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#32455006   2020/04/29 To Up

Argonaute proteins: Structural features, functions and emerging roles.

Argonaute proteins are highly conserved in almost all organisms. They not only involve in the biogenesis of small regulatory RNAs, but also regulate gene expression and defend against foreign pathogen invasion via small RNA-mediated gene silencing pathways. As a key player in these pathways, the abnormal expression and/or mis-modifications of Argonaute proteins lead to the disorder of small RNA biogenesis and functions, thus influencing multiply biological processes and disease development, especially cancer. In this review, we focus on the post-translational modifications and novel functions of Argonaute proteins in alternative splicing, host defense and genome editing.
Jin'en Wu, Jing Yang, William C Cho, Yadong Zheng

1964 related Products with: Argonaute proteins: Structural features, functions and emerging roles.

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#32454414   2020/05/19 To Up

Can we stop the long fusion at L5 for selected adult spinal deformity patients with less severe disability and less complex deformity?

It is controversial whether to stop the fusion at L5 or S1 in adult spinal deformity (ASD) surgery. Our hypothesis is that we can stop long fusion at L5 for selected patients with less severe disability and less complex deformity. Aim was to compare minimum 5-year outcomes between ASD patients with fusion to L5 versus S1.
Hiroshi Taneichi, Satoshi Inami, Hiroshi Moridaira, Daisaku Takeuchi, Tsuyoshi Sorimachi, Haruki Ueda, Hiromichi Aoki, Takuya Iimura

2570 related Products with: Can we stop the long fusion at L5 for selected adult spinal deformity patients with less severe disability and less complex deformity?

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#32453954   2020/05/26 To Up

Deciphering the Self-Cleavage Reaction Mechanism of Hairpin Ribozyme.

Hairpin ribozyme catalyzes the reversible self-cleavage of phosphodiester bonds which plays prominent roles in key biological processes involving RNAs. Despite impressive advances on ribozymatic self-cleavage, critical aspects of its molecular reaction mechanism remain controversially debated. Here, we generate and analyze the multi-dimensional free energy landscape that underlies the reaction using extensive QM/MM metadynamics simulations to investigate in detail the full self-cleavage mechanism. This allows us to answer several pertinent yet controversial questions concerning activation of the 2'-OH group, the mechanistic role of water molecules present in the active site and the full reaction pathway including the structures of transition states and intermediates. Importantly, we find that a sufficiently unrestricted reaction subspace must be mapped using accelerated sampling methods in order to compute the underlying free energy landscape. It is shown that lower-dimensional sampling where the bond formation and cleavage steps are coupled does not allow the system to sufficiently explore the landscape. Based on a three-dimensional free energy surface spanned by flexible generalized coordinates, we find that 2'-OH is indirectly activated by adjacent G8~nucleobase in conjunction with stabilizing H-bonding involving water. This allows the proton of the 2'-OH group to directly migrate toward the 5'-leaving group via a non-bridging oxygen of the phosphodiester link. At variance with similar enzymatic processes where water wires connected to protonable side chains of the protein matrix act as transient proton shuttles, no such de/reprotonation events of water molecules are found to be involved in this ribozymatic transesterification. Overall, our results support an acid-catalyzed reaction mechanism where A38 nucleobase directly acts as an acid whereas G8, in stark contrast, participates only indirectly via stabilizing the nascent nucleophile for subsequent attack. Moreover, we conclude that self-cleavage of hairpin ribozyme follows an A + D two-step associative pathway where the rate-determining step is the cleavage of the phosphodiester bond. These results provide a major advancement in our understanding of the unique catalytic mechanism of hairpin ribozyme which will fruitfully impact on the design of synthetic ribozymes.
Narendra Kumar, Dominik Marx

2836 related Products with: Deciphering the Self-Cleavage Reaction Mechanism of Hairpin Ribozyme.

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#32453410   2020/05/26 To Up

The regulatory effect of has-circ-0001146/miR-26a-5p/MNAT1 network on the proliferation and invasion of osteosarcoma.

