bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypersensitivity:
IgE
‐Mediated (Type
I
)
Authors: Delves Peter J 
Published: May 2017

Abstract

Hypersensitivity reactions, which are classified into 4 types (type I‐IV), are over‐zealous immune responses due to the fact that they are directed against harmless antigens, are of excessive magnitude, and/or are occurring in inappropriate body locations. Type I, or sometimes type IV, hypersensitivity reactions are responsible for the symptoms of allergy. Huge numbers of people suffer from allergic responses, which can vary in significance from being mildly inconvenient to resulting in rapid death. Allergic responses due to type I hypersensitivity are often referred to as atopic allergy and are mediated by the IgE class of antibody bound to tissue mast cells and to circulating blood basophils. Cross‐linking of the IgE by allergen results in the release of a plethora of inflammatory mediators that cause the symptoms. A variety of tests are available to assist in the diagnosis of type I hypersensitivity, and a range of therapies are used to control the diseases it causes.

Key Concepts

There are four main types of hypersensitivity reactions, which are characterised by inappropriate or exaggerated immune responses.

Type I hypersensitivity reactions involve the activation of tissue mast cells and blood basophils when IgE molecules bound to their surface become linked together by an allergen.

Substantial numbers of individuals develop allergies due to type I (IgE‐mediated) hypersensitivity, also referred to as atopic allergy.

Allergies that are caused by type I hypersensitivity include hay fever, asthma, eczema and food allergy.

The IgE antibodies are bound to the cell surface of the mast cells and basophils via a high affinity Fc receptor for IgE (FcϵR1).

Susceptibility to the development of type I hypersensitivity has been linked to polymorphisms in several different genes.

Activation of mast cells and basophils leads to the release of many different mediators of inflammation including histamine, prostaglandins and leukotrienes.

The release of inflammatory mediators by mast cells and basophils is a component of normal immune responses, but in atopic allergy the response is inappropriate because it is against a substance that would not normally pose a threat.

There are a number of different approaches to the treatment of atopic allergy, but the best strategy in individuals that have already become sensitised, and when feasible, is avoidance of re‐exposure to the allergen.
Hepatitis
A
Virus
Authors: Feng Zongdi 
Published: May 2017

Abstract

Hepatitis A virus (HAV) is one of the five human hepatitis viruses that replicate in and cause inflammation of the liver. HAV is transmitted through a faecal–oral route and has a unique life cycle in that it is shed as naked virions into the faeces but circulates in an enveloped form in the blood. In addition, the virus has several unique mechanisms to evade detection by the host immune system. The majority of HAV infections are self‐limited and asymptomatic, but severe forms sometimes occur, particularly in the elderly. HAV has only one serotype, and persons infected with HAV usually develop lifelong immunity. Incidence rates of HAV infections have been greatly reduced owing to improved sanitation and the use of very successful vaccines.

Key Concepts

The hepatitis A virus is transmitted via the faecal–oral route and is a major cause of acute hepatitis worldwide.

HAV only infects humans and non‐human primates, although HAV‐like viruses infect a range of animal species.

HAV infection is extraordinary ‘stealthy’, and the virus has multiple mechanisms to evade the host immune response.

HAV is shed as naked virions in the faeces but circulates as quasi‐enveloped virions in the blood.

Hepatitis A vaccine is one of the most successful vaccines ever developed, providing lifelong protection when given either pre‐exposure or post‐exposure.
Mononuclear Phagocyte System
Authors: Vegh Peter , Fletcher James , Dixon David , Haniffa Muzlifah 
Published: May 2017

Abstract

The mononuclear phagocyte system is part of the innate immune system and comprises dendritic cells (DCs), monocytes and macrophages, which fulfil a range of tasks essential for homeostasis and immunity. Macrophages and DCs were originally thought to be variations of monocytes, but recent evidence has defined the distinct origins of macrophages, monocytes and DCs. Mononuclear phagocytes are functionally specialised and play a critical role in all phases of the immune response. They detect and phagocytose pathogens, recruit cells, initiate adaptive immunity by presenting antigens to T cells and coordinate the resolution of inflammation and wound healing. Macrophages have additional vital functions in tissue development and homeostasis.

Key Concepts

Mononuclear phagocytes (dendritic cells, monocytes and macrophages) are a diverse group of cells with a wide range of functions essential for maintaining organism integrity.

Macrophages are tissue resident, play a central role in homeostasis, perform tissue‐specific functions and orchestrate immune responses.

