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https://www.readbyqxmd.com/read/29909595/disability-experiences-and-perspectives-regarding-reproductive-decisions-parenting-and-the-utility-of-genetic-services-a-qualitative-study
#1
C Roadhouse, C Shuman, K Anstey, K Sappleton, D Chitayat, E Ignagni
Genetic counselors adopt seemingly contradictory roles: advocating for individuals with genetic conditions while offering prenatal diagnosis and the option of selective termination to prevent the birth of a child with a disability. This duality contributes to the tension between the disability and clinical genetics communities. Varying opinions exist amongst the disability community: some value genetic services while others are opposed. However, there is limited research exploring the opinions of individuals with a disability regarding issues related to reproduction and genetic services in the context of personal experience...
June 16, 2018: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/29909422/expression-of-transcription-factor-21-tcf21-and-upregulation-its-level-inhibits-invasion-and-metastasis-in-esophageal-squamous-cell-carcinoma
#2
Yue Chen, Cheng Zhang, Jing Chen, Bohan Zhang, Hongqi Zhang, Xuetao Yang, Jingshu Liu, Qingchen Wu
BACKGROUND Transcription factor 21 (TCF21), a member of the class A of basic helix-loop-helix family, has been widely identified as a tumor suppressor. Growing evidence has demonstrated the downregulation of TCF21 in distinct cancers. The aim of this study was to explore the expression and biological functions of TCF21 in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS TCF21 expression in esophageal cancer cell lines and carcinomas tissues were detected, and its associations with clinical characteristics were analyzed...
June 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29909343/tanshinone-iia-inhibits-cervix-carcinoma-stem-cells-migration-and-invasion-via-inhibiting-yap-transcriptional-activity
#3
Jinghao Qin, Hongbing Shi, Yanjie Xu, Fang Zhao, Qing Wang
This study aims to explore the effects and related mechanisms of Tanshinone IIA in cervix carcinoma (CC) stemness-like cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that Tanshinone IIA suppressed CC stemness-like cells migration and invasion in a concentration- and time-dependent manner. And consistent results were obtained in CC cells stemness characterized as the decrease of CC stemness markers expression and cells spheroid formation ability. Mechanistically, we found that Tanshinone IIA suppressed RNA binding protein HuR translocation from nuclear to cytoplasm, and thus reduced YAP mRNAs stability and transcriptional activity...
June 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29908814/maternal-supply-of-methionine-during-late-pregnancy-is-associated-with-changes-in-immune-function-and-abundance-of-microrna-and-mrna-in-holstein-calf-polymorphonuclear-leukocytes
#4
C B Jacometo, A S Alharthi, Z Zhou, D Luchini, J J Loor
Pregnancy and early life are critical periods during which environmental factors such as nutrition can affect development. Rumen-protected methionine (Met; RPM) supplementation during the prepartum period improves not only performance but immune responses in dairy cows. We investigated the effects of enhanced maternal supply of Met via feeding RPM on whole-blood in vitro lipopolysaccharide (LPS; 0, 0.01, or 5 μg/mL of blood) challenge and targeted microRNA and mRNA abundance in calf blood polymorphonuclear leukocytes (PMNL)...
June 13, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29908722/ferulic-acid-a-dietary-polyphenol-suppresses-osteoclast-differentiation-and-bone-erosion-via-the-inhibition-of-rankl-dependent-nf-%C3%AE%C2%BAb-signalling-pathway
#5
Hari Madhuri Doss, Snigdha Samarpita, Ramamoorthi Ganesan, Mahaboobkhan Rasool
AIMS: Bone erosion induced by enhanced osteoclast formation is a debilitating pathological phenomenon in rheumatoid arthritis (RA). Recent finding has revealed that ferulic acid is associated with reduced osteoclast differentiation and bone erosion. However, the underlying mechanism through which ferulic acid inhibited osteoclast differentiation and bone erosion still remains to be elucidated. This study assessed the therapeutic effects of ferulic acid on osteoclast differentiation and bone erosion by targeting RANKL dependent NF-κB pathway...
June 14, 2018: Life Sciences
https://www.readbyqxmd.com/read/29908567/construction-of-an-improved-aspergillus-niger-platform-for-enhanced-glucoamylase-secretion
#6
Markus R M Fiedler, Lars Barthel, Christin Kubisch, Corrado Nai, Vera Meyer
BACKGROUND: The lifestyle of filamentous fungi depends on the secretion of hydrolytic enzymes into the surrounding medium, which degrade polymeric substances into monomers that are then taken up to sustain metabolism. This feature has been exploited in biotechnology to establish platform strains with high secretory capacity including Aspergillus niger. The accepted paradigm is that proteins become mainly secreted at the tips of fungal hyphae. However, it is still a matter of debate if the amount of growing hyphal tips in filamentous fungi correlates with an increase in secretion, with previous studies showing either a positive or no correlation...
