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https://www.readbyqxmd.com/read/29728527/disrupted-hypothalamic-functional-connectivity-in-patients-with-pd-and-autonomic-dysfunction
#1
Eran Dayan, Miriam Sklerov, Nina Browner
OBJECTIVE: To test whether symptoms of autonomic dysfunction in Parkinson disease (PD) are associated with alterations in intrinsic hypothalamic functional connectivity, given the regulatory role of the hypothalamus (HTH) in the autonomic nervous system. METHODS: Resting-state fMRI scans from patients with PD were analyzed, comparing patients with the highest (n = 24) and lowest (n = 28) quartile scores in a questionnaire assessing autonomic dysfunction in PD (Scales for Outcomes in Parkinson's Disease-Autonomic [SCOPA-AUT]), obtained from a larger pool of patients (n = 93)...
May 4, 2018: Neurology
https://www.readbyqxmd.com/read/29699632/mulberry-anthocyanins-improves-thyroid-cancer-progression-mainly-by-inducing-apoptosis-and-autophagy-cell-death
#2
Hou-Long Long, Feng-Feng Zhang, Hong-Ling Wang, Wen-Shi Yang, Hai-Tao Hou, Jing-Kui Yu, Bin Liu
Dietary anthocyanin compounds have multiple biological effects, including antioxidant, anti-inflammatory, and anti-atherosclerotic characteristics. The present study evaluated the anti-tumor capacity of mulberry anthocyanins (MA) in thyroid cancer cells. Our data showed that MA suppressed SW1736 and HTh-7 cell proliferation in a time- and dose-dependent manner. Meanwhile, flow cytometry results indicated that MA significantly increased SW1736 and HTh-7 cell apoptosis. We additionally observed that SW1736 and HTh-7 cell autophagy was markedly enhanced after MA treatment...
May 2018: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29683725/reliabilities-of-intraindividual-variability-indicators-with-autocorrelated-longitudinal-data-implications-for-longitudinal-study-designs
#3
Han Du, Lijuan Wang
Intraindividual variability can be measured by the intraindividual standard deviation ([Formula: see text]), intraindividual variance ([Formula: see text]), estimated hth-order autocorrelation coefficient ([Formula: see text]), and mean square successive difference ([Formula: see text]). Unresolved issues exist in the research on reliabilities of intraindividual variability indicators: (1) previous research only studied conditions with 0 autocorrelations in the longitudinal responses; (2) the reliabilities of [Formula: see text] and [Formula: see text] have not been studied...
April 23, 2018: Multivariate Behavioral Research
https://www.readbyqxmd.com/read/29667825/structure-based-design-of-inhibitors-targeting-prfa-the-master-virulence-regulator-of-listeria-monocytogenes
#4
Martina Kulén, Marie Lindgren, Sabine Hansen, Andrew Gerard Cairns, Christin Grundström, Afshan Begum, Ingeborg van der Lingen, Kristoffer Brännström, Michael Hall, Uwe H Sauer, Jörgen Johansson, A Elisabeth Sauer-Eriksson, Fredrik Almqvist
Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure-guided design and synthesis of a set of PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased virulence factor expression, reduced bacterial uptake into eukaryotic cells, and improved survival of chicken embryos infected with L. monocytogenes compared to previously identified compounds. Crystal structures identified an intra-protein "tunnel" as the main inhibitor binding site (AI), where the compounds participate in an extensive hydrophobic network that restricts the protein's ability to form functional DNA-binding helix-turn-helix (HTH) motifs...
April 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29566768/functional-genomics-identifies-specific-vulnerabilities-in-pten-deficient-breast-cancer
#5
Yew Chung Tang, Szu-Chi Ho, Elisabeth Tan, Alvin Wei Tian Ng, John R McPherson, Germaine Yen Lin Goh, Bin Tean Teh, Frederic Bard, Steven G Rozen
BACKGROUND: Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressors in breast cancer. While PTEN itself is not considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL) genes are potential drug targets in PTEN-deficient breast cancers. Therefore, with the aim of identifying potential targets for precision breast cancer therapy, we sought to discover PTEN-SSL genes present in a broad spectrum of breast cancers. METHODS: To discover broad-spectrum PTEN-SSL genes in breast cancer, we used a multi-step approach that started with (1) a genome-wide short interfering RNA (siRNA) screen of ~ 21,000 genes in a pair of isogenic human mammary epithelial cell lines, followed by (2) a short hairpin RNA (shRNA) screen of ~ 1200 genes focused on hits from the first screen in a panel of 11 breast cancer cell lines; we then determined reproducibility of hits by (3) identification of overlaps between our results and reanalyzed data from 3 independent gene-essentiality screens, and finally, for selected candidate PTEN-SSL genes we (4) confirmed PTEN-SSL activity using either drug sensitivity experiments in a panel of 19 cell lines or mutual exclusivity analysis of publicly available pan-cancer somatic mutation data...
