In vivo endoscopic autofluorescence microspectro-imaging of bronchi and alveoli

Fibered confocal fluorescence microscopy (FCFM) is a new technique that can be used during a bronchoscopy to analyze the nature of the human bronchial and alveolar mucosa fluorescence microstructure. An endoscopic fibered confocal fluorescence microscopy system with spectroscopic analysis capability was developed allowing real-time, simultaneous images and emission spectra acquisition at 488 nm excitation using a flexible miniprobe that could be introduced into small airways. This flexible 1.4 mm miniprobe can be introduced into the working channel of a flexible endoscope and gently advanced through the bronchial tree to the alveoli. FCFM in conjunction with bronchoscopy is able to image the in vivo autofluorescence structure of the bronchial mucosae but also the alveolar respiratory network outside of the usual field of view. Microscopic and spectral analysis showed that the signal mainly originates from the elastin component of the bronchial subepithelial layer. In non smokers, the system images the elastin backbone of the aveoli. In active smokers, a strong autofluorescence signal appears from alveolar macrophages. The FCFM technique appears promising for in vivo exploration of the bronchial and alveolar extracellular matrix

Discrete R-symmetries and Anomaly Universality in Heterotic Orbifolds

We study discrete R-symmetries, which appear in 4D low energy effective field theory derived from hetetoric orbifold models. We derive the R-symmetries directly from geometrical symmetries of orbifolds. In particular, we obtain the corresponding R-charges by requiring that the couplings be invariant under these symmetries. This allows for a more general treatment than the explicit computations of correlation functions made previously by the authors, including models with discrete Wilson lines, and orbifold symmetries beyond plane-by-plane rotational invariance. Surprisingly, for the cases covered by earlier explicit computations, the R-charges differ from the previous result. We study the anomalies associated with these R-symmetries, and comment on the results.Comment: 21 pages, 2 figures. Minor changes, typos corrected. Matches JHEP published versio

EMbaRC: designing training and e-learning materials for biological resource centres

The European Consortium of Microbial Resource Centres (EMbaRC, www.embarc.eu) is a research infrastructure project gathering together major microbial Biological Resource Centres (BRCs) in Europe. These culture collections have a long and respected tradition in training people that are involved in microbial taxonomy, preservation and management. Advanced and bespoke courses on related topics add high value to the European educational community and create a knowledge-based training network. Under the framework of EMbaRC, the training programmes offered by the consortium were surveyed and schemes were proposed to establish an educational community to create a knowledge-based training network. This would implement lifelong educational and continuing professional development (CPD) schemes for those working within microbial resource centres (MiRC). In parallel, a European Masters Course on MiRC was designed to address the formal education path for strengthening competences in (1) Microbial Preservation Technologies, (2) MiRC: Organisation and Management, (3) QC Standards and International Regulations, (4) Microbial Biosafety and Biosecurity, and (5) IT Technologies and Database Management. Finally, to support these actions, materials for e-learning activities were developed such as videos related to microbial preservation techniques, the Gram-staining technique and, preparing microscopic slides of fungi. All activities developed under this EMbaRC task will support the MIRRI and other EU ESFRI-BMS and EMTRAIN projects

Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility

Testicular germ cell tumour (TGCT) is the most common cancer in young men. Here we sought to identify risk factors for TGCT by performing whole-exome sequencing on 328 TGCT cases from 153 families, 634 sporadic TGCT cases and 1,644 controls. We search for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potentially damaging effects and evidence of segregation in families. A total of 8.7% of TGCT families carry rare disruptive mutations in the cilia-microtubule genes (CMG) as compared with 0.5% of controls (P=2.1 × 10¯⁸). The most significantly mutated CMG is DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumours from carriers. DNAAF1 mutation as a cause of TGCT is supported by a dnaaf1hu²⁵⁵h(+/−) zebrafish model, which has a 94% risk of TGCT. Our data implicate cilia-microtubule inactivation as a cause of TGCT and provide evidence for CMGs as cancer susceptibility genes

Rotating black hole entropy from M5-branes

We compute the superconformal index of 3d N = 2 superconformal field theories obtained from N M5-branes wrapped on a hyperbolic 3-manifold. Exploiting the 3d-3d correspondence, we use perturbative invariants of SL(N, \u2102) Chern-Simons theory to determine the superconformal index in the large N limit, including corrections logarithmic in N. The leading order partition function provides a microscopic foundation for the entropy function of the dual rotating asymptotically AdS4 black holes. We also verify that the supergravity one-loop contribution to the log N term coincides with the field theoretic result. We propose a 3d-3d formulation for the refined topologically twisted index, and provide strong evidence in support of its vanishing \u2014 which agrees with the fact that the expected dual rotating magnetically-charged black hole does not exist. This provides an interesting link between gravity and a tantalizing mathematical result

Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization

Ciliopathies are a large group of clinically and genetically heterogeneous disorders caused by defects in primary cilia. Here we identified mutations in TRAF3IP1 (TNF Receptor-Associated Factor Interacting Protein 1) in eight patients from five families with nephronophthisis (NPH) and retinal degeneration, two of the most common manifestations of ciliopathies. TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis. The identified mutations result in mild ciliary defects in patients but also reveal an unexpected role of IFT54 as a negative regulator of microtubule stability via MAP4 (microtubule-associated protein 4). Microtubule defects are associated with altered epithelialization/polarity in renal cells and with pronephric cysts and microphthalmia in zebrafish embryos. Our findings highlight the regulation of cytoplasmic microtubule dynamics as a role of the IFT54 protein beyond the cilium, contributing to the development of NPH-related ciliopathies