Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil‐predominant infiltration, thereby ...conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T‐helper (Th)2‐type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single‐nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen–driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.
The chemical functionality within porous architectures dictates their performance as heterogeneous catalysts; however, synthetic routes to control the spatial distribution of individual functions ...within porous solids are limited. Here we report the fabrication of spatially orthogonal bifunctional porous catalysts, through the stepwise template removal and chemical functionalization of an interconnected silica framework. Selective removal of polystyrene nanosphere templates from a lyotropic liquid crystal-templated silica sol-gel matrix, followed by extraction of the liquid crystal template, affords a hierarchical macroporous-mesoporous architecture. Decoupling of the individual template extractions allows independent functionalization of macropore and mesopore networks on the basis of chemical and/or size specificity. Spatial compartmentalization of, and directed molecular transport between, chemical functionalities affords control over the reaction sequence in catalytic cascades; herein illustrated by the Pd/Pt-catalysed oxidation of cinnamyl alcohol to cinnamic acid. We anticipate that our methodology will prompt further design of multifunctional materials comprising spatially compartmentalized functions.
The microbiological characteristics of both caries and periodontal disease show significant change from those in health. In both instances, there is evidence of co‐association of different organisms ...into consortia.
Aim
We review and summarize a number of issues pertinent to the community organization and functional activity of the bacterial populations resident on supra‐ and subgingival tooth surface and the influence of these populations on disease.
Methods
A literature review was undertaken with a particular emphasis on recent publications involving high‐throughput, deep sequencing approaches to the analysis of microbial populations and their functional activity.
Results
There is increasing evidence to suggest that both caries and periodontal disease represent dysbiotic states of the oral microbiome. The mode of acquisition of the oral microbial communities may be less passive than previously recognized but once established remains relatively stable within an individual although there are very significant site variations. A repertoire of stable dysbiotic states may occur in both caries and periodontitis involving different microbial community structures with potentially similar functional properties.
Conclusions
The processes which underlie the development and stability of microbial populations in the healthy mouth are fundamental to understanding how these populations are transformed into a dysbiotic state in disease.
Observations indicate that nearly all galaxies contain supermassive black holes at their centers. When galaxies merge, their component black holes form SMBH binaries (SMBHBs), which emit ...low-frequency gravitational waves (GWs) that can be detected by pulsar timing arrays. We have searched the North American Nanohertz Observatory for Gravitational Waves 11 yr data set for GWs from individual SMBHBs in circular orbits. As we did not find strong evidence for GWs in our data, we placed 95% upper limits on the strength of GWs from such sources. At = 8 nHz, we placed a sky-averaged upper limit of h0 < 7.3(3) × 10−15. We also developed a technique to determine the significance of a particular signal in each pulsar using "dropout" parameters as a way of identifying spurious signals. From these upper limits, we ruled out SMBHBs emitting GWs with = 8 nHz within 120 Mpc for , and within 5.5 Gpc for at our most sensitive sky location. We also determined that there are no SMBHBs with emitting GWs with = 2.8-317.8 nHz in the Virgo Cluster. Finally, we compared our strain upper limits to simulated populations of SMBHBs, based on galaxies in the Two Micron All-Sky Survey and merger rates from the Illustris cosmological simulation project, and found that only 34 out of 75,000 realizations of the local universe contained a detectable source.
Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into ...fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces.
Elementary processes associated with ionization of liquid water provide a framework for understanding radiation-matter interactions in chemistry and biology. Although numerous studies have been ...conducted on the dynamics of the hydrated electron, its partner arising from ionization of liquid water, H
O
, remains elusive. We used tunable femtosecond soft x-ray pulses from an x-ray free electron laser to reveal the dynamics of the valence hole created by strong-field ionization and to track the primary proton transfer reaction giving rise to the formation of OH. The isolated resonance associated with the valence hole (H
O
/OH) enabled straightforward detection. Molecular dynamics simulations revealed that the x-ray spectra are sensitive to structural dynamics at the ionization site. We found signatures of hydrated-electron dynamics in the x-ray spectrum.