Dendritic cells are specialised antigen‐presenting cells with superior ability to initiate immune responses.

Monocytes are circulating leucocytes that can enter the tissue and have important roles in phagocytosis, inflammation and wound healing.

Mononuclear phagocytes coordinate innate and adaptive immune response.
Protein–Protein Interactions: The Structural Foundation of Life Complexity
Authors: Paola Luisa Di , Giuliani Alessandro 
Published: May 2017

Abstract

The amazing variety of protein functions are often covered by protein complexes, so understanding protein–protein interactions means coming deeply into the functional role of proteins in life.
In the last years, the investigation of protein–protein interactions has become central in many fields, spanning from molecular biology to pharmacology. In this article, we present a state of the art of methods for such investigation, along with perspectives of applications. We stressed the multiscale nature of approaches, longing from genome‐wide analysis to the detailed study of protein–protein interface on single residues.
The most innovative approaches, based on complex network theory, shed a very bright light on future trends for protein–protein applications on drug design and on molecular therapy for diseases where protein association plays a pivotal role (misfolding).

Key Concepts

Protein–protein interactions underlie several physiological mechanisms.

The analysis of protein–protein interfaces is crucial to quantify protein complex stability.

Hotspot residues provide the largest contribution to protein–protein binding energy.

Experimental methods point to identify hotspots and quantify binding energy.

Molecular docking allows a fine analysis of protein–protein interface.

Network‐based approaches clarify the multiscale nature of protein–protein interactions.
Spleen: Disorders
Authors: Kuchar Ernest , Karlikowska‐Skwarnik Monika 
Published: May 2017

Abstract

The spleen is an important peripheral immunologic organ although not essential for life. The main functions of the spleen are filtering of blood, lymphopoiesis and immunoglobulin production. The spleen is abundantly supplied with blood, which the other secondary lymphoid organs do not have, and clears particulate material, for example, opsonised bacteria from the blood. Reduced function, known as functional asplenia, is observed in many various pathological conditions, for example, when the spleen is congested with blood or when infiltrated by metastatic tumours or contains large haemangiomas. Most common causes of splenic hypofunction are coeliac disease, sprue, sickle cell disease and haematologic disorders. Individuals with removed spleen or impaired splenic function are prone to serious and often fatal bacterial infections. The vast majority of these serious infections, caused by encapsulated bacteria (pneumococci, meningococci and
Haemophilus influenzae
type b) can be effectively prevented by immunisations and antibiotic prophylaxis.

Key Concepts

Spleen is an important secondary immunologic organ located in the left epigastrium beneath the lower rib cage, responsible for blood filtration and antibodies production.

Spleen is important but not essential for life and can be removed.

Reduced spleen function, known as functional asplenia, is observed in various pathological conditions including sickle cell disease, celiac disease and haematologic disorders.

Spleen dysfunction is associated with increased risk of serious and sometimes fatal bacterial sepsis or meningitis, usually caused by pneumococci and other capsular bacteria.

The vast majority of bacterial infections in asplenic individuals can be prevented by currently available immunisations and prophylactic antibiotics.
VitaminB12: Disorders of Absorption and Metabolism
Authors: Watkins David , Rosenblatt David S 
Published: May 2017

AbstractDerivatives of vitamin B12(cobalamin) are required for activity of two enzymes: methylmalonyl‐CoA mutase, which catalyses conversion of methylmalonyl‐CoA to succinyl‐CoA, and methionine synthase, which converts homocysteine to methionine. Cobalamin deficiency results in the accumulation of methylmalonic acid and homocysteine in blood and urine. Clinically, deficiency results in megaloblastic anaemia and subacute combined degeneration of the spinal cord, loss of sensation, ataxia, dementia and psychosis. Dietary cobalamin deficiency is rare in developed countries, except for individuals consuming a vegan diet. A more common cause of cobalamin deficiency is pernicious anaemia, an autoimmune disease that results in inability to absorb cobalamin from the intestine. A number of rare genetic disorders have been identified that result in either failure to absorb dietary cobalamin, to transport cobalamin from the intestine to cells that require it for metabolism or to convert intracellular cobalamin to one or both of its coenzyme derivatives, adenosylcobalamin and methylcobalamin.Key ConceptsCobalamin (vitamin B12) is required for activity of two enzymes, methylmalonyl‐CoA mutase and methionine synthase, in mammalian cells.Cobalamin deficiency results in accumulation of methylmalonic acid and homocysteine in blood and urine.Clinically, deficiency is characterised by megaloblastic anaemia and/or neurological problems.Uptake of dietary cobalamin requires the binding protein intrinsic factor, secreted by parietal cells of the stomach, and the intestinal receptor cubam.Autoimmune destruction of parietal cells results in pernicious anaemia.Mutations in the genes encoding intrinsic factor or the components of cubam (cubilin and amnionless) result in heritable cobalamin malabsorption and signs of cobalamin deficiency.Peripheral cells take up cobalamin bound to the transport protein transcobalamin by carrier‐mediated endocytosis.Cells convert cobalamin to adenosylcobalamin, required by methylmalonyl‐CoA mutase, and methylcobalamin, required by methionine synthase.Rare mutations affecting genes involved in cobalamin metabolism result in decreased synthesis of either or both cobalamin derivatives.Mutations in certain transcription regulators can affect expression of genes encoding cobalamin metabolising enzymes, resulting in altered cobalamin coenzyme synthesis.
Molecular Genetics of Galactosaemia
Authors: Timson David J 
Published: May 2017

