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Rosangela Ferese, Monica Bonetti, Federica Consoli, Valentina Guida, Anna Sarkozy, Francesca R Lepri, Paolo Versacci, Stefano Gambardella, Giulio Calcagni, Katia Margiotti, Francesca Piceci Sparascio, Hossein Hozhabri, Tommaso Mazza, Maria Cristina Digilio, Bruno Dallapiccola, Marco Tartaglia, Bruno Marino, Jeroen den Hertog, Alessandro De Luca
Atrioventricular septal defect (AVSD) may occur as part of a complex disorder (e.g., Down syndrome, heterotaxy), or as isolate cardiac defect. Multiple lines of evidence support a role of calcineurin/NFAT signaling in AVSD, and mutations in CRELD1, a protein functioning as a regulator of calcineurin/NFAT signaling have been reported in a small fraction of affected subjects. In this study, 22 patients with isolated AVSD and 38 with AVSD and heterotaxy were screened for NFATC1 gene mutations. Sequence analysis identified three missense variants in three individuals, including a subject with isolated AVSD [p...
July 14, 2018: Human Mutation
Darren M Hutt, Salvatore Loguercio, Daniela Martino Roth, Andrew I Su, William E Balch
Inherited and somatic rare diseases result from > 200,000 genetic variants leading to loss- or gain-of-toxic function, often caused by protein misfolding. Many of these misfolded variants fail to properly interact with other proteins. Understanding the link between factors mediating the transcription, translation, and protein folding of these disease-associated variants remains a major challenge in cell biology. Herein, we utilized the cystic fibrosis transmembrane conductance regulator (CFTR) protein as a model and performed a proteomics-based high-throughput screen (HTS) to identify pathways and components affecting the folding and function of the most common cystic fibrosis-associated mutation, the F508del variant of CFTR...
July 13, 2018: Journal of Biological Chemistry
Sudarshan Murthy, Jenny Desantis, Patricia Verheugd, Mirko M Maksimainen, Harikanth Venkannagari, Serena Massari, Yashwanth Ashok, Ezeogo Obaji, Yves Nkizinkinko, Bernhard Lüscher, Oriana Tabarrini, Lari Lehtiö
Human Diphtheria toxin-like ADP-ribosyltranferases (ARTD) 10 is an enzyme carrying out mono-ADP-ribosylation of a range of cellular proteins and affecting their activities. It shuttles between cytoplasm and nucleus and influences signaling events in both compartments, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and S phase DNA repair. Furthermore, overexpression of ARTD10 induces cell death. We recently reported on the discovery of a hit compound, OUL35 (compound 1), with 330 nM potency and remarkable selectivity towards ARTD10 over other enzymes in the human protein family...
June 20, 2018: European Journal of Medicinal Chemistry
Navaneethan Palanisamy
Tropheryma whipplei (T. whipplei) is the causative agent of Whipple's disease and blood culture-negative endocarditis. Due to the variability of symptoms, the disease is often poorly diagnosed. Treatment for this bacterial infection is often lengthy, and improper uptake of antibiotics has resulted in relapses in many patients. In the present study, using available bioinformatic tools and databases such as the Cluster Database at High Identity with Tolerance (CD-HIT), the Basic Local Alignment Search Tool for proteins (BLASTp), the Database of Essential Genes (DEG), and the DrugBank database, 13 putative drug targets were identified in T...
June 9, 2018: Computational Biology and Chemistry
Pingxian Liu, Yang Yang, Yuan Ju, Yunxiang Tang, Zitai Sang, Lijuan Chen, Tao Yang, Qi An, Tianyu Zhang, Youfu Luo
In an effort to discover novel inhibitors of M. tuberculosis Caseinolytic proteases (ClpP1P2), a combination strategy of virtual high-throughput screening and in vitro assay was employed and a new pyrrole compound, 1-(2-chloro-6-fluorobenzyl)-2, 5-dimethyl-4-((phenethylamino)methyl)-1H-pyrrole-3-carboxylate was found to display inhibitory effects against H37 Ra with an MIC value of 77 µM. In order for discovery of more potent anti-tubercular agents that inhibit ClpP1P2 peptidase in M. tuberculosis, a series of pyrrole derivatives were designed and synthesized based on this hit compound...
June 4, 2018: Bioorganic Chemistry
Jessica L Counihan, Amanda L Wiggenhorn, Kimberly E Anderson, Daniel K Nomura
Chemical genetics is a powerful approach for identifying therapeutically active small-molecules, but identifying the mechanisms of action underlying hit compounds remains challenging. Chemoproteomic platforms have arisen to tackle this challenge and enable rapid mechanistic deconvolution of small-molecule screening hits. Here, we have screened a cysteine-reactive covalent ligand library to identify hit compounds that impair cell survival and proliferation in non-small cell lung carcinoma cells, but not in primary human bronchial epithelial cells...
