Study of antitumor activity in breast cell lines using silver nanoparticles produced by yeast

In the present article, we describe a study of antitumor activity in breast cell lines using silver nanoparticles (Ag NPs) synthesized by a microbiological method. These Ag NPs were tested for their antitumor activity against MCF7 and T47D cancer cells and MCF10-A normal breast cell line. We analyzed cell viability, apoptosis induction, and endocytosis activity of those cell lines and we observed that the effects of the biosynthesized Ag NPs were directly related with the endocytosis activity. Moreover, Ag NPs had higher inhibition efficacy in tumor lines than in normal lines of breast cells, which is due to the higher endocytic activity of tumor cells compared to normal cells. In this way, we demonstrate that biosynthesized Ag NPs can be an alternative for the treatment of tumors.Support from Universidad Nacional de San Luis, to the Agencia Nacional de Promoción Científica y Tecnológica, from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (Argentina), and from GENYO, Centre for Genomics and Oncological Research: Pfizer-University of Granada, Andalusian Regional Government, Granada, Spain are acknowledged

Novel purine chemotypes with activity against Plasmodium 2 falciparum and Trypanosoma cruzi

Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose–response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.SAF2016-76080-R (Spanish Ministry of Economy (AEI/FEDER, UE))PID2019-110810RB-I00 (Spanish Ministry of Science and Innovation)Generalitat of Catalonia Universities and Research Department, Spain (AGAUR; 2017SGR00924)Carlos III Health Institute (ISCIII)RICET Network for Cooperative Research in Tropical Diseases (ISCIII; RD12/0018/0010)Generalitat of Catalonia Department of Health (PERIS 2016–2010 SLT008/18/00132)Spanish Ministry of Education, Culture, and Sports (FPU grant ref. 14/00818)Spanish Ministry of Science, Innovation, and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S)CERCA Progra

Protein crystallization in short-peptide supramolecular hydrogels: A versatile strategy towards biotechnological composite materials

Protein crystallization in hydrogels has been explored with the main purpose of facilitating the growth of high quality crystals while increasing their size to enhance their manipulation. New avenues are currently being built for the use of protein crystals as source materials to create sensors and drug delivery vehicles, to name just a few. In this sense, short-peptide supramolecular hydrogels may play a crucial role in integrating protein crystals within a wider range of applications. In this article, we show that protein crystallization in short-peptide supramolecular hydrogels is feasible and independent of the type of peptide that forms the hydrogel and/or the protein, although the output is not always the same. As a general trend, it is confirmed that hydrogel fibers are always incorporated within crystals so that novel composite materials for biotechnological applications with enhanced properties are produced.This research was funded by the MICINN (Spain) projects BIO2010-6800 (JAG), CTQ2012-34778 (JJDM), and “Factoría Española de Cristalización” Consolider-Ingenio 2010 (JAG & MCM), and by Junta de Andalucía (Spain) project P12-FQM- 2721 (LAC). EDRF funds JAG, LAC & JMC. JJDM thanks MICINN for a Ramon y Cajal Fellowship and MCM thanks CSIC for her JAE Fellowshi

Influence of the chirality of short peptide supramolecular hydrogels in protein crystallogenesis

For the first time the influence of the chirality of the gel fibers in protein crystallogenesis has been studied. Enantiomeric hydrogels 1 and 2 were tested with model proteins lysozyme and glucose isomerase and a formamidase from B. cereus. Crystallization behaviour and crystal quality of these proteins in both hydrogels are presented and compared.MICINN (Spain) projects BIO2010-16800 (JAG), CTQ-2011.22455 (LAC & JMC), CTQ2012-34778 (JJDM & ALG), “Factoría Española de Cristalización” Consolider-Ingenio 2010 (JAG & MCM) and EDRF Funds (JAG, LAC & JMC), P12-FQM-2721 (LAC) Junta de Andalucía.MINECO,Project No. FIS2013-41821-R

Design and Synthesis of 9-Dialkylamino-6-[(1H-1,2,3-triazol-4-yl)methoxy]-9H-purines

The purine ring is a common structural component of a large variety of biomolecules with important roles in both physiological and pathological processes. The biological ubiquity and versatility of this heterocyclic scaffold makes it a privileged structure in drug design. Consequently, the development of novel purine analogs remains of great interest in the medicinal chemistry field. Here, we report the design and synthesis of a series of 9-dialkylamino-6-[(1H-1,2,3-triazol-4 yl)methoxy]-9H-purines and their intermediates. This series of compounds aims to diversify the chemical space around the purine scaffold in the search towards the discovery of new biologically active small molecules.</p

Pharmaceutically active protein crystals grown in-situ within a hydrogel

The present invention providesa process to manufacture a composition comprising a hydrogel comprising pharmaceutically active protein crystals grown in-situwithin the hydrogel, wherein the pharmaceutically active protein crystals grown in-situhave an average size ofless than 20 microns, which comprises: a. Sequentially blending a pharmaceutically active protein solution in their appropriate buffer composition by using a value of supersaturation in the metastable zone width (MSZW) or nearby the supersolubility curve, with a precipitant solution, wherein acetone is absent, and a gelator solution, b. Inducing the nucleation by lowering the temperature, and c. Storing the resulting mixtureat a constant temperature, preferably at room temperatureat 1 atm.Peer reviewedUniversidad de Granada, Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

