Weight: 29.80 Paper Topics: environmental exception prokaryotic organisms developed strategies live specialized frequently extreme conditions monocultures feasible organisms survive highly competitive habitats complex microbiomes consequently diversity observed molecular architecture bacterial archaeal cell envelopes particularly structure outermost boundary layers reflects evolutionary adaptations organism specific environmental ecological conditions commonly observed prokaryotic cell surface structures two-dimensional arrays proteinaceous subunits forming surface layers termed s-layers prokaryotic cells sleytr 1976 sleytr et al 1988b table 'macromolecular monolayer' described houwink le poole 1952 houwink 1953 cell wall spirillum sp s-layers identified hundreds different species taxonomic group walled bacteria universal feature archaea fig compila-tion see
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Assembly in vitroThe capability of isolated S-layer proteins to assemble into two-dimensional arrays in vivo and in vitro is one of their key properties exploited in basic and application-oriented research. It occurs upon dialysis of the disrupting agents as described before (Fig. 4 ). The formation of the self-assembled arrays is only determined by the amino acid sequence of the polypeptide chains, and consequently the tertiary structure of the S-layer protein species (Sleytr, 1975) . As S-layer proteins have a high proportion of nonpolar amino acids, most likely, hydrophobic interactions are involved in the initial stage of the assembly process. Some S-layers are stabilized by divalent cations, such as Ca 2+ Norville et al., 2007; Baranova et al., 2012) and in the case of extremely halophiles by Mg 2+ (Mescher & Strominger, 1976; Cline et al., 1989; Eichler et al., 2010) interacting with acidic amino acids. Studies on the distribution of functional groups on the surface have shown that free carboxylic acid groups and amino groups are arranged in close proximity and thus contribute to the cohesion of the proteins by electrostatic interactions (S ara & Sleytr, 1987a; S ara et al., 1988a; Pum et al., 1989; Gy€ orvary et al., 2004) . S-layer proteins are noncovalently linked to each other and, in the case of their adhesion to supporting structures (e.g. silicon, metal or polymeric solid surfaces, or lipid membranes) differing combinations of weak bonds (hydrophobic bonds, ionic bonds involving divalent cations or direct interaction of polar groups, and hydrogen bonds), are responsible for the structural integrity as well. Nevertheless, disintegration and reassembly experiments led to the conclusion that the bonds holding the S-layer proteins together must be much stronger than those binding them to the support (Sleytr, 1975 (Sleytr, , 1976 (Sleytr, , 1978 . Once formed, S-layer proteins were never observed to leave the lattice, and thus, it was concluded that lattice growth is irreversible and no S-layer protein turnover occurs. The reason for this irreversibility may be that after the addition of the 'last' protein monomer to the (incomplete) morphological unit, this monomer is locked into place and now has a low probability of leaving (Chung et al., 2010; Comolli et al., 2013) because this final conformational arrangement in 'confinement' constitutes the state of lowest free energy (Chung et al., 2010) .
