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Joshua T Atkinson, Alicia M Jones, Quan Zhou, Jonathan J Silberg
Deep mutational scanning has been used to create high-resolution DNA sequence maps that illustrate the functional consequences of large numbers of point mutations. However, this approach has not yet been applied to libraries of genes created by random circular permutation, an engineering strategy that is used to create open reading frames that express proteins with altered contact order. We describe a new method, termed circular permutation profiling with DNA sequencing (CPP-seq), which combines a one-step transposon mutagenesis protocol for creating libraries with a functional selection, deep sequencing and computational analysis to obtain unbiased insight into a protein's tolerance to circular permutation...
April 18, 2018: Nucleic Acids Research
Mehmet Kaya, Vignesh Balasubramanian, Amit Patel, Yueya Ge, John K-J Li
Arterial compliance has been recognized as a critical parameter in governing pulsatile flow dynamics. It has traditionally been assumed constant throughout the cardiac cycle and its computation has been based either on the classic Windkessel model (C) in diastole or the stroke volume over pulse pressure (Cv ) method in systole. Other methods using area (Cam ) or two-area (Ctam ) and exponential (C(P)exp1 ) methods were used for the cardiac cycle. We proposed a novel compliance-pressure loop (CPP loop) approach for the quantification of arterial compliance and compared it to existing linear and nonlinear methods...
June 5, 2018: Computers in Biology and Medicine
Mariana Rae, Panos Zanos, Polymnia Georgiou, Priti Chivers, Alexis Bailey, Rosana Camarini
Environmental conditions, such as stress and environmental enrichment (EE), influence predisposition to alcohol use/abuse; however, the underlying mechanisms remain unknown. To assess the effect of environmental conditions on the initial rewarding effects of alcohol, we examined conditioned place-preference (CPP) to alcohol following exposure to EE in mice. Since social context is a major factor contributing to initial alcohol-drinking, we also assessed the impact of EE on the levels of the "social neuropeptide" oxytocin (OT) and its receptor, OTR...
June 13, 2018: Neuropharmacology
Chen Yuan-Hao, Tung-Tai Kuo, Eagle Yi-Kung Huang, Barry J Hoffer, Jen-Hsin Kao, Yu-Ching Chou, Yung-Hsiao Chiang, Jonathan Miller
Background: Traumatic brain injury (TBI) is known to impact dopamine-mediated reward pathways, but the underlying mechanisms have not been fully established. Methods: Nicotine-induced conditional place preference (CPP) was used to study rats exposed to a 6-psi fluid percussion injury (FPI) with and without prior exposure to nicotine. Preference was quantified as a score defined as (C1-C2) / (C1+C2), where C1 is time in the nicotine-paired compartment and C2 is time in the saline-paired compartment...
June 14, 2018: International Journal of Neuropsychopharmacology
Sena Cantas-Orsdemir, Jane L Garb, Holley F Allen
CONTEXT: Some pediatric endocrinologists recommend that girls with central precocious puberty (CPP) have cranial magnetic resonance imaging (MRI) performed only if they are younger than 6 years of age. However, no practice guidelines exist. OBJECTIVE: To assess the frequency of intracranial lesions in girls with CPP. STUDY DESIGN: We searched six electronic databases (PubMed, Cochrane, Web of Science, SCOPUS, ProQuest, and Dissertation & Theses) from 1990 through December 2015...
June 14, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
V L Collie-Akers, J A Schultz, S B Fawcett, S Landry, S Obermeier, E A Frongillo, M Forthofer, N Weinstein, S A Weber, A Logan, S S Arteaga, L Nebeling, L E Au
INTRODUCTION: Efforts to address the critical public health problem of childhood obesity are occurring across the USA; however, little is known about how to characterize the intensity of these efforts. OBJECTIVES: The purposes of this study are to describe the intensity of community programs and policies (CPPs) to address childhood obesity in 130 US communities and to examine the extent to which observed CPPs targeted multiple behaviours and employed a comprehensive array of strategies...
June 14, 2018: Pediatric Obesity
Ryo Soga, Tomoyo Isoguchi Shiramatsu, Hirokazu Takahashi
Conditioned place preference (CPP) tests in rodents have been well established to measure preference induced by secondary reinforcing properties, but conventional assays are not sensitive enough to measure innate, weak preference, or the primary reinforcing property of a conditioned stimulus. We designed a novel CPP assay with better sensitivity and efficiency in quantifying and ranking preference of particular sounds among multiple alternatives. Each test tone was presented according to the location of free-moving rats in the arena, where assignment of location to each tone changed in every 20-s session...
