An Abp1-Dependent Route of Endocytosis Functions when the Classical Endocytic Pathway in Yeast Is Inhibited

Clathrin-mediated endocytosis (CME) is a well characterized pathway in both yeast and mammalian cells. An increasing number of alternative endocytic pathways have now been described in mammalian cells that can be both clathrin, actin, and Arf6- dependent or independent. In yeast, a single clathrin-mediated pathway has been characterized in detail. However, disruption of this pathway in many mutant strains indicates that other uptake pathways might exist, at least for bulk lipid and fluid internalization. Using a combination of genetics and live cell imaging, here we show evidence for a novel endocytic pathway in S. cerevisiae that does not involve several of the proteins previously shown to be associated with the ‘classic’ pathway of endocytosis. This alternative pathway functions in the presence of low levels of the actin-disrupting drug latrunculin-A which inhibits movement of the proteins Sla1, Sla2, and Sac6, and is independent of dynamin function. We reveal that in the absence of the ‘classic’ pathway, the actin binding protein Abp1 is now essential for bulk endocytosis. This novel pathway appears to be distinct from another described alternative endocytic route in S. cerevisiae as it involves at least some proteins known to be associated with cortical actin patches rather than being mediated at formin-dependent endocytic sites. These data indicate that cells have the capacity to use overlapping sets of components to facilitate endocytosis under a range of conditions

Suono e Spettacolo. Athanasius Kircher, un percorso nelle Immagini sonore.

The Society of Jesus made great propaganda efforts throughout the seventeenth century and chose the images and the play as a privileged means to communicate and persuade. Athanasius Kircher, a key figure of the seventeenth century, he decided to dominate the wild nature of sound through Phonurgia Nova, which includes a gallery of powerful symbolic images for Baroque aesthetics. The essay, through the grant of the images from the Library of the Department of Mathematics "Guido Castelnuovo" Sapienza University of Rome, aims to understand, through the pictures offered by Kircher, the sound phenomenon and the spectacle that this produces. In Phonurgia Nova a process of dramatization sound effects takes place, often through machines and "visions" applied to the theatrical reality, as experimental and astonishing environment beloved in baroque. Kircher illustrates the sound through explanatory figures, so to dominate the sound through the eyes. Sound is seen, admired and represented: its spectacle not only takes place through the implementation of sound machines or the "wonders" applied to the theater, but even through images, creating create a sense of wonder in in the erudite person of the seventeenth century

Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches

The process of resonance assignment is fundamental to most NMR studies of protein structure and dynamics. Unfortunately, the manual assignment of residues is tedious and time-consuming, and can represent a significant bottleneck for further characterization. Furthermore, while automated approaches have been developed, they are often limited in their accuracy, particularly for larger proteins. Here, we address this by introducing the software COMPASS, which, by combining automated resonance assignment with manual intervention, is able to achieve accuracy approaching that from manual assignments at greatly accelerated speeds. Moreover, by including the option to compensate for isotope shift effects in deuterated proteins, COMPASS is far more accurate for larger proteins than existing automated methods. COMPASS is an open-source project licensed under GNU General Public License and is available for download from http://www.liu.se/forskning/foass/tidigare-foass/patrik-lundstrom/software?l=en. Source code and binaries for Linux, Mac OS X and Microsoft Windows are available.Funding Agencies|Swedish Research Council [Dnr. 2012-5136]</p

Diagnostic accuracy of septic markers for neonatal sepsis

Background Neonatal sepsis is a major cause of morbidity and mortality. A positive blood culture is the gold standard for diagnosis of neonatal sepsis. The signs and symptoms suggesting neonatal sepsis are non-specific. There is no rapid and reliable laboratory test findings for confirmation of etiologic diagnosis. Clinical signs, symptoms, and laboratory examinations are not perceived as sensitive or specific for diagnosis of sepsis. Objective The purpose of this study was to evaluate the accuracy of the septic markers for diagnosis of neonatal sepsis. Methods Blood culture was used as gold standard to compare septic markers to diagnose neonatal sepsis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratio (LR), and accuracy were calculated. Results We identified 130 cases suspected of neonatal sepsis during September 2005 until March 2006. Four patients were excluded because of major congenital anomalies. The mean age was 2.2 days and 51.6% were boys. We found fifty six (44.4%) neonates have positive blood culture. All of septic markers had sensitivity more than 80%. Immature to Total Neutrophil ratio (Iff) ratio had the highest sensitivity (96.4%) and C-Reactive Protein (CRP) had the lowest sensitivity (80.4o/o). Combination among leukocyte count, thrombocyte, and Iff ratio had the highest sensitivity (sensitivity was 85. 7%, specificity was 97.1 o/o, positive predictive value was 95.9%, negative predictive value was 89.5%, accuracy was 94.4%, and positive likelihood ratio was 30.0). Conclusion Septic markers can be used in the diagnostic evaluation of neonates with suspected sepsis

Improvement of intratumor microdistribution of PEGylated liposome via tumor priming by metronomic S-1 dosing

Yusuke Doi,1 Amr S Abu Lila,1&ndash;3 Haruna Matsumoto,1 Tomoko Okada,1 Taro Shimizu,1 Tatsuhiro Ishida1 1Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Hail University, Hail, Saudi Arabia Abstract: The efficient delivery of nanocarrier-based cancer therapeutics into tumor tissue is problematic. Structural abnormalities, tumor vasculature heterogeneity, and elevated intratumor pressure impose barriers against the preferential accumulation of nanocarrier-based cancer therapeutics within tumor tissues and, consequently, compromise their therapeutic efficacy. Recently, we have reported that metronomic S-1, orally available tegafur formulation, dosing synergistically augmented the therapeutic efficacy of oxaliplatin (l-OHP)-containing PEGylated liposome without increasing the toxicity in animal model. However, the exact mechanism behind such synergistic effect was not fully elucidated. In this study, therefore, we tried to shed the light on the contributions of metronomic S-1 dosing to the enhanced accumulation and/or spatial distribution of PEGylated liposome within tumor tissue. Tumor priming with metronomic S-1 treatment induced a potent apoptotic response against both angiogenic endothelial cells and tumor cells adjacent to tumor blood vessels, resulting in enhanced tumor blood flow via transient normalization of tumor vasculature, along with alleviation of intratumor pressure. Such a change in the tumor microenvironment imparted by S-1 treatment allows efficient delivery of PEGylated liposome to tumor tissue and permits their deep penetration/distribution into the tumor mass. Such a priming effect of S-1 dosing can be exploited as a promising strategy to enhance the therapeutic efficacy of nanocarrier-based cancer therapeutics suffering from inadequate/heterogeneous delivery to tumor tissues. Keywords: tumor microenvironment, metronomic chemotherapy, S-1, liposome, nanocarrier, EPR effec