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Rupak Saha, Aloke Kumar Ghosh, Rudra Narayan Samajdar, Partha Sarathi Mukherjee
A series of molecular spheroids (SP1-SP4) was synthesized using pseudolinear bisimidazole and bisbenzimidazole donors in combination with Pd(NO3 )2 acceptor via coordination-driven self-assembly. They were characterized by NMR and mass spectrometry, and the solid-state structures of SP1 and SP3 were confirmed by X-ray diffraction. Crystal packing revealed the presence of molecular channels with water molecules in the channels as proton source. All the systems showed proton conductivity across a wide range of temperature and relative humidity...
May 24, 2018: Inorganic Chemistry
John Biddlestone, Michael Batie, Daniel Bandarra, Ivan Munoz, Sonia Rocha
The SIN3A-HDAC complex is a master transcriptional repressor, required for development but often deregulated in disease. Here, we report that the recently identified new component of this complex, SINHCAF/FAM60A, links the SIN3A-HDAC co-repressor complex function to the hypoxia response. We show that SINHCAF specifically repress HIF 2α mRNA and protein expression, via its interaction with the transcription factor SP1, and recruitment of HDAC1 to the HIF 2α promoter. SINHCAF control over HIF 2α results in functional cellular changes in in vitro angiogenesis, and viability...
May 21, 2018: Biochemical Journal
Tingting Guo, Jinhu Huang, Changchao Huan, Fang He, Yujuan Zhang, Zohaib A Bhutto, Liping Wang
P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5'-RACE. A 1.9-kb fragment of the 5'-flanking region of the Abcb1 gene was cloned from pig genomic DNA and sequenced. The region critical for its promoter activity was investigated via progressive deletions. Further, using mutation assays, two proximal Sp1 binding sites within the 5'-flanking region of Abcb1 were proven to be important cis- regulatory elements involved in regulating the constitutive expression of porcine Abcb1 ...
2018: Frontiers in Pharmacology
Matías I Hepp, David Escobar, Carlos Farkas, Viviana Hermosilla, Claudia Álvarez, Roberto Amigo, José L Gutiérrez, Ariel F Castro, Roxana Pincheira
SALL2 is a transcription factor involved in development and disease. Deregulation of SALL2 has been associated with cancer, suggesting that it plays a role in the disease. However, how SALL2 is regulated and why is deregulated in cancer remain poorly understood. We previously showed that the p53 tumor suppressor represses SALL2 under acute genotoxic stress. Here, we investigated the effect of Histone Deacetylase Inhibitor (HDACi) Trichostatin A (TSA), and involvement of Sp1 on expression and function of SALL2 in Jurkat T cells...
May 17, 2018: Biochimica et Biophysica Acta
Lijie Sheng, Jing Wu, Xuewu Gong, Duo Dong, Xiaoxue Sun
Retinoblastoma (RB) is an intraocular malignancy for children and has a high mortality rate. Long non-coding RNAs (lncRNAs) are emerging as gene regulators and biomarkers in various malignancies. PANDAR is a novel cancer-related lncRNA that dysregulated in several types of cancers. However, its clinical value and potential effects on RB remains unclear. RT-qPCR was used to assess the relative expression of PANDAR in RB tissues and cells. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate whether SP1 could bind to the promoter region of PANDAR and activate its transcription...
May 17, 2018: Gene
Caroline Krug Vieira, Matheus Nicoletti Marascalchi, Arthur Vinicius Rodrigues, Rafael Dutra de Armas, Sidney Luiz Stürmer
Arbuscular mycorrhizal fungi (AMF) are important during revegetation of mining sites, but few studies compared AMF community in revegetated sites with pristine adjacent ecosystems. The aim of this study was to assess AMF species richness in a revegetated iron-mining site and adjacent ecosystems and to relate AMF occurrence to soil chemical parameters. Soil samples were collected in dry and rainy seasons in a revegetated iron-mining site (RA) and compared with pristine ecosystems of forest (FL), canga (NG), and Cerrado (CE)...
May 2018: Journal of Environmental Sciences (China)
Jin-Zhong Gu, Yan Cai, Zi-Yue Qian, Min Wen, Zi-Fa Shi, Dong-Yu Lv, Alexander M Kirillov
This study reports the hydrothermal synthesis of a novel series of twelve coordination compounds, namely, {[Cd(μ-Hnbtc)(H2O)4]·H2O}n (1), [Zn2(μ-Hnbtc)2(phen)2]·2H2O (2), [Zn(Hnbtc)(phen)2(H2O)]·4.5H2O (3), [Ni(Hnbtc)(phen)2(H2O)]·6H2O (4), [Zn2(μ-Hnbtc)2(2,2'-bipy)2]·2H2O (5), [Cd3(μ5-nbtc)(μ6-nbtc)(2,2'-bipy)2(H2O)]n (6), {[Zn3(μ3-nbtc)2(phen)3(H2O)2]·4H2O} (7), [Co(H2O)6][Co2(nbtc)2(μ-4,4'-bipy)(4,4'-bipy)2(H2O)6]·8H2O (8), {[Ni3(μ4-nbtc)2(μ-4,4'-bipy)2.5(μ-H2O)(H2O)3]·4H2O}n (9), {[Cd2(μ4-nbtc)(μ-OH)(2,2'-bipy)2]·H2O}n (10), [Cd2(μ4-nbtc)(μ-OH)(phen)2(H2O)]n (11), and {[Zn2(μ5-nbtc)(μ3-OH)(μ-4,4'-bipy)]·4,4'-bipy·H2O}n (12), which are derived from 3'-nitro-biphenyl-2,4,4'-tricarboxylic acid (H3nbtc) as a virtually unexplored building block...
