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Tat'ána Majerová, Tereza Streckerová, Lucie Bednarova, Edward Curtis
G-quadruplexes are four-stranded nucleic acid structures typically stabilized by GGGG tetrads. These structures are intrinsically fluorescent, which expands the known scope of nucleic acid function and raises the possibility that they could eventually be used as signaling components in label-free sensors constructed from DNA or RNA. In this study we systematically investigated the effects of mutations in tetrads, loops, and overhanging nucleotides on the fluorescence intensity and emission wavelength of more than 500 sequence variants of a reference DNA G-quadruplex...
June 13, 2018: Biochemistry
Xin Chen, Bing Yang, Zijing Lin
Computational determination of peptide conformations is challenging as it is a problem of finding minima in a high-dimensional space. The "divide and conquer" approach is promising for reliably reducing the search space size. A random forest learning model is proposed here to expand the scope of applicability of the "divide and conquer" approach. A random forest classification algorithm is used to characterize the distributions of the backbone φ-ψ units ("words"). A random forest supervised learning model is developed to analyze the combinations of the φ-ψ units ("grammar")...
June 11, 2018: Scientific Reports
Hongfang Guo, Rajwali Khan, Sayed Haidar Abbas Raza, Yue Ning, Dawei Wei, Sen Wu, Seyed Mahdi Hosseini, Irfan Ullah, Matthew D Garcia, Linsen Zan
The Krüppel-like factors (KLF) family plays an important role in adipogenesis, which is subject to internal hierarchical regulation. KLF3 is a member of KLF family, mainly responsible for adipocyte differentiation and fat deposition. However, the transcriptional regulation of bovine KLF3 gene and its relationship with KLF15 gene remains unclear during bovine adipogenesis. Here, we report that the expression pattern of KLF3 and KLF15 genes during bovine adipogenesis, when KLF15 gene was overexpressed through adenoviral vector (Ad-KLF15) in bovine adipocytes the expression level of KLF3 gene was increased, similarly when KLF15 was down regulated through siRNA the expression level of KLF3 was also reduced...
June 15, 2018: Gene
Qiong Chen, Hailan Yang, Yongliang Feng, Ping Zhang, Weiwei Wu, Shuzhen Li, Brian Thompson, Xin Wang, Tingting Peng, Fang Wang, Bingjie Xie, Pengge Guo, Mei Li, Ying Wang, Nan Zhao, Suping Wang, Yawei Zhang
Gestational diabetes mellitus is a growing public health concern due to its large disease burden; however, the underlying pathophysiology remains unclear. Therefore, we examined the relationship between 107 single-nucleotide polymorphisms in insulin signalling pathway genes and gestational diabetes mellitus risk using a nested case-control study. The SOS1 rs7598922 GA and AA genotype were statistically significantly associated with reduced gestational diabetes mellitus risk ( ptrend  = 0.0006) compared with GG genotype...
March 2018: Diabetes & Vascular Disease Research
Matthew R Arkenberg, Chien-Chi Lin
Stiffening of the extracellular matrix is a hallmark in cancer progression, embryonic development, and wound healing. To mimic this dynamic process, our work explored orthogonal enzymatic reactions capable of modulating the properties of poly(ethylene glycol) (PEG)-peptide hydrogels. A hepta-mutant bacterial transpeptidase sortase A (SrtA7M) was used to ligate two PEG-peptide macromers (i.e., PEG-YLPRTG and NH2-GGGG-PEG) into a primary hydrogel network. The hydrogels were dynamically stiffened using mushroom tyrosinase (MT), which oxidized tyrosine residues into di-tyrosine and led to increased matrix stiffness...
October 24, 2017: Biomaterials Science
Annalisa Vigorito, Camilla Calabrese, Ettore Paltanin, Sonia Melandri, Assimo Maris
The conformational space of antioxidant dihydrolipoic acid has been explored through the investigation of its pharmacophore, 1,3-propanedithiol. Five of the possible 25 non-equivalent isomers (namely: gGGg', gGGg, g'AGg, gAGg and g'AGg') were observed in the 59.6-74.4 GHz frequency region using free-jet absorption rotational spectroscopy. Furthermore, for three of them, the34 S mono-substituted isotopologues were also detected in natural abundance. Theoretical simulations show that the balance of steric and electronic intramolecular interactions arises on a shallow conformational potential energy surface and suggest that in polar solvents the flexibility of the dithiol chain is greater than that in the isolated phase...
