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K C Zhang, L Chen
Different proficiency in minimally invasive surgery has great impact on efficacy of minimally invasive surgery. Therefore, great importance should be attached to the standardization of minimally invasive surgery. Accurate preoperative staging plays a prerequisite role which emphasizes multiple diagnostic strategies. Precise intraoperative procedure plays an essential role which should be performed according to the evidence-based expert consensus and guideline. Standardized postoperative management plays a crucial role which includes ex vivo lymph node dissection, registry of complication and follow-up and establishment of medical database...
April 1, 2018: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
Patrick McGillivray, Russell Ault, Mayur Pawashe, Robert Kitchen, Suganthi Balasubramanian, Mark Gerstein
Upstream open reading frames (uORFs) latent in mRNA transcripts are thought to modify translation of coding sequences by altering ribosome activity. Not all uORFs are thought to be active in such a process. To estimate the impact of uORFs on the regulation of translation in humans, we first circumscribed the universe of all possible uORFs based on coding gene sequence motifs and identified 1.3 million unique uORFs. To determine which of these are likely to be biologically relevant, we built a simple Bayesian classifier using 89 attributes of uORFs labeled as active in ribosome profiling experiments...
March 19, 2018: Nucleic Acids Research
Jade-Emmanuelle Deshaies, Lulzim Shkreta, Alexander J Moszczynski, Hadjara Sidibé, Sabrina Semmler, Aurélien Fouillen, Estelle R Bennett, Uriya Bekenstein, Laurie Destroismaisons, Johanne Toutant, Quentin Delmotte, Kathryn Volkening, Stéphanie Stabile, Anaïs Aulas, Yousra Khalfallah, Hermona Soreq, Antonio Nanci, Michael J Strong, Benoit Chabot, Christine Vande Velde
The RNA binding proteins TDP-43 (encoded by TARDBP) and hnRNP A1 (HNRNPA1) are each mutated in certain amyotrophic lateral sclerosis cases and are often mislocalized in cytoplasmic aggregates within motor neurons of affected patients. Cytoplasmic inclusions of TDP-43, which are accompanied by a depletion of nuclear TDP-43, are observed in most amyotrophic lateral sclerosis cases and nearly half of frontotemporal dementia cases. Here, we report that TDP-43 binds HNRNPA1 pre-mRNA and modulates its splicing, and that depletion of nuclear TDP-43 results in increased inclusion of a cassette exon in the HNRNPA1 transcript, and consequently elevated protein levels of an isoform containing an elongated prion-like domain, referred to as hnRNP A1B...
March 19, 2018: Brain: a Journal of Neurology
Haijun Xiao, Yanghong Xu, Chenzi Ni, Qiannan Zhang, Feiya Zhong, Jishuai Huang, Wei Liu, Leilei Peng, Yingguo Zhu, Jun Hu
In flowering plants, various RNA editing events occur in the mitochondria and chloroplasts as part of post-transcriptional processes. Although several PPRs and MORFs have been identified as RNA editing factors, the underlying mechanism of PPRs and the cooperation among these proteins are still obscure. Here, we identified a rice dual-localized PPR protein, OsPGL1. The loss of function of OsPGL1 resulted in defects in both chloroplast RNA editing of ndhD-878 and mitochondrial RNA editing of ccmFc-543, both of which could be restored via complementary validation...
March 17, 2018: Journal of Experimental Botany
Carlos A Campos, Anna J Bowen, Carolyn W Roman, Richard D Palmiter
Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calcium transients in vivo from individual neurons in mice, we show that most CGRPPBN neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). The same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating...
March 21, 2018: Nature
Veronica Mendoza-Reinoso, Annemiek Beverdam
The skin constantly self-renews throughout adult life. Wnt/β-catenin signaling plays a key role in promoting keratinocyte proliferation in the hair follicles and in the interfollicular epidermis. A recent report demonstrated that epidermal YAP activity drives β-catenin activation to promote keratinocyte proliferation in the murine skin. However, it remains unclear whether this is caused by paracrine activation of canonical Wnt signaling or through other YAP/β-catenin regulatory interactions. In the present study, we found that XAV939-inhibition of canonical WNT signaling in skin of YAP2-5SA-ΔC mice resulted in diminished β-catenin activation, reduced keratinocyte proliferation, and a mitigation of the hyperplastic abnormalities in the interfollicular epidermis, signifying a canonical WNT ligand-dependent mechanism...
