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Contact pathway

Toshifumi Mori, Shinji Saito
Proteins involve motions over a wide range of spatial and temporal scales. While the large conformational changes such as folding and functioning are slow and appear to occur in a highly cooperative manner, how the hierarchical dynamics over different timescales play a role during these slow transitions has been of great interest over the decades. Here we study the folding mechanism of the villin headpiece subdomain (HP35) to understand the molecular mechanism behind this prototypical fast-folding protein. The ~ 400 µs molecular dynamics (MD) trajectories obtained by Piana et al...
October 21, 2016: Journal of Physical Chemistry. B
Sang-Jin Lee, Jeongmi Hwang, Hyeon-Ju Jeong, Miran Yoo, Ga-Yeon Go, Jae-Rin Lee, Young-Eun Leem, Jong Woo Park, Dong-Wan Seo, Yong Kee Kim, Myong-Joon Hahn, Jeung-Whan Han, Jong-Sun Kang, Gyu-Un Bae
Skeletal myogenesis is coordinated by multiple signaling pathways that control cell adhesion/migration, survival and differentiation accompanied by muscle-specific gene expression. A cell surface protein Cdo is involved in cell contact-mediated promyogenic signals through activation of p38MAPK and AKT. Protein kinase C-related kinase 2 (PKN2/PRK2) is implicated in regulation of various biological processes, including cell migration, adhesion and death. It has been shown to interact with and inhibit AKT thereby inducing cell death...
October 20, 2016: Cell Death & Disease
Amanda Faria Assoni, Giuliana Castello, Marcos Valadares, Melinda Beccari, Juliana Gomes, Mayra Pelatti, Miguel Mitne-Neto, Valdemir Melechco Carvalho, Mayana Zatz
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by null mutations in the dystrophin gene. Although the primary defect is the deficiency of muscle dystrophin, secondary events, including chronic inflammation, fibrosis and muscle regeneration failure are thought to actively contribute to disease progression. Despite several advances, there is still no effective therapy for DMD. Therefore, the potential regenerative capacities, as well as immune-privileged properties of Mesenchymal Stromal Cells (MSCs), have been the focus of intense investigation in different animal models aiming the treatment of these disorders...
October 20, 2016: Stem Cells and Development
Erik Richter, Manuela Harms, Katharina Ventz, Rolf Nölker, Martin J Fraunholz, Jörg Mostertz, Falko Hochgräfe
Internalization of Staphylococcus aureus by non-professional phagocytic cells is a major suspected cause of persistent and difficult-to-treat infections, including pneumonia. In this study, we established an infection model with 16HBE14o- human bronchial epithelial cells and demonstrated internalization, escape from phagosomal clearance and intracellular replication of S. aureus HG001 within the first four hours post-infection. We used quantitative phosphoproteomics to identify characteristic signaling networks in the host at different infection stages...
October 20, 2016: Journal of Proteome Research
Xinhui Wu, Yao Fu, Xulei Sun, Chang Liu, Menglong Chai, Chengzhen Chen, Lisheng Dai, Yan Gao, Hao Jiang, Jiabao Zhang
Porcine cumulus cells are localized around oocytes and act as a specific type of granulosa that plays essential roles in the development and maturation of oocytes, the development and atresia of follicles and the development of embryos. Studies of FAT1 have demonstrated its functions in cell-cell contact, actin dynamics, and cell growth suppression. To understand whether the FAT1 gene affects the apoptosis of porcine cumulus cells and to elucidate the mechanism of this potential action, FAT1 was knocked down using RNA interference...
October 20, 2016: Cell Biology International
Anna L Funk, Flavie Luce Goutard, Eve Miguel, Mathieu Bourgarel, Veronique Chevalier, Bernard Faye, J S Malik Peiris, Maria D Van Kerkhove, Francois Louis Roger
Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs...
2016: Frontiers in Veterinary Science
Nir Kampf, Chunxian Wu, Yilin Wang, Jacob Klein
The surface structure of the trimeric surfactant tri(dodecyldimethylammonioacetoxy)-diethyltriamine trichloride (DTAD) on mica, and the interactions between two such DTAD-coated surfaces were determined using atomic force microscopy and a surface force balance. In an aqueous solution of 3 mM, five times the critical aggregation concentration (CAC), the surfaces are coated with worm-like micelles or hemi-micelles and larger (ca. 80 nm) bilayer vesicles. Repulsive normal interactions between the surfaces indicate a net surface charge and a solution concentration of ions close to that expected from the CAC...
