In Vivo Dynamic-Clamp Manipulation of Extrinsic and Intrinsic Conductances: Functional Roles of Shunting Inhibition and I BK in Rat and Cat Cortex

Dynamic-Clamp ◽  
2009 ◽  
pp. 141-163 ◽  
Author(s):  
Lyle J. Graham ◽  
Adrien Schramm
Keyword(s):  
Dynamic Clamp ◽  
Functional Roles ◽  
Shunting Inhibition

scholarly journals Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Haoting Sun ◽  
Chaoqun Wang ◽  
Beiyuan Hu ◽  
Xiaomei Gao ◽  
Tiantian Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Tumor Metastasis ◽  
Metastatic Potential ◽  
Functional Roles ◽  
Stat3 Phosphorylation ◽  
Hcc Cells

AbstractIntercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

scholarly journals CoBold: a method for identifying different functional classes of transient RNA structure features that can impact RNA structure formation in vivo

2020 ◽  
Author(s):  
Adrián López Martín ◽  
Mohamed Mounir ◽  
Irmtraud M Meyer
Keyword(s):  
Structure Formation ◽  
Rna Structure ◽  
Rna Secondary Structure ◽  
Computational Method ◽  
Data Visualisation ◽  
Multiple Sequence ◽  
Functional Roles ◽  
Functional Classes ◽  
The Given

Abstract RNA structure formation in vivo happens co-transcriptionally while the transcript is being made. The corresponding co-transcriptional folding pathway typically involves transient RNA structure features that are not part of the final, functional RNA structure. These transient features can play important functional roles of their own and also influence the formation of the final RNA structure in vivo. We here present CoBold, a computational method for identifying different functional classes of transient RNA structure features that can either aid or hinder the formation of a known reference RNA structure. Our method takes as input either a single RNA or a corresponding multiple-sequence alignment as well as a known reference RNA secondary structure and identifies different classes of transient RNA structure features that could aid or prevent the formation of the given RNA structure. We make CoBold available via a web-server which includes dedicated data visualisation.

scholarly journals 220- and 130-kDa MLCKs have distinct tissue distributions and intracellular localization patterns

2002 ◽  
Vol 282 (3) ◽  
pp. C451-C460 ◽  
Author(s):  
Emily K. Blue ◽  
Zoe M. Goeckeler ◽  
Yijun Jin ◽  
Ling Hou ◽  
Shelley A. Dixon ◽  
...  
Keyword(s):  
Intracellular Trafficking ◽  
Myosin Light Chain ◽  
Adult Mouse ◽  
Intracellular Localization ◽  
Myosin Ii ◽  
Nonmuscle Myosin ◽  
Functional Roles ◽  
Nonmuscle Myosin Ii ◽  
Mouse Tissues

To better understand the distinct functional roles of the 220- and 130-kDa forms of myosin light chain kinase (MLCK), expression and intracellular localization were determined during development and in adult mouse tissues. Northern blot, Western blot, and histochemical studies show that the 220-kDa MLCK is widely expressed during development as well as in several adult smooth muscle and nonmuscle tissues. The 130-kDa MLCK is highly expressed in all adult tissues examined and is also detectable during embryonic development. Colocalization studies examining the distribution of 130- and 220-kDa mouse MLCKs revealed that the 130-kDa MLCK colocalizes with nonmuscle myosin IIA but not with myosin IIB or F-actin. In contrast, the 220-kDa MLCK did not colocalize with either nonmuscle myosin II isoform but instead colocalizes with thick interconnected bundles of F-actin. These results suggest that in vivo, the physiological functions of the 220- and 130-kDa MLCKs are likely to be regulated by their intracellular trafficking and distribution.

scholarly journals A review on the bio-functional roles of phospholipids from marine resources

Food Research ◽  
2021 ◽  
Vol 5 (5) ◽  
pp. 1-16
Author(s):  
M. Haq ◽  
S. Suraiya
Keyword(s):  
Synergistic Effects ◽  
Chemical Properties ◽  
Functional Roles ◽  
Functional Activities ◽  
Marine Phospholipids ◽  
Liver Functions ◽  
Anti Inflammatory ◽  
Unique Chemical

Marine phospholipids (PLs) rich in ω-3 polyunsaturated fatty acids (ω-3 PUFAs) have drawn keen interest recently among researchers and consumers and could be assumed as a “miracle drug”. Substantial amount of EPA and DHA, amazing and unique chemical properties and super bio-functional activities of marine PLs make it superior compared to terrestrial PLs, which lack long chain ω-3 PUFAs. Many comparative studies revealed that marine PLs showed higher health beneficial activities compared to PLs obtained from land sources. Marine PLs are not only beneficial in containing a high amount of ω-3 PUFAs but also in absorbing and assimilating ω-3 PUFAs in different tissues. Synergistic effects of PL compounds and ω-3 PUFAs in marine PLs showed super bio-functional performances like anti-atherosis and cardioprotective, anti-inflammatory, neuroprotective, immunological, and liver functions. A number of in vivo and in vitro studies on the administration of marine PLs extracted from fishes, mollusks, crustaceans, echinoderms reduced triacylglycerol (TAG) level and enhanced cardioprotective functions, demonstrated anti-inflammatory activity, reduced cell proliferation and tumor, increased cognitive functions and memory, and prevented hepatic damages. Therefore, this review paper provides detailed accounts on the present research status of critical biological and nutritional functions of marine ω-3 PUFAs rich phospholipids focusing on the origin, animal models, treatment, and roles.

