Heldu eta gazteen arteko ezberdintasunak gaztelerako generoaren hautuan euskaragaztelera kode txandakatze kasuetan. Ikerketa proposamena

Lan honen helburu nagusia ikerketa proposamen bat egitea da. Ikerketa proposamen horretan euskara- gaztelera kode txandakatzearen kasuan, gaztelerazko perpausak generoaren markapena eskatzen duen kasuetan, generoaren hautua nolakoa den heldu eta gazteen artean alderatu nahi da. Proposamen hau beste ikerketa batetan oinarritua egongo da, Parafita et al. (2015), bertan gazteen kode txandakatze kasuetan generoaren hautua nolakoa den eta zein kasutan egiten den ikertzen da. Ikerketa proposamen honetan, lehenik eta behin kode txandakatzearen fenomenoa zertan datzan azaltzen da eta historian zehar izan duen fama txarra gainditzeko zenbait autoreren esanak biltzen dira. Horrez gain, kode txandakatzearen kasua Euskal Herriko elebidunekin (euskara-gaztelera edo euskara-frantsesa) landu duten zenbait autoreren lanak aipatzen dira, batez ere, ondorengo ikerketa proposamena hobeto ulertzen lagunduko dutenak Garrantzi handia emango zaio adinari lan honetan, izan ere, lanaren funts nagusia gazteen kode txandakatzeari buruzko ikerketa bat helduen kasura moldatzea izango da eta hori ikertzeko proposamena egitea. Ikerketa proposamen honen funtsa generoan datza; Euskararen kasuan, hitanoaren kasua ezik (egon nauk(m) / naun (f)), Izen-adjektibo-det kategoria nominaletan generoa ez da morfologikoki markatzen, baina, gaztelerarekin ukipenean dagoenean sortzen diren kode txandakatze kasuetan, gaztelerazko perpaus baten erdian euskarazko izen bat agertzen denean, berez generorik ez duen euskarazko hitz hori gaztelerazko zein generorekin lotzen duen izen bakoitza jakin nahi da eta hautu hori egiterako orduan zein izan den faktore nagusia. Lan honetan bi faktorez hitz egiten da: bata marka morfo-fonologikoa, alegia, -a euskarazko determinataile markak gaztelerazko femeninoaren markarekin duen antzekotasunak, -a.z amaitzen diren euskal hitzak, determinatuak, gaztelerazko femeninorantz bideratzea genero hautua edota analogikoa dena, hautu fonologikoa euskararen kasuan zenbait ikerketaren ondoriotan oso zabaldua dagoena da. Bigarrena, adibidez, analogiko bezala izendatua, ingelera-gaztelera kode txandakatze kasuetan maskulinoranzko hautura eramaten duena omen da, adibididez, Poplack et al.en (1982) esanetan. Ikerketa proposamen honetan helduen kode txandakatze kasuetan genero hautua egiten denean zein faktorek duten garrantzia handiena ikusi nahi da, ondoren ikerketa originalean gazteekin lortutako datuekin alderatu ahal izateko. Parafita et al.-en (2015) ikerketa hiru ariketak osatzen dute: Lehena hizketa espontaneotik jasotako datuak, bigarrena ariketa semi-esperimentala egiten da, ikerlariak proposatutako jolas baten bidez lortzea corpusa, jolas hau ikerketarako beharrezko diren perpausak jasotzeko egokitua egongo dena, eta azkenik kode txandakatzean onarpen maila handiena duten perpausak bilatu nahi dira, beti ere, ikerketa proposamena oinarritzen den parametroetan, alegia, generoaren hautuan euskara-gaztelera kode txandakatze kasuetan . Ikerketa proposamen honetan ere hiru ariketa horiek aurkeztu eta lanerako moldatuko dira ahalik eta datu gehien eta esanguratsuenak jaso ahal izateko, amaieran Parafita et al. (2015) ikerketa lanean 25 urte inguruko gazteekin egindako lanean ateratako emaitza eta ondorioekin alderatzeko helduekin (40-60 urte arteko pertsonak) ateratako datuak

Heldu eta gazteen arteko ezberdintasunak gaztelerako generoaren hautuan euskaragaztelera kode txandakatze kasuetan. Ikerketa proposamena