Abstract

Galactosaemia is a relatively rare, genetic disease that commonly manifests with cataracts in childhood. More severe forms result in significant developmental abnormalities resulting in physical and cognitive disabilities. Three genes are affected: galactose 1‐phosphate uridylyltransferase (
GALT
; type I galactosaemia), galactokinase (
GALK1
; type II) and UDP‐galactose 4'‐epimerase (
GALE
; type III). Clinical outcomes vary widely in severity and depend on the gene affected, the precise mutation(s) present and the patient's environment. The disease can be diagnosed by altered metabolite levels, reduced enzyme activity and sequencing of the affected gene. In many cases, mutations in one of these three genes result in a protein that is unstable and/or misfolded with consequent reduction in enzymatic activity. Understanding how loss of activity of these enzymes results in the disease phenotypes is a key priority in current research.

Key Concepts

Galactosaemia is an inherited metabolic disease affecting the genes encoding enzymes of galactose metabolism.

Three types of galactosaemia are recognised depending on which gene is affected.

Type I galactosaemia is the most common and affects
GALT
that encodes galactose 1‐phosphate uridylyltransferase.

The severity of symptoms of galactosaemia is highly varied depending on the precise mutation(s) present and the patient's environment.

Our understanding of the normal regulation of these genes in humans is incomplete.

Diagnosis may be initially made by increased galactose or galactose 1‐phosphate levels.

Diagnosis is normally confirmed through measuring enzyme activities and sequencing the affected gene.

In many cases, point mutations result in proteins that are misfolded and/or unstable.

Our understanding of how mutated genes and altered biochemistry lead to the disease phenotypes is incomplete.

Bakers' yeast, fruit flies, nematode worms and mice have all been used successfully as models for galactosaemia.
Solid Supported Chiral N‐Picolylimidazolidinones: Recyclable Catalysts for the Enantioselective, Metal‐ and Hydrogen‐Free Reduction of Imines in Batch and in Flow Mode
Authors: Porta Riccardo , Benaglia Maurizio , Annunziata Rita , Puglisi Alessandra , Celentano Giuseppe 
Published: May 2017

AbstractA new class of solid supported chiral imidazolidinone organocatalysts for the catalytic reduction of imines with trichlorosilane has been developed. Polystyrene proved to be a more effective support than silica in terms of both chemical and stereochemical efficiency. Even with a loading as low as 1 mol% the best performing supported catalyst showed a remarkable activity and stereocontrol ability, promoting the reduction with stereoselectivities reaching 98% ee and in most cases ranging between 90–95% ee The general scope of the methodology and the good recyclability of the immobilized catalyst were demonstrated. The polystyrene‐anchored chiral catalyst was also used to prepare packed bed reactors for the continuous flow synthesis of chiral amines, that were obtained in excellent yields and enantioselectivities. By exploiting the chiral organocatalytic reactor, the in‐flow stereoselective synthesis of a common, immediate precursor of rivastigmine, of the calciomimetic (R)‐NPS 568 and of Acrylamide (S)‐A, currently under study for the treatment of neuropathic pain, was successfully accomplished.magnified image
Nonpublication of trial results for new neurological drugs: A systematic review
Authors: Hakala Amanda K , Fergusson Dean , Kimmelman Jonathan 
Published: May 2017

