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Eden A Dulka, Suzanne M Moenter
Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via LH pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether or not this is altered by sex or prenatal androgen treatment are unknown...
September 15, 2017: Endocrinology
Brady S Moffett, Marianne Galati, Donald Mahoney, YoungNa Lee-Kim, Jun Teruya, Mona D Shah, Donald L Yee
Aims Enoxaparin dosing requirements in the first year of life can be highly variable. Characterization of pharmacokinetics in this patient population can assist in dosing. METHODS: Patients less than one year post-natal age who received enoxaparin and had an anti-factor Xa activity level drawn as inpatients were identified through the pharmacy database over a five-year period. Patients on renal replacement therapy or with hyperbilirubinemia were excluded. Data collection included demographic variables, indication for enoxaparin, enoxaparin doses, anti-factor Xa activity levels, serum creatinine, hemoglobin, hematocrit, platelet count, and urine output over the previous 24 hours...
September 19, 2017: Therapeutic Drug Monitoring
J H Rothman, O Surriga, E de Stanchina, S D Vasudeva, G K Schwartz
Peptide nucleic acid (PNA) oligomers are DNA mimics, which are capable of binding gene sequences 1000-fold more avidly than complementary native DNA by strand invasion and effectively obstruct transcription. Irreversibly obstructing the transcription or replication of a gene sequence, such as BRAF(V600E), offers a potential route to specifically target the cancer cell itself. We have employed PNA oligomers to target BRAF(V600E) in a sequence-specific complementary manner. These PNAs have been modified by appending configurationally stabilizing cationic peptides in order to improve their cellular delivery and target avidity...
September 22, 2017: Cancer Gene Therapy
Ritva Rice, Judith Cebra-Thomas, Maarja Haugas, Juha Partanen, David P C Rice, Scott F Gilbert
Ectothermal reptiles have internal pigmentation, which is not seen in endothermal birds and mammals. Here we show that the development of the dorsal neural tube-derived melanoblasts in turtle Trachemys scripta is regulated by similar mechanisms as in other amniotes, but significantly later in development, during the second phase of turtle trunk neural crest emigration. The development of melanoblasts coincided with a morphological change in the dorsal neural tube between stages mature G15 and G16. The melanoblasts delaminated and gathered in the carapacial staging area above the neural tube at G16, and differentiated into pigment-forming melanocytes during in vitro culture...
September 21, 2017: Scientific Reports
Narumi Shigi, Jun Sumaoka, Makoto Komiyama
More than ten years ago, artificial restriction DNA cutters were developed by combining two pseudo-complementary peptide nucleic acid (pcPNA) strands with either Ce(IV)/EDTA or S1 nuclease. They have remarkably high site-specificity and can cut only one predetermined site in the human genome. In this article, recent progress of these man-made tools have been reviewed. By cutting the human genome site-selectively, desired fragments can be clipped from either the termini of chromosomes (telomeres) or from the middle of genome...
September 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Linda Piras, Concetta Avitabile, Luca Domenico D'Andrea, Michele Saviano, Alessandra Romanelli
We report the application of the arsenical complex FlAsH-EDT2 for the identification of oligonucleotide sequences. We designed PNA sequences conjugated to either a tetracysteine motif and to split tetracysteine sequences, that are recognized by FlAsH. The effect of conjugation of the PNA to the tetracysteine peptide and RNA hybridization on the fluorescence of the arsenical complex has been investigated. The reconstitution of the tetracysteine motif, starting from 15-mer PNAs conjugated to split tetracysteine sequences and hybridized to a complementary oligonucleotide was also explored...
September 14, 2017: Biochemical and Biophysical Research Communications
María Angélica Luque-González, Mavys Tabraue-Chávez, Bárbara López-Longarela, Rosario María Sánchez-Martín, Matilde Ortiz-González, Miguel Soriano-Rodríguez, José Antonio García-Salcedo, Salvatore Pernagallo, Juan José Díaz-Mochón
Protozoan parasites of the Trypanosomatidae family can cause devastating diseases in humans and animals, such as Human African Trypanosomiasis or Sleeping Sickness, Chagas disease and Leishmaniasis. Currently, there are molecular assays for detecting parasitic infections and their post-treatment monitoring based on nucleic acid amplification, but there are still certain limitations which limit the development of assays that can detect and discriminate between parasite infections with a single test. Here, we present the development of a novel molecular assay for the rapid identification of Trypanosomatids, integrating DNA analysis by dynamic chemistry in conjunction with Matrix-Assisted Laser Desorption Ionization - Time-of-Flight Mass Spectrometry (MALDI-ToF)...