March 10, 2018: Stem Cell Research
Yasir Mohamud, Junyan Shi, Junyan Qu, Tak Poon, Yuan Chao Xue, Haoyu Deng, Jingchun Zhang, Honglin Luo
Picornaviruses have evolved to hijack host cellular machinery, including the autophagic pathway. However, the mechanisms remain largely unclear. We use coxsackievirus B3 (CVB3) as a model organism to explore the possible role of picornavirus subversion of the autophagic pathway in viral infection. Our in vivo and in vitro experiments demonstrate that CVB3 infection causes a significant, albeit incomplete, inhibition of autophagic flux by limiting the fusion of autophagosomes with lysosomes and/or late endosomes...
March 20, 2018: Cell Reports
Kathrin Theil, Margareta Herzog, Nikolaus Rajewsky
In mRNA sequences, 3' UTRs are thought to contain most elements that specifically regulate localization, turnover, and translation. Although high-throughput experiments indicate that many RNA-binding proteins (RBPs) also bind 5' UTRs, much less is known about specific post-transcriptional control exerted by 5' UTRs. GLD-1 is a conserved RBP and a translational repressor with essential roles in Caenorhabditis elegans germ cell development. Previously, we showed that GLD-1 binds highly conserved sites in both 3' and 5' UTRs...
March 20, 2018: Cell Reports
Jennifer F Knight, Vanessa Y C Sung, Elena Kuzmin, Amber L Couzens, Danielle A de Verteuil, Colin D H Ratcliffe, Paula P Coelho, Radia M Johnson, Payman Samavarchi-Tehrani, Tina Gruosso, Harvey W Smith, Wontae Lee, Sadiq M Saleh, Dongmei Zuo, Hong Zhao, Marie-Christine Guiot, Ryan R Davis, Jeffrey P Gregg, Christopher Moraes, Anne-Claude Gingras, Morag Park
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2-35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro...
March 20, 2018: Cell Reports
Raul Vizcardo, Nicholas D Klemen, S M Rafiqul Islam, Devikala Gurusamy, Naritaka Tamaoki, Daisuke Yamada, Haruhiko Koseki, Benjamin L Kidder, Zhiya Yu, Li Jia, Amanda N Henning, Meghan L Good, Marta Bosch-Marce, Takuya Maeda, Chengyu Liu, Zied Abdullaev, Svetlana Pack, Douglas C Palmer, David F Stroncek, Fumito Ito, Francis A Flomerfelt, Michael J Kruhlak, Nicholas P Restifo
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+ CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs)...
March 20, 2018: Cell Reports
Qifan Zhu, Si Ming Man, Rajendra Karki, R K Subbarao Malireddi, Thirumala-Devi Kanneganti
Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida. Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice...
March 20, 2018: Cell Reports
Jie Gao, Jun Li, Wen-Chao Geng, Fang-Yuan Chen, Xingchen Duan, Zhe Zheng, Dan Ding, Dong-Sheng Guo
Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although displaying the efficacy in construction of activatable photosensitizers (PSs), direct covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host-guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state)...
March 21, 2018: Journal of the American Chemical Society
Dacheng Ma, Shuguang Peng, Weiren Huang, Zhiming Cai, Zhen Xie
Nuclease dead Cas9 (dCas9) has been widely used for modulating gene expression by fusing with different activation or repression domains. However, delivery of the CRISPR/Cas system fused with variant effector domains in a single adeno-associated virus (AAV) remains challenging due to the payload limit. Here, we engineered a set of downsized variants of Cas9 including Staphylococcus aureus Cas9 (SaCas9) that retained DNA binding activity by deleting conserved functional domains. We demonstrated that fusing FokI nuclease domain to the N-terminal of the minimal SaCas9 (mini-SaCas9) or to the middle of the split mini-SaCas9 can trigger efficient DNA cleavage...
