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Shivaji Thadke, J Dinithi R Perera, V M Hridya, Kirti Bhatt, Ashif Yasin Shaikh, Wei-Che Hsieh, Mengshen David Chen, Chakicherla Gayathri, Roberto R Gil, Gordon S Rule, Arnab Mukherjee, Charles A Thornton, Danith H Ly
We report the development of a new class of nucleic acid ligands that is comprised of Janus bases and MPPNA backbone and is capable of binding rCAG-repeats in a sequence-specific and selective manner via, inference, bivalent H-bonding interactions. Individually, the interactions between ligands and RNA are weak and transient. However, upon the installation of C-terminal thioester and N-terminal cystine and the reduction of disulfide bond, they undergo template-directed native chemical ligation to form concatenated oligomeric products that bind tightly to the RNA template...
March 21, 2018: Biochemistry
Marco Baldrighi, Pier Paolo Sainaghi, Mattia Bellan, Ettore Bartoli, Luigi Mario Castello
INTRODUCTION: Although hypovolemia remains the most relevant problem during acute decompensated diabetes in its clinical manifestations (diabetic ketoacidosis, DKA, and hyperglycemic hyperosmolar state, HHS), the electrolyte derangements caused by the global hydroelectrolytic imbalance usually complicate the clinical picture at presentation and may be worsened by treatment itself. AIM: This review article is focused on the management of dysnatremias during hyperglycemic hyperosmolar state with the aim of providing clinicians a useful tool to early indentify the sodium derangement in order to address properly its treatment...
March 19, 2018: Current Diabetes Reviews
Vasudevan Bakthavatchalu, Katherine J Wert, Yan Feng, Anthony Mannion, Zhongming Ge, Alexis Garcia, Kathleen E Scott, Tyler J Caron, Carolyn M Madden, Johanne T Jacobsen, Gabriel Victora, Rudolf Jaenisch, James G Fox
Immune-compromised mouse models allow for testing the preclinical efficacy of human cell transplantations and gene therapy strategies before moving forward to clinical trials. However, CRISPR/Cas9 gene editing of the Wsh/Wsh mouse strain to create an immune-compromised model lacking function of Rag2 and Il2rγ led to unexpected morbidity and mortality. This warranted an investigation to ascertain the cause and predisposing factors associated with the outbreak. Postmortem examination was performed on 15 moribund mice...
2018: PloS One
Adele S Ricciardi, Elias Quijano, Rachael Putman, W Mark Saltzman, Peter M Glazer
Peptide nucleic acids (PNAs) can bind duplex DNA in a sequence-targeted manner, forming a triplex structure capable of inducing DNA repair and producing specific genome modifications. Since the first description of PNA-mediated gene editing in cell free extracts, PNAs have been used to successfully correct human disease-causing mutations in cell culture and in vivo in preclinical mouse models. Gene correction via PNAs has resulted in clinically-relevant functional protein restoration and disease improvement, with low off-target genome effects, indicating a strong therapeutic potential for PNAs in the treatment or cure of genetic disorders...
March 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Tirayut Vilaivan
Fluorogenic oligonucleotide probes that can produce a change in fluorescence signal upon binding to specific biomolecular targets, including nucleic acids as well as non-nucleic acid targets, such as proteins and small molecules, have applications in various important areas. These include diagnostics, drug development and as tools for studying biomolecular interactions in situ and in real time. The probes usually consist of a labeled oligonucleotide strand as a recognition element together with a mechanism for signal transduction that can translate the binding event into a measurable signal...
2018: Beilstein Journal of Organic Chemistry
F G Fumuso, S M Giuliano, M G Chaves, D M Neild, M H Miragaya, M C Gambarotta, M I Carretero
The objectives of this study were to evaluate the effect over time of different percentages of seminal plasma (SP) on llama sperm characteristics in raw semen and correlate the techniques routinely used to evaluate sperm viability and acrosome status with the Fluorescein Isothiocyanate -Arachis hypogea agglutinin/Propidium Iodide (FITC-PNA/PI). Eighteen ejaculates, obtained from 6 male llamas using electroejaculation, were incubated in 0.1% collagenase in HEPES-TALP (HT), centrifuged and resuspended with SP and HT: 0, 10, 50 and 100% SP...
February 24, 2018: Animal Reproduction Science
Sudarat Khadsai, Noppadol Seeja, Nunthiya Deepuppha, Metha Rutnakornpituk, Tirayut Vilaivan, Maliwan Nakkuntod, Boonjira Rutanakornpituk
Magnetite nanoparticle conjugated with pyrrolidinyl peptide nucleic acid (MNP@PNA) was synthesized for use as both a magnetic nano-support and a probe for specific adsorption with complementary deoxyribonucleic acid (DNA). MNP@PNA with the size ranging between 120 and 170 nm in diameter was prepared via a free radical polymerization of acrylic acid in the presence of acrylamide-grafted MNP to obtain negatively charged magnetic nanoclusters, followed by ionic adsorption with PNA. According to fluorescence spectrophotometry and gel electrophoresis, this MNP@PNA can differentiate between fully matched, single-base mismatched and fully mismatched synthetic DNAs tagged with different fluorophores...
