Artefactos inéditos del paleolítico antiguo hallados en el territorio de Álava

En el presente trabajo se estudia un conjunto de cantos tallados, artefactos sobre lasca, núcleos y productos brutos de talla, en lutita, procedentes de los embalses de Urrúnaga y Ullibarri-Gamboa (Álava). Las características morfotécnicas de los instrumentos los sitúa en una etapa tardía dentro del Achelense Superior

El abrigo de Peña Parda (Laguardia - Álava) y su relleno arqueológico

Se presentan los resultados de las campañas de sondeo desarrolladas en el abrigo de Peña Parda (Laguardia, Álava) durante los años 1997-1998, así como el estudio pormenorizado del ajuar recuperado, que sitúa el yacimiento en una cronología del Calcolítico-Bronce Medio

La actividad pecuaria en la Rioja alavesa durante la prehistoria reciente

Se documenta la actividad pastoril en La Rioja Alavesa, desde el Neolítico, por el análisis de cuevas redil.-----------------The activity pastoril is documented in La Rioja from Álava, from the Neolithic one, for the analysis of sheepfold caves

Antifungal Activity of the Human Uterine Cervical Stem Cells Conditioned Medium (hUCESC-CM) Against Candida albicans and Other Medically Relevant Species of Candida

Background: Candidiasis is a major cause of human morbidity and mortality. Human uterine cervical stem cells conditioned medium (hUCESC-CM) is obtained from stromal stem cells of the cervical transformation zone, which are in permanent contact with a wide array of potential vaginal pathogens. In previous reports we have found that hUCESC-CM has antitumor and antibacterial potential. Since Candida is the most prevalent yeast in the human vagina, it seems plausible that hUCESC-CM might also show activity against it. Methods: In a preliminary step, to evaluate if hUCESC-CM showed any activity at all on Candida growth, in vitro activities of hUCESC-CM against fluconazole-susceptible reference strains of Candida albicans, Candida glabrata, Candida krusei, and Candida parapsilosis were studied with a microdilution method on RPMI 1640, using the BioScreen C microbiological incubator. Each measurement was repeated five times. The same methodology was used subsequently on fluconazole-susceptible and fluconazole-resistant Candida isolates from blood and vagina of those species corresponding to the reference strains of Candida against which activity had been detected in the previous study. Moreover, two fluconazole-resistant clinical isolates of Candida auris from blood and urine were also included. Findings: In vitro inhibitory activity of hUCESC-CM ranged from 57.5 to 96.6% growth-reduction against fluconazole-susceptible reference strains of Candida albicans, Candida glabrata, and Candida parapsilosis. hUCESC-CM also reduced the growth of all fluconazole-susceptible tested vaginal isolates by more than 50%. For fluconazole-resistant isolates, growth-reduction was higher than 67% for Candida albicans, regardless of its origin (vagina or blood). The isolate of Candida auris from urine with a MIC > 128 μ/ml for fluconazole was also significantly inhibited. However, hUCESC-CM was almost inactive against any of the fluconazole-resistant blood isolates of Candida glabrata, Candida parapsilosis, and Candida auris tested. Interpretation: This is the first report about the growth-inhibiting properties of conditioned medium from human stromal stem cells against different species of Candida. Antifungal activity of stromal stem cells depends on their site of origin, being most effective against Candida species most prevalent at that particular location. If confirmed in further studies, these findings might result in a completely new therapeutic approach against superficial and invasive candidiasisCM-A was a recipient of a grant from Fundación Once (Oportunidad al Talento). EM, CM-A, EE, and GQ have received grant support from Consejería de Educación, Universidades e Investigación (GIC15 IT-990-16), Fondo de Investigación Sanitaria (FIS PI11/00203), and UPV/EHU (UFI 11/25)S

Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center

Stone Age Yersinia pestis genomes shed light on the early evolution, diversity, and ecology of plague

The bacterial pathogenYersinia pestisgave rise to devastating outbreaks throughouthuman history, and ancient DNA evidence has shown it afflicted human populations asfar back as the Neolithic.Y. pestisgenomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to itsemergence from aYersinia pseudotuberculosis-like progenitor; however, the number ofreconstructed LNBA genomes are too few to explore its diversity during this criticalperiod of development. Here, we present 17Y. pestisgenomes dating to 5,000 to 2,500y BP from a wide geographic expanse across Eurasia. This increased dataset enabled usto explore correlations between temporal, geographical, and genetic distance. Ourresults suggest a nonflea-adapted and potentially extinct single lineage that persistedover millennia without significant parallel diversification, accompanied by rapid dis-persal across continents throughout this period, a trend not observed in other pathogensfor which ancient genomes are available. A stepwise pattern of gene loss provides fur-ther clues on its early evolution and potential adaptation. We also discover the presenceof theflea-adapted form ofY. pestisin Bronze Age Iberia, previously only identified inin the Caucasus and the Volga regions, suggesting a much wider geographic spread ofthis form ofY. pestis. Together, these data reveal the dynamic nature of plague’s forma-tive years in terms of its early evolution and ecology

The genomic history of the Iberian Peninsula over the past 8000 years

We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula.We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming.We reveal sporadic contacts between Iberia and North Africa by ~2500 BCE and, by ~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry.We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean

Understanding variations in the use of hypofractionated radiotherapy and its specific indications for breast cancer: A mixed-methods study

Background and purpose: Radiation oncology guidelines favour hypofractionated whole-breast radiotherapy (HWBRT) over more conventional schemes in the conservative treatment of breast cancer, but its adoption still varies in clinical practice. This study assessed the patterns of HWBRT adoption in Catalonia (Spain). Material and methods: We used a mixed-methods approach based on an explanatory sequential design, first collecting and analysing quantitative data on HWBRT use (>2.5 Gy per fraction) in 11 public radiotherapy centres (2005-2015) and then performing 25 semi-structured interviews with all department heads and reference radiation oncologist/s. Results: Of the 34,859 patients fulfiling the study criteria over the study period, just 12% were hypofractionated, reaching a percentage of 29% in 2015 (p < 0.001). Our analysis showed a narrowing age gap between patients receiving conventional fractionation and hypofractionation in centres leading adoption. However, there were important differences in clinicians' interpretation of evidence (e.g. regarding the perceived risk of long-term toxicity) and selection of patients for specific indications, both within and between departments. Conclusions: Differences observed in the rate of adoption of HWBRT could not be tackled only using a rational, evidence-based approach. Factors related to the management of radiotherapy departments play a major role in the diffusion of therapeutic strategies

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

La actividad pecuaria en la Rioja alavesa durante la prehistoria reciente

Se documenta la actividad pastoril en La Rioja Alavesa, desde el Neolítico, por el análisis de cuevas redil.-----------------The activity pastoril is documented in La Rioja from Álava, from the Neolithic one, for the analysis of sheepfold caves