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Petr Busek, Rosana Mateu, Michal Zubal, Lenka Kotackova, Aleksi Sedo
Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
Timothy C Ricard, Cody Haycraft, Srinivasan Sesha Iyengar
We introduce a new coarse-graining technique for ab initio molecular dynamics that is based on the adaptive generation of connected geometric networks or graphs specific to a given molecular ge- ometry. The coarse-grained nodes depict a local chemical environment and are networked to create edges, triangles, tetrahedrons and higher order simplexes based on (a) a Delaunay triangulation procedure and (b) a method that is based on molecular, bonded and non-bonded, local interac- tions. The geometric sub-entities thus created, that is nodes, edges, triangles, and tetrahedrons, each represent an energetic measure for a specific portion of the molecular system, capturing a spe- cific set of interactions...
May 17, 2018: Journal of Chemical Theory and Computation
Miguel Aguilera, Manuel G Bedia
Many biological and cognitive systems do not operate deep within one or other regime of activity. Instead, they are poised at critical points located at phase transitions in their parameter space. The pervasiveness of criticality suggests that there may be general principles inducing this behaviour, yet there is no well-founded theory for understanding how criticality is generated at a wide span of levels and contexts. In order to explore how criticality might emerge from general adaptive mechanisms, we propose a simple learning rule that maintains an internal organizational structure from a specific family of systems at criticality...
May 16, 2018: Scientific Reports
Mayibongwe J Lunga, Ruramai L Chisango, Carli Weyers, Michelle Isaacs, Dale Taylor, Adrienne L Edkins, Setshaba D Khanye, Heinrich C Hoppe, Clinton Veale
Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by reduced efficacy of artemisinin combination therapies (ACT). Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery compounds 13 and 14 whose activity was equipotent to chloroquine against the P...
May 13, 2018: ChemMedChem
Yi Yao, Carly Martin, Congcong Yin, Chunyuan Guo, Zheng Dong, Li Zhou, Qing-Sheng Mi
Our study demonstrates that miRNAs serve as critical epigenetic regulators in the ontogeny of LCs and TRMs in the skin and lungs, suggesting that miRNAs may be promising targets for LC and TRM-related allergic diseases.
May 8, 2018: Journal of Allergy and Clinical Immunology
Michiel Dusselier, Mark E Davis
In the past decade or so, small-pore zeolites have received greater attention than large- and medium-pore molecular sieves that have historically dominated the literature. This is primarily due to the commercialization of two major catalytic processes, NOx exhaust removal and methanol conversion to light olefins, that take advantage of the properties of these materials with smaller apertures. Small-pore zeolites possess pores that are constructed of eight tetrahedral atoms (Si4+ and Al3+ ), each time linked by a shared oxygen These eight-member ring pores (8MR) provide small molecules access to the intracrystalline void space, e...
May 10, 2018: Chemical Reviews
Julianne D Schmidt, Robert C Lynall, Landon Bryce Lempke, Michelle L Weber, Hannes Devos
Post-concussion driving restrictions are eminent, but we lack understanding of current behaviors and opinions about driving following concussion among populations at risk of concussion. We aimed to describe post-concussion driving behaviors and opinions among collegiate student-athletes. Student-athletes completed a survey (response rate=45.3%, 223/492) regarding their post-concussion driving behaviors and opinions. Response frequencies and percentages are presented. Student-athletes self-reported a total of 169 lifetime concussions (0...
May 8, 2018: Journal of Neurotrauma
Agnese Collino, Alberto Termanini, Paola Nicoli, Giuseppe Diaferia, Sara Polletti, Camilla Recordati, Vittoria Castiglioni, Donatella Caruso, Nico Mitro, Gioacchino Natoli, Serena Ghisletti
Chronic inflammation promotes oncogenic transformation and tumor progression. Many inflammatory agents also generate a toxic microenvironment, implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts. A paradigmatic case is represented by cancers occurring in pediatric patients with genetic defects of hepatocyte phosphatidylcholine transporters and in the corresponding mouse model (Mdr2-/- mice), in which impaired bile salt emulsification leads to chronic hepatocyte damage and inflammation, eventually resulting in oncogenic transformation...
