A phosphoinositide hub connects CLE peptide signaling and polar auxin efflux regulation

Auxin efflux through plasma-membrane-integral PIN-FORMED (PIN) carriers is essential for plant tissue organization and tightly regulated. For instance, a molecular rheostat critically controls PIN-mediated auxin transport in developing protophloem sieve elements of Arabidopsis roots. Plasma-membrane-association of the rheostat proteins, BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX), is reinforced by interaction with PHOSPHATIDYLINOSITOL-4-PHOSPHATE-5-KINASE (PIP5K). Genetic evidence suggests that BRX dampens autocrine signaling of CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 45 (CLE45) peptide via its receptor BARELY ANY MERISTEM 3 (BAM3). How excess CLE45-BAM3 signaling interferes with protophloem development and whether it does so directly or indirectly remains unclear. Here we show that rheostat polarity is independent of PIN polarity, but interdependent with PIP5K. Catalytically inactive PIP5K confers rheostat polarity without reinforcing its localization, revealing a possible PIP5K scaffolding function. Moreover, PIP5K and PAX cooperatively control local PIN abundance. We further find that CLE45-BAM3 signaling branches via RLCK-VII/PBS1-LIKE (PBL) cytoplasmic kinases to destabilize rheostat localization. Our data thus reveal antagonism between CLE45-BAM3-PBL signaling and PIP5K that converges on auxin efflux regulation through dynamic control of PAX polarity. Because second-site bam3 mutation suppresses root as well as shoot phenotypes of pip5k mutants, CLE peptide signaling likely modulates phosphoinositide-dependent processes in various developmental contexts

Coexistence of Two Rare Sarcomas: Primary Leiomyosarcoma of Bone and Epithelioid Hemangioendothelioma of the Liver

A 33-year-old woman sought medical attention for a painful swelling of the left ankle. Plain radiographs revealed an osteolytic lesion involving the left distal tibia. An excisional biopsy provided the diagnosis of leiomyosarcoma in the tibia. A staging work-up was performed and an abdominal CT showed 4 liver hypodense lesions in both lobes with peripheral contrast enhancement. A liver biopsy confirmed the diagnosis of epithelioid hemangioendothelioma of the liver. No association between these two entities has been described before. This case introduces the importance of the pathological confirmation of apparent metastatic lesions in low grade sarcomas and provides a review of the literature of both tumours

Left ventricular thrombus mimicking primary cardiac tumor in a patient with primary antiphospholipid syndrome and recurrent systemic embolism

Primary antiphospholipid syndrome (APS) is a well-defined entity characterized by spontaneous and recurrent abortion, thrombocytopenia and recurrent vascular thromboses (arterial and venous). Left ventricular thrombus mimicking primary cardiac tumor with recurrent systemic embolism has not been previously reported. In this report we describe a 39 year-old man admitted to hospital presenting with left hemiparesis and a peripheral embolism. He had no history of thrombotic events. Transthoracic echocardiography showed a large, polypoid and mobile mass (4.0 × 1.2 cm) attached to the apex of the left ventricle, highly suggestive of primary cardiac tumor. The patient subsequently underwent open heart surgery. The histological examination showed an older thrombus and a fresh thrombus. Post-operative laboratory tests showed lupus anticoagulant activity, confirming the primary APS diagnosis. The patient initiated treatment with oral anticoagulation (INR levels between 2 and 3) and was discharged 29 days after surgery. At ten month follow-up, he was symptom-free with long-term anticoagulation therapy. No evidence of intracardiac mass recurrence on two-dimensional echocardiography was seen. Intracardiac thrombus has been rarely reported as a complication of primary APS. Left ventricular mass mimicking primary cardiac tumor with recurrent systemic embolism has not been previously reported. Pre-operative investigations could not distinguish such a thrombus from a cardiac tumor and the diagnosis was made post-operatively

Feasibility study (I stage) of CO2 geological storage by ECBM tecniques in the Sulcis Coal Province (SW Sardinia).

An ECBM feasibility study started for the Sulcis Coal Province (SW Sardinia, Italy): available geochemical, structural-geology, stratigraphic and reservoir engineering considerations as well as the newly gathered experimental data are discussed, including: fluid geochemistry (major and minor elements, dissolved gases, C and He isotopic ratios) of different strata/reservoir, coal composition and experimental data on CO2/CH4 adsorption-desorption on coal. A MapInfo GIS structure was built up including stratigraphic, geo-structural, hydro-geochemical, coal-compositional and environmental-impact information as well as the CO2 sources location and typology. Despite preliminary, these data highlighted both the challenging positive and negative aspects of the Sulcis Coal Province versus the exploitation of the ECBM technique. The most important objective of this phase I of the project is the selection of the best Sulcis ECBM test-pilot site, which will be followed (Phase II-2007) by the choice of a scaled up site and possibly by a future network (Phase III-2008). CO2 geological storage and CH4 production potentials in Sulcis have been grossly evaluated as a whole, in the frame of the Sardinia region CO2 sources, including the coal-fired power plants, both existent and foreseen (hundreds of millions of tonnes of CO2 are possible to be stored underground in the next decades).UnpublishedTrondheim, Norway4.4. Scenari e mitigazione del rischio ambientaleope

Feasibility study (I stage) of CO2 geological storage by ECBM tecniques in the Sulcis Coal Province (SW Sardinia).

An ECBM feasibility study started for the Sulcis Coal Province (SW Sardinia, Italy): available geochemical, structural-geology, stratigraphic and reservoir engineering considerations as well as the newly gathered experimental data are discussed, including: fluid geochemistry (major and minor elements, dissolved gases, C and He isotopic ratios) of different strata/reservoir, coal composition and experimental data on CO2/CH4 adsorption-desorption on coal. A MapInfo GIS structure was built up including stratigraphic, geo-structural, hydro-geochemical, coal-compositional and environmental-impact information as well as the CO2 sources location and typology. Despite preliminary, these data highlighted both the challenging positive and negative aspects of the Sulcis Coal Province versus the exploitation of the ECBM technique. The most important objective of this phase I of the project is the selection of the best Sulcis ECBM test-pilot site, which will be followed (Phase II-2007) by the choice of a scaled up site and possibly by a future network (Phase III-2008). CO2 geological storage and CH4 production potentials in Sulcis have been grossly evaluated as a whole, in the frame of the Sardinia region CO2 sources, including the coal-fired power plants, both existent and foreseen (hundreds of millions of tonnes of CO2 are possible to be stored underground in the next decades)

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N= 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel