How PI3K-derived lipids control cell division

To succeed in cell division, intense cytoskeletal and membrane remodeling are required to allow accurate chromosome segregation and cytoplasm partitioning. Spatial restriction of the actin dynamics and vesicle trafficking define the cell symmetry and equivalent membrane scission events, respectively. Protein complexes coordinating mitosis are recruited to membrane microdomains characterized by the presence of the phosphatidylinositol lipid members (PtdIns), like PtdIns(3,4,5)P3, PtdIns(4,5)P2 and PtdIns(3)P. These PtdIns represent a minor component of cell membranes, defining membrane domain identity, ultimately controlling cytoskeleton and membrane dynamics during mitosis. The coordinated presence of PtdIns(3,4,5)P3 at the cell poles and PtdIns(4,5)P2 at the cleavage furrow controls the polarity of the actin cytoskeleton leading to symmetrical cell division. In the endosomal compartment, the trafficking of PtdIns(3)P positive vesicles allows the recruitment of the protein machinery required for the abscission

Early venous congestion after diep flap breast reconstruction: case report of a successful management

BACKGROUND AND AIM: More than 250 000 women estimated to be diagnosed with breast cancer in the USA every year. Mastectomy is primary treatment for more than a third of those with early-stage disease. Most of the patients undergoing mastectomy receive breast reconstruction. A number of. Surgical techniques have been described to reconstruct the breast. With autologous tissue breast reconstruction, the plastic surgeon uses patient's own tissues, taken from a different part of the body where there is an excess of fat and skin. Deep inferior epigastric perforator (DIEP) flap is the autologous breast reconstruction technique of choice in our department due to long lasting results, low donor site morbidity and positive patient reported outcomes have been described.   Case Report: We present the case of a 42-year-old woman who underwent neoadjuvant chemotherapy followed by left breast simple mastectomy, axillary lymph-nodes dissection and later adjuvant radiation therapy (RT). After conclusion of RT a DIEP flap breast reconstruction was performed. Nine-hours after the operation, signs of acute venous congestion were noted. The venous congestion was treated by a combined surgical and medical approach based on pedicle discharge and ICU resuscitation protocol. After take back surgery, the patient was tightly monitored in the intensive care unit where intravenous heparin infusion and leech therapy were performed for 2 days. Flap congestion resolved completely, and the patient was discharged.   Conclusions: Venous congestion is very difficult to treat due to its potential multifactorial nature. The most important step is to recognize this kind of emergency because irreversible microvascular damages will develop in 6-8 hours. Because of multiple causes of venous congestion a timely multidisciplinary approach is mandatory, to maximize flap salvage and success rates

The Impact of the Extent of Lymphadenectomy on Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer : A Systematic Review

Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewedPostprin

Precision Measurement of KS Meson Lifetime with the KLOE detector

Using a large sample of pure, slow, short lived K0 mesons collected with KLOE detector at DaFne, we have measured the KS lifetime. From a fit to the proper time distribution we find tau = (89.562 +- 0.029_stat +- 0.043_syst) ps. This is the most precise measurement today in good agreement with the world average derived from previous measurements. We observe no dependence of the lifetime on the direction of the Ks.Comment: 5 pages, 7 figure

Understanding Tumor-Stroma Interplays for Targeted Therapies by Armed Mesenchymal Stromal Progenitors: The Mesenkillers.

Tumor represents a complex structure containing malignant cells strictly coupled with a large variety of surroundingcells constituting the tumor stroma (TS). In recent years, the importance of TS for cancer initiation, development,local invasion and metastases became increasingly clear allowing the identification of TS as one of the possibleways to indirectly target tumors. Inside the heterogeneous stromal cell population, tumor associated fibroblasts(TAF) play a crucial role providing both functional and supportive environments. During both tumor and stroma development,several findings suggest that TAF could be recruited from different sources such as locally derived host fibroblasts,via epithelial/endothelial mesenchymal transitions or from circulating pools of fibroblasts deriving form mesenchymalprogenitors, namely mesenchymal stem/stromal cells (MSC). These insights prompted scientists to identifymultimodal approaches to target TS by biomolecules, monoclonal antibodies and, more recently, via cell basedstrategies. These latter appear extremely promising, although associated with still debated and unclear findings. Thisreview discusses on crosstalk between cancers and their stroma, dissecting specific tumor types, such as sarcoma,pancreatic and breast carcinoma where stroma plays distinct paradigmatic roles. The recognition of these distinctstromal functions may help in planning effective and safer approaches aimed either to eradicate or to substitute TSby novel compounds and/or MSC having specific killing activitie

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

Prevalence of hypospadias in Italy according to severity, gestational age and birthweight: an epidemiological study

<p>Abstract</p> <p>Background</p> <p>Hypospadias is a congenital displacement of the urethral meatus in male newborns, being either an isolated defect at birth or a sign of sexual development disorders. The aim of this study was to assess the prevalence rate of hypospadias in different Districts of Italy, in order to make a comparison with other countries all over the world.</p> <p>Methods</p> <p>We reviewed all the newborns file records (years 2001–2004) in 15 Italian Hospitals.</p> <p>Results</p> <p>We found an overall hypospadias prevalence rate of 3.066 ± 0.99 per 1000 live births (82.48% mild hypospadias, 17.52% moderate-severe). In newborns Small for Gestational Age (birthweight < 10^thpercentile) of any gestational age the prevalence rate of hypospadias was 6.25 per 1000 live births. Performing multivariate logistic regression analysis for different degrees of hypospadias according to severity, being born SGA remained the only risk factor for moderate-severe hypospadias (p = 0.00898) but not for mild forms (p > 0.1).</p> <p>Conclusion</p> <p>In our sample the prevalence of hypospadias results as high as reported in previous European and American studies (3–4 per 1000 live births). Pathogenesis of isolated hypospadias is multifactorial (genetic, endocrine and environmental factors): however, the prevalence rate of hypospadias is higher in infants born small for gestational age than in newborns with normal birth weight.</p

Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification

ObjectivesThe aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS).BackgroundElevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS.MethodsProspective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP &lt; 1.98 fold upper reference limit (URL) and hsTnI &lt; 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median.Results49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31–47] vs. 32 [29–41] vs. 26 [19–33]%; p &lt; 0.01) and right ventricular EF (62 [53–69] vs. 51 [35–63] vs. 30 [24–46]%; p &lt; 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8–30.7] vs. 28.2 [26.9–34.5] vs. 31.8 [28.9–35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2–39.1] vs. 28.8 [25.4–39.9] vs. 44.2 [36.4–51.2] ml/m2, respectively; p &lt; 0.01) from Group 1 to Group 3.ConclusionsHigher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13