January 1, 2018: Talanta
Anja Reithmeier, Elena Panizza, Michael Krumpel, Lukas M Orre, Rui M M Branca, Janne Lehtiö, Barbro Ek-Rylander, Göran Andersson
BACKGROUND: Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. METHODS: MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels...
September 15, 2017: BMC Cancer
Toshiki Chiba, Takaya Sato, Yusuke Sato, Seiichi Nishizawa
Red-emissive fluorescent probes have been developed by integration of quinoline blue or thiazole red as the base surrogate into triplex-forming PNAs, allowing selective sensing of a sequence of double-stranded RNA.
September 14, 2017: Organic & Biomolecular Chemistry
Guangxia Lu, Zichao Yu, Mengmeng Lu, Dongyang Liu, Feifei Wang, Yichen Wu, Yu Liu, Chao Liu, Lingling Wang, Linsheng Song
Executioner caspases play important roles in apoptotic pathway and immune defense, which is considered to coordinate the execution phase of apoptosis by cleaving multiple structural and repair proteins. However, the knowledge about the activation mechanism and function of executioner caspases in mollusks, especially marine bivalves is limited. In the present study, the full-length cDNA sequence of caspase-1 was cloned from oyster Crassostrea gigas, which encoded a predicted protein containing a small subunit (p10) and large subunit (p20) with a conserved caspase active site QACRG similar to that of human executioner caspase-3/7...
September 6, 2017: Developmental and Comparative Immunology
E Ibáñez-Martínez, A Ruiz-Gaitán, J Pemán-García
The number of patients at risk of suffering invasive fungal infection (IFI) is increasing. Because of its high mortality, new rapid and accurate diagnostic tools are needed. Last advances in invasive candidiasis diagnosis comprise Peptide Nucleic Acid Fluorescent In-Situ Hybridization (PNA-FISH), direct MALDI-TOF or multiplex acid nucleic testing. While all of them rely in positive blood cultures, T2Candida uses PCR coupled with T2Magnetic resonance detection directly in whole blood, allowing detection of 1-3 UFC/mL of Candida in about four hours...
September 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
John T M DiMaio, Todd M Doran, Derek M Ryan, Danielle M Raymond, Bradley L Nilsson
Self-assembled peptide-based hydrogels are emerging materials that have been exploited for wound healing, drug delivery, tissue engineering, and other applications. In comparison to synthetic polymer hydrogels, supramolecular peptide-based gels have advantages in biocompatibility, biodegradability, and ease of synthesis and modification. Modification of the emergent viscoelasticity of peptide hydrogels in a stimulus responsive fashion is a longstanding goal in the development of next-generation materials. In an effort to selectively modulate hydrogel viscoelasticity, we report herein a method to enhance the elasticity of β-sheet peptide hydrogels using specific molecular recognition events between functionalized hydrogel fibrils and biomolecules...
September 14, 2017: Biomacromolecules
N Kuru, K Cinar, E Demirbag, R Ilgun
We investigated carbohydrate residues on the epithelial surface, in the epithelial cells and in gland cells of the tongue of the mole rat using histochemical methods. We used horseradish peroxidase-conjugated lectins from Helix pomatia (HPA), Arachishypogaea (PNA), Ulexeuropaeus (UEA I), Canavaliaensiformis (Con A). The most intense reactivity was observed in the keratin layer with HPA, UEA I and Con A, and in the epithelial cells with UEA I and Con A. In the glands, we found strong reactivity in serous cells with HPA and Con A, and in mucous cells with HPA and UEA I...
