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https://www.readbyqxmd.com/read/29775474/the-cryptococcus-neoformans-titan-cell-is-an-inducible-and-regulated-morphotype-underlying-pathogenesis
#1
Ivy M Dambuza, Thomas Drake, Ambre Chapuis, Xin Zhou, Joao Correia, Leanne Taylor-Smith, Nathalie LeGrave, Tim Rasmussen, Matthew C Fisher, Tihana Bicanic, Thomas S Harrison, Marcel Jaspars, Robin C May, Gordon D Brown, Raif Yuecel, Donna M MacCallum, Elizabeth R Ballou
Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, highly polyploid cells termed Titan cells. Titan cells influence fungal interaction with host cells, including through increased drug resistance, altered cell size, and altered Pathogen Associated Molecular Pattern exposure...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29775418/prolonged-activation-of-camp-signaling-leads-to-endothelial-barrier-disruption-via-transcriptional-repression-of-rras
#2
Carole Y Perrot, Junko Sawada, Masanobu Komatsu
The increase in cAMP levels in endothelial cells triggers cellular signaling to alter vascular permeability. It is generally considered that cAMP signaling stabilizes the endothelial barrier function and reduces permeability. However, previous studies have only examined the permeability shortly after cAMP elevation and thus have only investigated acute responses. Because cAMP is a key regulator of gene expression, elevated cAMP may have a delayed but profound impact on the endothelial permeability by altering the expression of the genes that are vital for the vessel wall stability...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29773198/serum-concentrations-of-trace-elements-and-their-relationships-with-paraoxonase-1-in-morbidly-obese-women
#3
Fedra Luciano-Mateo, Noemí Cabré, Martí Nadal, Anabel García-Heredia, Gerard Baiges-Gaya, Anna Hernández-Aguilera, Jordi Camps, Jorge Joven, José Luis Domingo
The metabolic alterations associated with obesity include mineral dysregulation. Essential trace elements are nutrients with a relevant function in a large number of cellular processes and multiple roles in the correct functioning of metabolic enzymes. Paraoxonase-1 (PON1) is an antioxidant and anti-inflammatory enzyme that is compromised in obesity. In the present study, the potential alterations in trace elements in morbidly obese women were assessed in relation to serum PON1 activity and concentration, as well as to other obesity-related comorbidities such as diabetes mellitus and fatty liver...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772813/the-rights-of-children-on-the-move-and-the-budapest-declaration
#4
Charles Oberg
It has been estimated that more than 50,000,000 children and youth have migrated across borders or been forcibly displaced within their own country. They consist of refugees, asylum seekers, internally displaced persons (IDP), economic migrants, and exploited trafficked children. They are virtually "stateless", children deprived of the protective structures of state and family that they need and deserve and unrecognized by either their country of origin or the international community. This opinion piece starts with the personal reflections of its author on his recent work in Middle East refugee camps...
May 17, 2018: Children
https://www.readbyqxmd.com/read/29772544/antigen-specific-therapy-of-graves%C3%A2-disease-and-orbitopathy-by-induction-of-tolerance
#5
Martin Ungerer, Julia Fabbender, Hans-Peter Holthoff
Graves´ disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. The disease can be modelled in mice using adenoviral immunizations with the extracellular A subunit of the TSHR, which induces a long-term stable disease state. TSHR binding cAMP-stimulatory antibodies, thyroid enlargement, elevated serum thyroxin levels, tachycardia, cardiac hypertrophy and orbitopathy are observed in these Ad-TSHR-immunized mice...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772231/roles-of-14-3-3%C3%AE-and-%C3%AE-in-regulation-of-the-glucocorticoid-receptor-transcriptional-activation-and-hepatic-gluconeogenesis
#6
Yunhee Hwang, Hyoung-Tae An, Minsoo Kang, Jesang Ko
The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that mediates the effects of glucocorticoids, and plays a crucial role in cell growth, development, inflammation, and gluconeogenesis. The 14-3-3 proteins bind to target proteins via phosphorylation, and influence many cellular events by altering their subcellular localization or by acting as chaperones. However, the mechanisms by which 14-3-3 proteins regulate GR transactivation and their involvement in gluconeogenesis remain uncharacterized...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29771226/sanokondu
#7
Jamiu Busari, Ming-Ka Chan, Deepak Dath, Anne Matlow, Diane de Camps Meschino
Purpose This paper aims to describe the evolution of Sanokondu, highlighting the rationale, achievements and lessons learnt from this initiative. Sanokondu is a multinational community of practice dedicated to fostering health-care leadership education worldwide. This platform for health-care leadership education was conceived in 2014 at the first Toronto International Summit on Leadership Education for Physicians (TISLEP) and evolved into a formal network of collaborators in 2016. Design/methodology/approach This paper is a case study of a multinational collaboration of health-care leaders, educators, learners and other stakeholders...