February 19, 2018: Colloids and Surfaces. B, Biointerfaces
Sharna Tanzima Nuhat, Mamiko Sakata-Yanagimoto, Daisuke Komori, Keiichiro Hattori, Yasuhito Suehara, Kota Fukumoto, Manabu Fujisawa, Manabu Kusakabe, Kosei Matsue, Hirotake Wakamatsu, Mitsunobu Shimadzu, Shigeru Chiba
Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of nodal peripheral T-cell lymphomas. Somatic RHOA mutations, most frequently found at the hotspot site c.50G>T, p. Gly17Val (G17V RHOA mutation) are a genetic hallmark of AITL. Detection of the G17V RHOA mutations assists prompt and appropriate diagnosis of AITL. However, an optimal detection method for the G17V RHOA mutation remains to be elucidated. We compared the sensitivity and concordance of next generation sequencing (NGS), droplet digital PCR (ddPCR) and PNA-LNA clamp method for detecting the G17V RHOA mutations...
March 1, 2018: Cancer Science
Juexian Song, Yi Lyu, Miaomiao Wang, Jing Zhang, Li Gao, Xiaolin Tong
Aims: To evaluate the clinical efficacy of Human Urinary Kallidinogenase (HUK) and Maixuekang capsule in the treatment of acute ischemic stroke (AIS) patients. Methods: In this study, from January 2016 to July 2016, 60 patients with acute ischemic stroke were enrolled and 56 patients with complete information of whom 21 patients received HUK+ basic treatment (HUK group), 16 patients received HUK+ Maixuekang capsule + basic treatment (HUK+ Maixuekang group), 19 patients received basic treatment (control group)...
2018: Frontiers in Physiology
S Vernygorodskyi, V Shkolnikov, D Suhan
AIM: To analyze the glycoprotein binding sites of the gastric mucosa and its secreted mucus using lectin histochemistry in patients with chronic non-atrophic gastritis (CNAG) associated or not-associated with Helicobacter pylori infection with or without dysplasia. MATERIALS AND METHODS: In order to identify the areas with glycoconjugates expression in gastric mucosa, 6 lectins (Canavalia ensiformis agglutinin - Con A, Sambucus nigra agglutinin - SNA, wheat germ agglutinin - WGA, soybean agglutinin - SBA, Helix pomatia agglutinin - HPA, peanut agglutinin - PNA) were used...
July 2017: Experimental Oncology
Shermel Sherman, Nadeen Sarsour, Marziyeh Salehi, Allen Schroering, Blair Mell, Bina Joe, Jennifer W Hill
BACKGROUND: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant...
February 22, 2018: Gut Microbes
Kenneth N Robinson, Rory T Steven, Josephine Bunch
In ultraviolet matrix-assisted laser desorption/ionization mass spectrometry (UV-MALDI MS) matrix compound optical absorption governs the uptake of laser energy, which in turn has a strong influence on experimental results. Despite this, quantitative absorption measurements are lacking for most matrix compounds. Furthermore, despite the use of UV-MALDI MS to detect a vast range of compounds, investigations into the effects of laser energy have been primarily restricted to single classes of analytes. We report the absolute solid state absorption spectra of the matrix compounds α-cyano-4-hydroxycinnamic acid (CHCA), para-nitroaniline (PNA), 2-mercaptobenzothiazole (MBT), 2,5-dihydroxybenzoic acid (2,5-DHB), and 2,4,6-trihydroxyacetophenone (THAP)...
March 2018: Journal of the American Society for Mass Spectrometry
Iris Teubel, Elena Elchinova, Santiago Roura, Marco A Fernández, Carolina Gálvez-Montón, Pedro Moliner, Marta de Antonio, Josep Lupón, Antoni Bayés-Genís
BACKGROUND: Cross-sectional investigations report shorter telomeres in patients with heart failure (HF); however, no studies describe telomere length (TL) trajectory and its relationship with HF progression. Here we aimed to investigate telomere shortening over time and its relationship to outcomes. METHODS: Our study cohort included 101 ambulatory patients with HF. Blood samples were collected at baseline (n = 101) and at the 1-year follow-up (n = 54). Using flow-FISH analysis of circulating monocytes, we simultaneously measured three monocyte subsets-classical (CD14++ CD16- ), intermediate (CD14++ CD16+ ), and nonclassical (CD14+ CD16++ )-and their respective TLs based on FITC-labeled PNA probe hybridization...
