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Yilun Deng, Yuejuan Qin, Subramanya Srikantan, Anqi Luo, Zi-Ming Cheng, Shahida K Flores, Kris S Vogel, Exing Wang, Patricia L M Dahia
The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, in renal cancers. Tumors with inactivating TMEM127 mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that TMEM127 interacts with the lysosome-anchored complex comprised of Rag GTPases, the LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated mTORC1 activation. We found that in nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags...
March 14, 2018: Human Molecular Genetics
Lara M Wierenga, Marieke G N Bos, Elisabeth Schreuders, Ferdi Vd Kamp, Jiska S Peper, Christian K Tamnes, Eveline A Crone
The onset of adolescence in humans is marked by hormonal changes that give rise to secondary sexual characteristics, noted as puberty. It has, however, proven challenging to unravel to what extent pubertal changes may have organizing effects on the brain beyond chronological age, as reported in animal studies. The present longitudinal study aimed to characterize the unique effects of age and puberty on subcortical brain volumes and included three waves of data collection at two-year intervals and 680 T1-weighted MRI scans of 271 participants (54% females) aged between 8 and 29 years old...
March 8, 2018: Psychoneuroendocrinology
Joshua M Peterson, Carolyn Chlebek, Ashley M Clough, Alexandra K Wells, Eric H Ledet
STUDY DESIGN: In vitro biomechanical testing of human cadaveric cervical and goat cervical motion segments. OBJECTIVE: To measure the effects of plate stiffness on load-sharing, instantaneous axis of rotation (IAR), and posterior element loading after anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is intended to create an environment which facilitates sufficient stability and biomechanical conditions to promote bone formation...
March 15, 2018: Spine
Dalibor Hr Scaron Ak, Morten Steen Nørby, Sonia Coriani, Jacob Kongsted
We present a formulation of the polarizable density embedding (PDE) method in combination with the complex polarization propagator (CPP) method for the calculation of absorption spectra of molecules in solutions. The method is particularly useful for the calculation of near-edge X-ray absorption fine structure (NEXAFS) spectra. We compare the performance of PDE-CPP with the previously formulated polarizable embedding (PE) CPP model for the calculation of the NEXAFS spectra of adenine, formamide, glycine and adenosine triphosphate (ATP) in water at the carbon and nitrogen K-edges, as well as of formamide and glycine at the oxygen K-edge...
March 16, 2018: Journal of Chemical Theory and Computation
Muralidhar Pai K, R Chandrasekhar Naidu, A Raja, Y S Rai, Niranjan Kumar, Anand Kini, Santhosh Joseph, Vinod Hegde, H S Ballal, Ramoorthi Rao, Saroja V Sharma, Vinay Kumar Valakatte
Craniopagus twins are conjoined twins fused at the cranium. This is the rarest anomaly seen in conjoined twins and craniopagus twins account for 2- 6% of conjoined twins. Conjoined twins are also extremely rare, with the anomaly seen in about 10-20 subjects per billion births. A female preponderance has been noted. Craniopagus twins can be classified into complete or partial, depending on whether or not they have shared dural venous sinuses. They can be further classified into angular or total depending on the alignment of the inter-twin longitudinal axis...
March 2018: Neurology India
Charles S Dela Cruz, Richard G Wunderink, David C Christiani, Stephania A Cormier, Kristina Crothers, Claire M Doerschuk, Scott E Evans, Daniel R Goldstein, Purvesh Khatri, Lester Kobzik, Jay K Kolls, Bruce D Levy, Mark L Metersky, Michael S Niederman, Roomi Nusrat, Carlos J Orihuela, Paula Peyrani, Alice S Prince, Julio A Ramírez, Karen M Ridge, Sanjay Sethi, Benjamin T Suratt, Jacob I Sznajder, Ephraim L Tsalik, Allan J Walkey, Sachin Yende, Neil R Aggarwal, Elisabet V Caler, Joseph P Mizgerd
Pneumonia is a complex pulmonary disease in need of new clinical approaches. While triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as ARDS and to organ dysfunction beyond the lungs and overextended time-frames after pathogen clearance, some of which increase the risk for subsequent pneumonias...
March 16, 2018: American Journal of Respiratory and Critical Care Medicine
Jochem Deen, Su Wang, Sven Van Snick, Volker Leen, Kris Janssen, Johan Hofkens, Robert K Neely
The methyltransferase enzymes can be applied to deliver a range of modifications to pre-determined sites on large DNA molecules with exceptional specificity and efficiency. To date, however, a limited number of modifications have been delivered in this way because of the complex chemical synthesis that is needed to produce a cofactor analogue carrying a specific function, such as a fluorophore. Here, we describe a method for the direct transfer of a series of functional compounds (seven fluorescent dyes, biotin and polyethylene glycol) to the DNA duplex...