Lan honen helburu nagusia ikerketa proposamen bat egitea da. Ikerketa proposamen horretan euskara- gaztelera kode txandakatzearen kasuan, gaztelerazko perpausak generoaren markapena eskatzen duen kasuetan, generoaren hautua nolakoa den heldu eta gazteen artean alderatu nahi da. Proposamen hau beste ikerketa batetan oinarritua egongo da, Parafita et al. (2015), bertan gazteen kode txandakatze kasuetan generoaren hautua nolakoa den eta zein kasutan egiten den ikertzen da. Ikerketa proposamen honetan, lehenik eta behin kode txandakatzearen fenomenoa zertan datzan azaltzen da eta historian zehar izan duen fama txarra gainditzeko zenbait autoreren esanak biltzen dira. Horrez gain, kode txandakatzearen kasua Euskal Herriko elebidunekin (euskara-gaztelera edo euskara-frantsesa) landu duten zenbait autoreren lanak aipatzen dira, batez ere, ondorengo ikerketa proposamena hobeto ulertzen lagunduko dutenak Garrantzi handia emango zaio adinari lan honetan, izan ere, lanaren funts nagusia gazteen kode txandakatzeari buruzko ikerketa bat helduen kasura moldatzea izango da eta hori ikertzeko proposamena egitea. Ikerketa proposamen honen funtsa generoan datza; Euskararen kasuan, hitanoaren kasua ezik (egon nauk(m) / naun (f)), Izen-adjektibo-det kategoria nominaletan generoa ez da morfologikoki markatzen, baina, gaztelerarekin ukipenean dagoenean sortzen diren kode txandakatze kasuetan, gaztelerazko perpaus baten erdian euskarazko izen bat agertzen denean, berez generorik ez duen euskarazko hitz hori gaztelerazko zein generorekin lotzen duen izen bakoitza jakin nahi da eta hautu hori egiterako orduan zein izan den faktore nagusia. Lan honetan bi faktorez hitz egiten da: bata marka morfo-fonologikoa, alegia, -a euskarazko determinataile markak gaztelerazko femeninoaren markarekin duen antzekotasunak, -a.z amaitzen diren euskal hitzak, determinatuak, gaztelerazko femeninorantz bideratzea genero hautua edota analogikoa dena, hautu fonologikoa euskararen kasuan zenbait ikerketaren ondoriotan oso zabaldua dagoena da. Bigarrena, adibidez, analogiko bezala izendatua, ingelera-gaztelera kode txandakatze kasuetan maskulinoranzko hautura eramaten duena omen da, adibididez, Poplack et al.en (1982) esanetan. Ikerketa proposamen honetan helduen kode txandakatze kasuetan genero hautua egiten denean zein faktorek duten garrantzia handiena ikusi nahi da, ondoren ikerketa originalean gazteekin lortutako datuekin alderatu ahal izateko. Parafita et al.-en (2015) ikerketa hiru ariketak osatzen dute: Lehena hizketa espontaneotik jasotako datuak, bigarrena ariketa semi-esperimentala egiten da, ikerlariak proposatutako jolas baten bidez lortzea corpusa, jolas hau ikerketarako beharrezko diren perpausak jasotzeko egokitua egongo dena, eta azkenik kode txandakatzean onarpen maila handiena duten perpausak bilatu nahi dira, beti ere, ikerketa proposamena oinarritzen den parametroetan, alegia, generoaren hautuan euskara-gaztelera kode txandakatze kasuetan . Ikerketa proposamen honetan ere hiru ariketa horiek aurkeztu eta lanerako moldatuko dira ahalik eta datu gehien eta esanguratsuenak jaso ahal izateko, amaieran Parafita et al. (2015) ikerketa lanean 25 urte inguruko gazteekin egindako lanean ateratako emaitza eta ondorioekin alderatzeko helduekin (40-60 urte arteko pertsonak) ateratako datuak

Skin-Derived Precursor Cells as an In Vitro Modelling Tool for the Study of Type 1 Neurofibromatosis

The most characteristic feature of neurofibromatosis type 1 (NF1) is the development of neurofibromas. It has been suggested that these tumors are caused by somatic inactivation of the wild-type NF1 allele, but the cell that originally suffers this mutation remains controversial. Several lines of evidence support the clonal origin of these tumors, and it has been recently suggested that skin-derived precursor cells (SKPs) could be the cell of origin of dermal neurofibromas. Nullizygous (NF1−/−) SKPs do give rise to neurofibromas when transplanted to heterozygous mice. Moreover, a nullizygous population of cells that is S100β negative is present in human neurofibromas, and NF1+/− multipotent progenitor cells are seemingly recruited to the tumor. This evidence supports the neurofibroma stem cell hypothesis and a putative involvement of SKPs in the aetiopathogenesis of the disease, suggesting that SKPs could become a valuable tool for the in vitro study of NF1

