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Search results for: Cytoplasmic

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#34524872   2021/09/15 To Up

Ensconsin-dependent changes in microtubule organization and LINC complex-dependent changes in nucleus-nucleus interactions result in quantitatively distinct myonuclear positioning defects.

Nuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function. Although many genes that regulate nuclear movement have been identified, the mechanisms by which these genes act is not known. Using muscle development as a model system, and a combination of live-embryo microscopy and laser ablation of nuclei, we have found that clustered nuclei encompass at least two phenotypes that are caused by distinct mechanisms. Specifically, Ensconsin is necessary for productive force production to drive any movement of nuclei whereas Bocksbeutel and Klarsicht are necessary to form distinct populations of nuclei that move to different cellular locations. Mechanisitcally, Ensconsin regulates the number of growing microtubules that are used to move nuclei whereas Bocksbeutel and Klarsicht regulate interactions between nuclei. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].
Mary Ann Collins, L Alexis Coon, Riya Thomas, Torrey R Mandigo, Elizabeth Wynn, Eric S Folker

1136 related Products with: Ensconsin-dependent changes in microtubule organization and LINC complex-dependent changes in nucleus-nucleus interactions result in quantitatively distinct myonuclear positioning defects.

0.1mg100ug100ug100 ul100 ul50 ul50 ul

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#34524806   2021/09/15 To Up

Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy.

Cationic polymeric nanoformulations have been explored to increase the transfection efficiency of small molecules and nucleic acid-based drugs. However, an excessive positive charge density often leads to severe cell and tissue-based toxicity that restricts the clinical translation of cationic polymeric nanoformulations. Herein, we investigate a series of cationic poly(lactic--glycolic acid) (PLGA)-histidine-based nanoformulations for enhanced cytoplasmic delivery with minimal toxicity. PLGA/poly-l-histidine nanoparticles show promising physico-biochemical features and transfection efficiency in a series of in vitro and cell culture-based studies. Further, the use of acetone/dichloromethane as a solvent mixture during the formulation process significantly improves the morphology and size distribution of PLGA/poly-l-histidine nanoparticles. PLGA/poly-l-histidine nanoformulations undergo clathrin-mediated endocytosis. A contrast-matched small-angle neutron scattering experiment confirmed poly-l-histidine's distribution on the PLGA nanoformulations. PLGA/poly-l-histidine formulations containing paclitaxel as a small molecule-based drug and peptide nucleic acids targeting microRNA-155 as nucleic acid analog are efficacious in in vitro and in vivo studies. PLGA/poly-l-histidine NPs significantly decrease tumor growth in PNA-155 (∼6 fold) and paclitaxel (∼6.5 fold) treatment groups in a lymphoma cell line derived xenograft mice model without inducing any toxicity. Hence, PLGA/poly-l-histidine nanoformulations exhibit substantial transfection efficiency and are safe to deliver reagents ranging from small molecules to synthetic nucleic acid analogs and can serve as a novel platform for drug delivery.
Aniket Wahane, Shipra Malik, Kuo-Chih Shih, Ravinder Reddy Gaddam, Chaohao Chen, Yun Liu, Mu-Ping Nieh, Ajit Vikram, Raman Bahal

1442 related Products with: Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy.

96 tests

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#34524703   2021/09/15 To Up

Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses.

RNA viruses induce the formation of subcellular organelles that provide microenvironments conducive to their replication. Here we show that replication factories of rotaviruses represent protein-RNA condensates that are formed via liquid-liquid phase separation of the viroplasm-forming proteins NSP5 and rotavirus RNA chaperone NSP2. Upon mixing, these proteins readily form condensates at physiologically relevant low micromolar concentrations achieved in the cytoplasm of virus-infected cells. Early infection stage condensates could be reversibly dissolved by 1,6-hexanediol, as well as propylene glycol that released rotavirus transcripts from these condensates. During the early stages of infection, propylene glycol treatments reduced viral replication and phosphorylation of the condensate-forming protein NSP5. During late infection, these condensates exhibited altered material properties and became resistant to propylene glycol, coinciding with hyperphosphorylation of NSP5. Some aspects of the assembly of cytoplasmic rotavirus replication factories mirror the formation of other ribonucleoprotein granules. Such viral RNA-rich condensates that support replication of multi-segmented genomes represent an attractive target for developing novel therapeutic approaches.
Florian Geiger, Julia Acker, Guido Papa, Xinyu Wang, William E Arter, Kadi L Saar, Nadia A Erkamp, Runzhang Qi, Jack Pk Bravo, Sebastian Strauss, Georg Krainer, Oscar R Burrone, Ralf Jungmann, Tuomas Pj Knowles, Hanna Engelke, Alexander Borodavka

1926 related Products with: Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses.

