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The seesaw between normal function and protein aggregation: How functional interactions may increase protein solubility.

Bioessays 2021 Jun 29;43(6):e2100031. Epub 2021 Mar 29.

UK Dementia Research Institute at King's College London, The Maurice Wohl Institute, London, UK.

Protein aggregation has been studied for at least 3 decades, and many of the principles that regulate this event are relatively well understood. Here, however, we present a different perspective to explain why proteins aggregate: we argue that aggregation may occur as a side-effect of the lack of one or more natural partners that, under physiologic conditions, would act as chaperones. This would explain why the same surfaces that have evolved for functional purposes are also those that favour aggregation. Read More

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Observation of Ferrochiral Transition Induced by an Antiferroaxial Ordering of Antipolar Structural Units in Ba(TiO)Cu(PO).

J Am Chem Soc 2021 Mar 25;143(9):3638-3646. Epub 2021 Feb 25.

Department of Advanced Materials Science, University of Tokyo, Kashiwa, Chiba 277-8561, Japan.

Ferrochiral transition, i.e., a transition involving an emergence of chirality, provides an unique opportunity to achieve a nonvolatile reversible control of chirality with external fields. Read More

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OX-HDL: A Starring Role in Cardiorenal Syndrome and the Effects of Heme Oxygenase-1 Intervention.

Diagnostics (Basel) 2020 Nov 20;10(11). Epub 2020 Nov 20.

Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.

In this review, we will evaluate how high-density lipoprotein (HDL) and the reverse cholesterol transport (RCT) pathway are critical for proper cardiovascular-renal physiology. We will begin by reviewing the basic concepts of HDL cholesterol synthesis and pathway regulation, followed by cardiorenal syndrome (CRS) pathophysiology. After explaining how the HDL and RCT pathways become dysfunctional through oxidative processes, we will elaborate on the potential role of HDL dysfunction in CRS. Read More

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November 2020

Practitioners' Dilemmas and Strategies in Decision-making Conversations Where Patients and Companions Take Divergent Positions on a Healthcare Measure: An Observational Study Using Conversation Analysis.

Health Commun 2020 Sep 22:1-12. Epub 2020 Sep 22.

School of Social Sciences and Humanities, Loughborough University.

The presence of companions adds complexity to healthcare interactions. Few studies have characterized challenges arising when interactions involve healthcare professionals (HCPs), patients, and companions, or how those challenges are managed. Using conversation analysis, we examined recorded episodes where patients and companions adopt divergent positions on healthcare measures (e. Read More

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September 2020

Budgetary targets as cost-containment measure in the Swiss healthcare system? Lessons from abroad.

Health Policy 2020 06 16;124(6):605-614. Epub 2020 May 16.

University of Cologne and Swiss Federal Department of Finance, Bundesgasse 3, 3003 Berne, Switzerland. Electronic address:

Growing healthcare expenditure is a major concern for policy makers and calls for effective cost containment measures. For the decentralized Swiss healthcare system, ranking second among OECD countries in healthcare spending, a group of experts has proposed budgetary targets as key measure. In order to substantiate this proposal, we review the literature and analyse experiences with budgetary targets in comparable social health insurance systems, such as Germany and the Netherlands. Read More

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Zebrafish (Danio rerio) as an animal model for bath infection by Flavobacterium psychrophilum.

J Fish Dis 2020 May 20;43(5):561-570. Epub 2020 Mar 20.

Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile.

Flavobacterium psychrophilum is the causative agent of bacterial cold-water disease and rainbow trout syndrome in freshwater salmonid fish worldwide, generating injuries and high mortality rates. Despite several studies on this bacterium, the infection mechanism remains unknown due to limitations in the employed animal models. In this work, we propose using zebrafish (Danio rerio) as a model for studying bacterial pathogenicity. Read More

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Should oral exposure in Hypoaspis aculeifer tests be considered in order to keep them in Tier I test battery for ecological risk assessment of PPPs?

Environ Pollut 2019 Jan 27;244:871-876. Epub 2018 Oct 27.

CFE - Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, Portugal.