2018: PloS One
Elisangela G Cata-Preta, Yasmim A Serra, Eliseu da C Moreira-Junior, Henrique S Reis, Natali D Kisaki, Matheus Libarino-Santos, Raiany R R Silva, Thaísa Barros-Santos, Lucas C Santos, Paulo C R Barbosa, José L Costa, Alexandre J Oliveira-Lima, Lais F Berro, Eduardo A V Marinho
Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N -dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3...
2018: Frontiers in Pharmacology
Balachandran Manavalan, Sathiyamoorthy Subramaniyam, Tae Hwan Shin, Myeong Ok Kim, Gwang Lee
Cell-penetrating peptides (CPPs) can enter cells as a variety of biologically active conjugates and have various biomedical applications. To offset the cost and effort of designing novel CPPs in laboratories, computational methods need to be developed to identify candidate CPPs before in vitro experimental studies. In this study, we developed a two-layer prediction framework for machine-learning-based prediction of cell-penetrating peptides (MLCPP). The first layer predicts whether a given peptide is a CPP or non-CPP, whereas the second layer predicts the uptake efficiency of the predicted CPPs...
June 12, 2018: Journal of Proteome Research
Uma Keyal, Qiong Luo, Anil Kumar Bhatta, Hansen Luan, Ping Zhang, Qianqian Wu, Haiyan Zhang, Pei Liu, Linglin Zhang, Peiru Wang, Degang Yang, Guolong Zhang, Jing Yao, Xiuli Wang, Lei Shi
Zinc Pthalocyanine (ZnPc) is a second- generation photodynamic therapy (PDT) sensitizer with sufficient PDT activity for squamous cell carcinoma (SCC). ZnPc is hydrophobic and insoluble in water, which creates hurdles in systemic administration and hence restricts its use in clinic. Here we have loaded ZnPc on chitosan / methoxy polyethylene glycol - polylactic acid (CPP) nanoparticles to form Z-CPP to enhance PDT efficacy. In vitro and in vivo studies were performed to see dark toxicity of the compounds ZnPc, CPP, and Z-CPP...
June 12, 2018: Journal of Biophotonics
Yu Yuan Zhang, Hai Ming Wong, Colman P J McGrath, Quan Li Li
Casein phosphate-amorphous calcium phosphate (CPP-ACP), as a remineralisation agent, is extensively used in managing demineralised enamel; however, its remineralisation kinetics is low. This study aimed to improve remineralisation kinetics of CPP-ACP by introducing a rapid remineralisation method with electrophoresis. In vitro, a pH-cycling enamel model was used to test remineralisation potentials of electrophoresis-aided CPP-ACP. For verifying remineralisation potentials of electrophoresis-aided CPP-ACP in vivo in a rabbit model, acid-etched enamel surface on rabbit maxillary incisors was remineralised by electrophoresis-aided CPP-ACP with 1...
June 11, 2018: Scientific Reports
Hossein Aleyasin, Meghan E Flanigan, Sam A Golden, Aki Takahashi, Caroline Menard, Madeline L Pfau, Jacob Multer, Jacqueline Pina, Kathryn A McCabe, Naemal Bhatti, Georgia E Hodes, Mitra Heshmati, Rachael L Neve, Eric J Nestler, Elizabeth A Heller, Scott J Russo
A growing number of studies implicate the brain's reward circuitry in aggressive behavior. However, the cellular and molecular mechanisms within brain reward regions that modulate the intensity of aggression as well as motivation for it have been underexplored. Here, we investigate the cell-type-specific influence of ΔFosB, a transcription factor known to regulate a range of reward and motivated behaviors, acting in the nucleus accumbens (NAc)-a key reward region-in male aggression in mice. We show that ΔFosB is specifically increased in dopamine D1 receptor (Drd1) expressing medium spiny neurons (D1-MSNs) in NAc after repeated aggressive encounters...
June 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sheng Wang, Benjamin Brigoli, Jongseuk Lim, Alisha Karley, Man-Kyo Chung
Craniofacial muscle pain, such as spontaneous pain and bite-evoked pain, are major symptoms in patients with temporomandibular disorders and infection. However, the underlying mechanisms of muscle pain, especially mechanisms of highly prevalent spontaneous pain, are poorly understood. Recently, we reported that transient receptor potential vanilloid 1 (TRPV1) contributes to spontaneous pain but only marginally contributes to bite-evoked pain during masseter inflammation. Here, we investigated the role of transient receptor potential ankyrin 1 (TRPA1) in spontaneous and bite-evoked pain during masseter inflammation, and dissected the relative contributions of TRPA1 and TRPV1...