July 13, 2018: ACS Chemical Biology
Samuel D Todd, Jonathan D Wiles, Damian A Coleman, Mathew B Brown
During practice and competition, golfers are required to use submaximal effort to hit the ball a given distance, i.e., perform a partial shot. While the full golf swing has undergone extensive research, little has addressed partial shots and the biomechanical modifications golfers employ. This study investigates the biomechanical changes between full and partial swings, and determines if the partial swing is a scaled version of the full swing. Using a repeated measures design, 13 male golfers completed a minimum of 10 swings in the full and partial swing conditions, whilst club, ball, kinematic, and kinetic parameters were recorded...
July 13, 2018: Sports Biomechanics
Rymon Rofaiel, Nilesh Chande
Background/Aims: Many patients currently seek the Internet for health-related information without discerning the quality or bias of the evidence presented. Biologic agents have become the mainstay of therapy in inflammatory bowel disease (IBD), and it is important that patients have access to high-quality information when exploring the various available agents to make informed decisions about their therapy. The primary aim of this study was to evaluate the quality of patient-searched Internet websites that describe the biologic agents used as treatment options for IBD...
July 6, 2018: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Fahad A S Al-Eidan, Saud Alrawkan, Huda Alshammary, Mark A Crowther
Heparin-induced thrombocytopenia (HIT) is a serious complication of the administration of heparin and its derivatives. Non-heparin anticoagulants such as argatroban and fondaparinux are widely used in the management of HIT to compare the effectiveness of argatroban and fondaparinux in the resolution of thrombocytopenia and to compare clinical outcomes in patients with isolated HIT. A retrospective cohort analysis was performed at King Abdulaziz Medical City (KAMC) on patients diagnosed with isolated HIT between 31 Jan, 2014 and 30 June, 2017...
July 12, 2018: Annals of Hematology
(no author information available yet)
No abstract text is available yet for this article.
July 14, 2018: Veterinary Record
Jinyu Liu, Xiaoyan Su, Huachong Li, Li Fan, Yuanyuan Li, Xuemei Tang, Jufang Yan, Xin Chen, Feifei Chen, Jie Liu, Dacheng Yang
In accordance with the structural characteristics of thiazolidinedione drugs and highly bioactive tyrosine derivatives, we tentatively designed the l-phenylglycine derivatives TM1 and TM2 based on basic principles of drug design and then synthesized them. The in vitro screening of peroxisome proliferator-activated receptor gamma (PPARγ) activated activity, α-glucosidase inhibitory and dipeptidyl peptidase-4 inhibitory activities showed that the novel molecule M5 had efficient PPAR response element (PPRE) activated activity (PPRE relative activity 105...
July 5, 2018: Bioorganic & Medicinal Chemistry
Limin Wu, Joon Y Chung, Shivani Saith, Lorenzo Tozzi, Erin M Buckley, Bharat Sanders, Maria A Franceschini, Sevda Lule, Saef Izzy, Josephine Lok, William J Edmiston, Lauren M McAllister, Sloane Mebane, Gina Jin, Jiaxi Lu, John S Sherwood, Sarah Willwerth, Suzanne Hickman, Joseph El Khoury, Eng H Lo, David Kaplan, Michael J Whalen
Repetitive mild traumatic brain injury during adolescence can induce neurological dysfunction through undefined mechanisms. Interleukin-1 (IL-1) contributes to experimental adult diffuse and contusion TBI models, and IL-1 antagonists have entered clinical trials for severe TBI in adults; however, no such data exist for adolescent TBI. We developed an adolescent mouse repetitive closed head injury (rCHI) model to test the role of IL-1 family members in post-injury neurological outcome. Compared to one CHI, three daily injuries (3HD) produced acute and chronic learning deficits and emergence of hyperactivity, without detectable gliosis, neurodegeneration, brain atrophy, and white matter loss at one year...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Sarah L Berry, Hamza Hameed, Anna Thomason, Marissa L Maciej-Hulme, Somaia Saif Abou-Akkada, Paul Horrocks, Helen P Price
The protozoan parasite Leishmania causes leishmaniasis; a spectrum of diseases of which there are an estimated 1 million new cases each year. Current treatments are toxic, expensive, difficult to administer, and resistance to them is emerging. New therapeutics are urgently needed, however, screening the infective amastigote form of the parasite is challenging. Only certain species can be differentiated into axenic amastigotes, and compound activity against these does not always correlate with efficacy against the parasite in its intracellular niche...
