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Michael Platten, David A Reardon
Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined...
February 2018: Seminars in Neurology
Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Devin Ancona, Dan York, Robert J Higgins, Danika Bannasch, Peter J Dickinson
Choroid plexus tumors (CPTs) occur spontaneously in humans and dogs providing an opportunity for comparative cross species analysis of common tumor mechanisms. Large scale chromosomal copy number alterations are the hallmark of human CPTs and identification of driver genes within these regions is problematic. Copy number alterations in 12 spontaneous dog CPTs were defined using an Illumina 170 K single nucleotide polymorphism array and were characterized by highly recurrent whole chromosomal losses in up to 100% of cases with few chromosome wide gains...
March 14, 2018: Journal of Neuropathology and Experimental Neurology
Laura Miller, Gerardo J Pacheco, Jud C Janak, Rose C Grimm, Nicole A Dierschke, Janice Baker, Jean A Orman
Background: Military working dogs (MWDs) are a major asset in the theater of operations. Their unique abilities make them ideal for tasks such as tracking, patrol, and scent detection. MWDs deployed to a war zone are exposed to harsh environments and battlefield dangers that increase their risk of disease, injuries, and death. Although canines have been used extensively in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF), no published studies have reported detailed causes of death among MWDs deployed to these conflicts...
March 14, 2018: Military Medicine
Klemen Pavlic, Maja Pohar Perme
A common goal in the analysis of the long-term survival related to a specific disease is to estimate a measure that is comparable between populations with different general population mortality. When cause of death is unavailable or unreliable, as for example in cancer registry studies, relative survival methodology is used-in addition to the mortality data of the patients, we use the data on the mortality of the general population. In this article, we focus on the marginal relative survival measure that summarizes the information about the disease-specific hazard...
March 13, 2018: Biostatistics
Teresa Morales-Ruiz, Álvaro C Romero-Valenzuela, Vanessa M Vázquez-Grande, Teresa Roldán-Arjona, Rafael R Ariza, Dolores Córdoba-Cañero
Base excision repair (BER) is a major defense pathway against spontaneous DNA damage. This multistep process is initiated by DNA glycosylases that recognise and excise the damaged base, and proceeds by the concerted action of additional proteins that perform incision of the abasic site, gap filling and ligation. BER has been extensively studied in bacteria, yeasts and animals. Although knowledge of this pathway in land plants is increasing, there are no reports detecting BER in algae. We describe here an experimental in vitro system allowing the specific analysis of BER in the model alga Chlamydomonas reinhardtii...
March 5, 2018: DNA Repair
Rachel M Speer, Catherine F Wise, Jamie L Young, AbouEl-Makarim Aboueissa, Mark Martin Bras, Mike Barandiaran, Erick Bermúdez, Lirio Márquez-D'Acunti, John Pierce Wise
Hexavalent chromium [Cr(VI)] is a marine pollution of concern as recent studies show it has a global distribution, with some regions showing high Cr concentrations in marine animal tissue, and it is extensively used. Leatherback sea turtles (Dermochelys coriacea) are an endangered marine species that may experience prolonged exposures to environmental contaminants including Cr(VI). Human activities have led to global Cr(VI) contamination of the marine environment. While Cr(VI) has been identified as a known human carcinogen, the health effects in marine species are poorly understood...
March 4, 2018: Aquatic Toxicology
María Victoria Repetto, Matthew J Winters, Alan Bush, Wolfgang Reiter, David Maria Hollenstein, Gustav Ammerer, Peter M Pryciak, Alejandro Colman-Lerner
We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages...
March 15, 2018: Molecular Cell
Omar A Z Tutakhel, Frans Bianchi, Daniël A Smits, René J M Bindels, Joost G J Hoenderop, Jenny van der Wijst
The NaCl cotransporter (NCC) is essential for electrolyte homeostasis and control of blood pressure. The human SLC12A3 gene, which encodes NCC, gives rise to 3 isoforms, of which only the shortest isoform [NaCl cotransporter isoform 3 (NCC3 )] has been studied extensively. All NCC isoforms share key phosphorylation sites at T55 and T60 that are essential mediators of NCC function. Recently, a novel phosphorylation site at S811 was identified in isoforms 1 and 2 [NaCl cotransporter splice variant (NCCSV )], which are only present in humans and higher primates...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Hendrik Göddeke, M Hadi Timachi, Cedric A Hutter, Laura Galazzo, Markus A Seeger, Mikko Karttunen, Enrica Bordignon, Lars V Schäfer
ATP-binding cassette (ABC) transporters are ATP-driven molecular machines, in which ATP binding and hydrolysis in the nucleotide-binding domains (NBDs) is chemo-mechanically coupled to large-scale, alternating access conformational changes in the transmembrane domains (TMDs), ultimately leading to the translocation of substrates across biological membranes. The precise nature of the structural dynamics behind the large-scale conformational transition as well as the coupling of NBD and TMD motions is still unresolved...
March 16, 2018: Journal of the American Chemical Society
Alberto Perez, Florian Sittel, Gerhard Stock, Ken A Dill
The molecular actions of proteins occur along reaction coordinates. Current computer methods have limited ability to explore them. We describe a fast protocol called MELD-path that: (1) efficiently samples relevant conformational states via MELD, an accelerator of Molecular Dynamics (MD), (2) seeds multiple short MD trajectories from MELD states, then (3) constructs Markov State Models (MSM) that give the routes and kinetics. We tested the method against extensive (multi μs) MD simulations of the right-handed- to left-handed-helix transition of a 9-mer peptide of AIB, the symmetry of which allows us to establish convergence...