Weight: 28.71 Paper Topics: mice presented inhand project international harmonization nomenclature diagnostic criteria lesions rats wwwtoxpathorg/inhandasp joint initiative societies toxicologic pathology europe estp great britain bstp japan jstp north america stp develop internationally accepted nomenclature nonproliferative proliferative lesions laboratory animals purpose publication provide standardized nomenclature classifying proliferative nonproliferative lesions observed special sense organs ocular otic olfactory laboratory rodents standardized nomenclature presented document available electronically goreni website wwwgoreniorgthis document covers ocular olfactory otic systems ocular subdivided eye glands eye diagnostic criteria used terms publication generally seen standard hematoxylin eosin-stained h&e paraffin sections preferred terms nonproliferative proliferative lesions tissue spontaneous aging lesions appropriate lesions induced exposure
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Posterior Segment Vitreous Body• Providing an optically clear medium through which light may pass essentially unaltered. The maintenance of the spatial configuration between fibrils by the remaining macromolecules imparts this critical function. • Maintaining the shape of the vitreous chamber and posterior cavity, and overall shape of the ocular globe. • Maintaining the normal positions of the lens and the retina. Differential distribution of collagen and proteoglycans results in two basic zones (cortical and medullary) with variable densities within the vitreous. The cortical vitreous occupies the periphery of the vitreous and encases the core (medullary vitreous). The cortical vitreous is relatively more condensed and fibrillar compared to the medullary vitreous, and has the appearance of a smooth clear membrane due to the lamellar distribution of collagen fibrils and associated highly polymerized proteoglycans (primarily chondroitin sulfate). Although the cortical vitreous represents only 2% of the total vitreous volume, it is the metabolic center of the vitreous body, because it contains the hyalocytes (detailed below), which make up 90% of the cell population in the cortical vitreous; fibrocytes and glial cells make up the remaining 10%. The vitreous cortex extends anteriorly from the vitreous base to form the anterior vitreous cortex and posteriorly to form the posterior vitreous cortex. The vitreous body interfaces with a number of ocular structures through the vitreous cortex. The anterior vitreous cortex forms the posterior limits of the posterior chamber and functions in the physiologic communication between the vitreous cavity and the aqueous humor. The anterior surface of the vitreous body extends anterior and medially from the pars plana at the ora ciliaris to contact the lens posterior to the lens equator. Thus, the anterior vitreous cortex is in contact with the ciliary processes and the lens zonules, as well as the posterior lens capsule. The vitreous attaches to the lens capsule in a ring-like manner, forming the ligament of Wieger (Sebag 1992) . Posterior to the ora ciliaris, bundles of vitreous fibrils attach to the internal limiting laminae (ILL) (Balazs et al. 1964) . Cords of vitreous collagen insert into gaps between the neuroglia. The cortical vitreous is most firmly attached to the ILL in the area of the optic disc, the macula (in primates), and to retinal blood vessels. Retinal pathology such as neovascularization or vascular malformations occurs in the areas of vitreous attachment to the retina. Separation of the vitreous may transmit traction to these attachments, leading to vitreous hemorrhage or retinal tears. Persistent vitreous traction on retinal tears is an important factor in the development of a retinal detachment.
Weight: 26.40 Paper Topics: associated pneumococcal meningitis pm life-threatening disease recurrent pm relatively rare predisposing conditions study analyzed outcome patients recurrent versus non-recurrent pmwe conducted retrospective study analyzing records patients hospitalized 2005 2015 pm institution included patients diagnostic pm based appearance gram stain positive latex agglutination reaction cerebral spinal fluid csf samples and/or positive culture streptococcus pneumoniae csf culture blood culture concomitant meningitis defined "recurrent meningitis" episodes meningitis separated period weekswe identified total 194 pm episodes 182 patients thirty 20 % patients diagnosed recurrent meningitis 93 prior episodes recorded majority patients recurrent meningitis experienced meningitis episodes patients 7 11 40 recurrent episodes
