Truly unentangled photon pairs without spectral filtering.

We demonstrate that an integrated silicon microring resonator is capable of efficiently producing photon pairs that are completely unentangled; such pairs are a key component of heralded single-photon sources. A dual-channel interferometric coupling scheme can be used to independently tune the quality factors associated with the pump and signal and idler modes, yielding a biphoton wavefunction with a Schmidt number arbitrarily close to unity. This will permit the generation of heralded single-photon states with unit purity.

An incomplete form of childhood Behçet's disease treated with infliximab.

Behçet's disease (BD) is a multi-systemic vasculitis characterized by the possible presence of cutaneous, ocular, articular and neurological manifestations. In this report, we examine the case of a fifteen-year old boy with an incomplete form of juvenile Behçet's disease which began with joint involvement and developed into a complete form only after several years. The patient showed a rapid response to anti-TNF-alpha (infliximab) with an improvement of mucocutaneous lesions (oral and genital ulcers, pseudofolliculitis) and arthritis.

A case of subacute cutaneous lupus erythematosus in a patient with mixed connective tissue disease: successful treatment with plasmapheresis and rituximab.

A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE). Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL) IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE) followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX) (375 mg/m(2) weekly for 4 weeks). Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed.

Neurodegeneration by polyglutamine Atrophin is not rescued by induction of autophagy.

Polyglutamine pathologies are neurodegenerative diseases that manifest both general polyglutamine toxicity and mutant protein-specific effects. Dentatorubral-pallidoluysian Atrophy (DRPLA) is one of these disorders caused by mutations in the Atrophin-1 protein. We have generated several models for DRPLA in Drosophila and analysed the mechanisms of cellular and organism toxicity. Our genetic and ultrastructural analysis of neurodegeneration suggests that autophagy may have a role in cellular degeneration when polyglutamine proteins are overexpressed in neuronal and glial cells. Clearance of autophagic organelles is blocked at the lysosomal level after correct fusion between autophagosomes and lysosomes. This leads to accumulation of autofluorescent pigments and proteinaceous residues usually degraded by the autophagy-lysosome system. Under these circumstances, further pharmacological and genetic induction of autophagy does not rescue neurodegeneration by polyglutamine Atrophins, in contrast to many other neurodegenerative conditions. Our data thus provide a crucial insight into the specific mechanism of a polyglutamine disease and reveal important differences in the role of autophagy with respect to other diseases of the same family.

Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye.

BACKGROUND: The small GTPases Rac and Rho act as cellular switches in many important biological processes. In the fruit fly Drosophila, RhoA participates in the establishment of planar polarity, a process mediated by the receptor Frizzled (Fz). Thus far, analysis of Rac in this process has not been possible because of the absence of mutant Rac alleles. Here, we have investigated the role of Rac and Rho in establishing the polarity of ommatidia in the Drosophila eye. RESULTS: By expressing a dominant negative or a constitutively activated form of Rac1, we interfered specifically with Rac signaling and disrupted ommatidial polarity. The resulting defects were similar to the loss/gain-of-function phenotypes typical of tissue-polarity genes. Through genetic interaction and rescue experiments involving a polarity-specific, loss-of-function dishevelled (dsh) allele, we found that Rac1 acts downstream of Dsh in the Fz signaling pathway, but upstream of, or in parallel to, RhoA. Rac signaled to the nucleus through the Jun N-terminal kinase (JNK) cascade in this process. By generating point mutations in the effector loop of RhoA, we found that RhoA also signals to the nucleus during the establishment of ommatidial polarity. Nevertheless, Rac and RhoA activated transcription of distinct target genes. CONCLUSIONS: Rac is specifically required downstream of Dsh in the Fz pathway. It functions upstream or in parallel to RhoA and both signal to the nucleus, through distinct effectors, to establish planar polarity in the Drosophila eye.

Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling.

The small GTPase Ras plays an important role in many cellular signaling processes. Ras activity is negatively regulated by GTPase activating proteins (GAPs). It has been proposed that RasGAP may also function as an effector of Ras activity. We have identified and characterized the Drosophila homologue of the RasGAP-binding protein G3BP encoded by rasputin (rin). rin mutants are viable and display defects in photoreceptor recruitment and ommatidial polarity in the eye. Mutations in rin/G3BP genetically interact with components of the Ras signaling pathway that function at the level of Ras and above, but not with Raf/MAPK pathway components. These interactions suggest that Rin is required as an effector in Ras signaling during eye development, supporting an effector role for RasGAP. The ommatidial polarity phenotypes of rin are similar to those of RhoA and the polarity genes, e.g. fz and dsh. Although rin/G3BP interacts genetically with RhoA, affecting both photoreceptor differentiation and polarity, it does not interact with the gain-of-function genotypes of fz and dsh. These data suggest that Rin is not a general component of polarity generation, but serves a function specific to Ras and RhoA signaling pathways.

Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye.

Planar polarity is seen in epidermally derived structures throughout the animal kingdom. In the Drosophila eye, planar polarity is reflected in the mirror-symmetric arrangement of ommatidia (eye units) across the dorsoventral midline or equator; ommatidia on the dorsal and ventral sides of the equator exhibit opposite chirality. Photoreceptors R3 and R4 are essential in the establishment of the polarity of ommatidia. The R3 cell is thought to receive the polarizing signal, through the receptor Frizzled (Fz), before or at higher levels then the R4 cell, generating a difference between neighbouring R3 and R4 cells. Both loss-of-function and overexpression of Fz in the R3/R4 pair result in polarity defects and loss of mirror-image symmetry. Here we identify Notch and Delta (Dl) as dominant enhancers of the phenotypes produced by overexpression of fz and dishevelled (dsh), which encodes a signalling component downstream of Fz, and we show that D1-mediated activation of Notch is required for establishment of ommatidial polarity. Whereas fz signalling is required to specify R3, Notch signalling induces the R4 fate. Our data indicate that Dl is a transcriptional target of Fz/Dsh signalling in R3, and activates Notch in the neighbouring R4 precursor. This two-tiered mechanism explains how small differences in the level and/or timing of Fz activation reliably generate a binary cell-fate decision, leading to specification of R3 and R4 and ommatidial chirality.

Linking cell-fate specification to planar polarity: determination of the R3/R4 photoreceptors is a prerequisite for the interpretation of the Frizzled mediated polarity signal.

The adult eye of Drosophila is a highly ordered structure composed of about 800 ommatidia, each displaying precise polarity. The planar polarity is reflected in the mirror-symmetric arrangement of ommatidia relative to the dorso-ventral midline, the equator. This arrangement is generated when ommatidia rotate towards the equator and the photoreceptor R3 displaces R4 creating different chiral forms in each half. Analysis of ommatidia mosaic for the tissue polarity gene frizzled (fz) has shown that the presence of a single Fz+ photoreceptor cell within the R3/ R4 pair is critical for the direction of rotation and chirality. By analysing clones mutant for seven-up (svp), in which R3/R4 precursors reside in their normal positions and become photoreceptor neurones but fail to adopt the normal R3/R4 fate, we find that the R3/R4 photoreceptor subtype specification is a prerequisite for planar polarisation in the eye. Moreover, in mosaic R3/R4 pairs we find that the svp- cell always adopts the R4 position. This bias is reminiscent of what happens in fz mosaic R3/R4 pairs, where the fz- cell also almost always adopts the R4 position. In addition, we find that in genotypes where too many cells adopt the R3/R4 fate, ommatidial polarity is also disturbed. Taken together, these data imply that correct specification of a single R3 cell per ommatidium is essential for the normal interpretation of the Fz-mediated polarity signal.