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#34524512   2021/09/15 To Up

Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver.

Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression.
Eddie Wisse, Filip Braet, Gerald J Shami, Bartlomiej Zapotoczny, Celien Vreuls, Pauline Verhaegh, Peter Frederik, Peters J Peters, Steven Olde Damink, Ger Koek

2561 related Products with: Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver.

4 Sample Kit16 Arrays/Slide8 Sample Kit1.00 flask4 Sample Kit1.00 flask4 Arrays/Slide4 Membranes/Box96 tests8 Sample Kit4 Membranes/Box4 Sample Kit

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#34524078   2021/09/09 To Up

Comparison of the factors associated with the short-term prognosis between elderly and non-elderly patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective observational study.

The difference in factors associated with the prognosis between elderly and non-elderly patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is uncertain. We aimed to elucidate the clinical factors associated with the short-term prognosis (within 6 months from the start of the treatment) and investigate the differences in the associated factors between elderly and non-elderly individuals.
Makoto Harada, Akinori Yamaguchi, Kosuke Sonoda, Yosuke Yamada, Daiki Aomura, Yutaka Kamimura, Koji Hashimoto, Tohru Ichikawa, Mamoru Kobayashi, Yuji Kamijo

2238 related Products with: Comparison of the factors associated with the short-term prognosis between elderly and non-elderly patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective observational study.

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#34523975   2021/09/15 To Up

Grass Carp Reovirus VP56 Allies VP4, Recruits, Blocks, and Degrades RIG-I to More Effectively Attenuate IFN Responses and Facilitate Viral Evasion.

Grass carp reovirus (GCRV), the most virulent aquareovirus, causes epidemic hemorrhagic disease and tremendous economic loss in freshwater aquaculture industry. VP56, a putative fibrin inlaying the outer surface of GCRV-II and GCRV-III, is involved in cell attachment. In the present study, we found that VP56 localizes at the early endosome, lysosome, and endoplasmic reticulum, recruits the cytoplasmic viral RNA sensor retinoic acid-inducible gene I (RIG-I) and binds to it. The interaction between VP56 and RIG-I was detected by endogenous coimmunoprecipitation (co-IP), glutathione -transferase (GST) pulldown, and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) and was then confirmed by traditional co-IPs and a novel far-red mNeptune-based bimolecular fluorescence complementation system. VP56 binds to the helicase domain of RIG-I. VP56 enhances K48-linked ubiquitination of RIG-I to degrade it by the proteasomal pathway. Thus, VP56 impedes the initial immune function of RIG-I by dual mechanisms (blockade and degradation) and attenuates signaling from RIG-I recognizing viral RNA, subsequently weakening downstream signaling transduction and interferon (IFN) responses. Accordingly, host antiviral effectors are reduced, and cytopathic effects are increased. These findings were corroborated by RNA sequencing (RNA-seq) and VP56 knockdown. Finally, we found that VP56 and the major outer capsid protein VP4 bind together in the cytosol to enhance the degradation of RIG-I and more efficiently facilitate viral replication. Collectively, the results indicated that VP56 allies VP4, recruits, blocks, and degrades RIG-I, thereby attenuating IFNs and antiviral effectors to facilitate viral evasion more effectively. This study reveals a virus attacking target and an escaping strategy from host antiviral immunity for GCRV and will help understand mechanisms of infection of reoviruses. Grass carp reovirus (GCRV) fibrin VP56 and major outer capsid protein VP4 inlay and locate on the outer surface of GCRV-II and GCRV-III, which causes tremendous loss in grass carp and black carp industries. Fibrin is involved in cell attachment and plays an important role in reovirus infection. The present study identified the interaction proteins of VP56 and found that VP56 and VP4 bind to the different domains of the viral RNA sensor retinoic acid-inducible gene I (RIG-I) in grass carp to block RIG-I sensing of viral RNA and induce RIG-I degradation by the proteasomal pathway to attenuate signaling transduction, thereby suppressing interferons (IFNs) and antiviral effectors, facilitating viral replication. VP56 and VP4 bind together in the cytosol to more efficiently facilitate viral evasion. This study reveals a virus attacking a target and an escaping strategy from host antiviral immunity for GCRV and will be helpful in understanding the mechanisms of infection of reoviruses.
Hang Su, Zhiwei Liao, Chunrong Yang, Yongan Zhang, Jianguo Su

