Edad y tamaño empresarial y ciclo de vida financiero

The aim of this paper is to analyze whether some of the empirical implications of the Berger and Udell's (1998) financial growth cycle hold. We use a sample of 22.842 observations for year 2003 and test several hypothesis through MANOVA analysis. Results show that companies tend to have different financing structures depending on age and size. The hypothesis about equity is not confirmed, because the older the company is the higher tends to be its value, caused by the increasing reserves. On the other hand, the risk of the company decreases with age. Results related to trade credit, short term credit and financing deficit are mixed, not significant or contrary to the considered hypothesis. El objetivo de este trabajo es examinar si se cumplen algunas de las implicaciones empíricas del ciclo de vida financiero planteado por Berger y Udell (1998). Para ello se utiliza una muestra de 22.842 observaciones para el año 2003 y mediante tests MANOVAs se contrastan diversas hipótesis. Los resultados obtenidos muestran que las empresas tienen distintas estructuras financieras dependiendo de la edad y el tamaño. La tendencia general es que a mayor edad, mayor presencia de fondos propios, ocasionada por el fuerte incremento de los beneficios retenidos, siendo este resultado contrario a la hipótesis planteada. Por otro lado, el riesgo asumido por las empresas disminuye con la edad. La evidencia relativa al empleo de crédito comercial, deuda financiera a corto plazo y déficit financiero es mixta, no significativa, o contraria a las hipótesis planteadas, especialmente para el caso del factor edad.Edad, tamaño, ciclo de vida financiero, asimetría informativa, financiación empresarial. Age, size, financial growth cycle, information asymmetries, corporate finance.

Low-gluten, nontransgenic wheat engineered with CRISPR/Cas9

Coeliac disease is an autoimmune disorder triggered in genetically predisposed individuals by the ingestion of gluten proteins from wheat, barley and rye. The a-gliadin gene family of wheat contains four highly stimulatory peptides, of which the 33-mer is the main immunodominant peptide in patients with coeliac. We designed two sgRNAs to target a conserved region adjacent to the coding sequence for the 33-mer in the a-gliadin genes. Twenty-one mutant lines were generated, all showing strong reduction in a-gliadins. Up to 35 different genes were mutated in one of the lines of the 45 different genes identified in the wild type, while immunoreactivity was reduced by 85%. Transgene-free lines were identified, and no off-target mutations have been detected in any of the potential targets. The low-gluten, transgene-free wheat lines described here could be used to produce low-gluten foodstuff and serve as source material to introgress this trait into elite wheat varieties.Ministerio de Economía y Competitividad AGL2013-48946-C3-1-R ; AGL2016-80566-

Análisis de los factores de decaimiento en una repoblación de Pinus halepensis en el Sistema Ibérico zaragozano

Publishe

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License.Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.This work was supported by grants from the Spanish MINECO-ISCIII (PI12/02591, PI12/00624) and FEDER (European Funds for Regional Development); the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León; the Spanish Health Thematic Network of Cooperative Research in Cancer (RTICC RD12/0056/0058 and RD12/0036/0003), and Spanish FIS (PS09/01897 and PS09/00843). AG-G received support from the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León and from the Spanish Society of Hematology and Hemotherapy (SEHH), and EDR from the Spanish Association for Cancer Research (AECC).Peer Reviewe

Fatty Acid Profile Changes During Gradual Soil Water Depletion in Oats Suggests a Role for Jasmonates in Coping With Drought