June 16, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29908438/targeting-rna-polymerase-i-transcription-machinery-in-cancer-cells-by-a-novel-monofunctional-platinum-based-agent
#7
Zhen-Lei Zhang, Chun-Lai Zhao, Qian Chen, Kai Xu, Xin Qiao, Jing-Yuan Xu
Aberrant ribosome biogenesis and enlarged nucleoli have long been used by pathologists as a marker of aggressive tumors. Suppression of RNA polymerase I (Pol I) transcription machinery within the nucleolus could be a direct way to trigger the nucleolar stress and to inhibit the rapid proliferation of cancer cells. Here we modified cisplatin with an analogue of the selective inhibitor of RNA polymerase I-mediated transcription BMH-21 to develop a novel platinum-based Pol I selective inhibitor. We show that this novel monofunctional platinum-based agent, P1-B1, had enhanced antitumor activity of up to 17-fold greater than the clinical drug cisplatin in cisplatin-resistant non-small cell lung cancer cells...
June 1, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29908255/genetic-overexpression-of-glutathione-peroxidase-1-attenuates-microcystin-leucine-arginine-induced-memory-impairment-in-mice
#8
Eun-Joo Shin, Yeong Gwang Hwang, Duc Toan Pham, Ji Won Lee, Yu Jeung Lee, Dongjin Pyo, Xin Gen Lei, Ji Hoon Jeong, Hyoung-Chun Kim
Microcystin-leucine-arginine (MCLR) is the most common form of microcystins, which are environmental toxins produced by cyanobacteria, and its hepatotoxicity has been well-documented. However, the neurotoxic potential of MCLR remains to be further elucidated. In the present study, we investigated whether intracerebroventricular (i.c.v.) infusion of MCLR induces mortality and neuronal loss in the hippocampus of mice. Because we found that MCLR impairs memory function in the hippocampus at a low dose (4 ng/μl/mouse, i...
June 13, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29908210/the-tgf%C3%AE-induced-lncrna-tbila-promotes-non-small-cell-lung-cancer-progression-in-vitro-and-in-vivo-via-cis-regulating-hgal-and-activating-s100a7-jab1-signaling
#9
Zhiliang Lu, Yuan Li, Yun Che, Jianbing Huang, Shouguo Sun, Shuangshuang Mao, Yuanyuan Lei, Ning Li, Nan Sun, Jie He
Long non-coding RNAs (lncRNAs) play critical roles in multiple cellular processes in non-small cell lung cancer (NSCLC); however, the involvement of lncRNAs in the transforming growth factor-beta (TGFβ) signaling pathway, the critical tumor cell epithelial-mesenchymal transition (EMT) and metastasis pathway, remains poorly understood. To address this issue, we compared the lncRNAs expression patterns of NSCLC cells treated with and without TGFβ1 treatment. We observed that one of the most prominent hits, TGFβ-induced lncRNA (TBILA), promoted NSCLC progression and was upregulated in tumor tissues...
June 13, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29908050/australian-community-pharmacists-experience-of-implementing-a-chronic-kidney-disease-risk-assessment-service
#10
Pankti A Gheewala, Gregory M Peterson, Syed Tabish R Zaidi, Matthew D Jose, Ronald L Castelino
INTRODUCTION: Community pharmacists are well positioned to deliver chronic kidney disease (CKD) screening services. However, little is known about the challenges faced by pharmacists during service implementation. This study aimed to explore community pharmacists' experiences and perceived barriers of implementing a CKD risk assessment service. METHODS: Data collection was performed by using semistructured, open-ended interview questions. Pharmacists who had implemented a CKD screening service in Tasmania, Australia, were eligible to participate...
June 14, 2018: Preventing Chronic Disease
https://www.readbyqxmd.com/read/29908007/cocl-2-a-mimic-of-hypoxia-enhances-bone-marrow-mesenchymal-stem-cells-migration-and-osteogenic-differentiation-via-stat3-signaling-pathway
#11
Xin Yu, Qilong Wan, Gu Cheng, Xin Cheng, Jing Zhang, Janak L Pathak, Zubing Li
Mesenchymal stem cells homing and migration is a crucial step during bone fracture healing. Hypoxic environment in fracture site induces bone marrow mesenchymal stem cells (BMSCs) migration, but its mechanism remains unclear. Our previous study and studies by other groups have reported the involvement of signal transducer and activator of transcription 3 (STAT3) pathway in cell migration. However, the role of STAT3 pathway in hypoxia-induced cell migration is still unknown. In this study, we investigated the role of STAT3 signaling in hypoxia-induced BMSCs migration and osteogenic differentiation...