December 21, 2016: Physical Chemistry Chemical Physics: PCCP
Jordan M Anderson, Alexander A Shcherbakov, Brandon L Kier, Jackson Kellock, Irene Shu, Aimee L Byrne, Lisa A Eidenschink, Niels H Andersen
Protein loops make up a large portion of the secondary structure in nature. But very little is known concerning loop closure dynamics and the effects of loop composition on fold stability. We have designed a small system with stable β-sheet structures, including features that allow us to probe these questions. Using paired Trp residues that form aromatic clusters on folding, we are able to stabilize two β-strands connected by varying loop lengths and composition (an example sequence: RWITVTI - loop - KKIRVWE)...
March 2017: Biopolymers
Le Yang, Zhihe Qing, Changhui Liu, Qiao Tang, Jishan Li, Sheng Yang, Jing Zheng, Ronghua Yang, Weihong Tan
G-quadruplex analogues have been widely used as molecular tools for detection of potassium ion (K(+)). However, interference from a higher concentration of sodium ion (Na(+)), enzymatic degradation of the oligonucleotide, and background absorption and fluorescence of blood samples have all limited the use of G-quadruplex for direct detection of K(+) in blood samples. Here, we reported, for the first time, an intermolecular G-quadruplex-based assay capable of direct fluorescent detection of blood K(+). Increased stringency of intermolecular G-quadruplex formation based on our screened G-rich oligonucleotide (5'-TGAGGGA GGGG-3') provided the necessary selectivity for K(+) against Na(+) at physiological ion level...
September 20, 2016: Analytical Chemistry
Heewook Lee, Thomas G Doak, Ellen Popodi, Patricia L Foster, Haixu Tang
A majority of large-scale bacterial genome rearrangements involve mobile genetic elements such as insertion sequence (IS) elements. Here we report novel insertions and excisions of IS elements and recombination between homologous IS elements identified in a large collection of Escherichia coli mutation accumulation lines by analysis of whole genome shotgun sequencing data. Based on 857 identified events (758 IS insertions, 98 recombinations and 1 excision), we estimate that the rate of IS insertion is 3.5 × 10(-4) insertions per genome per generation and the rate of IS homologous recombination is 4...
September 6, 2016: Nucleic Acids Research
K Kajita, Y Kuwano, Y Satake, S Kano, K Kurokawa, Y Akaike, K Masuda, K Nishida, K Rokutan
Ultraconserved regions (UCRs) are >200 bp genomic segments with perfect human-to-rodent sequence identity. Transcribed UCRs constitute a new category of noncoding RNAs whose functions remain poorly understood. The human transformer 2β (TRA2B) gene contains a 419-bp UCR spanning the 276-bp exon 2 and its neighboring introns. TRA2B exon 2 has premature stop codons, whereas an exon 2-containing splice variant (TRA2β4) was expressed preferentially in the nuclei of human colon cancer cells. TRA2β4 knockdown p53-independently stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells...
2016: Oncogenesis
Gang Yang, Xiaoxing Peng, Pengju Guo, Ge Yang
To investigate the association of osteopontin gene -443 C>T, -156 G>GG, and -1748 A>G polymorphisms with cancer risk. The Medline, PubMed, PUBMED, EMBASE and Web of Science databases were searched. Meta-analyses were conducted using RevMan 5.2 software. After searching and evaluating the included papers, total 10 documents involved in -443 C>T, 8 papers involved in four articles involved in -156 G>GG and -1748 A>G were included into this meta analysis. There were no significant differences in genotype osteopontin -443 C>T distribution between cancer cases and control (OR=0...
2015: International Journal of Clinical and Experimental Medicine
Katrina F Tjhung, Pavel I Kitov, Simon Ng, Elena N Kitova, Lu Deng, John S Klassen, Ratmir Derda
In vitro selection of chemically modified peptide libraries presented on phage, while a powerful technology, is limited to one chemical post-translational modification (cPTM) per library. We use unique combinations of redundant codons to encode cPTMs with "silent barcodes" to trace multiple modifications within a mixed modified library. As a proof of concept, we produced phage-displayed peptide libraries Ser-[X]4-Gly-Gly-Gly, with Gly and Ser encoded using unique combinations of codons (TCA-[X]4-GGAGGAGGA, AGT-[X]4-GGTGGTGGT, etc...
January 13, 2016: Journal of the American Chemical Society
Jian Wu, Yihua Bao, Xiaolin Lu, Lihua Wu, Ting Zhang, Jin Guo, Jian Yang
BACKGROUND: The polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD1) has been reported as a risk factor for neural tube defects (NTDs). In the present study, we aimed to investigate whether the single-nucleotide polymorphisms (SNPs) of MTHFD1 gene are associated with NTDs in a Chinese population and to determine their mechanism of action. MATERIAL AND METHODS: MTHFD1 gene was scanned in a total of 270 NTDs cases and 192 healthy controls by using next-generation sequencing (NGS) method...