ObjectiveTo evaluate nonpublication rates among trials of new successful and unsuccessful neurological drugs.Methods“Licensed” drugs consisted of all novel agents receiving US Food and Drug Administration (FDA) licensure 2005–2012 inclusive in seven neurological disorders. “Stalled” drugs included all experimental agents tested in the same domains that had at least one completed phase III trial in the same time frame, but failed to receive FDA approval. Trials of these drugs were included in our sample if their primary outcome collection occurred before October 1, 2010. We determined the publication status of eligible trials using searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, sponsor websites, and direct electronic query of trial contacts and sponsors. The primary outcome was time to journal publication (or results reporting in other media) after study completion.ResultsThe adjusted hazard ratio for publication was 1.79 (95% confidence interval, 1.20–2.67) in favor of licensed drugs. Based on the criteria for nonpublication in this report, 14,092 and 33,882 volunteers participated in unpublished trials of licensed and stalled neurological drugs, respectively. Result data were not publicly available in any form for 10% (16 of 163) and 46% (94 of 203) of trials of licensed and stalled drugs, respectively.InterpretationResults of trials for stalled drugs are heavily under‐reported. This deprives research and care communities of evidence about pathophysiology, drug class effects, and the value of surrogate endpoints in trials. Ann Neurol 2017;81:782–789
Reversible Stabilisierung von Vesikeln: redox‐responsive Polymer‐Nanocontainer für den Transport in das Zellinnere
Authors: de Vries Wilke C. , Grill David , Tesch Matthias , Ricker Andrea , Nüsse Harald , Klingauf Jürgen , Studer Armido , Gerke Volker , Ravoo Bart Jan 
Published: May 2017

AbstractDie Selbstorganisation redox‐responsiver Polymer‐Nanocontainer aus einem Cyclodextrinvesikelkern und einer reduktiv spaltbaren Polymerhülle, die über Wirt‐Gast‐Erkennung auf der Vesikeloberfläche verankert ist, wird beschrieben. Die Nanocontainer weisen eine einheitliche Größe sowie eine hohe Stabilität auf und reagieren selektiv auf milde reduktive Bedingungen, was durch dynamische Lichtstreuung, Transmissionselektronenmikroskopie, Rasterkraftmikroskopie, einen quantitativen Thiolnachweis sowie Fluoreszenzspektroskopie nachgewiesen wird. Lebendzell‐Bildgebung zeigt eine spezifische redox‐responsive Freisetzung hydrophiler Frachten wie der pH‐Sonde Pyranin oder des Pilztoxins Phalloidin in Zellen. Die Ergebnisse belegen das hohe Potenzial dieser responsiven Nanocontainer für anspruchsvolle zellbiologische Anwendungen, die einen kontrollierten Transport in die Zelle erfordern.
Formation of Double‐Shelled Zinc–Cobalt Sulfide Dodecahedral Cages from Bimetallic Zeolitic Imidazolate Frameworks for Hybrid Supercapacitors
Authors: Zhang Peng , Guan Bu Yuan , Yu Le , Lou Xiong Wen (David) 
Published: May 2017

AbstractComplex metal–organic frameworks used as precursors allow design and construction of various nanostructured functional materials which might not be accessible by other methods. Here, we develop a sequential chemical etching and sulfurization strategy to prepare well‐defined double‐shelled zinc–cobalt sulfide (Zn‐Co‐S) rhombic dodecahedral cages (RDCs). Yolk‐shelled zinc/cobalt‐based zeolitic imidazolate framework (Zn/Co‐ZIF) RDCs are first synthesized by a controlled chemical etching process, followed by a hydrothermal sulfurization reaction to prepare double‐shelled Zn‐Co‐S RDCs. Moreover, the strategy reported in this work enables easy control of the Zn/Co molar ratio in the obtained double‐shelled Zn‐Co‐S RDCs. Owing to the structural and compositional benefits, the obtained double‐shelled Zn‐Co‐S RDCs exhibit enhanced performance with high specific capacitance (1266 F g−1 at 1 A g−1), good rate capability and long‐term cycling stability (91 % retention over 10,000 cycles) as a battery‐type electrode material for hybrid supercapacitors.
Stable Subporphyrin meso‐Aminyl Radicals without Resonance Stabilization by a Neighboring Heteroatom
Authors: Shimizu Daiki , Furukawa Ko , Osuka Atsuhiro 
Published: May 2017

