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Walderik W Zomerman, Sabine L A Plasschaert, Siobhan Conroy, Frank J Scherpen, Tiny G J Meeuwsen-de Boer, Harm J Lourens, Sergi Guerrero Llobet, Marlinde J Smit, Lorian Slagter-Menkema, Annika Seitz, Corrie E M Gidding, Esther Hulleman, Pieter Wesseling, Lisethe Meijer, Leon C van Kempen, Anke van den Berg, Daniël O Warmerdam, Frank A E Kruyt, Floris Foijer, Marcel A T M van Vugt, Wilfred F A den Dunnen, Eelco W Hoving, Victor Guryev, Eveline S J M de Bont, Sophia W M Bruggeman
The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling...
March 20, 2018: Cell Reports
Angela Maria Gomes, Liane Colliselli, Maria Elisabeth Kleba, Valéria Silvana Faganello Madureira
OBJECTIVE: to identify the participation dynamics of a municipal council and to develop a critical-reflexive process on "being a counselor", identifying weaknesses and possibilities of this council, in addition to collectively generating new knowledge and (re)elaborating the MHC Ordinary Law. METHOD: Convergent care research, including documentary analysis, non-participant observation and thematic workshops. The research was carried out in 2016, with municipal health counselors from a city in the Western Region of Santa Catarina...
2018: Revista Brasileira de Enfermagem
Agnieszka Drozd, Dominika Wojewska, Manuel David Peris-Díaz, Piotr Jakimowicz, Artur Krężel
Metallothioneins (MTs), small cysteine-rich proteins, present in four major isoforms, are key proteins involved in zinc and copper homeostasis in mammals. To date, only one X-ray crystal structure of a MT has been solved. It demonstrates seven bivalent metal ions bound in two structurally independent domains with M4S11 (α) and M3S9 (β) clusters. Recent discoveries indicate that Zn(ii) ions are bound with MT2 with the range from nano- to picomolar affinity, which determines its cellular zinc buffering properties that are demonstrated by the presence of partially Zn(ii)-depleted MT2 species...
March 21, 2018: Metallomics: Integrated Biometal Science
Johannes Eimer, Jan Vesterbacka, Irina Savitcheva, Rayomand Press, Homayoun Roshanisefat, Piotr Nowak
RATIONALE: Cognitive dysfunction is a common presenting symptom in patients with HIV/AIDS. It is usually directly associated with HIV infection or due to opportunistic infection. Rapidly progressive dementia, however, is rarely observed in acute HIV infection or during immune reconstitution. Recently, a case of Creutzfeld-Jakob disease (CJD) has been reported in a patient with chronic HIV infection. The incidence of CJD is not known to be increased among immunocompromised patients. PATIENT CONCERNS: We here report the case of a 59-year-old male patient with a recent diagnosis of HIV/AIDS and Pneumocystis jiroveci pneumonia presenting with secondary behavioral changes and disorientation...
March 2018: Medicine (Baltimore)
Ignacio Rebollo, Anne-Dominique Devauchelle, Benoît Béranger, Catherine Tallon-Baudry
Resting-state networks offer a unique window into the brain's functional architecture, but their characterization remains limited to instantaneous connectivity thus far. Here, we describe a novel resting-state network based on the delayed connectivity between the brain and the slow electrical rhythm (0.05 Hz) generated in the stomach. The gastric network cuts across classical resting-state networks with partial overlap with autonomic regulation areas. This network is composed of regions with convergent functional properties involved in mapping bodily space through touch, action or vision, as well as mapping external space in bodily coordinates...
March 21, 2018: ELife
Wanda Mastor
On the boundaries of life and, as a result, almost a question of metaphysics, still dividing science and continually fuelling debates, one question does seem to be legally insoluble, ie the question of the status of the human embryo. A comparatist look allows us to put into perspective the various national postures with regard to the embryo in order to confront them, by putting forward the areas where they converge or diverge. Although a very global approach allows us to note certain similarities, a more precise study of the question of abortion in particular reflects the evidence of the contextualisation of the embryo...
March 7, 2018: Journal International de Bioéthique et D'éthique des Sciences
Asuka Fujii, Natsuko Sugawara, Po-Jen Hsu, Takuto Shimamori, Ying-Cheng Li, Toru Hamashima, Jer-Lai Kuo
Because of the hydrogen bond coordination properties of alcohols, their possible hydrogen bond network structures are categorized into only a few types. Therefore, gas phase clusters of alcohols can be a very simple model system to examine the properties of hydrogen bond networks, such as structural development with cluster size and temperature dependence. In this perspective, we focus on the structural study of protonated short-chain alcohol clusters, whose excess protons (charge) enable size-selective spectroscopy in combination with mass spectrometric techniques...