October 19, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Hyejung Won, Luis de la Torre-Ubieta, Jason L Stein, Neelroop N Parikshak, Jerry Huang, Carli K Opland, Michael J Gandal, Gavin J Sutton, Farhad Hormozdiari, Daning Lu, Changhoon Lee, Eleazar Eskin, Irina Voineagu, Jason Ernst, Daniel H Geschwind
Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease...
October 19, 2016: Nature
Hongliang Yu, Jian He, Qian Lu, Da Huo, Shanmei Yuan, Zhengyang Zhou, Peipei Xu, Yong Hu
Emerging evidences suggest that introduction of Fas Ligand (FasL) can enhance the Fas-dependent apoptosis and induce durable immune responses against tumor. However, selective triggering of apoptosis in tumor cells while sparing normal cells remains a great challenge for the application of FasL based therapeutic strategies. Herein, smart nanoparticles (NPs) with sandwich structure were fabricated. These NPs consist of Matrix metalloproteinase (MMP) cleavable PEG outer layer, anti-Fas antibody middle layer and camptothecin (CPT) loaded inner core...
October 18, 2016: ACS Applied Materials & Interfaces
Katarzyna Anna Campbell, Katharine Anna Bowker, Felix Naughton, Melanie Sloan, Sue Cooper, Tim Coleman
Introduction: UK guidance recommends routine exhaled carbon monoxide (CO) screening for pregnant women and "opt-out" referrals to stop smoking services (SSS) of those with CO ≥ 4 ppm. We explored staff views on this referral pathway when implemented in one UK hospital Trust. Methods: Seventeen semi-structured interviews with staff involved in the implementation of the new referral pathway: six antenatal clinic staff (before and after implementation); five SSS staff (after). Data were analyzed using framework analysis...
October 12, 2016: International Journal of Environmental Research and Public Health
Elizabeth Wellsandt, Ashutosh Khandha, Kurt Manal, Michael J Axe, Thomas S Buchanan, Lynn Snyder-Mackler
Anterior cruciate ligament (ACL) injury results in altered knee joint mechanics which frequently continue even after ACL reconstruction. The persistence of altered mechanical loading of the knee is of concern due to its likely role in the development of post-traumatic osteoarthritis (OA). Joint contact forces are associated with post-traumatic OA development, but evaluation of factors influencing the magnitude of contact forces after ACL injury is needed to advance current strategies aimed at preventing post-traumatic OA...
October 17, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Raimundo Barbosa-Barros, Andrés Ricardo Pérez-Riera, Luiz Carlos de Abreu, Ricardo Paulo de Sousa-Rocha, Danielli Oliveira da Costa Lino, Adrian Baranchuk, Li Zhang
Left ventricular involvement in the advanced stage of arrhythmogenic cardiomyopathy (AC) is an evolution of this desmosomopathy. Mutation in intercalated discs explains the phenotypic variability. Abnormal trafficking of the intercalated discs at the site of end-to-end contacts between cardiomyocytes and the canonical Wnt/β-catenin and Hippo signaling pathways have been implicated. In AC, T-wave inversion in lateral leads is the hallmark of left ventricular (LV) involvement. We herein report a case of isolated LV AC in which the initial ECG has typical features: fragmented QRS (fQRS), Twave inversion (TWI) in lateral leads, and ventricular tachycardia from inferobasal LV wall...
September 8, 2016: Journal of Electrocardiology
Moshe Bronshtein, Zeev Blumenfeld, Asaad Choury, Ayala Gover
OBJECTIVES: To assess the natural history and outcome of fetal pulmonary stenosis [PS] detected at 14 to 16 weeks gestation. METHODS: This is a retrospective study, in the years 2004-2015, with serial follow up during pregnancy. Patients referred for complete early fetal ultrasound including all fetal systems and a fetal echocardiogram. Ninety seven percent of the women were low risk, and 3% had risk factors such as maternal type 1 diabetes mellitus, exposure to teratogenic drugs or anomalies in previous pregnancies or in other family members...
October 14, 2016: Ultrasound in Obstetrics & Gynecology
Sonia T Hegde, Hossain M S Sazzad, M Jahangir Hossain, Mahbub-Ul Alam, Eben Kenah, Peter Daszak, Pierre Rollin, Mahmudur Rahman, Stephen P Luby, Emily S Gurley
Human Nipah encephalitis outbreaks have been identified almost yearly in Bangladesh since 2001. Though raw date palm sap consumption and person-to-person contact are recognized as major transmission pathways, alternative pathways of transmission are plausible and may not have been identified due to limited statistical power in each outbreak. We conducted a risk factor analysis using all 157 cases and 632 controls surveyed in previous investigations during 2004-2012 to identify exposures independently associated with Nipah, since date palm sap was first asked about as an exposure in 2004...