June 8, 2018: Neuroscience
Keith L Williams, Melissa M Nickel, Justin T Bielak
Aims: To determine if oral ethanol self-administration produces a conditioned place preference (CPP) and to determine if ethanol pre-exposure conditions during the juvenile/adolescent period alter the conditioned effects of ethanol and subsequent ethanol self-administration. Short summary: Modified conditioned place preference paradigm allowed rats to orally self-administer ethanol followed by short duration exposure to conditioning chambers. Ethanol produced a conditioned place aversion even though rats self-administered ethanol following the final conditioning test...
June 8, 2018: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
Jiayan Wu, Guangbin Liu, Yongcan Sun, Xuepeng Wang, Hao Fang, Heng Jiang, Zhiming Guo, Jinggang Dong
The animal intestine provides a competitive environment for the microbiota. Successful colonization by pathogens requires sensing chemical signals to regulate the expression of virulence genes. Some bacteria rely on a two-component chemical signal transduction system, named FusKR, to regulate virulence genes expression by intestinal fucose. Here we construct the fucP gene deletion strain prove FucP regulation of the T3SS in E. tarda. The result showed that the mutant strain had down-regulated significantly the gene expression of FusKR and T3SS compared to the wild-type strain (p < 0...
June 7, 2018: Fish & Shellfish Immunology
Dong Keon Lee, Yong Sung Cha, Oh Hyun Kim, Kyoung Chul Cha, Kang Hyun Lee, Sung Oh Hwang, Hyun Kim, Young Hwan Lee, Minjung Kathy Chae
BACKGROUND: An automatic simultaneous sternothoracic cardiopulmonary resuscitation (SST-CPR) device is an apparatus that performs CPR by providing simultaneous cyclic compressions of the thorax with a thoracic strap and compression of the sternum with a piston. OBJECTIVE: This study was conducted to compare the hemodynamic effects of CPR with an automatic SST-CPR device to those with standard CPR (STD-CPR) in cardiac arrest patients. METHODS: A randomized trial was performed on victims of out-of-hospital cardiac arrest resistant to initial 20 min of CPR after emergency department (ED) arrival...
June 6, 2018: Journal of Emergency Medicine
Paola Frallonardo, Roberta Ramonda, Luca Peruzzo, Anna Scanu, Paola Galozzi, Leonardo Tauro, Leonardo Punzi, Francesca Oliviero
The current study aimed to investigate the association of calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals in synovial fluid (SF) of patients with osteoarthritis (OA) with disease severity, clinical symptoms, and synovial inflammation. One-hundred-and-ten patients with knee OA completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) self-assessment questionnaire, the Lequesne algofunctional index survey, and the visual analogic scale forms; they also underwent power Doppler ultrasonography (PDUS) to assess synovial inflammation...
June 7, 2018: Clinical Rheumatology
Melanie A Blevins, Caiguo Zhang, Lingdi Zhang, Hong Li, Xueni Li, David A Norris, Mingxia Huang, Rui Zhao
The carboxyl-terminal binding proteins (CtBP) are transcriptional co-repressors that regulate the expression of multiple epithelial-specific and pro-apoptotic genes. Overexpression of CtBP occurs in many human cancers where they promote the epithelial-to-mesenchymal transition, stem cell-like features, and cell survival, while knockdown of CtBP in tumor cells results in p53-independent apoptosis. CtBPs are recruited to their target genes by binding to a conserved PXDLS peptide motif present in multiple DNA-binding transcription factors...
June 7, 2018: Molecular Oncology
Xi He, Xinli Chen, Lisha Liu, Yu Zhang, Yifei Lu, Yujie Zhang, Qinjun Chen, Chunhui Ruan, Qin Guo, Chao Li, Tao Sun, Chen Jiang
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive malignancy with a five year survival rate of <5%. The aberrant expression of extracellular matrix (ECM) in the tumor stroma forms a compact physical barrier, which that leads to insufficient extravasation and penetration of nanosized therapies. To overcome the severe resistance of PDAC to conventional therapies, a sequentially triggered nanoparticle (aptamer/cell-penetrating peptide-camptothecin prodrug, i.e., Apt/CPP-CPTD NPs) with tumor penetration and intelligent drug release profile is designed...
May 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Yingkang Yang, Xiaoqi Wang, Guijie Chen, Wenhua Zhou, Xiaoxiong Zeng, Bing Hu, Yunqi Li, Qingrong Huang
In the present study, small angle X-ray scattering (SAXS) is applied to investigate the interaction between caseinophosphopeptides (CPP), the major digested product of milk protein, and chitosan (CS) under simulated gastrointestinal (GI) pH conditions. The change in pH value from the gastric to small intestinal environment induces complexation between CPP and CS, which is mainly driven by electrostatic interactions. The fractal dimension (Df) value of the domains inside the CPP-CS complexes is greater than 3, indicating the formation of dense particles/aggregates at the nanoscale...
June 6, 2018: Food & Function
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