June 16, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29907991/lipopolysaccharide-induced-the-proliferation-of-mouse-lung-fibroblasts-by-suppressing-foxo3a-p27-pathway
#12
Nannan Gu, Shunpeng Xing, Sihan Chen, Yuxi Zhou, Tao Jiang, Yingfu Jiao, Yuan Gao, Weifeng Yu, Zhengyu He, Daxiang Wen
Aberrant aggregation and activation of lung fibroblasts is a key process in pulmonary fibrosis, but the underlying mechanism remains enigmatic. Forkhead Box O3a (FoxO3a) is considered to be an important transcription factor that could regulate both cell cycle and cell viability. To investigate the role of FoxO3a on LPS-induced lung fibroblast proliferation, we transfected FoxO3a-SiRNA or FoxO3a-OE lentivirus into cultured mouse lung fibroblasts to knockdown or overexpress FoxO3a and pretreated mouse lung fibroblasts with gefitinib to enhance FoxO3a activity...
June 16, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29907877/electroporation-mediated-delivery-of-fer-gene-enhances-innate-immune-response-and-improves-survival-in-a-murine-model-of-pneumonia
#13
Vladislav Dolgachev, Sreehari Panicker, Sanjay Balijepalli, Lane Kelly McCandless, Yue Yin, Samantha Swamy, M V Suresh, Matthew J Delano, Mark R Hemmila, Krishnan Raghavendran, David Machado-Aranda
Previously, we reported that electroporation-mediated (EP) delivery of the FER gene improved survival in a combined trauma-pneumonia model. The mechanism of this protective effect is unknown. In this paper, we performed a pneumonia model in C57/BL6 mice with 500 CFU of Klebsiella pneumoniae. After inoculation, a plasmid encoding human FER was delivered by EP into the lung (PNA/pFER-EP). Survival of FER-treated vs. controls (PNA; PNA/EP-pcDNA) was recorded. In parallel cohorts, bronchial alveolar lavage (BAL) and lung were harvested at 24 and 72 h with markers of infection measured...
June 15, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29907876/in-vitro-evaluation-of-a-lentiviral-two-step-transcriptional-amplification-system-using-gal4ff-transactivator-for-gene-therapy-applications-in-bone-repair
#14
Sofia Bougioukli, Osamu Sugiyama, Ram K Alluri, Robert Yoho, Daniel A Oakes, Jay R Lieberman
In this study, we developed a lentiviral two-step transcriptional amplification (TSTA) system expressing bone morphogenetic protein-2 (BMP-2) under the control of a GAL4FF transactivator to enhance gene expression and limit toxicity for bone repair applications. To this end human MSCs, isolated from bone marrow or adipose tissue, were transduced overnight with a LV-TSTA system (GAL4FF or GAL4vp16) expressing BMP-2 or GFP and evaluated in vitro for transduction efficiency, mean fluorescence intensity, cell viability, and BMP-2 production...
June 15, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29907762/duplication-of-a-germline-promoter-downstream-of-the-igh-3-regulatory-region-impairs-class-switch-recombination
#15
Joana M Santos, Fatima-Zohra Braikia, Chloé Oudinet, Dania Haddad, Caroline Conte, Audrey Dauba, Ahmed Amine Khamlichi
During an adaptive immune response, B cells can change their surface immunoglobulins from IgM to IgG, IgE or IgA through a process called class switch recombination (CSR). Switching is preceded by inducible non-coding germline transcription (GLT) of the selected constant gene(s), which is largely controlled by a super-enhancer called the 3' regulatory region (3'RR). Despite intense efforts, the precise mechanisms that regulate GLT are still elusive. In order to gain additional insights into these mechanisms, we analyzed GLT and CSR in mutant B cells carrying a duplication of the promoter of the α constant gene (Iα) downstream of 3'RR...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29907707/-leishmania-donovani-exploits-tollip-a-multitasking-protein-to-impair-tlr-il-1r-signaling-for-its-survival-in-the-host
#16
Naveen Parmar, Pragya Chandrakar, Preeti Vishwakarma, Kavita Singh, Kalyan Mitra, Susanta Kar
IL-1R/TLR signaling plays a significant role in sensing harmful foreign pathogens and mounting effective innate and adaptive immune responses. However, the precise mechanism by which Leishmania donovani, an obligate intramacrophagic pathogen, breaches IL-1R/TLR signaling and host-protective immunity remains obscure. In this study, we report the novel biphasic role of Toll-interacting protein (Tollip), a negative regulator of the IL-1R/TLR pathway, in the disease progression of experimental visceral leishmaniasis...