2852 related Products with: Grass Carp Reovirus VP56 Allies VP4, Recruits, Blocks, and Degrades RIG-I to More Effectively Attenuate IFN Responses and Facilitate Viral Evasion.

25 mg10 mg150μg10 500 MG100 µg50 mg200 ug100.00 ul25 mg96 wells (1 kit)

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#34523970   2021/09/15 To Up

The ORF45 protein of Kaposi Sarcoma-associated Herpesvirus (KSHV) is an inhibitor of p53 signaling during viral reactivation.

Kaposi Sarcoma-associated herpesvirus (KSHV) is a carcinogenic double-stranded DNA virus and the etiological agent of Kaposi's Sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's Disease (MCD). To prevent premature apoptosis and support its replication cycle, KSHV expresses a series of open reading frames (ORFs) that regulate signaling by the p53 tumor suppressor protein. Here we describe a novel viral inhibitor of p53 encoded by KSHV ORF45 and identify its mechanism of action. ORF45 binds to p53 and prevents its interactions with USP7, a p53 deubiquitinase. This results in decreased accumulation, localization of p53 to the cytoplasm, and diminished transcriptional activity. Unlike in other cancers, the tumor suppressor protein p53 is rarely mutated in Kaposi Sarcoma (KS). Rather, Kaposi Sarcoma-associated herpesvirus (KSHV) inactivates p53 through multiple viral proteins. One possible therapeutic approach to KS is the activation of p53, which would result in apoptosis and tumor regression. In this regard, it is important to understand all the mechanisms used by KSHV to modulate p53 signaling. This work describes a novel inhibitor of p53 signaling and a potential drug target, ORF45, and identifies the mechanisms of its action.
Dina Alzhanova, James O Meyo, Angelica Juarez, Dirk P Dittmer

2321 related Products with: The ORF45 protein of Kaposi Sarcoma-associated Herpesvirus (KSHV) is an inhibitor of p53 signaling during viral reactivation.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized

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#34523682   2021/09/15 To Up

Electrical polarity-dependent gating and a unique subconductance of RyR2 induced by S-adenosyl methionine via the ATP binding site.

S-Adenosyl-l-methionine (SAM) was used to probe the functional effects exerted via the RyR2 adenine nucleotide binding site. Single channel experiments revealed that SAM applied to the cytoplasmic face of RyR2 had complex voltage dependent effects on channel gating and conductance. At positive transmembrane holding potentials, SAM caused a striking reduction in channel openings and a reduced channel conductance. In contrast, at negative potentials SAM promoted a clearly resolved subconductance state. At membrane potentials between -75 and -25 mV the open probability of the subconductance state was independent of voltage. ATP, but not the non-adenosine based RyR activator 4-chloro-m-cresol interfered with the effects of SAM at both negative and positive potentials. This suggests that ATP and SAM interact with a common binding site. Molecular docking showed SAM bound to the adenine nucleotide-binding site and formed a hydrogen bond to Glu4886 in the C-terminal end of the S6 alpha helix. In this configuration SAM may alter the conformation of the RyR2 ion conduction pathway. This work provides novel insight into potential functional outcomes of ligand binding to the RyR adenine nucleotide binding site.
Angela J Kampfer, Edward M Balog

2667 related Products with: Electrical polarity-dependent gating and a unique subconductance of RyR2 induced by S-adenosyl methionine via the ATP binding site.