May 8, 2018: Leadership in Health Services
https://www.readbyqxmd.com/read/29770155/neuroprotective-effect-and-molecular-mechanism-of-6-gingerol-against-scopolamine-induced-amnesia-in-c57bl-6-mice
#8
Chang-Yul Kim, Yongtaek Seo, Chan Lee, Gyu Hwan Park, Jung-Hee Jang
We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN), a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p.) was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (%) in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day)...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29770106/perceptions-about-authentic-leadership-development-south-african-occupational-therapy-students-camp-experience
#9
Fatima Hendricks, Susan Toth-Cohen
Background: Twenty-three years into democracy, concern is deepening regarding the slow progress of Occupational Therapy (OT) in South Africa, especially with regard to diversity and inclusion within OT. Methods: This study explores authentic leadership development primarily among Black OT students attending a pilot Occupational Therapy Association of South Africa (OTASA) National Student Leadership Camp. It seeks to ascertain their perceptions on leadership and leadership development...
2018: Occupational Therapy International
https://www.readbyqxmd.com/read/29769602/computational-identification-and-validation-of-alternative-splicing-in-zsf1-rat-rna-seq-data-a-preclinical-model-for-type-2-diabetic-nephropathy
#10
Chi Zhang, Ken Dower, Baohong Zhang, Robert V Martinez, Lih-Ling Lin, Shanrong Zhao
Obese ZSF1 rats exhibit spontaneous time-dependent diabetic nephropathy and are considered to be a highly relevant animal model of progressive human diabetic kidney disease. We previously identified gene expression changes between disease and control animals across six time points from 12 to 41 weeks. In this study, the same data were analysed at the isoform and exon levels to reveal additional disease mechanisms that may be governed by alternative splicing. Our analyses identified alternative splicing patterns in genes that may be implicated in disease pathogenesis (such as Shc1, Serpinc1, Epb4...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769519/optical-functionalization-of-human-class-a-orphan-g-protein-coupled-receptors
#11
Maurizio Morri, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J Gerrard, Priscila P Hirschfeld, Jan Schwarz, Harald Janovjak
G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+ -, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769318/structural-basis-for-selective-inhibition-of-human-pkg-i%C3%AE-by-the-balanol-like-compound-n46
#12
Liying Qin, Banumathi Sankaran, Sahar Aminzai, Darren Casteel, Choel Kim
Activation of PKG Iα in nociceptive neurons induces a long-term hyperexcitability that causes chronic pain. Recently, a derivative of the fungal metabolite balanol, N46, has been reported to inhibit PKG Iα with high potency and selectivity and attenuates thermal hyperalgesia and osteoarthritic pain. Here, we determined co-crystal structures of the PKG Iα C-domain and cAMP-dependent protein kinase (PKA) Cα, each bound with N46, at 1.98 Å and 2.65 Å, respectively. N46 binds the active site with its external phenyl ring specifically interacting with the glycine-rich loop and the αC helix...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29769306/first-person-gerg%C3%A5-szanda
#13
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Gergő Szanda is the first author on 'Mitochondrial cAMP exerts positive feedback on mitochondrial Ca2+ uptake via the recruitment of Epac1', published in Journal of Cell Science. Gergő is an assistant professor and leads a group at Semmelweis University, Budapest, Hungary, investigating Ca2+ signaling and mitochondrial biology, and the role of endocannabinoids in metabolism...
May 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29769246/small-molecule-positive-allosteric-modulators-of-the-%C3%AE-2-adrenoceptor-isolated-from-dna-encoded-libraries
#14
Seungkirl Ahn, Biswaranjan Pani, Alem W Kahsai, Eva K Olsen, Gitte Husemoen, Mikkel Vestrgaard, Lei Jin, Shuai Zhao, Laura M Wingler, Paula K Rambarat, Rishabh K Simhal, Thomas T Xu, Lillian D Sun, Paul J Shim, Dean P Staus, Li-Yin Huang, Thomas Franch, Xin Chen, Robert J Lefkowitz
Conventional drug discovery efforts at the β2 -adrenoceptor (β2 AR) have led to the development of ligands that bind almost exclusively to the receptor's hormone-binding orthosteric site. However, targeting the largely unexplored and evolutionarily unique allosteric sites has potential for developing more specific drugs with fewer side effects than orthosteric ligands. Using our recently developed approach for screening G protein-coupled receptors (GPCRs) with DNA-encoded small molecule libraries, we have discovered and characterized the first β2 AR small molecule positive allosteric modulators (PAMs) - compound-6 [(R)-N-(4-amino-1-(4-(tert-butyl)phenyl)-4-oxobutan-2-yl)-5-(N-isopropyl-N-methylsulfamoyl)-2-((4-methoxyphenyl) thio)benzamide] and its analogs...