May 18, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Yu-Hsuan Lai, Chin Kuo, Macus Tien Kuo, Helen H W Chen
Platinum (Pt)-based antitumor agents have been effective in treating many human malignancies. Drug importing, intracellular shuffling, and exporting-carried out by the high-affinity copper (Cu) transporter ( hCtr1 ), Cu chaperone (Ato x1), and Cu exporters (ATP7A and ATP7B), respectively-cumulatively contribute to the chemosensitivity of Pt drugs including cisplatin and carboplatin, but not oxaliplatin. This entire system can also handle Pt drugs via interactions between Pt and the thiol-containing amino acid residues in these proteins; the interactions are strongly influenced by cellular redox regulators such as glutathione...
May 16, 2018: International Journal of Molecular Sciences
Ta-Wei Liu, Wesley F Zandberg, Tracey M Gloster, Lehua Deng, Kelsey D Murray, Xiaoyang Shan, David Jaro Vocadlo
O-linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT). O-GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes. Here we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice. These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA) to generate a common OGT inhibitor within cells...
May 14, 2018: Angewandte Chemie
Somchit Jaruratanasirikul, Jutarat Piriyaphan, Tansit Saengkaew, Waricha Janjindamai, Hutcha Sriplung
BACKGROUND: Congenital hypothyroidism (CH) is one of the common causes of intellectual disability which can be prevented by early detection of an elevated thyroid stimulating hormone (TSH) level in the newborn and by treatment with thyroxine. In Thailand, neonatal TSH screening was implemented nationwide in 2005. The objective of the study was to determine the etiologies and the estimated incidences of CH in southern Thailand before and after the implementation of a neonatal TSH screening program in 2005...
May 11, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
Charles Bachy, Christina J Charlesworth, Amy M Chan, Jan F Finke, Chee-Hong Wong, Chia-Lin Wei, Sebastian Sudek, Maureen L Coleman, Curtis A Suttle, Alexandra Z Worden
Prasinophytes are widespread marine algae for which responses to nutrient limitation and viral infection are not well understood. We studied the picoprasinophyte, Micromonas pusilla, grown under phosphate-replete (0.65±0.07 d-1 ) and 10-fold lower (low)-phosphate (0.11±0.04 d-1 ) conditions, and infected by the phycodnavirus MpV-SP1. Expression of 17% of Micromonas genes in uninfected cells differed by >1.5-fold (q<0.01) between nutrient conditions, with genes for P-metabolism and the uniquely-enriched Sel1-like repeat (SLR) family having higher relative transcript abundances, while phospholipid-synthesis genes were lower in low-P than P-replete...
May 11, 2018: Environmental Microbiology
Ji-Eun Kim, Ah-Reum Ko, Hye-Won Hyun, Su-Ji Min, Tae-Cheon Kang
Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE...
May 10, 2018: Cell Death & Disease
Wei Wang, Chuan Yang, Xiao Yi Wang, Li Yan Zhou, Guo Juan Lao, Dan Liu, Chuan Wang, Meng Die Hu, Ting Ting Zeng, Li Yan, Meng Ren
Diabetic wounds are recalcitrant to healing. However, the mechanism causing this dysfunction is not fully understood. High expression of matrix metalloproteinase-9 (MMP-9) is indicative of poor wound healing. Here, we show that specificity protein-1 (Sp1), a regulator of MMP-9, binds directly to its promoter and enhances its expression. Additionally, we demonstrated that Sp1 is the direct target of two miRNAs, miR-129 and -335, which are significantly downregulated in diabetic skin tissues. In vitro experiments confirmed that miR-129 or -335 overexpression inhibits MMP-9 promoter activity and protein expression by targeting Sp1, whereas the inhibition of these miRNAs has the opposite effect...
May 10, 2018: Diabetes
Moon-Chang Choi, Woo Hee Choi
Osteoarthritis (OA) is the most common and increasing joint disease worldwide. Current treatment for OA is limited to control of symptoms. The purpose of this study was to determine the effect of specificity protein 1 (SP1) inhibitor Mithramycin A (MitA) on chondrocyte catabolism and OA pathogenesis and to explore the underlying molecular mechanisms involving SP1 and other key factors that are critical for OA. Here, we show that MitA markedly inhibited expressions of matrix-degrading enzymes induced by pro-inflammatory cytokine interleukin-1&beta; (IL-1&beta;) in mouse primary chondrocytes...