Osteosarcoma is a malignant bone tumour with the lowest survival rates out of all paediatric cancers and is primarily diagnosed in children and adolescents. MNAT1 is a subunit in the cyclin-dependent kinase-activating kinase complex. Abnormal up-regulation of MNAT1 has been associated with the poor prognosis of multiple cancers. Bioinformatics analysis showed that has-circ-0001146 and miR-26a-5p were involved in the regulation of MNAT1 in osteosarcoma. This study investigated the regulatory effects of has-circ-0001146 and miR-26a-5p on MNAT1 expression using luciferase reporter and RNA-pull down assays. The effects of the has-circ-0001146/miR26a-5p/Mnat1 network on the proliferation and invasion of osteosarcoma were evaluated by cell viability, apoptosis, migration, and invasion assays. Osteosarcoma tissues showed higher MNAT1 and has-circ-0001146 expression than adjacent normal tissues, although the expression of MNAT1 was not significantly up-regulated in sarcomas according to TCGA databases. As indicated by luciferase reporter and RNA-pull down assays, miR-26a-5p was able to bind to both has-circ-0001146 and MNAT1 mRNA. The depletion of has-circ-0001146 as well as the increase of miR-26a-5p decreased MNAT1 expression in osteosarcoma cells, while the reduction of miR-26a-5p was associated with increased MNAT1 expression. These data suggested that has-circ-0001146 promoted MNAT1 expression by competitively binding to miR-26a-5p with MNAT1 mRNA. The depletion of has-circ-0001146 or MNAT1 or the increase of miR-26a-5p inhibited osteosarcoma cell viability and invasion, and increased apoptosis. Reduction of miR-26a-5p conversely promoted osteosarcoma cell viability and invasion. This study confirmed that has-circ-0001146 blocked miR-26a-5p targeting MNAT1 in osteosarcoma cells, thereby promoting the malignant behaviours of osteosarcoma cells.
Junjie Wang, Jiangdong Ni, Deye Song, Muliang Ding, Jun Huang, Wenzhao Li, Guangxu He

1387 related Products with: The regulatory effect of has-circ-0001146/miR-26a-5p/MNAT1 network on the proliferation and invasion of osteosarcoma.

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#32453136   2020/05/19 To Up

ADAM17-EGFR signaling contributes to oral cancer pain.

Cancer cells secrete pro-nociceptive mediators that sensitize adjacent sensory neurons and cause pain. Identification and characterization of these mediators could pinpoint novel targets for cancer pain treatment. In the present study we identified candidate genes in cancer cell lines that encode for secreted or cell surface proteins that may drive nociception. To undertake this work, we utilized an acute cancer pain mouse model, transcriptomic analysis of publicly available human tumor-derived cell line data, and a literature review. Cancer cell line supernatants were assigned a phenotype based on evoked nociceptive behavior in an acute cancer pain mouse model. We compared gene expression data from nociceptive and non-nociceptive cell lines. Our analyses revealed differentially expressed genes (DEGs) and pathways; many of the identified genes were not previously associated with cancer pain signaling. Epidermal growth factor receptor (EGFR) and disintegrin metalloprotease domain 17 (ADAM17) were identified as potential targets among the DEGs. We found that the nociceptive cell lines contained significantly more ADAM17 protein in the cell culture supernatant compared to non-nociceptive cell lines. Cytoplasmic EGFR was present in almost all (>90%) tongue primary afferent neurons in mice. Monoclonal antibody against EGFR, cetuximab, inhibited cell line supernatant-induced nociceptive behavior in an acute oral cancer pain mouse model. We infer from these data that ADAM17-EGFR signaling is involved in cancer mediator-induced nociception. The differentially expressed genes and their secreted protein products may serve as candidate therapeutic targets for oral cancer pain and warrant further evaluation.
Nicole N Scheff, Yi Ye, Zachary Conley, Jen Wui Quan, Yat Vong Ronald Lam, Richard Klares, Kamalpreet Singh, Brian L Schmidt, Bradley E Aouizerat

1839 related Products with: ADAM17-EGFR signaling contributes to oral cancer pain.

