Zebrafish mutants in vegfab can affect endothelial cell proliferation without altering ERK phosphorylation and are phenocopied by loss of PI3K signaling.

The formation of appropriately patterned blood vessel networks requires endothelial cell migration and proliferation. Signaling through the Vascular Endothelial Growth Factor A (VEGFA) pathway is instrumental in coordinating these processes. mRNA splicing generates short (diffusible) and long (extracellular matrix bound) Vegfa isoforms. The differences between these isoforms in controlling cellular functions are not understood. In zebrafish, vegfaa generates short and long isoforms, while vegfab only generates long isoforms. We found that mutations in vegfaa had an impact on endothelial cell (EC) migration and proliferation. Surprisingly, mutations in vegfab more strongly affected EC proliferation in distinct blood vessels, such as intersegmental blood vessels in the zebrafish trunk and central arteries in the head. Analysis of downstream signaling pathways revealed no change in MAPK (ERK) activation, while inhibiting PI3 kinase signaling phenocopied vegfab mutant phenotypes in affected blood vessels. Together, these results suggest that extracellular matrix bound Vegfa might act through PI3K signaling to control EC proliferation in a distinct set of blood vessels during angiogenesis.We would like to thank Reinhild Bussmann, Mona Finch Stephen, Nadine Greer and Bill Vought for excellent fish care. In addition, we would like to thank Roman Tsaryk and Zeenat Diwan for critically reading of the manuscript and Caitlyn Parker for excellent technical assistance. We are grateful to Federica Lunella for help with the mouse retina dissection and immunohistochemistry. We would like to thank William Jones and Mary Mullins for providing the pCS2þ β-galactosidase plasmid. This work was funded by the Max-Planck-Society (A.F.S.), the Deutsche Forschungsgemeinschaft (DFG SI-1374/4-1, DFG SI-1374/5-1 and DFG SI-1374/6-1; A.F.S.) and start-up funds from the Cardiovascular Institute and the Department of Cell and Developmental Biology of the University of Pennsylvania Perelman School of Medicine (A.F.S.). We further acknowledge support from the NIH R01HL152086 (A.F.S.). Work in R.B.’s lab was funded by the Ministerio de Economía, Industría y Competitividad (MEIC: SAF2017-89299-P and RYC-2013-13209) and the European Research Council (ERC-2014-StG – 638028 AngioGenesHD).S

Degradation prediction model for friction in highways

The purpose of this paper is to develop a multiple linear regression model that describes the pavement’s friction behaviour using a degradation evo- lution law that also considers the effects of weather, vertical alignment and traf- fic factors. This study is based on real data obtained from two different highways with an approximate total length of 43 km. These sections present different alignment features (plan/profile), different Annual Average Daily Traffic and are subject- ed to different weather conditions. Nevertheless, both comprise the same type of upper layer. The efficiency of the linear regression model in approaching and explaining da- ta was demonstrated. The most relevant factors involved in the degradation pro- cess of pavements’ friction were identified.Fundação para a Ciência e a Tecnologia (FCT

Biocompatibility of a self-assembled crosslinkable hyaluronic acid nanogel

Hyaluronic acid nanogel (HyA-AT) is a redox sensitive crosslinkable nanogel, obtained through the conjugation of a thiolated hydrophobic molecule to the hyaluronic acid chain. Engineered nanogel was studied for its biocompatibility, including immunocompatibility and hemocompatability. The nanogel did not compromise the metabolic activity or cellular membrane integrity of 3T3, microvascular endothelial cells, and RAW 264.7 cell lines, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase release assays. Also, we didn't observe any apoptotic effect on these cell lines through the Annexin V-FITC test. Furthermore, the nanogel cell internalization was analyzed using murine bone marrow derived macrophages, and the in vivo and ex vivo biodistribution of the Cy5.5 labeled nanogel was monitored using a non-invasive near-infrared fluorescence imaging system. The HyA-AT nanogel exhibits fairly a long half-live in the blood stream, thus showing potential for drug delivery applications.The authors thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/ BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the Project “BioHealth – Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124- FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors would like to acknowledge also the support of FCT for the PhD grant reference SFRH/BD/61516/2009. They would also like to thank Bioimaging department on Molecular Medicine Institute (IMM) in Lisbon, namely Dr José Rino and Dr António Temudo. Also thank the animal facilities in IMM (Lisbon), specially Dr. Dolores Bonaparte and Dr. Joana Marques. Finally, the authors thank Dr Africa Gonzalez and Mercedes Pelletero the performance of the studies on the activation of complement

Prediction of friction degradation in highways with linear mixed models

The development of a linear mixed model to describe the degradation of friction on flexible road pavements to be included in pavement management systems is the aim of this study. It also aims at showing that, at the network level, factors such as temperature, rainfall, hypsometry, type of layer, and geometric alignment features may influence the degradation of friction throughout time. A dataset from six districts of Portugal with 7204 sections was made available by the Ascendi Concession highway network. Linear mixed models with random effects in the intercept were developed for the two-level and three-level datasets involving time, section and district. While the three-level models are region-specific, the two-level models offer the possibility to be adopted to other areas. For both levels, two approaches were made: One integrating into the model only the variables inherent to traffic and climate conditions and the other including also the factors intrinsic to the highway characteristics. The prediction accuracy of the model was improved when the variables hypsometry, geometrical features, and type of layer were considered. Therefore, accurate predictions for friction evolution throughout time are available to assist the network manager to optimize the overall level of road safety.This research was funded by FCT—Fundação para a Ciência e Tecnologia (Foundation for Science and Technology), Grants No. UIDB/04029/2020 and UIDB/00319/2020