The laboratory reproduction test with the predatory mite Hypoaspis aculeifer is currently a mandatory test in the new EU data requirements for prospective environmental risk assessment of Plant Protection Products (PPPs). However, the low sensitivity often shown by this mite towards PPPs, when compared to other invertebrates (namely Folsomia candida and Eisenia fetida), makes the test with this species not very useful in the lower tier test battery. However, the current test protocol only considers exposure to contaminants via contaminated soil, disregarding exposure via contaminated food and does not take into account the fact that H. Read More

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January 2019

JAK-STAT signaling pathway inhibition: a role for treatment of discoid lupus erythematosus and dermatomyositis.

Int J Dermatol 2018 Aug 5;57(8):1007-1014. Epub 2018 Jun 5.

Tufts University School of Medicine, Boston, MA, USA.

Background: Discoid lupus erythematosus (DLE) and dermatomyositis (DM) are inflammatory autoimmune diseases that manifest primarily in the skin but can be linked to systemic complications. Although there is an in-depth understanding of the clinical presentation of these two diseases, much less is known regarding the pathophysiology. This has limited the effective treatment options for patients. Read More

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Am I Self-Conscious? (Or Does Self-Organization Entail Self-Consciousness?).

Karl Friston

Front Psychol 2018 24;9:579. Epub 2018 Apr 24.

Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London (UCL), London, United Kingdom.

Is self-consciousness necessary for consciousness? The answer is yes. So there you have it-the answer is yes. This was my response to a question I was asked to address in a recent AEON piece (https://aeon. Read More

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On the relation between theory of mind and executive functioning: A developmental cognitive neuroscience perspective.

Psychon Bull Rev 2018 Dec;25(6):2119-2140

Dr Eric Jackman Institute of Child Study, University of Toronto, Toronto, Ontario, Canada.

Theory of mind (ToM) and executive functioning (EF) show marked interrelatedness across childhood, and developmental psychologists have long been interested in understanding the nature of this association. The present review addresses this issue from a cognitive neuroscience perspective by exploring three hypotheses regarding their functional overlap: (1) ToM relies on EF (EF→ToM); (2) EF relies on ToM (ToM→EF); and (3) ToM and EF are mutually related, owing to shared neural structures or networks (ToM↔EF). Drawing on evidence from normative brain development, neurodevelopmental and neurodegenerative diseases, patient lesion studies, and brain-imaging studies, we suggest that only a strict version of the ToM↔EF proposal of complete neural overlap can be confidently ruled out on the basis of existing evidence. Read More

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December 2018

Correlation of P300 ERPs with visual stimuli and its application to vigilance detection.

Annu Int Conf IEEE Eng Med Biol Soc 2017 Jul;2017:2590-2593

Vigilance or sustained attention is defined as the ability to maintain concentrated attention over prolonged time periods. It is an important aspect in industries such as aerospace and nuclear power, which involve tremendous man-machine interaction and where safety of any component/system or environment as a whole is extremely crucial. Many methods for vigilance detection, based on biological and behavioral characteristics, have been proposed in the literature. Read More

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Making sense of the past: hyperstability of ancestral thioredoxins explained by free energy simulations.

Phys Chem Chem Phys 2017 Aug;19(34):23239-23246

Área de Farmacología, Departamento de Ciencias Biomédicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, E-28805 Alcalá de Henares, Madrid, Spain.

Thioredoxin (Trx), a small and globular protein, is present in all kinds of organisms, from Archea to higher mammals. Throughout evolution, the Trx sequence has undergone subtle modifications to adapt to varying environmental conditions. The high degree of sequence conservation makes Trx very amenable to ancestral protein reconstruction techniques. Read More

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Therapeutic use of the rebound effect of modern drugs: "New homeopathic medicines".

Rev Assoc Med Bras (1992) 2017 Feb;63(2):100-108

MD, PhD, Postdoctoral Student of the Department of Obstetrics and Gynecology, Faculdade de Medicina da Universidade de São Paulo (FMUSP). Coordinator of the Elective Discipline Fundamentals of Homeopathy (MCM0773), FMUSP, São Paulo, SP, Brazil.