March 13, 2018: Nucleic Acids Research
Emily C White, Ashley Houlden, Allison J Bancroft, Kelly S Hayes, Marie Goldrick, Richard K Grencis, Ian S Roberts
Intestinal dwelling parasites have evolved closely with the complex intestinal microbiota of their host, but the significance of the host microbiota for metazoan pathogens and the role of their own intestinal microbiota are still not fully known. We have found that the parasitic nematode Trichuris muris acquired a distinct intestinal microbiota from its host, which was required for nematode fitness. Infection of germ-free mice and mice monocolonized with Bacteroides thetaiotaomicron demonstrated that successful T...
March 2018: Science Advances
Cameron K Schmidt, Shehzad Khalid, Marios Loukas, R Shane Tubbs
Anxiety disorders are among the most prevalent psychological issues worldwide, displaying the youngest age of onset and greatest chronicity of any mood or substance abuse disorder. Given the high social and economic cost imposed by these disorders, developing effective treatments is of the utmost importance. Anxiety disorders manifest in a variety of symptomatic phenotypes and are highly comorbid with other psychological diseases such as depression. These facts have made unraveling the complex underlying neural circuity an ever-present challenge for researchers...
January 12, 2018: Curēus
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Frank Birklein, Seena K Ajit, Andreas Goebel, Roberto S G M Perez, Claudia Sommer
Complex regional pain syndrome (CRPS) is a pain condition that usually affects a single limb, often following an injury. The underlying pathophysiology seems to be complex and probably varies between patients. Clinical diagnosis is based on internationally agreed-upon criteria, which consider the reported symptoms, presence of signs and exclusion of alternative causes. Research into CRPS biomarkers to support patient stratification and improve diagnostic certainty is an important scientific focus, and recent progress in this area provides an opportunity for an up-to-date topical review of measurable disease-predictive, diagnostic and prognostic parameters...
March 16, 2018: Nature Reviews. Neurology
Alison S Brooks, John E Yellen, Richard Potts, Anna K Behrensmeyer, Alan L Deino, David E Leslie, Stanley H Ambrose, Jeffrey R Ferguson, Francesco d'Errico, Andrew M Zipkin, Scott Whittaker, Jeffrey Post, Elizabeth G Veatch, Kimberly Foecke, Jennifer B Clark
Previous research suggests that the complex symbolic, technological, and socio-economic behaviors that typify Homo sapiens had roots in the middle Pleistocene <200 ka, but data bearing on human behavioral origins are limited. We present a series of excavated Middle Stone Age sites from the Olorgesailie Basin, southern Kenya, dated ≥295 to ~320 ka by40 Ar/39 Ar and U-Series methods. Hominins at these sites made prepared cores and points, exploited iron-rich rocks to obtain red pigment, and procured stone tool materials from ≥25-50 km distance...
March 15, 2018: Science
Jeffrey Hsu, Shamone Gore-Panter, Gregory Tchou, Laurie Castel, Beth Lovano, Christine S Moravec, Gosta B Pettersson, Eric E Roselli, A Marc Gillinov, Kenneth R McCurry, Nicholas G Smedira, John Barnard, David R Van Wagoner, Mina K Chung, Jonathan D Smith
BACKGROUND: Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined. METHODS: To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects...
March 2018: Circ Genom Precis Med
M Killer-Oberpfalzer, N Kocer, C J Griessenauer, H Janssen, T Engelhorn, M Holtmannspötter, J H Buhk, T Finkenzeller, G Fesl, J Trenkler, W Reith, A Berlis, K Hausegger, M Augustin, C Islak, B Minnich, M Möhlenbruch
BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow-diverting stents represents a widely accepted technique for the treatment of complex intracranial aneurysms. This European registry study analyzed the initial experience of 15 neurovascular centers with the Flow-Redirection Intraluminal Device (FRED) system. MATERIALS AND METHODS: Consecutive patients with intracranial aneurysms treated with the FRED between February 2012 and March 2015 were retrospectively reviewed...
March 15, 2018: AJNR. American Journal of Neuroradiology
Sarah Caughlin, Shikhar Maheshwari, Yuksel Agca, Cansu Agca, Aaron J Harris, Kristina Jurcic, Ken K-C Yeung, David F Cechetto, Shawn N Whitehead
BACKGROUND: Accumulation of simple gangliosides GM2 and GM3, and gangliosides with longer long-chain bases (d20:1) have been linked to toxicity and the pathogenesis of Alzheimer's disease (AD). Conversely, complex gangliosides, such as GM1, have been shown to be neuroprotective. Recent evidence using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) has demonstrated that a-series gangliosides are differentially altered during normal aging, yet it remains unclear how simple species are shifting relative to complex gangliosides in the prodromal stages of AD...