March 22, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29545880/allicin-activates-autophagic-cell-death-to-alleviate-the-malignant-development-of-thyroid-cancer
#6
Yangfeng Xiang, Jianqiang Zhao, Ming Zhao, Kejing Wang
Allicin has been reported to inhibit cancer cell proliferation, induce cell apoptosis and enhance the accumulation of reactive oxygen species. However, it has remained elusive whether allicin improves multidrug resistance in thyroid cancer cells through modulating autophagy. The present study demonstrated that combined use of allicin and cisplatin or carboplatin resulted in an enhanced growth inhibitory effect on SW1736 and HTh-7 cells. Furthermore, treatment with allicin significantly increased SW1736 and HTh-7 cell autophagy...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29545146/reduced-learning-and-memory-performances-in-high-fat-treated-hamsters-related-to-brain-neurotensin-receptor1-expression-variations
#7
Gilda Fazzari, Merylin Zizza, Anna Di Vito, Raffaella Alò, Maria Mele, Rosalinda Bruno, Barni Tullio, Rosa Maria Facciolo, Canonaco Marcello
Recent indications are suggesting that high fat and sugar-enriched foods do not only evoke harmful physiological conditions, but they also endure evident structural alterations in cerebral regions controlling cognitive and feeding behaviors. Food consumption plus neuronal energy regulatory mechanisms seem to constitute a complex system assuring that food calories do not exceed body requirements. At the same time obesogenic-related properties of limbic feeding stations like the hypothalamus (HTH), hippocampus (HIP) and amygdala (AMY) tend to control eating habits through the interaction of distinct neuropeptides...
March 12, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29500665/computational-redesign-of-human-respiratory-syncytial-virus-epitope-as-therapeutic-peptide-vaccines-against-pediatric-pneumonia
#8
Xiangxiang Shi, Jun Zheng, Tingting Yan
Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. Here, the RSV fusion (F) glycoprotein epitope FFL was redesigned based on its complex crystal structure with motavizumab, an mAb drug in development for the prevention of RSV infections, aiming to obtain therapeutic peptide vaccines with high affinity to induce RSV-specific neutralizing antibodies. Computational modeling and analysis found that only a small region covering the helix-turn-helix (HTH) motif of FFL can directly interact with motavizumab and confer stability and specificity to the complex system, while the rest of the epitope primarily serves as a structural scaffold that stabilizes the HTH conformation of motavizumab-binding site...
March 2, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29432690/sequential-dna-binding-and-dimerization-processes-of-the-photosensory-protein-el222
#9
Akira Takakado, Yusuke Nakasone, Masahide Terazima
EL222 is a blue light sensor protein, which consists of a light-oxygen-voltage domain as a light sensor and a LuxR-type helix-turn-helix DNA-binding domain. The reaction dynamics of the protein-DNA binding were observed for the first time using the time-resolved transient grating method. The reaction scheme was determined, showing that photoexcited EL222 first binds DNA and the ground state EL222 monomer is subsequently associated with the complex. Rate constants on the millisecond scale were determined for these processes...
March 13, 2018: Biochemistry
https://www.readbyqxmd.com/read/29382315/genetic-engineering-of-escherichia-coli-to-improve-l-phenylalanine-production
#10
Yongfei Liu, Yiran Xu, Dongqin Ding, Jianping Wen, Beiwei Zhu, Dawei Zhang
BACKGROUND: L-phenylalanine (L-Phe) is an essential amino acid for mammals and applications expand into human health and nutritional products. In this study, a system level engineering was conducted to enhance L-Phe biosynthesis in Escherichia coli. RESULTS: We inactivated the PTS system and recruited glucose uptake via combinatorial modulation of galP and glk to increase PEP supply in the Xllp01 strain. In addition, the HTH domain of the transcription factor TyrR was engineered to decrease the repression on the transcriptional levels of L-Phe pathway enzymes...