Time is ticking faster for long genes in aging

Recent studies of aging organisms have identified a systematic phenomenon, characterized by a negative correlation between gene length and their expression in various cell types, species, and diseases. We term this phenomenon gene-length-dependent transcription decline (GLTD) and suggest that it may represent a bottleneck in the transcription machinery and thereby significantly contribute to aging as an etiological factor. We review potential links between GLTD and key aging processes such as DNA damage and explore their potential in identifying disease modification targets. Notably, in Alzheimer's disease, GLTD spotlights extremely long synaptic genes at chromosomal fragile sites (CFSs) and their vulnerability to postmitotic DNA damage. We suggest that GLTD is an integral element of biological aging.</p

Time is ticking faster for long genes in aging

Recent studies of aging organisms have identified a systematic phenomenon, characterized by a negative correlation between gene length and their expression in various cell types, species, and diseases. We term this phenomenon gene-length-dependent transcription decline (GLTD) and suggest that it may represent a bottleneck in the transcription machinery and thereby significantly contribute to aging as an etiological factor. We review potential links between GLTD and key aging processes such as DNA damage and explore their potential in identifying disease modification targets. Notably, in Alzheimer's disease, GLTD spotlights extremely long synaptic genes at chromosomal fragile sites (CFSs) and their vulnerability to postmitotic DNA damage. We suggest that GLTD is an integral element of biological aging.</p

The puzzling situation of hospital exemption for advanced therapy medicinal products in Europe and stakeholders' concerns

N/AIn Europe, advanced therapy medicinal products (ATMPs), including cell and gene medicinal products , tissue-engineered products and combined ATMPs, are governed by Directive 2001/ 83/EC and Regulation 726/2004, amended by Regulation 1394/2007, which sets specific rules concerning their centralized marketing authorization (MA), supervision and pharmacovigilance. Nevertheless, ATMPs not intended to be marketed and not industrially prepared are beyond the scope of Directive 2001/83/EC, according to article 28 of Regulation 1394/2007. This is commonly called “hospital exemption” (HE) and is restricted to any ATMP “which is prepared on a non-routine basis according to specific quality standards, and used within the same Member State in a hospital under the exclusive professional responsibility of amedical practitioner, in order to comply with an individual medical prescription for a custom-made product for an individual patient.” Member States must ensure that the manufacture of ATMPs under HE is authorized by the competent national authority and that traceability, pharmacovigilance and specific quality standards are equivalent to those applying to ATMPs granted centralized MA

Triku: a feature selection method based on nearest neighbors for single-cell data

Abstract BACKGROUND: Feature selection is a relevant step in the analysis of single-cell RNA sequencing datasets. Most of the current feature selection methods are based on general univariate descriptors of the data such as the dispersion or the percentage of zeros. Despite the use of correction methods, the generality of these feature selection methods biases the genes selected towards highly expressed genes, instead of the genes defining the cell populations of the dataset. RESULTS: Triku is a feature selection method that favors genes defining the main cell populations. It does so by selecting genes expressed by groups of cells that are close in the k-nearest neighbor graph. The expression of these genes is higher than the expected expression if the k-cells were chosen at random. Triku efficiently recovers cell populations present in artificial and biological benchmarking datasets, based on adjusted Rand index, normalized mutual information, supervised classification, and silhouette coefficient measurements. Additionally, gene sets selected by triku are more likely to be related to relevant Gene Ontology terms and contain fewer ribosomal and mitochondrial genes. CONCLUSION: Triku is developed in Python 3 and is available at https://github.com/alexmascension/triku.This work was supported by grants from Instituto de Salud Carlos III (AC17/00012 and PI19/01621), cofunded by the Euro- pean Union (European Regional Development Fund/European Sci- ence Foundation, Investing in your future) and the 4D-HEALING project (ERA-Net program EracoSysMed, JTC-2 2017); Diputación Foral de Gipuzkoa, and the Department of Economic Devel- opment and Infrastructures of the Basque Government (KK- 2019/00006, KK-2019/00093); European Union FET project Cir- cular Vision (H2020-FETOPEN, Project 899417), Ministry of Sci- ence and Innovation of Spain; and PID2020-119715GB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe. A.M.A. was supported by a Basque Govern- ment Postgraduate Diploma fellowship (PRE_2020_2_0081), and O.I.S. was supported by a Postgraduate Diploma fellowship from la Caixa Foundation (identification document 100010434; code LCF/BQ/IN18/11660065)