March 21, 2018: Physical Chemistry Chemical Physics: PCCP
Samantha G Farris, Angelo M DiBello, Erika Litvin Bloom, Ana M Abrantes
INTRODUCTION: The Smoking and Weight Eating Episodes Test (SWEET; Adams et al. 2011) is a self-report measure designed to assess multiple reasons why and when smokers use cigarettes for appetite, weight, and shape management, that was initially developed and validated in young female smokers. PURPOSE: The aim of the current study was to evaluate the factor structure and psychometric properties of the SWEET measure among both male and female daily cigarette smokers...
March 20, 2018: International Journal of Behavioral Medicine
Greg Rulifson, Angela R Bielefeldt
Engineers should learn how to act on their responsibility to society during their education. At present, however, it is unknown what students think about the meaning of socially responsible engineering. This paper synthesizes 4 years of longitudinal interviews with engineering students as they progressed through college. The interviews revolved broadly around how students saw the connections between engineering and social responsibility, and what influenced these ideas. Using the Weidman Input-Environment-Output model as a framework, this research found that influences included required classes such as engineering ethics, capstone design, and some technical courses, pre-college volunteering and familial values, co-curricular groups such as Engineers Without Borders and the Society of Women Engineers, as well as professional experiences through internships...
March 20, 2018: Science and Engineering Ethics
Danielle E Mor, Harry Ischiropoulos
In Parkinson's disease (PD), the loss of dopamine-producing neurons in the substantia nigra (SN) leads to severe motor impairment, and pathological inclusions known as Lewy bodies contain aggregated α-synuclein protein. The relationship of α-synuclein aggregation and dopaminergic degeneration is unclear. This commentary highlights a recent study showing that the interaction of α-synuclein with dopamine may be an important mechanism underlying disease. Elevating dopamine levels in mice expressing human α-synuclein with the A53T familial PD mutation recapitulated key features of PD, including progressive neurodegeneration of the SN and decreased ambulation...
2018: Journal of Experimental Neuroscience
Laura Pérez-Benito, Henrik Keränen, Herman van Vlijmen, Gary Tresadern
A congeneric series of 21 phosphodiesterase 2 (PDE2) inhibitors are reported. Crystal structures show how the molecules can occupy a 'top-pocket' of the active site. Molecules with small substituents do not enter the pocket, a critical leucine (Leu770) is closed and water molecules are present. Large substituents enter the pocket, opening the Leu770 conformation and displacing the waters. We also report an X-ray structure revealing a new conformation of the PDE2 active site domain. The relative binding affinities of these compounds were studied with free energy perturbation (FEP) methods and it represents an attractive real-world test case...
March 20, 2018: Scientific Reports
Leabaneng Tawe, Thato Motshoge, Pleasure Ramatlho, Naledi Mutukwa, Charles Waithaka Muthoga, Ghyslaine Bruna Djeunang Dongho, Axel Martinelli, Elias Peloewetse, Gianluca Russo, Isaac Kweku Quaye, Giacomo Maria Paganotti
Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499)...
March 20, 2018: Scientific Reports
Peyman Tavallali, Hana Koorehdavoudi, Joanna Krupa
Intrinsic Frequency (IF) has recently been introduced as an ample signal processing method for analyzing carotid and aortic pulse pressure tracings. The IF method has also been introduced as an effective approach for the analysis of cardiovascular system dynamics. The physiological significance, convergence and accuracy of the IF algorithm has been established in prior works. In this paper, we show that the IF method could be derived by appropriate mathematical approximations from the Navier-Stokes and elasticity equations...
March 20, 2018: Scientific Reports
James B T Sanders, J Doyne Farmer, Tobias Galla
We study adaptive learning in a typical p-player game. The payoffs of the games are randomly generated and then held fixed. The strategies of the players evolve through time as the players learn. The trajectories in the strategy space display a range of qualitatively different behaviours, with attractors that include unique fixed points, multiple fixed points, limit cycles and chaos. In the limit where the game is complicated, in the sense that the players can take many possible actions, we use a generating-functional approach to establish the parameter range in which learning dynamics converge to a stable fixed point...