July 12, 2018: PLoS Neglected Tropical Diseases
Kelly J Brunst, Nicole Tignor, Allan Just, Zhonghua Liu, Xihong Lin, Michele R Hacker, Michelle Bosquet Enlow, Robert O Wright, Pei Wang, Andrea A Baccarelli, Rosalind J Wright
Evolving evidence links maternal stress exposure to changes in placental DNA methylation of specific genes regulating placental function that may have implications for the programming of a host of chronic disorders. Few studies have implemented an epigenome-wide approach. Using the Infinium HumanMethylation450 BeadChip (450K), we investigated epigenome-wide placental DNA methylation in relation to maternal experiences of traumatic and non-traumatic stressors over her lifetime assessed using the Life Stressor Checklist-Revised (LSC-R) survey (n = 207)...
July 12, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Christian Starzynski, Alexander Gutschalk
Disappearance of a voice or other sound source may often go unnoticed when the auditory scene is crowded. We explored the role of selective attention for this change deafness with magnetoencephalography in multi-speaker scenes. Each scene was presented two times in direct succession, and one target speaker was frequently omitted in Scene 2. When listeners were previously cued to the target speaker, activity in auditory cortex time locked to the target speaker's sound envelope was selectively enhanced in Scene 1, as was determined by a cross-correlation analysis...
July 12, 2018: Human Brain Mapping
Syeda A Hadi, Wade R Waters, Mitchell Palmer, Konstantin P Lyashchenko, Srinand Sreevatsan
Objective: To evaluate a high-resolution method to identify pathogen-specific biomarkers in serum of calves infected with Mycobacterium bovis . Methods: Serum samples from four calves infected with M. bovis were collected before and after infection at weeks 9, 14, 15, 31, and 36. Immune-complex-associated mycobacterial antigens in the serum were enriched using an immunochromatography method termed, dual path platform (DPP). All regions of antigen capture zones, that consisted of monospecific rabbit polyclonal antibodies raised against M...
2018: Frontiers in Veterinary Science
Patricio H Contreras, Felipe G Serrano, Ana M Salgado, Pilar Vigil
A cohort of 141 males (18-80 yo, 42.9 ± 12.9) strongly suspected of being Insulin Resistant (IR) was prospectively studied by determining their insulin sensitivity (Pancreatic Suppression Test, PST) and testicular function (total testosterone and SHBG). The subjects were labeled as IR when the Steady State Plasma Glucose (SSPG) was ≥150 mg/dL and Non-Insulin Resistant (NIR) when SSPG was <150 mg/dl; similarly, the subjects were labeled as Hypogonadal (HYPOG) when total testosterone was ≤3.0 ng/mL and Eugonadal (EUG) when total testosterone was >3...
2018: Frontiers in Medicine
Natalia Sierra, Christelle Folio, Xavier Robert, Mathieu Long, Christophe Guillon, Guzmán Álvarez
Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses. It causes acquired immunodeficiency syndrome (AIDS) in worldwide domestic and non-domestic cats and is a cause of an important veterinary issue. The genome organization of FIV and the clinical characteristics of the disease caused by FIV are similar to human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes, and macrophages, with a similar replication cycle in infected cells. Thus, the infection of cats with FIV is also a useful tool for the study and development of novel drugs and vaccines against HIV...
July 10, 2018: Pharmaceuticals
Yuanshuai Zhou, Zhongjuan Xu, Daniel Quan, Fan Zhang, Hai Zhang, Tongqian Xiao, Shulan Hou, Hong Qiao, Olivier Harismendy, Jean Y J Wang, Guangli Suo
Epithelial cells aggregate into spheroids when deprived of matrix, and the proclivity for spheroid formation and survival is a hallmark of normal and tumorigenic mammary stem cells. We show here that Nuclear Respiratory Factor 1 (NRF1) is a spheroid promoter by in silico identification of this transcription factor as highly connected to top shRNA-hits deduced from re-iterative selections for shRNAs enriched in MCF10A spheroids. NRF1-promoted spheroid survival is linked to its stimulation of mitochondrial OXPHOS, cell migration, invasion, and mesenchymal transition...
July 11, 2018: Oncogene
Lu Liu, Yang Wang, Roberta Sinatra, C Lee Giles, Chaoming Song, Dashun Wang
The hot streak-loosely defined as 'winning begets more winnings'-highlights a specific period during which an individual's performance is substantially better than his or her typical performance. Although hot streaks have been widely debated in sports1,2 , gambling3-5 and financial markets6,7 over the past several decades, little is known about whether they apply to individual careers. Here, building on rich literature on the lifecycle of creativity8-22 , we collected large-scale career histories of individual artists, film directors and scientists, tracing the artworks, films and scientific publications they produced...
July 11, 2018: Nature
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