September 1, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Irina Novosjolova, Scott D Kennedy, Eriks Rozners
Development of nucleic acid base pair analogues that use new modes of molecular recognition is important for fundamental research and practical applications. The goal of this study was to evaluate 2-methoxypyridine as a cationic thymidine mimic in the A-T base pair. The hypothesis was that including protonation in the Watson-Crick base pairing scheme could enhance the thermal stability of DNA double helix without compromising the sequence selectivity. DNA and peptide nucleic acid (PNA) sequences containing the new 2-methoxypyridine nucleobase (P) were synthesized and studied using UV thermal melting and NMR spectroscopy...
August 31, 2017: Chembiochem: a European Journal of Chemical Biology
Jihong Cui, Hanxue Zheng, Jing Zhang, Liyuan Jia, Yalong Feng, Wenjun Wang, Hongmin Li, Fulin Chen
Glycans are known to play important roles in molecular recognition, cell-cell adhesion, molecular trafficking, receptor activation and signal transduction during development and regeneration. Despite numerous investigations of regenerating salamander limbs, global analysis of the precise variation of glycans during the limb regeneration process has received little attention. Here, we have used lectin microarrays and lectin histochemistry to analyze the alterations and distribution of glycans during the early stages leading to blastema formation during Cynops orientalis limb regeneration in response to limb amputation...
August 30, 2017: Wound Repair and Regeneration
Yu-Lan Wang, Ming He, Richard J Miron, Ao-Ying Chen, Yan-Bing Zhao, Yu-Feng Zhang
Treatment of bacterial infections due to the fast emergence of drug-resistant bacteria is a significant challenge faced in modern medicine. Here the authors report a drug-induced self-assembly nanoantibiotic for treating bacterial infection, with temperature/pH-sensitivity, synergistic antibacterial effect of silver and antibiotics, and immunoregulatory effect. In this nanoantibiotic, smart polymer p(N-isopropylacrylamide-b-acrylic acid) triblock polymer (PNA) utilized to encapsulate the drugs provides convenience in preparing this structure simply through drug-induced self-assembly and controllable release profile by changing the sequence of addition of different drugs...
September 20, 2017: ACS Applied Materials & Interfaces
Edmund C Jenkins, Elaine J Marchi, Milen T Velinov, Lingling Ye, Sharon J Krinsky-McHale, Warren B Zigman, Nicole Schupf, Wayne P Silverman
Telomere shortening was shown to parallel Alzheimer's disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T-lymphocyte interphases from individuals with Down syndrome (DS) with and without "mild cognitive impairment" (MCI-DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI-DS in this high-risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (N = 4 Female, N = 6 Male) developing MCI-DS...
August 30, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Derek Reichel, Louis T Curtis, Elizabeth Ehlman, B Mark Evers, Piotr Rychahou, Hermann B Frieboes, Younsoo Bae
PURPOSE: To develop polymer nanoassemblies (PNAs) modified with halofluorochromic dyes to allow for the detection of liver metastatic colorectal cancer (CRC) to improve therapeutic outcomes. METHODS: We combine experimental and computational approaches to evaluate macroscopic and microscopic PNA distributions in patient-derived xenograft primary and orthotropic liver metastatic CRC tumors. Halofluorochromic and non-halofluorochromic PNAs (hfPNAs and n-hfPNAs) were prepared from poly(ethylene glycol), fluorescent dyes (Nile blue, Alexa546, and IR820), and hydrophobic groups (palmitate), all of which were covalently tethered to a cationic polymer scaffold [poly(ethylene imine) or poly(lysine)] forming particles with an average diameter < 30 nm...
August 24, 2017: Pharmaceutical Research
Wes Onland, Martin Offringa, Anton van Kaam
BACKGROUND: Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative...
August 24, 2017: Cochrane Database of Systematic Reviews
Yuqian Zhang, Ankit Rana, Yiwen Stratton, Maria F Czyzyk-Krzeska, Leyla Esfandiari
MicroRNAs (miRs) are small noncoding RNAs that play a critical role in gene regulation. Recently, traces of cancer-related miRs have been identified in body fluids, which make them remarkable noninvasive biomarkers. In this study, a new nanopore-based detection scheme utilizing a borosilicate micropipette and an assay of complementary γ-peptide nucleic acid (γ-PNA) probes conjugated to polystyrene beads have been reported for the detection of miR-204 and miR-210 related to the clear cell Renal Cell Carcinoma (ccRCC)...
September 5, 2017: Analytical Chemistry
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