaussian decomposition (Gaussian model), and partial least squares (PLS) regression (PLS model) were compared. Both the Gaussian model and the PLS model were applied to hyperspectral phytoplankton absorption data. Statistical analysis revealed the advantages and limitations of each model. The Chl-a model performed well for chlorophyll-c (Chl-c), diadinoxanthin, fucoxanthin, photosynthetic carotenoids (PSC), and photoprotective carotenoids (PPC), with a median absolute percent difference for cross-validation (MAPDCV) CV < 43%). The performance of the PLS model was comparable to that of the Chl-a model, and it exhibited improved retrievals of chlorophyll-b, alloxanthin, peridinin, and zeaxanthin. Additional work undertaken with the PLS model revealed the prospects of hyperspectral-resolution data and spectral derivative analyses for retrieving marker pigment concentrations. This study demonstrated the applicability of in situ hyperspectral phytoplankton absorption data for retrieving pigment composition and provided useful insights regarding the development of bio-optical algorithms from hyperspectral and satellite-based ocean-colour observations

    Automated Functional Analysis of Astrocytes from Chronic Time-Lapse Calcium Imaging Data

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    Recent discoveries that astrocytes exert proactive regulatory effects on neural information processing and that they are deeply involved in normal brain development and disease pathology have stimulated broad interest in understanding astrocyte functional roles in brain circuit. Measuring astrocyte functional status is now technically feasible, due to recent advances in modern microscopy and ultrasensitive cell-type specific genetically encoded Ca2+ indicators for chronic imaging. However, there is a big gap between the capability of generating large dataset via calcium imaging and the availability of sophisticated analytical tools for decoding the astrocyte function. Current practice is essentially manual, which not only limits analysis throughput but also risks introducing bias and missing important information latent in complex, dynamic big data. Here, we report a suite of computational tools, called Functional AStrocyte Phenotyping (FASP), for automatically quantifying the functional status of astrocytes. Considering the complex nature of Ca2+ signaling in astrocytes and low signal to noise ratio, FASP is designed with data-driven and probabilistic principles, to flexibly account for various patterns and to perform robustly with noisy data. In particular, FASP explicitly models signal propagation, which rules out the applicability of tools designed for other types of data. We demonstrate the effectiveness of FASP using extensive synthetic and real data sets. The findings by FASP were verified by manual inspection. FASP also detected signals that were missed by purely manual analysis but could be confirmed by more careful manual examination under the guidance of automatic analysis. All algorithms and the analysis pipeline are packaged into a plugin for Fiji (ImageJ), with the source code freely available online at https://github.com/VTcbil/FASP

    Application of plantaricin Q7 in the storage and preservation of milk

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    Plantaricin Q7 is a bacteriocin produced by Lactobacillus plantarum Q7 with broad-spectrum antibacterial activity.It has the advantages of safety,high efficiency and good stability.In this study,plantaricin Q7 with a titer of 533 AU·mL-1 was added to milk to explore its preservation effects in the process of milk storage.The result showed that plantaricin Q7 maintained the good sense of milk.There was no peculiar smell on the 13th day of storage,and the milk remained white and slightly yellow,without stratification and precipitation.Pseudomonas fluorescens was the dominant psychrophilic spoilage bacteria in milk.Without adding plantaricin Q7,the number of P.fluorescens in milk exceeded the national standard on the 7th day.After adding plantaricin Q7,the time of P. fluorescens exceeding the national standard was postponed for 4 days.Plantaricin Q7 effectively slowed down the increase of milk acidity and the decrease of milk pH value.The results provided a basis for the development and application of plantaricin Q7
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