January 30, 2018: BMC Biotechnology
https://www.readbyqxmd.com/read/29318690/lactose-repressor-hinge-domain-independently-binds-dna
#11
Joseph S Xu, Madeleine N Hewitt, Jaskeerat S Gulati, Matthew A Cruz, Hongli Zhan, Shirley Liu, Kathleen S Matthews
The short 8-10 amino acid "hinge" sequence in lactose repressor (LacI), present in other LacI/GalR family members, links DNA and inducer-binding domains. Structural studies of full-length or truncated LacI-operator DNA complexes demonstrate insertion of the dimeric helical "hinge" structure at the center of the operator sequence. This association bends the DNA ∼40° and aligns flanking semi-symmetric DNA sites for optimal contact by the N-terminal helix-turn-helix (HtH) sequences within each dimer...
April 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29248914/whole-genome-analysis-of-an-extensive-drug-resistant-acinetobacter-baumannii-st195-isolate-from-a-recipient-after-dcd-renal-transplantation-in-china
#12
Hong Jiang, Luxi Cao, Qixia Shen, Lihui Qu, Yan Jiang, Tingting Qu, Jian Zhang, Yingying Lu, Bingjue Li, Chaohong Zhu, Guangjun Liu, Rending Wang, Miao Chen, Yucheng Wang, Yanfei Wang, Shi Feng, Junwen Wang, Yunsong Yu, Jianyong Wu, Jianghua Chen
BACKGROUND/AIMS: Infection with Acinetobacter baumannii was emerging as one of the leading causes of mortality after donation after cardiac death transpalantion. METHODS: We reported a case of a recipient who underwent DCD renal transplantation and later got infected by A.baumannii. Etests were done to verify the susceptibility test results in clinic. Whole-genome analysis was applied to investigate the resistant mechanism at gene level. RESULTS: The pathogen was isolated from his draining liquid the day after the surgery, and susceptibility test reavealed that it was sensitive to tigecycline...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29239168/variation-in-lov-photoreceptor-activation-dynamics-probed-by-time-resolved-infrared-spectroscopy
#13
James N Iuliano, Agnieszka A Gil, Sergey P Laptenok, Christopher R Hall, Jinnette Tolentino Collado, Andras Lukacs, Safaa A Hag Ahmed, Jenna Abyad, Taraneh Daryaee, Gregory M Greetham, Igor V Sazanovich, Boris Illarionov, Adelbert Bacher, Markus Fischer, Michael Towrie, Jarrod B French, Stephen R Meech, Peter J Tonge
The light, oxygen, voltage (LOV) domain proteins are blue light photoreceptors that utilize a noncovalently bound flavin mononucleotide (FMN) cofactor as the chromophore. The modular nature of these proteins has led to their wide adoption in the emerging fields of optogenetics and optobiology, where the LOV domain has been fused to a variety of output domains leading to novel light-controlled applications. In this work, we extend our studies of the subpicosecond to several hundred microsecond transient infrared spectroscopy of the isolated LOV domain AsLOV2 to three full-length photoreceptors in which the LOV domain is fused to an output domain: the LOV-STAS protein, YtvA, the LOV-HTH transcription factor, EL222, and the LOV-histidine kinase, LovK...
February 6, 2018: Biochemistry
https://www.readbyqxmd.com/read/29141951/selector-genes-display-tumor-cooperation-and-inhibition-in-drosophila-epithelium-in-a-developmental-context-dependent-manner
#14
Ram Prakash Gupta, Anjali Bajpai, Pradip Sinha
During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey), and the segment selector, Ultrabithorax (Ubx), readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth), and/or the Zinc-finger protein, Teashirt (Tsh)...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29095143/nuclear-microenvironments-modulate-transcription-from-low-affinity-enhancers
#15
Albert Tsai, Anand K Muthusamy, Mariana Rp Alves, Luke D Lavis, Robert H Singer, David L Stern, Justin Crocker
Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby ( svb ) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains...