Weight: 25.03 Paper Topics: 1 relationships virus infection mechanisms lipid rafts studied complexes caveolae 2 lipid rafts membrane microdomains enriched cholesterol sphingolipids represented gm1 globotriaosylceramide gb3cer defined keystone symposium lipid rafts cell function march 23 24 25 26 27 28 2006 steamboat springs co follows: "membrane rafts small 10-200 nm heterogeneous highly dynamic steroland sphingolipid-enriched domains compartmentalize cellular processes small rafts stabilized form larger platforms protein-protein proteinlipid interactions" definition led term "lipid raft" discarded favor term "membrane raft" term "membrane raft" underlies concept proteins lipids solely lipid-driven interactions play important role formation membrane microdomains caveola cholesterol/sphingolipid-rich small pit depression invagination site cell
Weight: 23.37 Paper Topics: clearance et virus infect cell reach receptors cell surface avoiding neutralization 'decoy' receptors surrounding environment viruses bind sialic 25 acid receptor abundant surface cells secreted extracellular mucosal environment attachment detachment controlled receptor-binding receptordestroying activities viral surface rosenthal et al 1998 zeng et al 2008 influenza viruses iavs respiratory pathogens contribute seasonal flu pandemic potential achieve balance hemagglutinin ha-mediated receptor binding neuraminidase 30 na-catalyzed receptor destruction air laver 1989 skehel wiley 2000 importance genetic basis functional balance ha na iav thoroughly characterized wagner et al 2002 xu et al 2012 yen al 2011 clear transmissibility influenza viruses hosts
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DiscussionAdvances in electron microscopy over the past several decades have presented an increasingly detailed picture of the morphology and organization of influenza A virus. This has revealed organizational features of filamentous IAV whose origins and functional significance remain unclear. By using site-specific fluorescent labeling to measure the organization of a virus while 10 preserving its function, we are able to corroborate key observations of envelope protein nonuniformity obtained from electron microscopy and extend them to dynamic observations of both protein motion on the surface of the virus, as well as the surprising finding of persistent influenza A virus motion while engaged with its receptor, sialic acid. These observations demonstrate that the morphology of a virus, the spatial organization of proteins in its membrane, and constraints 15 on the diffusion of these proteins collectively confer the tendency for viral particles to exhibit persistent directional mobility, enhancing the virus's rate of diffusion without diminishing its strength of adhesion. Importantly, our simulations show that this advantage of filamentous morphology would not be limited to the extremely large particles whose length is easily measured using diffraction limited microscopy, but rather extends to particles <200nm in length ( Although more work is needed to understand if these characteristics of IAV organization are adaptive during in vivo replication, a simple model of viral transport suggests how the directional viral mobility we observe could contribute during host-to-host transmission. On first entering the respiratory tract, viruses must diffuse through the mucosal barrier to infect the underlying airway 25 epithelial cells. Competing with this process is mucocilliary clearance, which carries particles bound to mucus towards the pharynx where they are neutralized ( Fig. 4 -figure supplement 1A ). If the transport of a virus through a mucosal barrier is modeled as a first passage problem with a time limit imposed by the rate of mucociliary clearance, a five-fold increase in the diffusion coefficient (as predicted in Figure 2D ) would lead to a proportional reduction in the first passage 30 time. More dramatically, it would also increase the fraction of particles that reach the cell surface when the rate of mucociliary clearance is high and would normally prevent most particles from reaching the cell surface. Our experiments on two-dimensional sialic acid-coated surfaces suggest a diffusion coefficient of ~1000 nm 2 /s for polarized viruses; adapting this value for a onedimensional first passage model suggests that persistent motion increases the number of 35 particles that reach the epithelium before being cleared by ~5000-fold (Supplementary Text, Fig. 4 -figure supplement 1B). Although there are multiple ways that a virus's passage through mucus can be accelerated (reducing its size, decreasing the number of HAs on its surface, increasing the number of NAs, or making the spatial distribution of NA more uniform), each of these changes would likely reduce binding stability once the virus has managed to reach the cell surface. In 40 contrast, the polarized distributions of NA on the viral surface that we observe increase virus diffusion without compromising binding stability.