March 16, 2018: Journal of Chemical Theory and Computation
Harsha T Garimella, Reuben H Kraft, Andrzej J Przekwas
Subject-specific computer models (male and female) of the human head were used to investigate the possible axonal deformation resulting from the primary phase blast-induced skull flexures. The corresponding axonal tractography was explicitly incorporated into these finite element models using a recently developed technique based on the embedded finite element method. These models were subjected to extensive verification against experimental studies which examined their pressure and displacement response under a wide range of loading conditions...
2018: PloS One
Sangrok Jin, Jeongae Bak, Jongwon Kim, TaeWon Seo, Hwa Soo Kim
This paper presents a switching PD-based sliding mode control (PD-SMC) method for the 6-degree-of-freedom (DOF) hovering motion of the underwater robot with tilting thrusters. Four thrusters of robot can be tilted simultaneously in the horizontal and vertical directions, and the 6-DOF motion is achieved by switching between two thruster configurations. Therefore, the tilting speed of thruster becomes the most essential parameter to determine the stability of hovering motion. Even though the previous PD control ensures stable hovering motion within a certain ranges of tilting speed, a PD-SMC is suggested in this paper by combining PD control with sliding mode control in order to achieve acceptable hovering performance even at the much lower tilting speeds...
2018: PloS One
Waqas Hameed, Bilal Iqbal Avan
INTRODUCTION: Respectful and dignified healthcare is a fundamental right for every woman. However, many women seeking childbirth services, especially those in low-income countries such as Pakistan, are mistreated by their birth attendants. The aim of this epidemiological study was to estimate the prevalence of mistreatment and types of mistreatment among women giving birth in facility- and home-based settings in Pakistan in order to address the lack of empirical evidence on this topic...
2018: PloS One
Shuming Qiu, Guoai Xu, Haseeb Ahmad, Yanhui Guo
The Session Initiation Protocol (SIP) is an extensive and esteemed communication protocol employed to regulate signaling as well as for controlling multimedia communication sessions. Recently, Kumari et al. proposed an improved smart card based authentication scheme for SIP based on Farash's scheme. Farash claimed that his protocol is resistant against various known attacks. But, we observe some accountable flaws in Farash's protocol. We point out that Farash's protocol is prone to key-compromise impersonation attack and is unable to provide pre-verification in the smart card, efficient password change and perfect forward secrecy...
2018: PloS One
Ana Catarina Lopes, Ariane Sagasti, Andoni Lasheras, Virginia Muto, Jon Gutiérrez, Dimitris Kouzoudis, José Manuel Barandiarán
The main parameters of magnetoelastic resonators in the detection of chemical (i.e., salts, gases, etc.) or biological (i.e., bacteria, phages, etc.) agents are the sensitivity S (or external agent change magnitude per Hz change in the resonance frequency) and the quality factor Q of the resonance. We present an extensive study on the experimental determination of the Q factor in such magnetoelastic resonant platforms, using three different strategies: (a) analyzing the real and imaginary components of the susceptibility at resonance; (b) numerical fitting of the modulus of the susceptibility; (c) using an exact mathematical expression for the real part of the susceptibility...
March 16, 2018: Sensors
Elisa Fiume, Jacopo Barberi, Enrica Verné, Francesco Baino
Nowadays, bioactive glasses (BGs) are mainly used to improve and support the healing process of osseous defects deriving from traumatic events, tumor removal, congenital pathologies, implant revisions, or infections. In the past, several approaches have been proposed in the replacement of extensive bone defects, each one with its own advantages and drawbacks. As a result, the need for synthetic bone grafts is still a remarkable clinical challenge since more than 1 million bone-graft surgical operations are annually performed worldwide...
March 16, 2018: Journal of Functional Biomaterials
Kavita Nair, Ahmad Iskandarani, Roda Al-Thani, Ramzi Mohammad, Samir Jaoua
Cyt1A protein is a cytolytic protein encoded by the cyt gene of Bacillus thuringiensis subsp. israelensis (Bti) as part of the parasporal crystal proteins produced during the sporulation. Cyt1A protein is unique compared to the other endotoxins present in these parasporal crystals. Unlike δ-endotoxins, Cyt1A protein does not require receptors to bind to the target cell and activate the toxicity. It has the ability to affect a broad range of cell types and organisms, due to this characteristic. Cyt1A has been recognized to not only target the insect cells directly, but also recruit other endotoxins by acting as receptors...
March 16, 2018: Toxins
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
Puneet Kapur, Melanie Baimel, Jordan Chenkin
Left ventricular outflow tract pseudoaneurysms are a rare but life-threatening disorder, often caused by complications of cardiac surgery or myocardial infarction. We present a case report of a patient with no prior risk factors who presented with a six-month history of progressive exertional dyspnea, bilateral leg swelling and cough. Point-of-care ultrasound revealed an unexpected outpouching of the left ventricle. He was diagnosed with a left ventricular outflow tract pseudoaneurysm and subsequently went into cardiogenic shock secondary to extension of pseudoaneurysm causing extrinsic compression of the coronary arteries...
March 16, 2018: CJEM
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