March 21, 2018: ACS Synthetic Biology
Tianzhe Liu, Rabia Mazmouz, Brett A Neilan
Phosphopantetheinyl transferases catalyze the post-translational modification of carrier proteins involved in both primary and secondary metabolism. The functional expression of polyketide synthases and non-ribosomal peptide synthetases requires the activation of all carrier protein domains by phosphopantetheinyl transferases. Here we describe the characterization of five bacterial phosphopantetheinyl transferases by their substrate specificity and catalytic efficiency of four bacterial carrier proteins. Comparative in vitro phosphopantetheinylation analysis showed Sfp possesses the highest catalytic efficiency over various carrier proteins...
March 21, 2018: ACS Synthetic Biology
Biljana K Tubić, Sandra S Vladimirov, Bojan D Marković, Tibor J Sabo
O,O'-diethyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate (DE-EDCP) is novel substance with cytotoxic activity in human leukemic cells. The aim of this study has been to predict in vivo bioavailability of the DE-EDCP and its potential metabolite (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) by in vitro characterization which includes determination of lipophilicity and passive membrane permeability. There has also been evaluated inter-laboratory reproducibility of the bio-analytical method which was previously developed and validated for non-clinical study of the DE-EDCP and EDCP...
March 2018: Acta Chimica Slovenica
Carlos A Gómez, Jason Sutin, Weicheng Wu, Buyin Fu, Hana Uhlirova, Anna Devor, David A Boas, Sava Sakadžić, Mohammad A Yaseen
Investigating cerebral metabolism in vivo at a microscopic level is essential for understanding brain function and its pathological alterations. The intricate signaling and metabolic dynamics between neurons, glia, and microvasculature requires much more detailed understanding to better comprehend the mechanisms governing brain function and its disease-related changes. We recently demonstrated that pharmacologically-induced alterations to different steps of cerebral metabolism can be distinguished utilizing 2-photon fluorescence lifetime imaging of endogenous reduced nicotinamide adenine dinucleotide (NADH) fluorescence in vivo...
2018: PloS One
Francesca Bagnato, Simon Hametner, Emma Boyd, Verena Endmayr, Yaping Shi, Vasiliki Ikonomidou, Guanhua Chen, Siddharama Pawate, Hans Lassmann, Seth Smith, E Brian Welch
T2*-weighted multi-echo gradient-echo magnetic resonance imaging and its reciprocal R2* are used in brain imaging due to their sensitivity to iron content. In patients with multiple sclerosis who display pathological alterations in iron and myelin contents, the use of R2* may offer a unique way to untangle mechanisms of disease. Coronal slices from 8 brains of deceased multiple sclerosis patients were imaged using a whole-body 7.0 Tesla MRI scanner. The scanning protocol included three-dimensional (3D) T2*-w multi-echo gradient-echo and 2D T2-w turbo spin echo (TSE) sequences...
2018: PloS One
Weijuan Du, Lisha Jin, Liping Li, Wei Wang, Su Zeng, Huidi Jiang, Hui Zhou
The tuber of Corydalis yanhusuo is a famous traditional Chinese medicine and found to have potent pharmacological effects, such as antinociceptive, antitumor, antibacterial, anti-inflammatory, and anti-depressive activities. Although there are several methods to be developed for the analysis and detection of the bioactive ingredients' alkaloids, so far, only few prominent alkaloids could be quantified, and in vitro and in vivo changes of comprehensive alkaloids after oral administration are still little known...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Beatrice Xuan Ho, Nicole Min Qian Pek, Boon-Seng Soh
The rising interest in human induced pluripotent stem cell (hiPSC)-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D) structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D) cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo...
March 21, 2018: International Journal of Molecular Sciences
Benjamin B Kasten, Patsy G Oliver, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. There is a clinical need for effective, targeted therapy strategies that destroy both differentiated TNBC cells and TNBC cancer initiating cells (CICs), as the latter are implicated in the metastasis and recurrence of TNBC. Chondroitin sulfate proteoglycan 4 (CSPG4) is overexpressed on differentiated tumor cells and CICs obtained from TNBC patient specimens, suggesting that CSPG4 may be a clinically relevant target for the imaging and therapy of TNBC...
March 21, 2018: International Journal of Molecular Sciences
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