10(B) Model for virus binding and diffusion accounting for multivalent adhesion of HA, turnover of proximal substrates by NA, and thermal fluctuations constrained by the position of bound HA-SA pairs. The virus is modeled as a lattice of HA and NA whose distributions are specified. Viruses interact with uniform distributions of sialic acid on a two-dimensional surface. HA's within a 7.5nm radius of sialic acid can probabilistically bind, while NA's within the same radius can probabilistically cleave. Once bound, virus 15 position and bearing can change only if it does not displace any bound HA-SA pairs beyond the specified binding radius (7.5nm in these simulations). (C) Results of simulations with varying organizations of NA on the virus's surface. Although localizing NA to one of the virus's poles ('polar' configuration) produces consistent oriented motion, introducing separation between HA-rich and NA-rich regions with the same NA localization ('gapped' configuration) eliminates this tendency, as does localizing NA to both viral poles 20
Weight: 22.84 Paper Topics: irritant examination digestive tract entry site body orally administered test articles test article lead local acute lesions site contact body digestive tract identified organ commonly affected british patients admitted hospital adverse drug reactions pirmohamed et al 2004 on hand orally administered test articles highly toxic organs yet having little noticeable effect digestive tracta distinctive feature digestive tract high proliferative rate epithelium making particularly sensitive agents interfering cell division resulting high regenerative capacity villi enhance surface intestine 400-500 m² humans large surface area tissues accurate assessment potential treatment effects entirely dependent thorough gross sampling focal lesionsstandardized nomenclature diagnostic criteria essential harmonize
Weight: 22.03 Paper Topics: classes cells influenza major acute respiratory infection causes mortality morbidity worldwide conventional antivirals m2 ion channel blockers neuraminidase inhibitors mainstays managing influenza disease lessen symptoms minimizing hospitalization death patients severe influenza however development viral resistance drug classes major public health concern vaccines prophylaxis mainstays limited efficacy difficulty matching predicted dominant viral strains circulating strains such potential interventions explored viruses rely host cellular functions replicate recent therapeutic developments focus targeting host factors involved virus replication controlling virus replication potential targets drug development include controlling virus-induced host immune responses recently suggested involvement innate lymphoid nadph oxidases influenza virus pathogenesis immune cell metabolism
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Apical Transport of Viral ComponentsKIF13A, a kinesin-3 family member, was recently identified as a molecular motor for plasma membrane transportation of vRNP-loaded Rab11A + vesicles (117) . KIF13A knockdown was found to reduce progeny virus production. Overexpression of a mutant form of KIF13A lacking in motor capacity resulted in disruption of the plasma membrane distribution of vRNP complex during later stages of infection. This data suggest that the apical transport of viral components via Rab11A or KIF13A could potentially serve as therapeutic targets against IAV infection. Further examination is merited.
Weight: 21.65 Paper Topics: behavior extracellular environment cells provides chemical mechanical stimuli influence cell function chien et al 2005 geiger et al 2009 extracellular matrix stiffness ecm mechanical forces acting cells important determinant cellular behavior adherent mammalian cells wells 2008 gattazzo et al 2014 cells sense stiffness matrix vary orders magnitude accordingly alter motility adhesion growth differentiation discher et al 2005 birukova et al 2013 yet exact pathways cells sense mechanical signals transduce generate biological signal cascades specific cellular responses yet fully understood trepat et al 2008 in context host-pathogen interactions effects matrix stiffness variation interesting infectious agents capacity infect different
Weight: 20.53 Paper Topics: steroid purpose study demonstrate efficacy of suggest regimen for oral treatment csu patients refractory high dosage antihistamines conducted retrospective chart review patients diagnosed urticaria feburary 1 2012 december 31 2014 total 98 patients csu included these 16 patients 163% antihistamineresistant prescribed 2-week course steroid thirteen patients 812% successfully controlled antihistamines stopping course second course steroid induced remission additionally patients 125% adverse events complications associated oral steroid observed study period study demonstrated excellence 2-week course oral corticosteroid antihistamine-resistant csu propose standardized corticosteroid treatment regimenthe altered distribution follicular helper cells predict pronounced clinical course primary sjogren's syndrome margit zeher division