May 7, 2018: PLoS Genetics
Leslie S Kean
Cellular therapies play a major and expanding role in the treatment of hematologic diseases. For each of these therapies, a critical therapeutic window exists, where efficacy is maximized and toxicities minimized. This review focuses on one of the most established cellular therapies, hematopoietic stem cell transplant (HCT), and one of the newest cellular therapies, CAR-T cells. In this review I will discuss the current state-of-the field for analysis of their key clinical endpoints and critical toxicities, and focus on the major elements of success for each of these complex therapies...
May 4, 2018: Blood
Bo Zhang, Sheng He, Xuchu Weng
In human occipitotemporal cortex, category-specific processing for visual objects seems to involve pairs of cortical regions, often with one located in the occipital cortex and another more anteriorly. We investigated whether such an arrangement might be the case for visual word processing. In addition to the Visual Word Form Area (VWFA) located in the occipitotemporal sulcus, we observed that another region in occipital lobe with robust responses to written words (Chinese characters). The current fMRI study investigated this area's precise location and its functional selectivity using Chinese characters and other categories of visual images (cars, chairs and insects)...
April 30, 2018: Scientific Reports
Jang Hwan Cho, James J Collins, Wilson W Wong
T cells expressing chimeric antigen receptors (CARs) are promising cancer therapeutic agents, with the prospect of becoming the ultimate smart cancer therapeutics. To expand the capability of CAR T cells, here, we present a split, universal, and programmable (SUPRA) CAR system that simultaneously encompasses multiple critical "upgrades," such as the ability to switch targets without re-engineering the T cells, finely tune T cell activation strength, and sense and logically respond to multiple antigens...
April 17, 2018: Cell
Jong-Hyuk Kim, Won-Taek Oh, Ji-Hun Choi, Jong-Chan Park
In various types of traffic accidents, including car-to-car crash, vehicle-pedestrian collision, and hit-and-run accident, driver overspeed is one of the critical issues of traffic accident analysis. Hence, analysis of vehicle speed at the moment of accident is necessary. The present article proposes a vehicle speed estimate method (VSEM) applying a virtual plane and a virtual reference line to a forensic video. The reliability of the VSEM was verified by comparing the results obtained by applying the VSEM to videos from a test vehicle driving with a global positioning system (GPS)-based Vbox speed...
April 9, 2018: Forensic Science International
Tobey Mandel, David M Dunkley, Maxim Lewkowski, David C Zuroff, Sonia J Lupien, Robert-Paul Juster, N M K Ng Ying Kin, J Elizabeth Foley, Gail Myhr, Ruta Westreich
This study of depressed outpatients (N = 43) examined daily stress-sadness reactivity and the cortisol awakening response (CAR) as moderators of the relationship between self-critical (SC) perfectionism and depression over one year. Participants completed perfectionism measures at baseline (Time 1), daily diaries and salivary sampling six months later (Time 2), and an interviewer-rated depression measure at Time 1, Time 2, and one year after baseline (Time 3). Hierarchical multiple regression analyses of moderator effects demonstrated that patients with higher SC perfectionism and higher levels of daily stress-sadness reactivity (i...
April 2018: Journal of Counseling Psychology
Sylvia C Kurz, Patrick Y Wen
PURPOSE OF REVIEW: More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies. RECENT FINDINGS: The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma...
April 18, 2018: Current Treatment Options in Neurology
Marianne Ryghaug, Tomas Moe Skjølsvold, Sara Heidenreich
Transitions towards low-carbon energy systems will be comprehensive and demanding, requiring substantial public support. One important contribution from STS is to highlight the roles of citizens and public engagement. Until recently, energy users have often been treated as customers and passive market actors, or as recipients of technology at the margins of centralized systems. With respect to the latter role, critical or hesitant public action has been explained in terms of NIMBYism and knowledge deficits...