October 13, 2016: EcoHealth
Yuantai Wu, Mehmet Takar, Andrea A Cuentas-Condori, Todd R Graham
NEO1 is an essential gene in budding yeast and belongs to a highly conserved subfamily of P-type ATPase genes that encode phospholipid flippases. Inactivation of temperature sensitive neo1(ts) alleles produces pleiomorphic defects in the secretory and endocytic pathways, including fragmented vacuoles. A screen for multicopy suppressors of neo1-2(ts) growth defects yielded YPT7, which encodes a Rab7 homolog involved in SNARE-dependent vacuolar fusion. YPT7 suppressed the vacuole fragmentation phenotype of neo1-2, but did not suppress Golgi-associated protein trafficking defects...
July 2016: Cellular Logistics
David J Keene, Dipesh Mistry, Julian Nam, Elizabeth Tutton, Robert Handley, Lesley Morgan, Emma Roberts, Bridget Gray, Andrew Briggs, Ranjit Lall, Tim Js Chesser, Ian Pallister, Sarah E Lamb, Keith Willett
BACKGROUND: Close contact casting (CCC) may offer an alternative to open reduction and internal fixation (ORIF) surgery for unstable ankle fractures in older adults. OBJECTIVES: We aimed to (1) determine if CCC for unstable ankle fractures in adults aged over 60 years resulted in equivalent clinical outcome compared with ORIF, (2) estimate cost-effectiveness to the NHS and society and (3) explore participant experiences. DESIGN: A pragmatic, multicentre, equivalence randomised controlled trial incorporating health economic evaluation and qualitative study...
October 2016: Health Technology Assessment: HTA
Vera P Pisareva, Andrey V Pisarev
Eukaryotic translation initiation is a complex process involving many components. eIF3 is a scaffold for multiple initiation factors and plays multiple roles in initiation, and DHX29 helicase enhances the formation of the 48S initiation complex on structured mRNAs. Because DHX29 is not a processive helicase, the mechanism underlying its activity is unclear. Here, we show that DHX29 establishes many points of contact with eIF3. In particular, the unique N terminus of DHX29 associates with the RNA recognition motif of eIF3b and the C terminus of the eIF3a subunits of eIF3, and the disruption of either contact impairs DHX29 activity...
October 12, 2016: RNA
Jingjing Sherry Wu, Eric D Young, Elisabeth Glowatzki
: Auditory nerve fibers (ANFs) exhibit a range of spontaneous firing rates (SRs) that are inversely correlated with threshold for sounds. To probe the underlying mechanisms and time course of SR differentiation during cochlear maturation, loose-patch extracellular recordings were made from ANF dendrites using acutely excised rat cochlear preparations of different ages after hearing onset. Diversification of SRs occurred mostly between the second and the third postnatal week. Statistical properties of ANF spike trains showed developmental changes that approach adult-like features in older preparations...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jia Zeng, Laimonas Kelbauskas, Aida Rezaie, Kristen Lee, Benjamin Ueberroth, Weimin Gao, Dmitry Derkach, Thai Tran, Dean Smith, Kimberly J Bussey, Deirdre R Meldrum
In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett's esophagus. Using whole transcriptome profiling we found that in the presence of normal epithelial cells, dysplastic cells but not normal cells, exhibit marked down-regulation of a number of key signaling pathways, including the transforming growth factor beta (TGFβ) and epithelial growth factor (EGF)...
October 12, 2016: Scientific Reports
Abdallah Ibrahim, Sidua Hor, Ozge S Bahar, Duah Dwomoh, Mary M McKay, Reuben K Esena, Irene A Agyeponge
BACKGROUND: The process to seek for care by patients who experience episodes of mental disorders may determine how and where they receive the needed treatment. This study aimed to understand the pathways that people with mental disorders traversed for psychiatric services, particularly where these individuals will first seek treatment and the factors that influence such pathways to mental health care. METHODS: A cross-sectional study conducted at Pantang psychiatric hospital in Accra, Ghana involving 107 patients of ages 18 and older and their family members...
2016: International Journal of Mental Health Systems
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