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#32452870   2020/05/22 To Up

An Update on Endocrine Mucin-producing Sweat Gland Carcinoma: Clinicopathologic Study of 63 Cases and Comparative Analysis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.
Meghana Agni, Meisha L Raven, Randy C Bowen, Nora V Laver, Patricia Chevez-Barrios, Tatyana Milman, Charles G Eberhart, Steven Couch, Daniel D Bennett, Daniel M Albert, R Nick Hogan, Paul O Phelps, Hillary Stiefel, Norberto Mancera, Martin Hyrcza, Ami Wang, Eric A Steele, Ashley A Campbell, Heather D Potter, Mark J Lucarelli

1535 related Products with: An Update on Endocrine Mucin-producing Sweat Gland Carcinoma: Clinicopathologic Study of 63 Cases and Comparative Analysis.



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#32452625   2020/05/26 To Up

Planar cell polarity governs the alignment of the nasopharyngeal epithelium in mammals.

Planar cell polarity (PCP) signalling specifies the orientation of epithelial cells and regulates directional beating of motile cilia of multiciliated epithelial cells. Clinically, defects in cilia function are associated with nasopharyngeal symptoms. The polarity of the nasopharyngeal epithelium is poorly understood. Here, we demonstrated PCP in the nasopharyngeal epithelium. Multiciliated cells were uniformly aligned with their long axis parallel to the tissue axis of the nasopharynx (NP). In addition, PCP proteins exhibited an asymmetrical localisation between adjacent cells. Motile cilia were uniformly aligned in the same direction within both individual cells and neighbouring cells, which manifested as cilial polarity in multiciliated cells. Mutation of Vangl2, a mammalian homologue of the Drosophila PCP gene, resulted in significant disruption of the orientation of epithelial cells. Finally, keratin-5-positive basal cells constantly replenished the luminal ciliated cells; the new dynamic ciliated cells were also oriented parallel to the tissue axis. These results indicate a role for the PCP pathway in the uniform orientation of dynamically replenished epithelial cells in the NP.
Wen-Wei Luo, Bin-Jun Chen, Yan-Mei Wang, Juan-Mei Yang, Xiang Liu, Ya-Sheng Yuan, Xi Lin, Fang-Lu Chi, Ping Chen, Dong-Dong Ren

2702 related Products with: Planar cell polarity governs the alignment of the nasopharyngeal epithelium in mammals.

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#32452538   2020/05/26 To Up

Nectin-2α is localized at cholinergic neuron dendrites and regulates synapse formation in the medial habenula.

The medial habenula (MHb) receives afferents from the triangular septum and the medial septal complex, projects efferents to the interpeduncular nucleus (IPN) in the midbrain to regulate dopamine and serotonin levels, and is implicated in stress, depression, memory, and nicotine withdrawal syndrome. We previously showed that the cell adhesion molecule nectin-2α is localized at the boundary between adjacent somata of clustered cholinergic neurons and regulates the voltage-gated A-type K channel Kv4.2 localization at membrane specializations in the MHb. This adhesion apparatus, named nectin-2α spots, is not associated with the nectin-binding protein afadin or any classic cadherins and their binding proteins p120-catenin and β-catenin. We showed here that nectin-2α was additionally localized at cholinergic neuron dendrites in synaptic regions of the MHb. The genetic ablation of nectin-2 reduced the number of synapses in the MHb without affecting their morphology. Nectin-2α was associated with afadin, cadherin-8, p120-catenin, β-catenin, and αN-catenin, forming puncta adherentia junctions (PAJs). Nectin-2α was observed in the IPN, but not in the triangular septum or the medial septal complex. The genetic ablation of nectin-2 did not affect synapse formation in the IPN. These results indicate that nectin-2α forms two types of adhesion apparatus in the MHb, namely nectin-2α spots at neighboring somata and PAJs at neighboring dendrites, and that dendritic PAJs regulate synapse formation in the MHb. This article is protected by copyright. All rights reserved.
Hajime Shiotani, Muneaki Miyata, Takeshi Kameyama, Kenji Mandai, Miwako Yamasaki, Masahiko Watanabe, Kiyohito Mizutani, Yoshimi Takai

2391 related Products with: Nectin-2α is localized at cholinergic neuron dendrites and regulates synapse formation in the medial habenula.