March 12, 2018: Biochimica et Biophysica Acta
Edward J Steele, Shirwan Al-Mufti, Kenneth A Augustyn, Rohana Chandrajith, John P Coghlan, S G Coulson, Sudipto Ghosh, Mark Gillman, Reginald M Gorczynski, Brig Klyce, Godfrey Louis, Kithsiri Mahanama, Keith R Oliver, Julio Padron, Jiangwen Qu, John A Schuster, W E Smith, Duane P Snyder, Julian A Steele, Brent J Stewart, Robert Temple, Gensuke Tokoro, Christopher A Tout, Alexander Unzicker, Milton Wainwright, Jamie Wallis, Daryl H Wallis, Max K Wallis, John Wetherall, D T Wickramasinghe, J T Wickramasinghe, N Chandra Wickramasinghe, Yongsheng Liu
We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H- W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explosion of ∼500 Ma. Such viruses are known to be plausibly associated with major evolutionary genomic processes. We believe this coincidence is not fortuitous but is consistent with a key prediction of H-W theory whereby major extinction-diversification evolutionary boundaries coincide with virus-bearing cometary-bolide bombardment events...
March 12, 2018: Progress in Biophysics and Molecular Biology
A J Ullmann, J M Aguado, S Arikan-Akdagli, D W Denning, A H Groll, K Lagrou, C Lass-Flörl, R E Lewis, P Munoz, P E Verweij, A Warris, F Ader, M Akova, M C Arendrup, R A Barnes, C Beigelman-Aubry, S Blot, E Bouza, R J M Brüggemann, D Buchheidt, J Cadranel, E Castagnola, A Chakrabarti, M Cuenca-Estrella, G Dimopoulos, J Fortun, J-P Gangneux, J Garbino, W J Heinz, R Herbrecht, C P Heussel, C C Kibbler, N Klimko, B J Kullberg, C Lange, T Lehrnbecher, J Löffler, O Lortholary, J Maertens, O Marchetti, J F Meis, L Pagano, P Ribaud, M Richardson, E Roilides, M Ruhnke, M Sanguinetti, D C Sheppard, J Sinkó, A Skiada, M J G T Vehreschild, C Viscoli, O A Cornely
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended...
March 12, 2018: Clinical Microbiology and Infection
Sajal Kole, Ranjeeta Kumari, Deepika Anand, Saurav Kumar, Rupam Sharma, Gayatri Tripathi, M Makesh, K V Rajendran, Megha Kadam Bedekar
DNA-based immunization has proven to be an effective prophylactic measure to control aquatic animal diseases. In order to improve the efficiency of vaccine against fish pathogen, novel delivery mechanism needs to be adopted. In the present study we nanoconjugated the previously constructed DNA vaccine (pGPD + IFN) with chitosan nanoparticles (CNPs) by complex coacervation process. After construction of the vaccine, an in vivo vaccination trial was conducted in which 2 groups of rohu (L. rohita) fingerlings were vaccinated with CNPs-pGPD + IFN, one group by oral route (incorporated in feed for 14 days) and the other by immersion route (primary and booster immunised), whereas, a third group was intramuscularly (I/M) injected (initial and booster immunised) with naked pGPD + IFN and subsequently challenged with E...
March 12, 2018: Vaccine
K M J Menon, Bindu Menon, Thippeswamy Gulappa
The expression of luteinizing hormone receptor (LHR) in the mammalian ovary is regulated in response to changes in the secretion of follicle-stimulating hormone and luteinizing hormone by the anterior pituitary, at least in part, through posttranscriptional mechanisms. The steady-state levels of LHR mRNA are maintained by controlling its rate of degradation by an RNA-binding protein designated as LHR mRNA-binding protein (LRBP). LRBP forms a complex with LHR mRNA and targets it for degradation in the p bodies...
2018: Vitamins and Hormones
Khaled R Alkharsah, Suriya Rehman, Fatimah Alkhamis, Amani Alnimr, Asim Diab, Amein K Al-Ali
BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) constitutes a major global health concern causing hospital and community acquired infections. A wide diversity of MRSA genotypes are circulating in geographically related regions. Therefore understanding the molecular epidemiology of MRSA is fundamental to design control and clearance measures. METHODS: A total of 106 MRSA isolates from infection (51) and carrier colonization sites (55) are characterized genetically based on SCCmec and MLST genotyping methods in addition to detection of PVL, TSST-1 and enterotoxins...
March 15, 2018: Annals of Clinical Microbiology and Antimicrobials
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