May 9, 2018: International Journal of Molecular Sciences
Xin Sui, Jianye Cai, Hongyu Li, Chenchen He, Congya Zhou, Yiping Dong, Li Chen, Bin Zhang, Yingnan Wang, Yanan Zhang, Yuan Qiu, Yuanyuan Zhang, Yang Zhao, Yinong Huang, Yutian Shen, Haoxiang Wu, Jiaqi Xiao, Clifford Mason, Qing Zhu, Suxia Han
Castration-resistant prostate cancer (CRPC), which is considered to contain cancer stem cells (CSCs), leads to a high relapse rate in patients with prostate cancer (PCa). However, the markers of prostate CSCs are controversial. Here we demonstrate that CD51, in part, correlates with the poor prognosis of PCa patients. Further, we find that CD51 is a functional molecule that is able to promote the malignancy of PCa through enhancing tumor initiation, metastatic potential, and chemoresistance. Moreover, we find that elevated CD51 expression in PCa specimens correlates with p53 loss of function...
May 9, 2018: Cell Death & Disease
Ming Qian, Haiyi Gong, Xinghai Yang, Jian Zhao, Wangjun Yan, Yan Lou, Dongyu Peng, Zhenxi Li, Jianru Xiao
Osteosarcoma (OS) is the most common type of primary bone tumor and accounts for ~60% of all malignant bone tumors in children and adolescents. A large number of studies have proposed that the dysregulated and dysfunctional microRNAs may serve important roles in the occurrence, progression and metastasis of various types of human cancer, including OS. MicroRNA-493 (miR-493) has been identified to act as a tumor suppressor in several types of human cancer. However, little is known regarding the expression pattern and clinical significance of miR-493 in OS...
May 2018: Oncology Letters
Patricia Dauer, Nikita S Sharma, Vineet K Gupta, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Chemoresistance is a major therapeutic challenge that plays a role in the poor statistical outcomes in pancreatic cancer. Unfolded Protein Response or UPR is one of the homeostasis mechanisms in cancer cells that have been correlated with chemoresistance in a number of cancers including pancreatic cancer. In the current study, we show that modulating glucose regulatory protein 78 (GRP78), the master regulator of the UPR, can have a profound effect on multiple pathways that mediate chemoresistance. Our study showed for the first time that silencing GRP78 can diminish efflux activity of ATP-binding cassette (ABC) transporters, and it can decrease the antioxidant response resulting in an accumulation of reactive oxygen species (ROS)...
May 8, 2018: Molecular Oncology
Zi-Ming Liu, Xian-Long Zhu, Jun Lu, Wan-Jun Cai, Ya-Ping Ye, Yao-Ping Lv
The present study aimed to investigate the effect rapid temperature change from moderate temperature to high temperatures on heat shock protein (HSP) expression and antioxidant enzyme activities in mud crabs. Two mud crabs, one with one spine on the outer margin of the carpus of cheliped (Sp1) and another with two spines (Sp2), were acclimated at 25 °C and then transferred to a 33 °C environment, and HSP expression and antioxidant enzyme activity were assessed. HSP70 and HSP60 were markedly up-regulated in the gills and hepatopancreas of Sp1 and Sp2 after exposure to 35 °C...
May 3, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Kenneth J Dery, Craig Silver, Lu Yang, John E Shively
The adhesion protein Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in epithelial cells as a short cytoplasmic isoform (S-iso) and in leukocytes as a long cytoplasmic isoform (L-iso) and is frequently silenced in cancer by unknown mechanisms. Previously, we reported that interferon response factor 1 (IRF1) biases alternative splicing (AS) to include the variable exon 7 in CEACAM1, generating L-iso. We now show that IRF1 and a variant of heterogeneous nuclear ribonucleoprotein L (Lv1) coordinately silence the CEACAM1 gene...
May 2, 2018: Journal of Biological Chemistry
Sara S Alhakeem, Mary K McKenna, Karine Z Oben, Sunil K Noothi, Jacqueline R Rivas, Gerhard C Hildebrandt, Roger A Fleischman, Vivek M Rangnekar, Natarajan Muthusamy, Subbarao Bondada
Chronic lymphocytic leukemia (CLL) patients progressively develop an immunosuppressive state. CLL patients have more plasma IL-10, an anti-inflammatory cytokine, than healthy controls. In vitro human CLL cells produce IL-10 in response to BCR cross-linking. We used the transgenic Eμ-T cell leukemia oncogene-1 ( TCL1 ) mouse CLL model to study the role of IL-10 in CLL associated immunosuppression. Eμ-TCL mice spontaneously develop CLL because of a B cell-specific expression of the oncogene, TCL1. Eμ- TCL1 mouse CLL cells constitutively produce IL-10, which is further enhanced by BCR cross-linking, CLL-derived IL-10 did not directly affect survival of murine or human CLL cells in vitro...
April 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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