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Background: Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. Objective: We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar'' CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. Methods: Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-gamma, IL-13, IL-9, IL-17, and IL-22 cytokines, defining T(H)1/cytotoxic T(T-C) 1, T(H)2/T(C)2, TH9/T(C)9, T(H)17/T(C)17, and T(H)22/T(C)22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). Results: Selective inducible costimulator activation (P <. 001) was seen in children. CLA(+)T(H)2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+)T(H)1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of T(H)22 T cells within the CLA(+) or CLA(-) compartments. adults with AD hAD increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P <. 001), as well as increased HLA-DR activation (P < .01). Conclusions: These data suggest that T(H)2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by T(H)1 T cells might contribute to excess T(H)2 activation. T(H)22 "spreading'' of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.

Biological systems are influenced by random processes at all scales, including molecular, demographic, and behavioral fluctuations, as well as by their interactions with a fluctuating environment. We previously established microbial closed ecosystems (CES) as model systems for studying the role of random events and the emergent statistical laws governing population dynamics. Here, we present long-term measurements of population dynamics using replicate digital holographic microscopes that maintain CES under precisely controlled external conditions while automatically measuring abundances of three microbial species via single-cell imaging. With this system, we measure spatiotemporal population dynamics in more than 60 replicate CES over periods of months. In contrast to previous studies, we observe strongly deterministic population dynamics in replicate systems. Furthermore, we show that previously discovered statistical structure in abundance fluctuations across replicate CES is driven by variation in external conditions, such as illumination. In particular, we confirm the existence of stable ecomodes governing the correlations in population abundances of three species. The observation of strongly deterministic dynamics, together with stable structure of correlations in response to external perturbations, points towards a possibility of simple macroscopic laws governing microbial systems despite numerous stochastic events present on microscopic levels.

Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using gamma H2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360 degrees arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response. (C) 2015 Elsevier Inc. All rights reserved.

The first direct search for lepton-flavour-violating decays of the recently discovered Higgs boson (H) is described. The search is performed in the H -> mu tau(e) and H -> mu tau(h) channels, where tau(e) and tau(h) are tau leptons reconstructed in the electronic and hadronic decay channels, respectively. The data sample used in this search was collected in pp collisions at a centre-of-mass energy of root s = 8 TeV with the CMS experiment at the CERN LHC and corresponds to an integrated luminosity of 19.7 fb(-1). The sensitivity of the search is an order of magnitude better than the existing indirect limits. A slight excess of signal events with a significance of 2.4 standard deviations is observed. The p-value of this excess at M-H = 125 GeV is 0.010. The best fit branching fraction is beta(H -> mu tau) = (0.84(-0.37)(+0.39))%. A constraint on the branching fraction, beta(H -> mu tau) < 1.51% at 95% confidence level is set. This limit is subsequently used to constrain the mu-tau Yukawa couplings to be less than 3.6 x 10(-3). (C) 2015 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.

Piwi-interacting RNAs (piRNAs), a class of 26- to 32-nt non-coding RNAs (ncRNAs), function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference somatic tissues. This revealed abundant piRNAs originating from 150 piRNA-encoding genes, including some exhibiting gender-specific expression, in fetal ovary and adult testis-developmental periods coinciding with mitotic cell divisions expanding fetal germ cells prior to meiotic divisions. The absence of reads mapping uniquely to annotated piRNA genes demonstrated their paucity in fetal testis and adult ovary and absence in somatic tissues. We curated human piRNA-expressing regions and defined their precise borders and observed piRNA-guided cleavage of transcripts antisense to some piRNA-producing genes. This study provides insights into sex-specific mammalian piRNA expression and function and serves as a reference for human piRNA analysis and annotation.

Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) ATP-dependent chromatin-remodeling complex, occurring in the nucleus accumbens of stress-susceptible mice and depressed humans, is necessary for stress-induced depressive-like behaviors. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the ACF chromatin-remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress-related behaviors.

The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC80 value of 0.42 mu g/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans.

Apoptosis, in contrast to other forms of cell death such as necrosis, was originally regarded as a 'silent' mechanism of cell elimination designed to degrade the contents of doomed cells. However, during the past decade it has become clear that apoptotic cells can produce diverse signals that have a profound impact on neighboring cells and tissues. For example, apoptotic cells can release factors that influence the proliferation and survival of adjacent tissues. Apoptosis can also affect tissue movement and morphogenesis by modifying tissue tension in surrounding cells. As we review here, these findings reveal unexpected roles for apoptosis in tissue remodeling during development, as well as in regeneration and cancer.

We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The t-channel cross section is measured to be sigma(t) = 2.25(-0.31)(+0.29) pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s + t channel cross section measurement resulting in sigma(s+t) = 3.30(-0.40)(+0.52) pb, without assuming the standard model value for the ratio sigma(s)/sigma(t). The resulting value of the magnitude of the top-to-bottom quark coupling is vertical bar V-tb vertical bar = 1.02(-0.05)(+0.06), corresponding to vertical bar V-tb vertical bar > 0.92 at the 95% C. L.