scholarly journals Differential FSH Glycosylation Modulates FSHR Oligomerization and Subsequent cAMP Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Uchechukwu T. Agwuegbo ◽  
Emily Colley ◽  
Anthony P. Albert ◽  
Viktor Y. Butnev ◽  
George R. Bousfield ◽  
...  
Keyword(s):  
Super Resolution ◽  
Hek293 Cells ◽  
Camp Signaling ◽  
Camp Production ◽  
Functional Roles ◽  
Menopausal Women ◽  
Resolution Imaging ◽  
Post Menopausal

Follicle-stimulating hormone (FSH) and its target G protein-coupled receptor (FSHR) are essential for reproduction. Recent studies have established that the hypo-glycosylated pituitary FSH glycoform (FSH21/18), is more bioactive in vitro and in vivo than the fully-glycosylated variant (FSH24). FSH21/18 predominates in women of reproductive prime and FSH24 in peri-post-menopausal women, suggesting distinct functional roles of these FSH glycoforms. The aim of this study was to determine if differential FSH glycosylation modulated FSHR oligomerization and resulting impact on cAMP signaling. Using a modified super-resolution imaging technique (PD-PALM) to assess FSHR complexes in HEK293 cells expressing FSHR, we observed time and concentration-dependent modulation of FSHR oligomerization by FSH glycoforms. High eFSH and FSH21/18 concentrations rapidly dissociated FSHR oligomers into monomers, whereas FSH24 displayed slower kinetics. The FSHR β-arrestin biased agonist, truncated eLHβ (Δ121-149) combined with asparagine56-deglycosylated eLHα (dg-eLHt), increased FSHR homomerization. In contrast, low FSH21/18 and FSH24 concentrations promoted FSHR association into oligomers. Dissociation of FSHR oligomers correlated with time points where higher cAMP production was observed. Taken together, these data suggest that FSH glycosylation may modulate the kinetics and amplitude of cAMP production, in part, by forming distinct FSHR complexes, highlighting potential avenues for novel therapeutic targeting of the FSHR to improve IVF outcomes.

scholarly journals The STAGA Subunit ADA2b Is an Important Regulator of Human GCN5 Catalysis

2008 ◽  
Vol 29 (1) ◽  
pp. 266-280 ◽  
Author(s):  
Armin M. Gamper ◽  
Jaehoon Kim ◽  
Robert G. Roeder
Keyword(s):  
Saga Complex ◽  
Histone Tails ◽  
Functional Roles ◽  
Enzymatic Function ◽  
Core Histones ◽  
Human Proteins ◽  
Important Regulator ◽  
And Function

ABSTRACT Human STAGA is a multisubunit transcriptional coactivator containing the histone acetyltransferase GCN5L. Previous studies of the related yeast SAGA complex have shown that the yeast Gcn5, Ada2, and Ada3 components form a heterotrimer that is important for the enzymatic function of SAGA. Here, we report that ADA2a and ADA2b, two human homologues of yeast Ada2, each have the ability to form a heterotrimer with ADA3 and GCN5L but that only the ADA2b homologue is found in STAGA. By comparing the patterns of acetylation of several substrates, we found context-dependent requirements for ADA2b and ADA3 for the efficient acetylation of histone tails by GCN5. With human proteins, unlike yeast proteins, the acetylation of free core histones by GCN5 is unaffected by ADA2b or ADA3. In contrast, the acetylation of mononucleosomal substrates by GCN5 is enhanced by ADA2b, with no significant additional effect of ADA3, and the efficient acetylation of nucleosomal arrays (chromatin) by GCN5 requires both ADA2b and ADA3. Thus, ADA2b and ADA3 appear to act at two different levels of histone organization within chromatin to facilitate GCN5 function. Interestingly, although ADA2a forms a complex(es) with GCN5 and ADA3 both in vitro and in vivo, ADA2a-containing complexes are unable to acetylate nucleosomal H3. We have also shown the preferential recruitment of ADA2b, relative to ADA2a, to p53-dependent genes. This finding indicates that the previously demonstrated presence and function of GCN5 on these promoters reflect the action of STAGA and that the ADA2a and ADA2b paralogues have nonredundant functional roles.

Glycan Labeling and Analysis in Cells and In Vivo

2021 ◽  
Vol 14 (1) ◽  
pp. 363-387
Author(s):  
Bo Cheng ◽  
Qi Tang ◽  
Che Zhang ◽  
Xing Chen
Keyword(s):  
Chemical Modification ◽  
Biological Function ◽  
Biological Processes ◽  
Affinity Tags ◽  
Functional Roles ◽  
Antibody Conjugates ◽  
Living Organisms ◽  
In Cells

As one of the major types of biomacromolecules in the cell, glycans play essential functional roles in various biological processes. Compared with proteins and nucleic acids, the analysis of glycans in situ has been more challenging. Herein we review recent advances in the development of methods and strategies for labeling, imaging, and profiling of glycans in cells and in vivo. Cellular glycans can be labeled by affinity-based probes, including lectin and antibody conjugates, direct chemical modification, metabolic glycan labeling, and chemoenzymatic labeling. These methods have been applied to label glycans with fluorophores, which enables the visualization and tracking of glycans in cells, tissues, and living organisms. Alternatively, labeling glycans with affinity tags has enabled the enrichment of glycoproteins for glycoproteomic profiling. Built on the glycan labeling methods, strategies enabling cell-selective and tissue-specific glycan labeling and protein-specific glycan imaging have been developed. With these methods and strategies, researchers are now better poised than ever to dissect the biological function of glycans in physiological or pathological contexts.

scholarly journals Exploring In Vivo Dynamics of Bovine Milk Derived Gangliosides

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 711
Author(s):  
Welma Stonehouse ◽  
Bradley Klingner ◽  
Paul McJarrow ◽  
Bertram Fong ◽  
Nathan O’Callaghan
Keyword(s):  
Bovine Milk ◽  
Storage Conditions ◽  
Sample Type ◽  
Acute Effects ◽  
Fasting Serum ◽  
Functional Roles ◽  
Fasted State ◽  
Habitual Diet ◽  
Overnight Fasting

Gangliosides are glycosphingolipids present in mammalian cell membranes, playing important structural and functional roles. Human studies on the health benefits of gangliosides are increasing, but knowledge gaps regarding ganglioside analysis exist. The study aimed to investigate blood sample type (serum/plasma), storage conditions, diurnal, day-to-day variation and acute effects of consuming bovine-derived gangliosides on circulating monosialylated gangliosides. Seventy-one women (18–40 yrs, 20–≤30.0 kg/m2) were enrolled and 61 completed the intervention. They visited the clinic three times following overnight fasting. Serum/plasma gangliosides were analyzed over 2 h (visit-1), 8 h (visit-2) and 8 h following either zero or high ganglioside meals (visit-3). Samples stored at −20 °C and −70 °C were analyzed at 3-, 6-, 12- and 18-months. Plasma and serum GM3-gangliosides did not differ, plasma GM3 did not change diurnally, from day-to-day, in response to a high vs. low ganglioside meal or after 7-days low ganglioside vs. habitual diet (P > 0.05). GM3 concentrations were lower in samples stored at −70 °C vs. −20 °C from 6-months onwards and decreased over time with lowest levels at 12- and 18-months stored at −70 °C. In conclusion, either serum/plasma stored at −20- or −70 °C for up to 6 months, are acceptable for GM3-ganglioside analysis. Blood samples can be collected at any time of the day and participants do not have to be in the fasted state.

Dynamic Clamp with High-Resistance Electrodes Using Active Electrode Compensation In Vitro and In Vivo

Dynamic-Clamp ◽  
2009 ◽  
pp. 347-382
Author(s):  
Romain Brette ◽  
Zuzanna Piwkowska ◽  
Cyril Monier ◽  
José Francisco ◽  
Gómez González ◽  
...  
Keyword(s):  
High Resistance ◽  
Dynamic Clamp ◽  
Active Electrode

scholarly journals The Beneficial Effects of Morusin, an Isoprene Flavonoid Isolated from the Root Bark of Morus

2020 ◽  
Vol 21 (18) ◽  
pp. 6541
Author(s):  
Dong Wook Choi ◽  
Sang Woo Cho ◽  
Seok-Geun Lee ◽  
Cheol Yong Choi
Keyword(s):  
Inflammatory Diseases ◽  
Root Bark ◽  
Biological Processes ◽  
Functional Roles ◽  
Beneficial Effects ◽  
Biochemical Identification ◽  
Underlying Mechanisms ◽  
Clinical Potential

The root bark of Morus has long been appreciated as an antiphlogistic, diuretic and expectorant drug in Chinese herbal medicine, albeit with barely known targets and mechanisms of action. In the 1970s, the development of analytic chemistry allowed for the discovery of morusin as one of 7 different isoprene flavonoid derivatives in the root bark of Morus. However, the remarkable antioxidant capacity of morusin with the unexpected potential for health benefits over the other flavonoid derivatives has recently sparked scientific interest in the biochemical identification of target proteins and signaling pathways and further clinical relevance. In this review, we discuss recent advances in the understanding of the functional roles of morusin in multiple biological processes such as inflammation, apoptosis, metabolism and autophagy. We also highlight recent in vivo and in vitro evidence on the clinical potential of morusin treatment for multiple human pathologies including inflammatory diseases, neurological disorders, diabetes, cancer and the underlying mechanisms.

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