We have designed and synthesized an isoreticular series of luminescent metal–organic frameworks (LMOFs) by incorporating a strongly emissive molecular fluorophore and functionally diverse colinkers ...into Zn-based structures. The three-dimensional porous networks of LMOF-261, -262, and -263 represent a unique/new type of nets, classified as a 2-nodal, (4,4)-c net (mot-e type) with 4-fold, class IIIa interpenetration. All compounds crystallize in a body-centered tetragonal crystal system (space group I41/a). A systematic study has been implemented to analyze their interactions with heavy metals. LMOF-263 exhibits impressive water stability, high porosity, and strong luminescence, making it an excellent candidate as a fluorescent chemical sensor and adsorbent for aqueous contaminants. It is extremely responsive to toxic heavy metals at a parts per billion level (3.3 ppb Hg2+, 19.7 ppb Pb2+) and demonstrates high selectivity for heavy metals over light metals, with detection ratios of 167.4 and 209.5 for Hg2+/Ca2+ and Hg2+/Mg2+, respectively. Mixed-metal adsorption experiments also show that LMOF-263 selectively adsorbs Hg2+ over other heavy metal ions in addition to light metals. The Pb2+ KSV value for LMOF-263 (55,017 M–1) is the highest among LMOFs reported to date, and the Hg2+ KSV value is the second highest (459,446 M–1). LMOF-263 exhibits a maximum adsorption capacity of 380 mg Hg2+/g. The Hg2+ adsorption process follows pseudo-second-order kinetics, removing 99.1% of the metal within 30 min. An in situ XPS study provides insight to help understand the interaction mechanism between Hg2+ and LMOF-263. No other MOFs have demonstrated such a high performance in both the detection and the capture of Hg2+ from aqueous solution.
The Boston University-Five College Radio Astronomy Observatory Galactic Ring Survey is a new survey of Galactic super(13)CO J = 1 1 0 emission. The survey used the SEQUOIA multipixel array on the ...Five College Radio Astronomy Observatory 14m telescope to cover a longitude range of l = 18-55.7 and a latitude range of |b| < 1, a total of 75.4 deg super(2). Using both position-switching and On-The-Fly mapping modes, we achieved an angular sampling of 22, better than half of the telescope's 46 angular resolution. The survey's velocity coverage is -5 to 135 km s super(-1) for Galactic longitudes l, 40 and -5 to 85 km s super(-1) for Galactic longitudes l > 40. At the velocity resolution of 0.21 km s super(-1), the typical rms sensitivity is s(T super(*)A) 6 0.13 K. The survey comprises a total of 1,993,522 spectra. We show integrated intensity images (zeroth moment maps), channel maps, position-velocity diagrams, and an average spectrum of the completed survey data set. We also discuss the telescope and instrumental parameters, the observing modes, the data reduction processes, and the emission and noise characteristics of the data set. The Galactic Ring Survey data are available to the community online or in DVD form by request.
A recent genome-wide screen identified ~300 essential or growth-supporting genes in the dental caries pathogen Streptococcus mutans. To be able to study these genes, we built a CRISPR interference ...tool around the Cas9 nuclease (Cas9Smu) encoded in the S. mutans UA159 genome. Using a xylose-inducible dead Cas9Smu with a constitutively active single-guide RNA (sgRNA), we observed titratable repression of GFP fluorescence that compared favorably to that of Streptococcus pyogenes dCas9 (Cas9Spy). We then investigated sgRNA specificity and proto-spacer adjacent motif (PAM) requirements. Interference by sgRNAs did not occur with double or triple base-pair mutations, or if single base-pair mutations were in the 3' end of the sgRNA. Bioinformatic analysis of >450 S. mutans genomes allied with in vivo assays revealed a similar PAM recognition sequence as Cas9Spy. Next, we created a comprehensive library of sgRNA plasmids that were directed at essential and growth-supporting genes. We discovered growth defects for 77% of the CRISPRi strains expressing sgRNAs. Phenotypes of CRISPRi strains, across several biological pathways, were assessed using fluorescence microscopy. A variety of cell structure anomalies were observed, including segregational instability of the chromosome, enlarged cells, and ovococci-to-rod shape transitions. CRISPRi was also employed to observe how silencing of cell wall glycopolysaccharide biosynthesis (rhamnose-glucose polysaccharide, RGP) affected both cell division and pathogenesis in a wax worm model. The CRISPRi tool and sgRNA library are valuable resources for characterizing essential genes in S. mutans, some of which could prove to be promising therapeutic targets.
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