February 20, 2018: Journal of Translational Medicine
M N Islam, T Tazmin, M Siddika, M A Hossain, M A Ali, M K Bhuiyan
Multiple pregnancies are a significant risk factor for maternal and perinatal morbidity due to inherent biological risks. The present study was aimed to determine the risk factors and to evaluate the immediate neonatal outcome of multiple pregnancies. This descriptive observational study was conducted in the newly established Special Care Neonatal Unit (SCANU) of Mymensingh Medical College Hospital (MMCH), Bangladesh from January 2015 to March 2015. Total 86 newborns of multiple pregnancies who were admitted during the study period were included in the study...
January 2018: Mymensingh Medical Journal: MMJ
Luiza Rayanna Amorim de Lima, Lúcia Patrícia Bezerra Gomes da Silva, Sinara Mônica Vitalino de Almeida, Thiago Barbosa Cahú, Eduardo Isidoro Carneiro Beltrão, Luiz Bezerra de Carvalho Júnior
In order to characterize the affinity between specific carbohydrate-binding proteins such as lectins, a model is proposed to study these interactions using a polysaccharide membrane to simulate such adsorption. Here, lectin-carbohydrate interactions were chemiluminescently investigated using lectins conjugated to acridinium ester (AE) and polysaccharides composed of their respective specific carbohydrates. The lectin-AE conjugates were incubated with discs (0.0314-0.6358 cm2 ) of phytagel, chitosan and carrageenan...
February 16, 2018: Analytical Biochemistry
Eunseon Oh, Yuhong Liu, Mahesh V Sonar, Diane Merry, Eric Wickstrom
Huntington's disease (HD) is an autosomal-dominant neurodegenerative genetic disorder caused by CAG repeat expansion in exon 1 of the HTT gene. Expression of the mutant gene results in the production of a neurotoxic polyglutamine (polyQ)-expanded huntingtin (Htt) protein. Clinical trials of knockdown therapy of mutant polyglutamine-encoding HTT mRNA in Huntington's disease (HD) have begun. To measure HTT mRNA knockdown effectiveness in human cells, we utilized a fluorescent hybridization imaging agent specific to the region encompassing the human HTT mRNA initiation codon...
February 16, 2018: Bioconjugate Chemistry
Kristina Westerlund, Mohamed Altai, Bogdan Mitran, Mark Konijnenberg, Maryam Oroujeni, Christina Atterby, Marion de Jong, Anna Orlova, Johanna Mattsson, Patrick Micke, Amelie Eriksson Karlström, Vladimir Tolmachev
Affibody molecules are small proteins engineered using a non-antibody scaffold. Radiolabeled affibody molecules are excellent imaging probes, but their application for radionuclide therapy was so far prevented by high renal reabsorption. The aim of this study was to test the hypothesis that affibody-based peptide nucleic acid (PNA)-mediated pretargeted therapy of HER2-expressing cancer extends survival without accompanying renal toxicity. Methods: Human epidermal growth factor (HER2)-targeting affibody molecule ligated with AGTCGTGATGTAGTC PNA hybridization probe (ZHER2:342-SR-HP1) was used as the primary pretargeting agent...
February 9, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Jae Uk Song, Jonghoo Lee
PURPOSE: Molecular testing in non-small cell lung cancer (NSCLC) aids in identifying oncogenic alterations. The aim of this study was to compare the rates of detection of oncogenic alterations and responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) according to EGFR mutation status as determined by peptide nucleic acid (PNA) clamping or direct sequencing (DS). MATERIALS AND METHODS: We performed a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register...
March 2018: Yonsei Medical Journal
N Pospiech, H Cibis, L Dietrich, F Müller, T Bange, S Hennig
Interactions of long non-coding RNAs (lncRNA) with proteins play important roles in the regulation of many cellular processes. PANDAR (Promotor of CDKN1A Antisense DNA damage Activated RNA) is a lncRNA that is transcribed in a p53-dependent manner from the CDKN1A promoter and is involved in the regulation of proliferation and senescence. Overexpression of PANDAR has been observed in several tumor species and correlated with a poor prognosis for patient survival rate. Depending on the cellular state, PANDAR is known to interact with proteins such as the nuclear transcription factor Y subunit A (NF-YA) and the scaffold attachment factor A (SAF-A)...
February 12, 2018: Scientific Reports
Seungyong Lee, Ashley Bice, Brianna Hood, Juan Ruiz, Jahyun Kim, Rhonda D Prisby
Inflammation coincides with diminished marrow function, vasodilation of blood vessels and bone mass. Intermittent parathyroid hormone (PTH) administration independently improves marrow and vascular function, potentially impacting bone accrual. Currently, the influence of marrow and intermittent PTH administration on aged bone blood vessels have not been examined. Vasodilation of the femoral principal nutrient artery (PNA) was assessed in the presence and absence of marrow. Further, we determined the influence of PTH 1-34 on 1) endothelium-dependent vasodilation and signaling pathways (i...
February 8, 2018: Journal of Applied Physiology
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