Although often investigated within the context of plant growth and development and/or seed composition, plant lipids have roles in responses to environment. To dissect changes in lipid and fatty acid composition linked to drought tolerance responses in oats, we performed a detailed profiling of ( > 90) different lipids classes during a time course of water stress. We used two oat cultivars, Flega and Patones previously characterized as susceptible and tolerant to drought, respectively. Significant differences in lipid classes (mono, di and triacylglycerols; [respectively MAG, DAG, and TAG] and free fatty acids [FFA]) and in their fatty acid (FA) composition was observed between cultivars upon drought stress. In Flega there was an increase of saturated FAs, in particular 16:0 in the DAG and TAG fractions. This led to significant lower values of the double bond index and polyunsaturated/saturated ratio in Flega compared with Patones. By contrast, Patones was characterized by the early induction of signaling- related lipids and fatty acids, such as DAGs and linolenic acid. Since the latter is a precursor of jasmonates, we investigated further changes of this signaling molecule. Targeted measurements of jasmonic acid (JA) and Ile-JA indicated early increases in the concentrations of these molecules in Patones upon drought stress whereas no changes were observed in Flega. Altogether, these data suggest a role for jasmonates and specific fatty acids in different lipid classes in coping with drought stress in oat

Web-GIS approach to preventive conservation of heritage buildings

The effective implementation of preventive conservation approaches demands the employment of standardized and robust tools able to integrate the data coming from multiple sources, inspection and diagnosis techniques, as well as to ensure the proper information transfer between expert and non-expert users. Aiming to make a step forward in the state of the art of current conservation approaches, a cutting edge Web-GIS technology resorting to the intuitiveness of 360° panoramas and 3D point clouds in combination with the Internet of Things is presented in this work, demonstrating how physical and digital worlds can be linked for proper documentation and management of cultural heritage. To validate such a pioneering approach, one of the most representative and complex heritage buildings of Spain is used as a case study: the General Historical Library of Salamanca.This work was financed by ERDF funds through the V Sudoe Interreg program within the framework of the HeritageCare project (Ref. SOE1/P5/P0258), by project Patrimonio 5.0 (SA075P17), by FEDER funds through the Competitive Factors Operational Program (COMPETE) and by the Foundation for Science and Technology (FCT) within the scope of projects POCI-01-0145-FEDER-007633. The authors would like to express their gratitude to the personnel from the General Historical Library of the University of Salamanca as well as to the Centre for Computer Graphics of the University of Minho for the web implementation of the platform

Repurposing drugs for highly prevalent diseases: pentoxifylline, an old drug and a new opportunity for diabetic kidney disease

Diabetic kidney disease is one of the most frequent complications in patients with diabetes and constitutes a major cause of end-stage kidney disease. The prevalence of diabetic kidney disease continues to increase as a result of the growing epidemic of diabetes and obesity. Therefore, there is mounting urgency to design and optimize novel strategies and drugs that delay the progression of this pathology and contain this trend. The new approaches should go beyond the current therapy focussed on the control of traditional risk factors such as hyperglycaemia and hypertension. In this scenario, drug repurposing constitutes an economic and feasible approach based on the discovery of useful activities for old drugs. Pentoxifylline is a nonselective phosphodiesterase inhibitor currently indicated for peripheral artery disease. Clinical trials and meta-analyses have shown renoprotection secondary to anti-inflammatory and antifibrotic effects in diabetic patients treated with this old known drug, which makes pentoxifylline a candidate for repurposing in diabetic kidney diseaseThis work was supported by Instituto de Salud Carlos III (ISCIII): PI07/0870, PI15/00298, PI16/02057, PI16/00024, PI19/00035, PI20/00744, PI21/00251, PI21/01037, PI19/00815, DTS18/00032 ISCIII-RETIC REDinREN RD16/0009, and RICORS2040. We acknowledge cofunding by Fondo Europeo de Desarrollo Regional [FEDER], Unión Europea [‘Una forma de hacer Europa’]. J.D.-C. is the recipient of a contract from Miguel Servet Program (CP20/00122) of the ISCIII. A.G.-L. and C.F. are recipients of contracts from Agencia Canaria de Investigación Innovación y Sociedad de la Información del Gobierno de Canarias (ACIISI) (TESIS2021010045 and TESIS2018010110). E.M.-N. is funded by a research contract from REDinREN-ISCIII (RD16/0009/0022). V.G.- T. is supported by Cabildo de Tenerife, TF Innova, Fondo de Desarrollo de Canarias (FDCAN) and Marco Estratégico de Desarrollo Insular (MEDI), in the Agustín de Betancourt programm