The homeopathic treatment is based on the principle of therapeutic similitude, employing medicines that cause certain disorders to treat similar manifestations, stimulating a reaction of the organism against its own ailments. The occurrence of this secondary reaction of the organism, opposite in nature to the primary action of the medicines, is evidenced in the study of the rebound (paradoxical) effect of several classes of modern drugs. In this work, in addition to substantiate the principle of similitude before the experimental and clinical pharmacology, we suggest a proposal to employ hundreds of conventional drugs according to homeopathic method, applying the therapeutic similitude between the adverse events of medicines and the clinical manifestations of patients. Read More

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February 2017

Pathogenesis of Rushton bodies: A novel hypothesis.

Med Hypotheses 2016 Aug 6;93:166-9. Epub 2016 Jun 6.

Department of Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia. Electronic address:

Rushton bodies (RBs) are one of the characteristic features seen in the epithelial lining of odontogenic cysts mainly radicular, dentigerous and odontogenic keratocyst. It has two different histo-morphological appearances; granular and homogeneous. Although widely investigated, the exact pathogenesis and histogenesis of RBs is still an enigma. Read More

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Whole brain mapping of visual and tactile convergence in the macaque monkey.

Neuroimage 2015 Aug 16;117:93-102. Epub 2015 May 16.

Centre de Neuroscience Cognitive, CNRS UMR 5229, Université Claude Bernard Lyon I, 67 Bd Pinel, 69675 Bron cedex, France. Electronic address:

The proposal that sensory processing is achieved in segregated anatomical pathways has been profoundly revisited following the description of cross-modal anatomical connections both at higher and at lower processing levels. However, an understanding of the cortical extent of these long range cross-modal functional influences has been missing. Here, we use functional magnetic resonance imaging (fMRI) to map, in the non-human primate brain, the cortical regions which are activated by both visual and tactile stimulations. Read More

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Constructing kinetic models to elucidate structural dynamics of a complete RNA polymerase II elongation cycle.

Phys Biol 2014 Dec 5;12(1):016004. Epub 2014 Dec 5.

Beijing Computational Science Research Center, Beijing, 100084, People's Republic of China.

The RNA polymerase II elongation is central in eukaryotic transcription. Although multiple intermediates of the elongation complex have been identified, the dynamical mechanisms remain elusive or controversial. Here we build a structure-based kinetic model of a full elongation cycle of polymerase II, taking into account transition rates and conformational changes characterized from both single molecule experimental studies and computational simulations at atomistic scale. Read More

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December 2014

Sensing membrane stresses by protein insertions.

PLoS Comput Biol 2014 Apr 10;10(4):e1003556. Epub 2014 Apr 10.

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Protein domains shallowly inserting into the membrane matrix are ubiquitous in peripheral membrane proteins involved in various processes of intracellular membrane shaping and remodeling. It has been suggested that these domains sense membrane curvature through their preferable binding to strongly curved membranes, the binding mechanism being mediated by lipid packing defects. Here we make an alternative statement that shallow protein insertions are universal sensors of the intra-membrane stresses existing in the region of the insertion embedding rather than sensors of the curvature per se. Read More

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Model of T-cell nuclear deformation by the cortical actin layer.

Biophys J 2013 Sep;105(6):1316-23

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.

Deformations of cell nuclei accompany a number of essential intracellular processes. Although evidence is being accumulated on the primary role actin structures play in controlling the shape of the nucleus, the mechanisms behind this phenomenon remain unknown. Here, we consider theoretically a specific paradigm of nuclear deformation, and a related actin rearrangement, in T cells stimulated by contact with a bead covered by surrogate antigens. Read More

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September 2013

Characterization of assembly intermediates containing subunit 1 of yeast cytochrome oxidase.

J Biol Chem 2013 Sep 29;288(37):26546-56. Epub 2013 Jul 29.

From the Department of Biological Sciences, Columbia University, New York, New York 10027.

Mitochondrial-encoded Cox1p, one of the three core subunits of yeast cytochrome oxidase (COX), was previously shown to associate with regulatory proteins and nuclear-encoded subunits into five high molecular weight complexes that were proposed to constitute the pathway for biogenesis of the Cox1p assembly module. One of the intermediates (D5) was inferred, but not directly shown to exist. In the present study mitochondria of strains expressing C-terminal-tagged subunits of COX that had not been looked at previously were pulse-labeled and analyzed for the presence of newly translated Cox1p in the immunoprecipitates. Read More

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September 2013

Comparative analysis of 126 cyanobacterial genomes reveals evidence of functional diversity among homologs of the redox-regulated CP12 protein.