April 1, 2018: Social Studies of Science
Christopher J Fassnidge, Elliot D Freeman
Some people hear what they see: car indicator lights, flashing neon shop signs, and people's movements as they walk may all trigger an auditory sensation, which we call the visual-evoked auditory response (vEAR or 'visual ear'). We have conducted the first large-scale online survey (N > 4000) of this little-known phenomenon. We analysed the prevalence of vEAR, what induces it, and what other traits are associated with it. We assessed prevalence by asking whether respondents had previously experienced vEAR...
March 9, 2018: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Moanaro Biswas, Sandeep R P Kumar, Cox Terhorst, Roland W Herzog
Gene therapy aims to replace a defective or a deficient protein at therapeutic or curative levels. Improved vector designs have enhanced safety, efficacy, and delivery, with potential for lasting treatment. However, innate and adaptive immune responses to the viral vector and transgene product remain obstacles to the establishment of therapeutic efficacy. It is widely accepted that endogenous regulatory T cells (Tregs) are critical for tolerance induction to the transgene product and in some cases the viral vector...
2018: Frontiers in Immunology
Panupong Puttarak, Patarachai Pornpanyanukul, Thunyaluk Meetam, Katha Bunditanukul, Nathorn Chaiyakunapruk
BACKGROUND & OBJECTIVE: Several randomized controlled trials have investigated Vernonia cinerea (L.) Less. for smoking cessation but there remains no critical summary of overall findings. This study uses systematic review and meta-analysis to summarize the efficacy and safety of V. cinerea. METHODS: Nine databases were searched through November 2017. Randomized controlled trials that reported the smoking cessation effect of V. cinerea were included. Data were extracted by two independent researchers...
April 2018: Complementary Therapies in Medicine
Milu T Cherian, Sergio C Chai, William C Wright, Aman Singh, Morgan Alexandra Casal, Jie Zheng, Jing Wu, Richard E Lee, Patrick R Griffin, Taosheng Chen
The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic sensors that regulate the expression of drug-metabolizing enzymes and efflux transporters. CAR activation promotes drug elimination, thereby reducing therapeutic effectiveness, or causes adverse drug effects via toxic metabolites. CAR inhibitors could be used to attenuate these adverse drug effects. CAR and PXR share ligands and target genes, confounding the understanding of the regulation of receptor-specific activity. We previously identified a small-molecule inhibitor, CINPA1, that inhibits CAR (without activating PXR at lower concentrations) by altering CAR-coregulator interactions and reducing CAR recruitment to DNA response elements of regulated genes...
March 30, 2018: Biochemical Pharmacology
Franziska Blaeschke, Dana Stenger, Theresa Kaeuferle, Semjon Willier, Ramin Lotfi, Andrew Didier Kaiser, Mario Assenmacher, Michaela Döring, Judith Feucht, Tobias Feuchtinger
Relapsed/refractory B-precursor acute lymphoblastic leukemia (pre-B ALL) remains a major therapeutic challenge. Chimeric antigen receptor (CAR) T cells are promising treatment options. Central memory T cells (Tcm) and stem cell-like memory T cells (Tscm) are known to promote sustained proliferation and persistence after T-cell therapy, constituting essential preconditions for treatment efficacy. Therefore, we set up a protocol for anti-CD19 CAR T-cell generation aiming at high Tcm/Tscm numbers. 100 ml peripheral blood from pediatric pre-B ALL patients was processed including CD4+ /CD8+ -separation, T-cell activation with modified anti-CD3/-CD28 reagents and transduction with a 4-1BB-based second generation CAR lentiviral vector...
March 31, 2018: Cancer Immunology, Immunotherapy: CII
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