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#32452520   2020/05/25 To Up

Technical Note: Relationship between placentome location and gene expression in bovine pregnancy.

A novel, non-terminal surgical procedure to remove a single placentome from the pregnant ewe for gene expression and histological analyses was recently developed in our laboratory. This technique allows for evaluation of nutritional insults on placental development at more than one stage of gestation using a single animal. Early attempts to develop a similar technique in cattle were met with complications due to inaccessibility of the gravid uterine horn because of its location and mass. One alternative is to collect a placentome from the contralateral uterine horn: however, the question remains as to whether gene expression varies among placentomes based on location relative to the fetus. Pregnant heifers were maintained on forage during early gestation and later moved into pens with a Calan gate system (American Calan, Northwood, NH). On gestational day (GD) 158, five heifers were assigned to receive a hay-based diet formulated to meet 100% of NRC requirements, and five heifers were fed 70% of NRC requirements until necropsy on GD 244. At necropsy, a single representative placentome was selected for analysis from the antimesometrial side: 1) of the gravid uterine horn central to the amnion, 2) over the allantois immediately adjacent to the amnion, 3) in the tip of the gravid uterine horn, and 4) in the tip of the contralateral uterine horn. Mean placentome weight was greater (P<0.05) for locations central to the amnion and allantois compared to locations within the tips of the ipsilateral and contralateral horns, respectively. Gene expression for angiogenic factors (FGF2, ODC1, VEGFA,FLT1), nutrient transporters (SLC7A1, SLC2A1), and factors associated with hormone action (ESR1, IGF1, IGFBP3, CSH1,PAG1) were unaffected (P>0.05) by dietary treatment or location of the placentome. Results indicate that location of the placentome in relation to the fetus does not impact gene expression, enhancing the efficacy of non-terminal methodologies for sampling gene expression in placentomes.
Elizabeth M Picking, Levi A Trubenbach, Fuller W Bazer, Jason E Sawyer, Tryon A Wickersham, M Carey Satterfield

1870 related Products with: Technical Note: Relationship between placentome location and gene expression in bovine pregnancy.

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#32452283   2020/05/26 To Up

Presentation, Diagnostic Imaging, and Clinical Outcome of Conventional Ameloblastoma in Dogs.

A noninductive tumor of odontogenic epithelium occurs within the tooth bearing regions of the jaw in dogs and fits the conventional definition of ameloblastoma, which is distinct from, and less common than, canine acanthomatous ameloblastoma. In order to clarify the clinical and radiological features of this uncommon odontogenic tumor in dogs, we performed a retrospective study of 20 dogs that were diagnosed between 2007 and 2015. Follow-up information was obtained for 17 of 20 dogs. The study group of dogs showed no apparent age, breed, or gender predilection. Conventional ameloblastoma is typically slow growing, well demarcated, and locally destructive. Tumors most commonly occurred as a mass or focal bony swelling within the maxilla (13/20) or mandible (7/20). Based on cases with available diagnostic imaging, as either dental radiographs or computed tomographic images, the tumors were usually intraosseous and caused mixed lytic/proliferative bone changes. Nevertheless, conventional ameloblastomas did not aggressively infiltrate adjacent tissues and recurrence was not observed within the study group, even in patients with narrow surgical margins or treatment by cyst enucleation.
Jennifer Tjepkema, Cynthia M Bell, Jason W Soukup

1458 related Products with: Presentation, Diagnostic Imaging, and Clinical Outcome of Conventional Ameloblastoma in Dogs.



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