1,195 research outputs found
Singular points in N=2 SQCD
We revisit the study of singular points in N=2 SQCD with classical gauge
groups. Using a technique proposed recently by Gaiotto, Seiberg and Tachikawa
we find that the low-energy physics at the maximally singular point involves
two superconformal sectors coupled to an infrared free SU(2) gauge group. When
one softly breaks extended supersymmetry to N=1 adding a mass term for the
chiral multiplet in the adjoint representation, a finite number of vacua remain
and the theory becomes confining. Our analysis allows to identify the
low-energy physics at these distinguished points in the moduli space. In some
cases, which we will describe in detail, two sectors coupled to an infrared
free SU(2) gauge group emerge as before. For USp and SO gauge groups one of
these sectors is always free, contrary to the SU case.Comment: 22 pages, 2 figure
A role for core planar polarity proteins in cell contact-mediated orientation of planar cell division across the mammalian embryonic skin
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017. Supplementary information accompanies this paper at doi:10.1038/s41598-017-01971-2.The question of how cell division orientation is determined is fundamentally important for understanding tissue and organ shape in both healthy or disease conditions. Here we provide evidence for cell contact-dependent orientation of planar cell division in the mammalian embryonic skin. We propose a model where the core planar polarity proteins Celsr1 and Frizzled-6 (Fz6) communicate the long axis orientation of interphase basal cells to neighbouring basal mitoses so that they align their horizontal division plane along the same axis. The underlying mechanism requires a direct, cell surface, planar polarised cue, which we posit depends upon variant post-translational forms of Celsr1 protein coupled to Fz6. Our hypothesis has parallels with contact-mediated division orientation in early C. elegans embryos suggesting functional conservation between the adhesion-GPCRs Celsr1 and Latrophilin-1. We propose that linking planar cell division plane with interphase neighbour long axis geometry reinforces axial bias in skin spreading around the mouse embryo body.Peer reviewe
Localization of supersymmetric field theories on non-compact hyperbolic three-manifolds
We study supersymmetric gauge theories with an R-symmetry, defined on
non-compact, hyperbolic, Riemannian three-manifolds, focusing on the case of a
supersymmetry-preserving quotient of Euclidean AdS. We compute the exact
partition function in these theories, using the method of localization, thus
reducing the problem to the computation of one-loop determinants around a
supersymmetric locus. We evaluate the one-loop determinants employing three
different techniques: an index theorem, the method of pairing of eigenvalues,
and the heat kernel method. Along the way, we discuss aspects of supersymmetry
in manifolds with a conformal boundary, including supersymmetric actions and
boundary conditions.Comment: v3:79p, minor clarifications and references adde
Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells
Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins
Variation in dopamine D2 and serotonin 5-HT2A receptor genes is associated with working memory processing and response to treatment with antipsychotics
Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with
antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these
phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal
working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T
allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics
compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect
on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with secondgeneration
antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the
rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the
attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during
working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment
in two independent samples of patients with schizophrenia (n¼63 and n¼54, respectively), consistent with the previously reported
separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological
prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that
further exploration is needed to better understand the clinical consequences of these genotype–phenotype relationships
A Functional Variant of the Dimethylarginine Dimethylaminohydrolase-2 Gene Is Associated with Insulin Sensitivity
Background: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, which was associated with insulin resistance. Dimethylarginine dimethylaminohydrolase (DDAH) is the major determinant of plasma ADMA. Examining data from the DIAGRAM+ (Diabetes Genetics Replication And Meta-analysis), we identified a variant (rs9267551) in the DDAH2 gene nominally associated with type 2 diabetes (P =3610 25). Methodology/Principal Findings: initially, we assessed the functional impact of rs9267551 in human endothelial cells (HUVECs), observing that the G allele had a lower transcriptional activity resulting in reduced expression of DDAH2 and decreased NO production in primary HUVECs naturally carrying it. We then proceeded to investigate whether this variant is associated with insulin sensitivity in vivo. To this end, two cohorts of nondiabetic subjects of European ancestry were studied. In sample 1 (n = 958) insulin sensitivity was determined by the insulin sensitivity index (ISI), while in sample 2 (n = 527) it was measured with a euglycemic-hyperinsulinemic clamp. In sample 1, carriers of the GG genotype had lower ISI than carriers of the C allele (67633 vs.79644; P = 0.003 after adjusting for age, gender, and BMI). ADMA levels were higher in subjects carrying the GG genotype than in carriers of the C allele (0.6860.14 vs. 0.5760.14 mmol/l; P = 0.04). In sample 2, glucose disposal was lower in GG carriers as compared with C carriers (9.364.1 vs. 11.064.2 mg6Kg 21 free fat mass6min 21; P = 0.009)
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