March 20, 2018: Scientific Reports
Weston Testo, Benjamin Øllgaard, Ashley Field, Thaís Almeida, Michael Kessler, David Barrington
The Neotropical clade of the lycophyte genus Phlegmariurus is comprised of an estimated 150 described species and exhibits exceptional morphological and ecological diversity. Because of their simple morphology, frequent convergent evolution, and the recentness of the group's diversification, the delimitation of species and species groups has remained challenging. Here, we present a robustly support phylogeny of Neotropical Phlegmariurus based on six chloroplast markers and ca. 70% of known species, and use ancestral character state reconstruction to investigate morphological evolution in the clade, and define natural species groups...
March 17, 2018: Molecular Phylogenetics and Evolution
Brian C Kok, Vanessa K Ma, Christine E Gould
BACKGROUND: Social anxiety disorder (SAD) (formerly called social phobia) is among the most common mental health diagnoses among older adults; however, the research on late-life social anxiety is scarce. A limited number of studies have examined the assessment and diagnosis of social anxiety disorder in this population, and there are few social anxiety measures that are validated for use with older adults. One such measure, the Older Adult Social Evaluative Scale (OASES), was designed for use with this population, but until now has lacked validation against a gold-standard diagnostic interview...
March 21, 2018: International Psychogeriatrics
Qin Wang, Luisette Delva, Paul H Weinreb, Robert B Pepinsky, Danielle Graham, Elvana Veizaj, Anne E Cheung, Weiping Chen, Ivan Nestorov, Ellen Rohde, Robin Caputo, Geoffrey M Kuesters, Tonika Bohnert, Liang-Shang Gan
BACKGROUND: Many studies have focused on the challenges of small molecule uptake across the blood-brain barrier, whereas few in-depth studies have assessed the challenges with the uptake of antibodies into the central nervous system (CNS). In drug development, cerebrospinal fluid (CSF) sampling is routinely used as a surrogate for assessing CNS drug exposure and biomarker levels. In this report, we have studied the kinetic correlation between CSF and serum drug concentration-time profiles for five humanized monoclonal antibodies in rats and cynomolgus monkeys and analyzed factors that affect their CSF exposure...
March 20, 2018: Fluids and Barriers of the CNS
James R Rodrigue, Richard Luskin, Helen Nelson, Alexandra Glazier, Galen V Henderson, Francis L Delmonico
INTRODUCTION: Unfavorable attitudes and insufficient knowledge about donation after cardiac death among critical care providers can have important consequences for the appropriate identification of potential donors, consistent implementation of donation after cardiac death policies, and relative strength of support for this type of donation. The lack of reliable and valid assessment measures has hampered research to capture providers' attitudes. Design and Research Aims: Using stakeholder engagement and an iterative process, we developed a questionnaire to measure attitudes of donation after cardiac death in critical care providers (n = 112) and examined its psychometric properties...
January 1, 2018: Progress in Transplantation
Shahid Khan, Jonathan M Scholey
Cells from all three domains of life on Earth utilize motile macromolecular devices that protrude from the cell surface to generate forces that allow them to swim through fluid media. Research carried out on archaea during the past decade or so has led to the recognition that, despite their common function, the motility devices of the three domains display fundamental differences in their properties and ancestry, reflecting a striking example of convergent evolution. Thus, the flagella of bacteria and the archaella of archaea employ rotary filaments that assemble from distinct subunits that do not share a common ancestor and generate torque using energy derived from distinct fuel sources, namely chemiosmotic ion gradients and FlaI motor-catalyzed ATP hydrolysis, respectively...
March 19, 2018: Current Biology: CB
Yu-Chuan Chiu, Shen-Ing Liu, Chen-Ju Lin, Yu-Shin Huang, Chun-Kai Fang, Fang-Ju Sun, Kai-Liang Kao, Yo-Ping Huang, Shu-I Wu
This study examines the reliability, factor structure, convergent, and construct validities of the Mandarin Chinese version of the Reasons For Living Inventory (RFL) among Taiwanese psychiatric patients. Demographical characteristics of patients who hold these adaptive cognitions and differences on the level of endorsement between suicidal and non-suicidal individuals were also investigated. All adult patients that had visited the psychiatric ambulatory clinic or had been admitted to the psychiatric ward in a general hospital in Taiwan over a 3-month period were consecutively invited to complete an inventory that included background information, the Mandarin Chinese versions of the RFL, the Suicidal Behaviors Questionnaire- Revised (SBQ-R), and the Beck Hopeless Scale (BHS)...
March 20, 2018: Behavioral Medicine
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