May 16, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29768676/ccl19-with-ccl21-tail-displays-enhanced-glycosaminoglycan-binding-with-retained-chemotactic-potency-in-dendritic-cells
#15
Astrid S Jørgensen, Pontian E Adogamhe, Julia M Laufer, Daniel F Legler, Christopher T Veldkamp, Mette M Rosenkilde, Gertrud M Hjortø
CCL19 is more potent than CCL21 in inducing chemotaxis of human dendritic cells (DC). This difference is attributed to 1) a stronger interaction of the basic C-terminal tail of CCL21 with acidic glycosaminoglycans (GAGs) in the environment and 2) an autoinhibitory function of this C-terminal tail. Moreover, different receptor docking modes and tissue expression patterns of CCL19 and CCL21 contribute to fine-tuned control of CCR7 signaling. Here, we investigate the effect of the tail of CCL21 on chemokine binding to GAGs and on CCR7 activation...
May 16, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29768201/activation-of-ephb2-forward-signaling-enhances-memory-consolidation
#16
Jessica M Alapin, Monica Dines, Maria Vassiliev, Tal Tamir, Alon Ram, Clifford Locke, Ji Yu, Raphael Lamprecht
EphB2 is involved in enhancing synaptic transmission and gene expression. To explore the roles of EphB2 in memory formation and enhancement, we used a photoactivatable EphB2 (optoEphB2) to activate EphB2 forward signaling in pyramidal neurons in lateral amygdala (LA). Photoactivation of optoEphB2 during fear conditioning, but not minutes afterward, enhanced long-term, but not short-term, auditory fear conditioning. Photoactivation of optoEphB2 during fear conditioning led to activation of the cAMP/Ca2+ responsive element binding (CREB) protein...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768061/structural-re-positioning-in-silico-molecular-modelling-oxidative-degradation-and-biological-screening-of-linagliptin-as-adenosine-3-receptor-adora3-modulators-targeting-hepatocellular-carcinoma
#17
Bassam M Ayoub, Yasmeen M Attia, Mahmoud S Ahmed
Chemical entities with structural diversity were introduced as candidates targeting adenosine receptor with different clinical activities, containing 3,7-dihydro-1H-purine-2,6-dione, especially adenosine 3 receptors (ADORA3). Our initial approach started with pharmacophore screening of ADORA3 modulators; to choose linagliptin (LIN), approved anti-diabetic drug as Dipeptidyl peptidase-4 inhibitors, to be studied for its modulating effect towards ADORA3. This was followed by generation, purification, analytical method development, and structural elucidation of oxidative degraded product (DEG)...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29768041/getting-hit-by-pitch-in-professional-baseball-analysis-of-injury-patterns-risk-factors-concussions-and-days-missed-for-batters
#18
Christopher L Camp, Dean Wang, Alec S Sinatro, John D'Angelo, Struan H Coleman, Joshua S Dines, Stephen Fealy, Stan Conte
BACKGROUND: Although batters are frequently hit by pitch (HBP) in baseball, the effect of HBP injuries remains undefined in the literature. PURPOSE: To determine the effect of HBP injuries in terms of time out of play, injury patterns resulting in the greatest time out of play, and the value of protective gear such as helmets and elbow pads. STUDY DESIGN: Descriptive laboratory study. METHODS: Based on the Major League Baseball (MLB) Health and Injury Tracking System, all injuries to batters HBP during the 2011-2015 MLB and Minor League Baseball (MiLB) seasons were identified and analyzed...
May 1, 2018: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29767281/hiv-risk-among-displaced-adolescent-girls-in-ethiopia-the-role-of-gender-attitudes-and-self-esteem
#19
Laura Gauer Bermudez, Gary Yu, Lily Lu, Kathryn Falb, Jennate Eoomkham, Gizman Abdella, Lindsay Stark
Adolescent girls in sub-Saharan Africa have been deemed one of the most critical populations to address in the campaign for an HIV-free generation. Experiences of intimate partner violence (IPV), harmful gender norms, diminished personal agency, and age-disparate sex have been identified as factors in the increasing rate of new infections among this population. Using baseline data from a cluster-randomized controlled trial in three refugee camps in Benishangul-Gumuz Regional State in Ethiopia, our study quantitatively examined the associations between HIV risk factors, attitudes on gender inequality, IPV acceptability, and self-esteem for female adolescent refugees primarily from Sudan and South Sudan (n = 919)...
May 16, 2018: Prevention Science: the Official Journal of the Society for Prevention Research
https://www.readbyqxmd.com/read/29766727/-human-life-as-goodness-why-euthanasia-is-morally-unacceptable
#20
David Černý
The current discussion of the moral admissibility or inadmissibility of euthanasia should, in my opinion, consider the greatest possible number of the shared premises of the two opinion camps. That is why I followed a thesis in this paper that the question of the good life is the focus of ethical interest, as this is what connects the advocates and the opponents to euthanasia. In the first part of the paper I critically discuss the two main theories of the good life widely embraced among the advocates of euthanasia: hedonism and desire-fulfilment theory...
2018: Vnitr̆ní Lékar̆ství
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