Plant Physiol 2013 Feb 26;161(2):824-35. Epub 2012 Nov 26.

Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.

CP12 is found almost universally among photosynthetic organisms, where it plays a key role in regulation of the Calvin cycle by forming a ternary complex with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase. Newly available genomic sequence data for the phylum Cyanobacteria reveals a heretofore unobserved diversity in cyanobacterial CP12 proteins. Cyanobacterial CP12 proteins can be classified into eight different types based on primary structure features. Read More

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February 2013

Photophysical investigation of neutral and diprotonated free-base bis(arylethynyl)porphyrins.

J Phys Chem A 2011 Sep 1;115(38):10452-60. Epub 2011 Sep 1.

Department of Chemistry, Macalester College, 1600 Grand Avenue, Saint Paul, Minnesota 55105, USA.

The photophysical properties for a series of free-base arylethynyl porphyrins and the corresponding trans-disubstituted tetraphenylporphyrin (H(2)TPP) derivatives lacking arylethynyl functionalities have been studied via electronic absorption and emission spectroscopy in both neutral and diacid forms. Enhanced substituent effects on porphyrin absorption spectra are observed in the arylethynyl porphyrins relative to the H(2)TPP derivatives, owing to the presence of the ethynyl spacer that allows for a coplanar geometry between the porphyrin macrocycle and the appended phenyl substituents. Upon protonation, both series of porphyrins exhibit substantially red shifted absorption and emission spectra and enhanced oscillator strengths, with the magnitude of the spectral shifts being more substantial in the presence of the ethynyl functionalities. Read More

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September 2011

["Expert approved international standards of evidence-based medicine": a proposal].

Z Evid Fortbild Qual Gesundhwes 2010 20;104(8-9):653-60. Epub 2010 Oct 20.

Institut für Sozialmedizin, Universität Lübeck und Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck.

Section 35b of the German Code of Social Law Book V (SGB V) mentions "expert approved international standards of evidence-based medicine" (EbM). An idea which started as a reform movement in and for clinical medicine more than twenty years ago is here, from a socio-legal perspective, being utilised as a normative concept in terms of a standard-creating methodology, which is meant to form the basis for the "methods and criteria" of comparative benefit/risk assessment of medical drugs mentioned in the respective law. The present paper places the standards in a hierarchy between "description and analysis of benefits" at the bottom and, at the top, "fundamental concerns of EbM". Read More

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Connecting chronic and recurrent stress to vascular dysfunction: no relaxed role for the renin-angiotensin system.

Am J Physiol Renal Physiol 2011 Jan 27;300(1):F1-10. Epub 2010 Oct 27.

Department of Physiology, University of Alberta, and University of Alberta Hospital, Department of Medicine/Division of Nephrology and Immunology, 11-132 CSB Clinical Sciences Bldg., Edmonton, Alberta, Canada T6G 2G3.

The renin-angiotensin system (RAS) is classically considered to be a protective system for volume balance and is activated during states of volume depletion. Interestingly, one of the major pathways activating the system is the sympathetic nervous system, also the primary mediator of the acute stress response. When one further examines the cells mediating the immune site of the response, which is primarily an inflammatory response leading to defense at a locally injured area, these cells all express the ANG II type 1 receptor (AGTR1). Read More

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January 2011

Paclitaxel and carboplatin-induced complete remission in peritoneal carcinomatosis of unknown origin: a report of two cases and review of the literature.

Tumori 2010 Mar-Apr;96(2):336-9

Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Peritoneal carcinomatosis is a common evolution of digestive-tract cancer with a poor prognosis. However, a small subgroup unrelated to the digestive tract or any other primary cancer has a relatively better prognosis, especially in women. There are no published data to recommend a treatment regimen for this distinct group. Read More

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Orbital interpretation of kinetic energy density and a direct space comparison of chemical bonding in tetrahedral network solids.

J Phys Chem A 2008 Aug 31;112(33):7705-16. Epub 2008 Jul 31.

Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604, USA.