November 2, 2017: ELife
https://www.readbyqxmd.com/read/29029697/the-identification-of-transcriptional-regulation-related-gene-of-laccase-poxc-through-yeast-one-hybrid-screening-from-pleurotus-ostreatus
#16
Yuancheng Qi, Chao Liu, Xiankai Sun, Liyou Qiu, Jinwen Shen
Pleurotus ostreatus laccase gene poxc is transcriptionally induced by copper, and several putative MREs have been found and confirmed in its promoter region. However, the related transcription factors mediating copper response via MREs have not been reported. To isolate MRE binding proteins, we carried out yeast one-hybrid screens. Reporter genes containing two trimers of the cMRE2 and cMRE3 element were prepared and introduced into a yeast strain. The yeast was transformed with library cDNA that represents RNA isolated from CuSO4-treated fungi of P...
November 2017: Fungal Biology
https://www.readbyqxmd.com/read/28972158/ligand-dependent-corepressor-lcor-represses-the-transcription-factor-c-ebp%C3%AE-during-early-adipocyte-differentiation
#17
Hongchao Cao, Shengjie Zhang, Shifang Shan, Chao Sun, Yan Li, Hui Wang, Shuxian Yu, Yi Liu, Feifan Guo, Qiwei Zhai, Yu-Cheng Wang, Jingjing Jiang, Hui Wang, Jun Yan, Wei Liu, Hao Ying
Nuclear receptors (NRs) regulate gene transcription by recruiting coregulators, involved in chromatin remodeling and assembly of the basal transcription machinery. The NR-associated protein ligand-dependent corepressor (LCoR) has previously been shown to suppress hepatic lipogenesis by decreasing the binding of steroid receptor coactivators to thyroid hormone receptor. However, the role of LCoR in adipogenesis has not been established. Here, we show that LCoR expression is reduced in the early stage of adipogenesis in vitro LCoR overexpression inhibited 3T3-L1 adipocyte differentiation, whereas LCoR knockdown promoted it...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28926338/melk-is-not-necessary-for-the-proliferation-of-basal-like-breast-cancer-cells
#18
Hai-Tsang Huang, Hyuk-Soo Seo, Tinghu Zhang, Yubao Wang, Baishan Jiang, Qing Li, Dennis L Buckley, Behnam Nabet, Justin M Roberts, Joshiawa Paulk, Shiva Dastjerdi, Georg E Winter, Hilary McLauchlan, Jennifer Moran, James E Bradner, Michael J Eck, Sirano Dhe-Paganon, Jean J Zhao, Nathanael S Gray
Thorough preclinical target validation is essential for the success of drug discovery efforts. In this study, we combined chemical and genetic perturbants, including the development of a novel selective maternal embryonic leucine zipper kinase (MELK) inhibitor HTH-01-091, CRISPR/Cas9-mediated MELK knockout, a novel chemical-induced protein degradation strategy, RNA interference and CRISPR interference to validate MELK as a therapeutic target in basal-like breast cancers (BBC). In common culture conditions, we found that small molecule inhibition, genetic deletion, or acute depletion of MELK did not significantly affect cellular growth...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28838125/hothead-like-hth1-is-involved-in-anther-cutin-biosynthesis-and-is-required-for-pollen-fertility-in-rice
#19
Ya Xu, Shasha Liu, Yaqin Liu, Sheng Ling, Caisheng Chen, Jialing Yao
The cuticle covering the outer surface of anthers is essential for male reproductive development in plants. However, the mechanism underlying the synthesis of these lipidic polymers remains unclear. HOTHEAD (HTH) in Arabidopsis thaliana is a presumptive glucose-methanol-choline (GMC) oxidoreductase involved in the biosynthesis of long-chain α-,ω-dicarboxylic fatty acids. In this study, we characterized the function of an anther-specific gene HTH1 in rice. HTH1 contains a conserved GMC oxidoreductase-like domain, and the sequence of HTH1 was highly similar to that of HTH in A...
July 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28794035/crystal-structure-of-the-dna-binding-domain-of-human-herpesvirus-6a-immediate-early-protein-2
#20
Mitsuhiro Nishimura, Junjie Wang, Aika Wakata, Kento Sakamoto, Yasuko Mori
Immediate early proteins of human herpesvirus 6A (HHV-6A) are expressed at the outset of lytic infection and thereby regulate viral gene expression. Immediate early protein 2 (IE2) of HHV-6A is a transactivator that drives a variety of promoters. The C-terminal region of HHV-6A IE2 is shared among IE2 homologs in betaherpesviruses and is involved in dimerization, DNA binding, and transcription factor binding. In this study, the structure of the IE2 C-terminal domain (IE2-CTD) was determined by X-ray crystallography at a resolution of 2...
November 1, 2017: Journal of Virology
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