Role of bulge epidermal stem cells and TSLP signaling in psoriasis

Psoriasis is a common inflammatory skin disease involving a cross-talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF-SCs) in psoriasis is not well defined. Here, we show reduced expression of c-JUN and JUNB in bulge HF-SCs in patients with scalp psoriasis. Using lineage tracing in mouse models of skin inflammation with inducible deletion of c-Jun and JunB, we found that mutant bulge HF-SCs initiate epidermal hyperplasia and skin inflammation. Mechanistically, thymic stromal lymphopoietin (TSLP) was identified in mutant cells as a paracrine factor stimulating proliferation of neighboring non-mutant epidermal cells, while mutant inter-follicular epidermal (IFE) cells are lost over time. Blocking TSLP in psoriasis-like mice reduced skin inflammation and decreased epidermal proliferation, VEGFα expression, and STAT5 activation. These findings unravel distinct roles of HF-SCs and IFE cells in inflammatory skin disease and provide novel mechanistic insights into epidermal cell interactions in inflammation.We thank Drs. M. Serrano and M. Perez-Moreno for the Gt(ROSA)26Sortrn4(ACTB-tdTomato,-EGFP)Luo/J and K15-Cre-PGR mouse lines. We are very grateful to Drs. M. Perez-Moreno, F. Real, O. Uluckan, L. Bakiri and the laboratory members of the Sibilia and Wagner groups for critical reading of the manuscript and valuable suggestions. We thank V. Bermeo, G. Medrano, S. Leceta, O. Grana, and M. Perez for their technical help and IT support. We acknowledge R. Paus laboratory members for the shipment of hair follicle samples. N.G.L. received funding from the People programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no 608765. A.I is funded by the Institute of Health Carlos III (PI16/01430). The Wagner laboratory was funded by a grant from the Spanish Ministry of Economy and competitiveness (SAF2015-70857RE, cofounded by the European Regional Development Fund) and is supported by the ERC (ERC-AdG 2016 CSI-Fun).S

Physicochemical and Biological Performance of Aloe Vera-Incorporated Native Collagen Films

Collagen was obtained from porcine skin by mechanical pretreatments with the aim of preserving the triple helix structure of native collagen, which was indirectly corroborated by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) results. Moreover, aloe vera (AV), with inherent biological properties, was incorporated into collagen film formulations, and films were prepared by compression and characterized to assess their suitability for biomedical applications. SEM images showed that the fibrillar structure of collagen changed to a rougher structure with the addition of AV, in accordance with the decrease in the lateral packaging of collagen chains observed by XRD analysis. These results suggested interactions between collagen and AV, as observed by FTIR. Considering that AV content higher than 20 wt % did not promote further interactions, this formulation was employed for biological assays and the suitability of AV/collagen films developed for biomedical applications was confirmed.This research was funded by the Basque Government, grant number KK-2019/00006

A neural extracellular matrix-based method for in vitro hippocampal neuron culture and dopaminergic differentiation of neural stem cells

BACKGROUND: The ability to recreate an optimal cellular microenvironment is critical to understand neuronal behavior and functionality in vitro. An organized neural extracellular matrix (nECM) promotes neural cell adhesion, proliferation and differentiation. Here, we expanded previous observations on the ability of nECM to support in vitro neuronal differentiation, with the following goals: (i) to recreate complex neuronal networks of embryonic rat hippocampal cells, and (ii) to achieve improved levels of dopaminergic differentiation of subventricular zone (SVZ) neural progenitor cells. METHODS: Hippocampal cells from E18 rat embryos were seeded on PLL- and nECM-coated substrates. Neurosphere cultures were prepared from the SVZ of P4-P7 rat pups, and differentiation of neurospheres assayed on PLL- and nECM-coated substrates. RESULTS: When seeded on nECM-coated substrates, both hippocampal cells and SVZ progenitor cells showed neural expression patterns that were similar to their poly-L-lysine-seeded counterparts. However, nECM-based cultures of both hippocampal neurons and SVZ progenitor cells could be maintained for longer times as compared to poly-L-lysine-based cultures. As a result, nECM-based cultures gave rise to a more branched neurite arborization of hippocampal neurons. Interestingly, the prolonged differentiation time of SVZ progenitor cells in nECM allowed us to obtain a purer population of dopaminergic neurons. CONCLUSIONS: We conclude that nECM-based coating is an efficient substrate to culture neural cells at different stages of differentiation. In addition, neural ECM-coated substrates increased neuronal survival and neuronal differentiation efficiency as compared to cationic polymers such as poly-L-lysine