YRITYKSEN KASVUSTRATEGIAN SUUNNITTELU

Työ on tehty ulkovalaistuksen asiantuntijayritykselle nimeltä FIXULUX OY, jonka toiminta on käynnistynyt muutamia vuosia sitten. Yritys on vakiinnuttanut asemansa toimialalla ja ajatuksena on kasvattaa ja kehittää liiketoimintaa. Yrityksen päätuotteita ovat valmistajista riippumattomat, puolueettomat valaistussuunnittelu- ja asiantuntijapalvelut kattaen koko ulkovalaistuksen. Työssä kerättiin teoriatietoa liiketoiminnan kehittämisestä ja kasvattamisesta strategisen johtamisen keinoin ja kerätyistä tiedoista koottiin teoriaosuuteen referaatti. Tutkimuksessa selvitettiin mihin asioihin kannattava kasvu mikroyrityksessä voi perustua ja mitkä ovat yrityksen keinot kannattavan kasvun mahdollistamiseksi. Tutkimuksen perusteella mikroyrityksessä kasvu kannattaa perustaa olemassa olevaan osaamiseen, innovaatioihin, asiakaslähtöiseen liiketoimintaan sekä toiminnan sijoittamiseen oikeaan ympäristöön. Yrityksen keinot kannattavan kasvun mahdollistamiseksi ovat tämän tutkimuksen mukaan seuraavat: asiakkuuksien johtaminen, toiminnan ja osaamisen jatkuva kehittäminen, kilpailukykyinen hinnoittelu, ydinliiketoiminnan lähialueelle siirtyminen sekä yritysostot. Teoriapohjaksi on valittu strateginen johtaminen, mutta myös operatiivinen johtaminen nousi tärkeään asemaan työn edetessä. Tässä työssä on hyödynnetty tutkimuksellisen kehitystyön menetelmiä ja lähestymistapana on konstruktiivinen tutkimus. Aineistona on käytetty strategiseen johtamiseen sekä yritystoiminnan kehittämiseen liittyvää kirjallisuutta sekä digitaalisia lähteitä. Konstruktiivisen tutkimuksen päätuloksena tuotettiin kolme kasvuvaihtoehtoa sisältävä palveluliiketoiminnan kasvusuunnitelma. Sisällön perusteella yrityksen johto voi muodostaa oman näkemyksensä, tehdä tarvittavia päätöksiä sekä lähteä kehittämään tarkempaa kasvusuunnitelmaa.This thesis was made as an assignment to an outdoor lighting company called FIXULUX OY which was established a few years ago. The company has established its position in the industry with the idea of expanding and growing its business. The main products of the company are manufacturerindependent and neutral lighting design solutions and expert services throughout all kinds of outdoor lighting. The theory part of this thesis was made by gathering and summarizing information about developing and growing businesses with the help of strategic leadership. Thesis gives answers to questions such as which aspects should be taken into consideration when trying to find profitable growth in a micro sized company and what the means to enable that growth are. Research showed that in a micro sized company growth should be based on existing know-how, innovation, clientbased business and by placing the operations into the right environment. The means to enable profitable growth according to this research are as follows: managing customerships, continuous improvement of operations and know-how, competitive pricing, moving the business close enough to core business areas and business buy-outs. Strategic leadership was selected as the basis of this thesis but approaches from the perspective of operative leadership became equally important once the research progressed. The thesis utilized the research method of development through research with the approach of constructive research. The material used includes literature on strategic leadership and business development as well as digital sources. The main outcome of this thesis is a growth plan for service business including three different approaches for growth. With the help of this content the company management can make up their own opinions, make necessary decisions and start to develop a more precise growth plan

DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain.

The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented global health crisis, with several countries imposing lockdowns to control the coronavirus spread. Important research efforts are focused on evaluating the association of environmental factors with the survival and spread of the virus and different works have been published, with contradictory results in some cases. Data with spatial and temporal information is a key factor to get reliable results and, although there are some data repositories for monitoring the disease both globally and locally, an application that integrates and aggregates data from meteorological and air quality variables with COVID-19 information has not been described so far to the best of our knowledge. Here, we present DatAC (Data Against COVID-19), a data fusion project with an interactive web frontend that integrates COVID-19 and environmental data in Spain. DatAC is provided with powerful data analysis and statistical capabilities that allow users to explore and analyze individual trends and associations among the provided data. Using the application, we have evaluated the impact of the Spanish lockdown on the air quality, observing that NO2, CO, PM2.5, PM10 and SO2 levels decreased drastically in the entire territory, while O3 levels increased. We observed similar trends in urban and rural areas, although the impact has been more important in the former. Moreover, the application allowed us to analyze correlations among climate factors, such as ambient temperature, and the incidence of COVID-19 in Spain. Our results indicate that temperature is not the driving factor and without effective control actions, outbreaks will appear and warm weather will not substantially limit the growth of the pandemic. DatAC is available at https://covid19.genyo.es

Purine derivatives as dapk1 inhibitors

Número de publicación: ES2548927 B1. Número de solicitud: 201400229.Derivados de purina como inhibidores de Dapk-1. La presente invención describe una nueva familia de derivados de purina que actúan como inhibidores selectivos de Dapk1. Se describe también el proceso para la obtención de los compuestos farmacéuticos y su uso como medicamento para el tratamiento o la profilaxis de enfermedades que precisan la inhibición de Dapk1, especialmente para el tratamiento del cáncer.Universidad de Granad