We present how the kinetic energy density (KED) can be interpreted on the basis of the orbital interactions within the Kohn-Sham theory and propose how to utilize a direct space function in chemical bonding analysis, the relative entropy density (RED), which is constructed from the KED, the Thomas-Fermi KED (TF-KED), and the electron density. From the detailed analysis of the KED of wave functions and the TF-KED from the free electron model, it is shown that the RED can reveal the nodal properties of individual wave functions and provide a variationally meaningful way of accumulating chemical bonding information from the wave functions, hence allowing quantitative bonding analysis in direct space. To substantiate the proposal, the RED function has been tested on the tetrahedral network solids, including the group 14 elements and the III-V binary compounds with the zinc blende structure. Read More

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Kinetics and mechanism of O-O bond cleavage in the reaction of [RuIII(edta)(H2O)]- with hydroperoxides in aqueous solution.

Dalton Trans 2008 Aug 13(29):3851-6. Epub 2008 Jun 13.

Chemistry Group, Central Mechanical Engineering Research Institute, Durgapur, 713209, India.

The reactions of [Ru(III)(edta)(H(2)O)](-) (1) (edta = ethylenediaminetetraacetate) with tert-butylhydroperoxide ((t)BuOOH) and potassium hydrogenpersulfate (KHSO(5)) were studied kinetically as a function of oxidant concentration and temperature (10-30 degrees C) at a fixed pH of 6.1 using stopped-flow techniques. Kinetic results were analyzed by using global kinetic analysis techniques. Read More

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Successful expression and purification of human CIAPIN1 in baculovirus-insect cell system and application of this system to investigation of its potential methyltransferase activity.

Int J Biol Macromol 2008 Jan 8;42(1):27-32. Epub 2007 Sep 8.

Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.

CIAPIN1 is a newly identified anti-apoptosis molecule which plays an important role in definitive haematopoiesis in mouse fetal liver and confers multidrug resistance in gastric cancer cells. However, the biophysical function of CIAPIN1 is far from elucidated. Bioinformatics predicts that CIAPIN1 may contain a generic methyltransferase motif and a Zn-ribbon-like motif. Read More

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January 2008

Evidence from Raman spectroscopy that InhA, the mycobacterial enoyl reductase, modulates the conformation of the NADH cofactor to promote catalysis.

J Am Chem Soc 2007 May 2;129(20):6425-31. Epub 2007 May 2.

Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.

InhA, the enoyl reductase from Mycobacterium tuberculosis, catalyzes the NADH-dependent reduction of trans-2-enoyl-ACPs. In the present work, Raman spectroscopy has been used to identify catalytically relevant changes in the conformation of the nicotinamide ring that occur when NADH binds to InhA. For 4(S)-NADD, there is an 11 cm-1 decrease in the wavenumber of the C4-D stretching band (nuC-D) and a 50% decrease in the width of this band upon binding to InhA. Read More

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Reaction of [RuIII(edta)(H2O)]- with H2O2 in aqueous solution. Kinetic and mechanistic investigation.

Dalton Trans 2007 Mar 30(9):943-8. Epub 2007 Jan 30.

Chemistry Group, Central Mechanical Engineering Research Institute, Durgapur, 713209, India.

The reaction of [Ru(III)(edta)(H(2)O)](-) (1) (edta = ethylenediaminetetraacetate) with hydrogen peroxide was studied kinetically as a function of [H(2)O(2)], temperature (5-35 degrees C) and pressure (1-1300 atm) at a fixed pH of 5.1 using stopped-flow techniques. The reaction was found to consist of two steps involving the rapid formation of a [Ru(III)(edta)(OOH)](2-) intermediate which subsequently undergoes parallel heterolytic and homolytic cleavage to produce [(edta)Ru(V)=O](-) (45%) and [(edta)Ru(IV)(OH)](-) (55%), respectively. Read More

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[The psychic cross-sectional finding, cardinal point of psychiatric-psychotherapeutic expertise].

M Fabra

Versicherungsmedizin 2004 Sep;56(3):115-22

Medizinischen Gutachteninstitut, Hamburg.

Expertise is based on history and clinical findings. Anamnestic data and clinical results have to be differentiated carefully. Clinical findings are of special importance because they are helpful in verifying anamnestic information with regard to extent and impairment quality of complaints, plausibility and thereby their significance for the expertise. Read More

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September 2004