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ConclusionsThis study showed that most of children hospitalized with asthma in our setting were moderate exacerbation with frequent asthma, male, aged under 5 years old and first diagnosed at 2 years old, had history of hospitalization before, normal nutrition status, history of atopic in family, and cigarette smoking exposed. Keywords: asthma in children, hospitalized, characteristic Background: Allergic bronchopulmonary aspergillosis (ABPA) is known as type I and III allergic disease for Aspergillus. Clinical presentation of ABPA ranges from asymptomatic mucus plugs to severe asthmatic symptoms or destructive and fibrotic lung disease. The heterogeneity may reflect not only the different clinical stages of the disease, but also different phenotypes. We herein attempt to identify phenotypes in ABPA using cluster analysis. Methods: We analyzed the data of 332 patients with possible ABPA from national-wide survey in Japan executed between 2013 and 2014. Definition of possible ABPA were, (1) positive skin test or specific IgE for Aspergillus, and (2) either a) positive precipitation or IgG antibody for Aspergillus or b) mucoid impaction or bronchiectasis in chest computed tomography. Non-hierarchical cluster analysis using k-means method was performed. Results: Three clusters were identified. Cluster 1 (n=141) included the patients with later age at onset (mean ages, 68 years), femaledominance, and less frequent prevalence of asthma (76%). The patients in cluster 2 (n=95) were middle age at onset (55 years), female-dominant, and showed lower values of total serum IgE. Cluster 3 (n=96) was characterized with early-onset (37 years), maledominance, and frequent recurrences (59%). Conclusions: Three distinct clinical phenotypes were identified characterized by ages of onset, gender, asthma prevalence, total serum IgE levels, and the frequency of recurrences. Background: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases, and little is understood about its pathogenesis. Eosinophils are considered to play a major role in its pathology, but we still know little which is causing chronic immune activation and persistent eosinophilic inflammation in CRS. Recently, type 2 innate lymphoid cells (ILC2s, lineage (-), CD45 (+), CD127 (+), CD294 (+)) were identified as a candidate, which produce highly levels of Th2 cytokines such as IL-5 and IL-13, which activates eosinophils. We hypothesized that ILC2s are enriched in blood and nasal polyps in patients with eosinophilic CRS (ECRS) and are associated with its pathology. Methods: FThe patients with CRS or pituitary adenoma (normal sinus) who underwent Endoscopic sinus surgery (ESS) in Jikei University Hospital were enrolled. We used PBMC and nasal polyps (NPs) from patients with CRS or normal subjects, and analyzed the amount of ILC2 by flow cytometry. We also investigated the distribution of ILC2s in NPs by immunohistochemistry. EDN and cytokines in NPs were measured by ELISA to investigate correlation with ILC2s. Lineage negative cells from nasal polyps were cultured in vitro with IL-33 or/and IL-2 to investigate the amount of cytokine produced by ILC2s. Results: EDN and Th2 cytokines are significantly higher in ECRS than non-eosinophilic CRS (NECRS). EDN had strongly correlated with the numbers of ILC2s in NPs. The counts of ILC2s in NPs were significantly higher in ECRS than NECRS. Immunostained ILC2 were showed accumulated in nasal polyps of ECRS, but not in NECRS or normal subjects. ILC2's CD25 surface expression in PBMC was significantly higher in ECRS than NECRS. ILC2's IL-17RB surface expression in NPs was significantly higher in NECRS than ECRS. Lineage negative cells from ECRS' NP, but not from NECRS' , produced IL-5 and IL-13 in both IL-2 and IL-33 stimulation. Conclusions: ILC2 are considered as candidate of the commander in ECRS, which strongly induce Th2 inflammation. There are possibility that ILC2s have several subtypes and the characteristic of ILC2s are differ from their environment.
Weight: 18.83 Paper Topics: 2017 d human immunodeficiency virus hiv infections pose global challenge given according world health organization data 369 million people living hiv additional 18 million people newly infected globally table 1 hiv targets immune cells impairs human defense pneumonia tuberculosis shingles certain types cancer 1 advanced stage hiv infection acquired immunodeficiency syndrome aids 15 years develop depending individual 2 hiv viral forms: hiv-1 the common form accounts 95% infections worldwide hiv-2 relatively uncommon infectious hiv-1 consists groups m n o genetically distinct subtypes hiv-1 group a b c f g h j k additionally different subtypes