September 4, 2015: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Alessandro Pandini, Jens Kleinjung, Willie R Taylor, Wolfgang Junge, Shahid Khan
The proton-driven ATP synthase (FOF1) is comprised of two rotary, stepping motors (FO and F1) coupled by an elastic power transmission. The elastic compliance resides in the rotor module that includes the membrane-embedded FO c-ring. Proton transport by FO is firmly coupled to the rotation of the c-ring relative to other FO subunits (ab2). It drives ATP synthesis. We used a computational method to investigate the contribution of the c-ring to the total elastic compliance. We performed principal component analysis of conformational ensembles built using distance constraints from the bovine mitochondrial c-ring x-ray structure...
September 1, 2015: Biophysical Journal
Yulan Liu, Hongbo Lei, Jixiang Zhang, Jun Wang, Kui Li, Weiguo Dong
BACKGROUND AND AIM: Several studies have been conducted to examine the associations between osteopontin (OPN) promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility. METHODS: All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions...
2015: PloS One
Katsunori Hase, Yuuki Fujiwara, Hisae Kikuchi, Shu Aizawa, Fumihiko Hakuno, Shin-Ichiro Takahashi, Keiji Wada, Tomohiro Kabuta
Lysosomes can degrade various biological macromolecules, including nucleic acids, proteins and lipids. Recently, we identified novel nucleic acid-degradation systems termed RNautophagy/DNautophagy (abbreviated as RDA), in which RNA and DNA are directly taken up by lysosomes in an ATP-dependent manner and degraded. We also found that a lysosomal membrane protein, LAMP2C, the cytoplasmic region of which binds to RNA and DNA, functions, at least in part, as an RNA/DNA receptor in the process of RDA. However, it has been unclear whether RDA possesses selectivity for RNA/DNA substrates and the RNA/DNA sequences that are recognized by LAMP2C have not been determined...
July 27, 2015: Nucleic Acids Research
J X Hou, X P An, P Han, J Y Peng, B Y Cao
Guanzhong (n = 321) and Boer (n = 191) goat breeds were used to detect single nucleotide polymorphisms (SNPs) in the coding regions of the prolactin receptor (PRLR) gene by DNA sequencing and PCR-RFLP. Two SNPs (c.1457G>A and c.1645G>A) were identified that caused amino acid variations p.Ser485Asn and p.Val548Met respectively. Statistical results indicated that the c.1457G>A and c.1645G>A SNPs were significantly associated with litter size in Boer and Guanzhong goat breeds. Further analysis revealed that combined genotype C4 (GGGG) and haplotype G-G were better than the others for litter size in both goat breeds...
February 2015: Animal Genetics
Jenna Oberstaller, Yoanna Pumpalova, Ariel Schieler, Manuel Llinás, Jessica C Kissinger
We provide the first comprehensive analysis of any transcription factor family in Cryptosporidium, a basal-branching apicomplexan that is the second leading cause of infant diarrhea globally. AP2 domain-containing proteins have evolved to be the major regulatory family in the phylum to the exclusion of canonical regulators. We show that apicomplexan and perkinsid AP2 domains cluster distinctly from other chromalveolate AP2s. Protein-binding specificity assays of C. parvum AP2 domains combined with motif conservation upstream of co-regulated gene clusters allowed the construction of putative AP2 regulons across the in vitro life cycle...
July 2014: Nucleic Acids Research
Diako Ebrahimi, Hamid Alinejad-Rokny, Miles P Davenport
We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3' end (in +1 and +2 positions) were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3'polypurine tracts (PPTs) which remain double stranded during the HIV reverse transcription...
2014: PloS One
Junfang Zhao, Justin Kai-Chi Lau, Josipa Grzetic, Udo H Verkerk, Jos Oomens, K W Michael Siu, Alan C Hopkinson
Infrared multiple-photon dissociation (IRMPD) spectroscopy and DFT calculations have been used to probe the most stable structures of a3(*) and a4(*) ions derived from both protonated pentaglycine (denoted G5) and pentaalanine (A5). The a3(*) and a4(*) ions derived from protonated A5 feature a CHR=N-CHR'- group at the N-terminus and an oxazolone ring at the C-terminus, as proposed previously [J. Am. Soc. Mass Spectrom. 19, 1788-1798 (2008)]. The isomeric a4(*) ion derived from A5 with a 3,5-dihydro-4H-imidazol-4-one ring structure was calculated to have a slightly better energy than the oxazolone, but the barrier to its formation is higher and there was no evidence of this ion in the IRMPD spectrum...
December 2013: Journal of the American Society for Mass Spectrometry
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