AbstractMost aminyl radicals studied so far are resonance‐stabilized by neighboring heteroatoms, and those without such stabilization are usually short‐lived. We report herein that subporphyrin meso‐2,4,6‐trichlorophenylaminyl radicals and a bis(5‐subporphyrinyl)aminyl radical are fairly stable under ambient conditions without such stabilization. The subporphyrin meso‐2,4,6‐trichlorophenylaminyl radical crystal structure displays a characteristically short Cmeso−N bond and a perpendicular arrangement of the meso‐arylamino group. The stabilities of these radicals have been ascribed to extensive spin delocalization over the subporphyrin π‐electronic network as well as steric protection around the aminyl radical center.
Synthesis of a Fluorescent Analogue of Paclitaxel That Selectively Binds Microtubules and Sensitively Detects Efflux by P‐Glycoprotein
Authors: Lee Molly M. , Gao Zhe , Peterson Blake R. 
Published: May 2017

AbstractThe anticancer drug paclitaxel (Taxol) exhibits paradoxical and poorly understood effects against slow‐growing tumors. To investigate its biological activity, fluorophores such as Oregon Green have been linked to this drug. However, this modification increases its polarity by approximately 1000‐fold and reduces the toxicity of Taxol towards cancer cell lines by over 200‐fold. To construct more drug‐like fluorescent probes suitable for imaging by confocal microscopy and analysis by flow cytometry, we synthesized derivatives of Taxol linked to the drug‐like fluorophore Pacific Blue (PB). We found that PB‐Gly‐Taxol bound the target protein β‐tubulin with both high affinity in vitro and high specificity in living cells, exhibited substantial cytotoxicity towards HeLa cells, and was a highly sensitive substrate of the multidrug resistance transporter P‐glycoprotein (P‐gp).
Comparative study of EMI shielding effectiveness for carbon fiber pultruded polypropylene/poly(lactic acid)/multiwall CNT composites prepared by injection molding versus screw extrusion
Authors: Lee Seung Hwan , Lee Yeongbeom , Jang Myung Geun , Han Chonghun , Kim Woo Nyon 
Published: May 2017

ABSTRACTThe electrical conductivity and electromagnetic interference (EMI) shielding effectiveness of the composites of polypropylene/poly(lactic acid) (PP/PLA) (70/30, wt %) with single filler of multiwall carbon nanotube (CNT) or hybrid fillers of nickel‐coated carbon fiber (CF) and CNT were investigated. For the single filler composite, higher electrical conductivity was observed when the PP‐g‐maleic anhydride was added as a compatibilizer between the PP and PLA. For the composite of the PP/PLA (70/30)/CF (20 phr)/CNT (5 phr), the composite prepared by injection molding observed a higher EMI shielding effectiveness of 50.5 dB than the composite prepared by screw extrusion (32.3 dB), demonstrating an EMI shielding effectiveness increase of 49.8%. The higher values in EMI shielding effectiveness and electrical conductivity of the PP/PLA/CF (20 phr)/CNT (5 phr) composite seemed mainly because of the increased CF length when the composites were prepared using injection molding machine, compared with the composites prepared by screw extrusion. This result suggests that the fiber length of the conductive filler is an important factor in obtaining higher values of electrical conductivity and EMI shielding effectiveness of the PP/PLA/CF/CNT composites. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45222.
A Tunable Cyclic Container: Guest‐Induced Conformational Switching, Efficient Guest Exchange, and Selective Isolation of C70 from a Fullerene Mixture
Authors: Mondal Pritam , Rath Sankar Prasad 
Published: May 2017

AbstractAn adaptable cyclic porphyrin dimer with highly flexible linkers has been used as an artificial molecular container that can efficiently encapsulate various aromatic guests (TCNQ/C60/C70) through strong π–π interactions by adjusting its cavity size and conformation. The planar aromatic guest (TCNQ) can be easily and selectively exchanged with larger aromatic guests (C60/C70). During the guest‐exchange process, the two porphyrin rings switch their relative orientation according to the size and shape of the guests. This behavior of the cyclic container has been thoroughly investigated by using UV/Vis spectroscopy, NMR spectroscopy, and X‐ray crystal structure determination of the host–guest assemblies. The electrochemical and photophysical studies demonstrated the occurrence of photoinduced electron transfer from bisporphyrin to TCNQ/C60/C70 in the respective host–guest assemblies. The cyclic host can form complexes with C60 and C70 with association constants of (2.8±0.2)×105 and (1.9±0.3)×108 m−1, respectively; the latter value represents the highest binding affinity for C70 reported so far for zinc(II) bisporphyrinic receptors. This high selectivity for the binding of C70 versus C60 allows the easy extraction and efficient isolation of C70 from a C60/C70 fullerene mixture. Experimental evidence was substantiated by DFT calculations.