Infrared permittivity of the biaxial van der Waals semiconductor α\alpha-MoO3_3 from near- and far-field correlative studies

The biaxial van der Waals semiconductor $\alpha$-phase molybdenum trioxide ($\alpha$-MoO$_3$) has recently received significant attention due to its ability to support highly anisotropic phonon polaritons (PhPs) -infrared (IR) light coupled to lattice vibrations in polar materials-, offering an unprecedented platform for controlling the flow of energy at the nanoscale. However, to fully exploit the extraordinary IR response of this material, an accurate dielectric function is required. Here, we report the accurate IR dielectric function of $\alpha$-MoO$_3$ by modelling far-field, polarized IR reflectance spectra acquired on a single thick flake of this material. Unique to our work, the far-field model is refined by contrasting the experimental dispersion and damping of PhPs, revealed by polariton interferometry using scattering-type scanning near-field optical microscopy (s-SNOM) on thin flakes of $\alpha$-MoO$_3$, with analytical and transfer-matrix calculations, as well as full-wave simulations. Through these correlative efforts, exceptional quantitative agreement is attained to both far- and near-field properties for multiple flakes, thus providing strong verification of the accuracy of our model, while offering a novel approach to extracting dielectric functions of nanomaterials, usually too small or inhomogeneous for establishing accurate models only from standard far-field methods. In addition, by employing density functional theory (DFT), we provide insights into the various vibrational states dictating our dielectric function model and the intriguing optical properties of $\alpha$-MoO$_3$

Sodium-glucose co-transporter-2 inhibitors increase Klotho in patients with diabetic kidney disease: a clinical and experimental study

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) provide cardiorenal protection. However, the molecular mechanisms remain poorly understood. We explored the impact of SGLT2i on Klotho, a kidney-derived protein with antiaging, renal-protective and heart-protective properties. A real world prospective observational study addressed the impact of initiating SGLT2i (canagliflozin, dapagliflozin, empagliflozin) or dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with early diabetic kidney disease (DKD). Serum and urinary soluble Klotho, albuminuria and serum and urinary tumor necrosis factor-alpha (TNFa) were measured. The effect of SGLT2i on Klotho mRNA and protein was explored in vitro in kidney proximal tubular cells stressed with high glucose concentrations to simulate the diabetic milieu, albumin to simulate albuminuria, and the inflammatory cytokine TWEAK to simulate the inflammatory environment in DKD. Baseline urinary Klotho was negatively associated with albuminuria (r − 0.45, P < 0.001) and urinary TNFa (r − 0.40, P < 0.01). Both DPP4i and SGLT2i reduced HbA1c similarly, but only SGLT2i decreased eGFR, albuminuria and urinary TNFa and increased (P < 0.001) serum (5.2 %) and urinary Klotho (38.9 %). Changes in urinary TNFa (β − 0.53, P = 0.001) and albuminuria (β − 0.31, P < 0.05) were independently associated with changes in urinary Klotho (adjusted R2 = 0.54, P < 0.001). Studies in renal tubular cells demonstrated that high glucose, albumin and TWEAK decreased Klotho mRNA expression and protein levels, an effect similarly prevented by SGLT2i. SGLT2i increase Klotho availability in type 2 diabetic patients with poorly controlled diabetes and early DKD, as well as in stressed tubular cells. This effect on Klotho may contribute to the kidney and heart protection afforded by SGLT2iThe authors thank all the study participants, without whom this study would not have been possible. The authors acknowledge the support from Instituto de Salud Carlos III (ISCIII) FIS/Fondos FEDER (PI18/01366, PI19/00815, PI19/00035, PI20/00744, PI21/00251, DTS18/00032), ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064, ISCIII-RETIC REDinREN RD16/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM, Fundacion ´ Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), PIFUN05/18. Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001 and RD21/0005/0013) and SPACKDc PMP21/00109, FEDER funds, Cátedra Mundipharma-UAM of Diabetic Kidney Disease and Cátedra Astrazeneca-UAM of Chronic Kidney Disease and Electrolytes. J.D.C is recipient of a contract from Miguel Servet Programme (CP20/00122), ISCII