Flat clathrin lattices are linked to metastatic potential in colorectal cancer

Clathrin assembles at the cells' plasma membrane in a multitude of clathrin-coated structures (CCSs). Among these are flat clathrin lattices (FCLs), alternative clathrin structures that have been found in specific cell types, including cancer cells. Here we show that these structures are also present in different colorectal cancer (CRC) cell lines, and that they are extremely stable with lifetimes longer than 8 h. By combining cell models representative of CRC metastasis with advanced fluorescence imaging and analysis, we discovered that the metastatic potential of CRC is associated with an aberrant membranous clathrin distribution, resulting in a higher prevalence of FCLs in cells with a higher metastatic potential. These findings suggest that clathrin organization might play an important yet unexplored role in cancer metastasis.The authors would like to thank colleagues from KU Leuven MIP division, especially from the group of Prof. Rocha, for their input and critical questions. We thank Fidler’s lab (MD Anderson Cancer Center) for sharing KM12 model cell lines and Dr. Zhuang for making the EYFP-CLTA plasmid available (Addgene plasmid #20921). We also thank Prof. R. Vitale (Universite´ de Lille) for guidance and feedback on the statistical analysis. This work was funded by the Research Foundation - Flanders (C.C. is recipient of a PhD fellowship for fundamental research, FWO grant number 1121221N. G.S.-F. is recipient of a predoctoral contract, FWO grant number 1193818N), and the AES-ISCIII program to R.B. (PI17CIII/00045 and PI20CIII/00019 grants partially supported by FEDER funds). J.H. acknowledges financial support from the Research Foundation Flanders (FWO grant numbers G0C1821N and ZW15 09-G0H6316N), from the Flemish Government through long-term structural funding Methusalem (CASAS2, Meth/15/04), and from the MPI as a fellow. S.R. acknowledges financial support from KU Leuven (grant numbers KA/20/026 and IDN/20/021).S

Alocação de recursos para aquisição de livros para o Sistema de Bibliotecas da UFPE

O desenvolvimento de coleção em bibliotecas universitárias depende amplamente da existência de uma política coerente de alocação de recursos. O Sistema de Bibliotecas da Universidade Federal de Pernambuco, existente desde 1975, não possui um instrumento que direcione a política de aquisição para suas bibliotecas, principalmente no que se refere à distribuição da verba orçamentaria. Com o objetivo de estabelecer critérios adequados foi feito um estudo sobre alocação de recursos para aquisição de livros para servir de base a todas as bibliotecas do Sistema. Palavras-chave Bibliotecas universitárias. Aquisição bibliográfica. Desenvolvimento de coleções. Recursos orçamentários. Funds allocation for books acquisition for the Libraries System of the Federal University of Pernambuco. Abstract A suitable collection development in university libraries depends strongly on the funds allocation policy applied to it. University Library System of Pernambuco State (Brazil), created in 1975, does not nave any stated acquisition procedure for its libraries, mainly about a rational distribution of book funds among them. In order to fulfíll this gap, a study was carried out to serve as basis for an adequate allocation of resources for books acquisition, which could be used for all libraries of the system. Keywords Collection development Book budget. Book-fund allocation

Publisher Correction: High mitogenic stimulation arrests angiogenesis

The original version of this Article contained errors in Fig. 8. In panel a, the labels ‘VEGF’, ‘Notch’, ‘p21’, and ‘P-ERK’ were inadvertently omitted. This has been corrected in the PDF and HTML versions of the Article

TREATMENT OF COGNITIVE DEFICITS IN ALZHEIMER\u27S DISEASE: A PSYCHOPHARMACOLOGICAL REVIEW

The growing and aging population has contributed to the increased prevalence of Alzheimer\u27s disease (AD) and other types of dementia in the world. AD is a progressive and degenerative brain disease with an onset characterized by episodic memory impairments, although progressive deficits can be observed in several domains including language, executive functions, attention and working memory. The relationship between cognitive impairments and the topography and progression of brain neuropathology is well established. The pathophysiologic mechanisms and processes that underline the course of cognitive and clinical decline have been the theoretical support for the development of pharmacological treatments for AD. Cholinesterase inhibitors (ChEIs) and Nmethyl- D-aspartate (NMDA) antagonists are the main drugs used in the management of global cognitive impairment and several studies also explore the effects of both in specific cognitive measures. Recent research trends also examine the effects of combination therapy using both compounds. This review aims to update practical recommendations for the treatment of global cognitive functioning and specific neurocognitive deficits in AD using ChEIs, NMDA antagonists and combination therapy with both drugs