5 MG10 mg1000 TESTS/0.65ml1 mg10 mg100ul100ug/vial100ug Lyophilized100ug100ug Lyophilized100 µg100ug Lyophilized

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#34523043   2021/09/15 To Up

Octyl syringate is preferentially cytotoxic to cancer cells via lysosomal membrane permeabilization and autophagic flux inhibition.

The autophagy-mediated lysosomal pathway plays an important role in conferring stress tolerance to tumor cells during cellular stress such as increased metabolic demands. Thus, targeted disruption of this function and inducing lysosomal cell death have been proved to be a useful cancer therapeutic approach. In this study, we reported that octyl syringate (OS), a novel phenolic derivate, was preferentially cytotoxic to various cancer cells but was significantly less cytotoxic to non-transformed cells. Treatment with OS resulted in non-apoptotic cell death in a caspase-independent manner. Notably, OS not only enhanced accumulation of autophagic substrates, including lapidated LC3 and sequestosome-1, but also inhibited their degradation via an autophagic flux. In addition, OS destabilized the lysosomal function, followed by the intracellular accumulation of the non-digestive autophagic substrates such as bovine serum albumin and stress granules. Furthermore, OS triggered the release of lysosomal enzymes into the cytoplasm that contributed to OS-induced non-apoptotic cell death. Finally, we demonstrated that OS was well tolerated and reduced tumor growth in mouse xenograft models. Taken together, our study identifies OS as a novel anticancer agent that induces lysosomal destabilization and subsequently inhibits autophagic flux and further supports development of OS as a lysosome-targeting compound in cancer therapy. • Octyl syringate, a phenolic derivate, is preferentially cytotoxic to various cancer cells. • Octyl syringate destabilizes the lysosomal function. • Octyl syringate blocks the autophagic flux. • Octyl syringate is a potential candidate compound for cancer therapy.
Minho Won, Sunkyung Choi, Seonghye Cheon, Eun-Mi Kim, Taeg Kyu Kwon, Jaewhan Kim, Yong-Eun Kim, Kyung-Cheol Sohn, Gang Min Hur, Kee K Kim

2063 related Products with: Octyl syringate is preferentially cytotoxic to cancer cells via lysosomal membrane permeabilization and autophagic flux inhibition.

96T100|uI x 10 vials1 mg100ug/vial0.1ml (1.3mg/ml)1 mg200 ug1.5x10(6) cells100 ug/vial100ìl x 10 vials100 ug

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#34522823   2021/08/30 To Up

Isolation of Bovine leukemia virus from cows with persistent lymphocytosis in Iraq.

This is the first study to report on the isolation of bovine leukemia virus (BLV) from peripheral blood mononuclear cells of two cross bred cows in Iraq. The cattle were seropositive by ELISA when selected while being surveyed for the detection of BLV. Among six cows, two were cases of persistent lymphocytosis (PL). Cytopathology was characterized by the formation of multinucleated giant cells (syncytia) and cytoplasmic vacuoles. Moreover, the viruses produced clear plaques on the monolayer of the primary fetal calf kidney (FCK) cells. Inhibition of plaque formation by BLV-antisera suggested a diagnosis of BLV, which was further confirmed by PCR. Cells infected with the isolates were positive to a monoclonal antibody against the viral gp51 trans-membrane glycoprotein by immunocytochemistry. Both isolates replicated and induced cytopathic effects in bovine and human cell line cultures. Phylogenetic analysis based on partial gp51 gene sequences revealed that Iraqi strain highly homogenous with Turkey strain (100%) and had 1% distance value with other world strains. In conclusion, this present study found that BLV-infected cattle with PL can be a source for viral isolation, and the cytopathological features of the virus infection are arranged and differ depending on the cell type. This is the first study to report on the isolation of the EBL virus in Iraq, and it provides the basis for further studies about a BLV Iraqi strain that can help control this disease.
Yahia Ismail Khudhair, Ahmed Majeed Al-Shammari, Saleem Amin Hasso, Nahi Yaseen

2484 related Products with: Isolation of Bovine leukemia virus from cows with persistent lymphocytosis in Iraq.

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