June 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29907679/the-tumour-suppressor-opcml-promotes-axl-inactivation-by-the-phosphatase-ptprg-in-ovarian-cancer
#17
Jane Antony, Elisa Zanini, Zoe Kelly, Tuan Zea Tan, Evdoxia Karali, Mohammad Alomary, Youngrock Jung, Katherine Nixon, Paula Cunnea, Christina Fotopoulou, Andrew Paterson, Sushmita Roy-Nawathe, Gordon B Mills, Ruby Yun-Ju Huang, Jean Paul Thiery, Hani Gabra, Chiara Recchi
In ovarian cancer, the prometastatic RTK AXL promotes motility, invasion and poor prognosis. Here, we show that reduced survival caused by AXL overexpression can be mitigated by the expression of the GPI-anchored tumour suppressor OPCML Further, we demonstrate that AXL directly interacts with OPCML, preferentially so when AXL is activated by its ligand Gas6. As a consequence, AXL accumulates in cholesterol-rich lipid domains, where OPCML resides. Here, phospho-AXL is brought in proximity to the lipid domain-restricted phosphatase PTPRG, which de-phosphorylates the RTK/ligand complex...
June 15, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29907651/lncrna-papas-tethered-to-the-rdna-enhancer-recruits-hypophosphorylated-chd4-nurd-to-repress-rrna-synthesis-at-elevated-temperatures
#18
Zhongliang Zhao, Nevcin Sentürk, Chenlin Song, Ingrid Grummt
Attenuation of pre-rRNA synthesis in response to elevated temperature is accompanied by increased levels of PAPAS ("promoter and pre-rRNA antisense") , a long noncoding RNA (lncRNA) that is transcribed in an orientation antisense to pre-rRNA. Here we show that PAPAS interacts directly with DNA, forming a DNA-RNA triplex structure that tethers PAPAS to a stretch of purines within the enhancer region, thereby guiding associated CHD4/NuRD (nucleosome remodeling and deacetylation) to the rDNA promoter...
June 15, 2018: Genes & Development
https://www.readbyqxmd.com/read/29907596/inflammation-leads-through-pge-ep-3-signaling-to-hdac5-mef2-dependent-transcription-in-cardiac-myocytes
#19
András D Tóth, Richard Schell, Magdolna Lévay, Christiane Vettel, Philipp Theis, Clemens Haslinger, Felix Alban, Stefanie Werhahn, Lina Frischbier, Jutta Krebs-Haupenthal, Dominique Thomas, Hermann-Josef Gröne, Metin Avkiran, Hugo A Katus, Thomas Wieland, Johannes Backs
The myocyte enhancer factor 2 (MEF2) regulates transcription in cardiac myocytes and adverse remodeling of adult hearts. Activators of G protein-coupled receptors (GPCRs) have been reported to activate MEF2, but a comprehensive analysis of GPCR activators that regulate MEF2 has to our knowledge not been performed. Here, we tested several GPCR agonists regarding their ability to activate a MEF2 reporter in neonatal rat ventricular myocytes. The inflammatory mediator prostaglandin E2 (PGE2 ) strongly activated MEF2...
June 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29907572/mechanistic-insights-into-avian-reovirus-p17-modulated-suppression-of-cell-cycle-cdk-cyclin-complexes-and-enhancement-of-p53-and-cyclin-h-interaction
#20
Hung-Chuan Chiu, Wei-Ru Huang, Tsai-Ling Liao, Pei-I Chi, Brent L Nielsen, Jyung-Hurng Liu, Hung-Jen Liu
The avian reovirus (ARV) p17 protein is a nucleocytoplasmic shuttling protein. Although we have demonstrated that p17 causes cell growth retardation via activation of p53, the precise mechanisms remains unclear. This is the first report that ARV p17 possesses broad inhibitory effects on cell-cycle CDKs, cyclins, CDK/cyclin complexes, and CDK activating kinase (CAK) activity in various mammalian, avian, and cancer cell lines. Suppression of CDK activity by p17 occurs by direct binding to CDKs, cyclins, and CDK/cyclin complexes, transcriptional downregulation of CDKs, cytoplasmic retention of CDKs and cyclins, and inhibition of CAK activity by promoting p53/cyclin H interaction...
June 15, 2018: Journal of Biological Chemistry
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