29 research outputs found

    La religión de los Vascones. Una mirada comparativa. Concomitancias y diferencias con la de sus vecinos

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    Comparing the religious beliefs of the Vascons with those of the peoples bordering (vardulos, autrigones, berones, celtiberos and aquitanos) we can state that: a) The Vascons owned quite distinctive and particular beliefs, rather peculiar because their etymology cannot be explained under Indo-European basis and they seem to refer to nature forces or to certain totemic animals, b) According to linguistics the Vascons are closely connected with their northern neighbours; despite unavoidable caution upon etymological interpre- tations, just both of them agree on having gods regarding to nature forces with an “euskaro” name. This is not the same for the rest of the surrounding peoples whose deities can be explained into the Indo-European sphere according to function and etymology. And, c) The native inhabitants of the land are, under sociological terms, those who have preserved these beliefs even in an already romanized background. On the whole, the Hispanic peoples adopted Latin structures and onomastics, though in most cases their autochthonous origin can be traced. These indigenous features are more clearly marked in the peoples from Aquitaine; only one third of them followed the Roman pattern for structures and onomastics.La comparación de las creencias religiosas de los vascones con las de sus vecinos (várdulos, caristos, autrigones, berones, celtíberos y aquitanos) constata: a) que los vascones tuvieron unas creencias peculiares y distintivas: peculiares, porque su etimología no tiene explicación por el indoeuropeo y parecen referirse a fuerzas naturales o a ciertos animales totémicos; b) que lingüísticamente se relacionan estrechamente con sus vecinos septentrionales, ya que ambos pueblos, a pesar de las cautelas insoslayables sobre las interpretaciones etimológicas, coinciden en exclusiva en tener dioses de nombre “éuskaro”, relacionados, además, con las fuerzas de la naturaleza. Muy distinto es el caso de los demás vecinos, cuyas divinidades se explican, tanto etimológica como funcionalmente, en el ámbito indoeuropeo: c) que, sociológicamente, son los autóctonos los que han conservado estas creencias, incluso en un ambiente ya romanizado. Los pueblos hispánicos han adoptado, de forma casi generalizada, la estructura y onomástica latina, pero dejan percibir su origen autóctono en la mayoría de los casos. Los aquitanos presentan un indigenismo mucho más acusado: tan solo un tercio ha adoptado la estructura y onomástica romana

    Diet-sourced carbon-based nanoparticles induce lipid alterations in tissues of zebrafish (Danio rerio) with genomic hypermethylation changes in brain

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    With rising environmental levels of carbon-based nanoparticles (CBNs), there is an urgent need to develop an understanding of their biological effects in order to generate appropriate risk assessment strategies. Herein, we exposed zebrafish via their diet to one of four different CBNs: C60 fullerene (C60), single-walled carbon nanotubes (SWCNT), short multi-walled carbon nanotubes (MWCNTs) or long MWCNTs. Lipid alterations in male and female zebrafish were explored post-exposure in three target tissues (brain, gonads and gastrointestinal tract) using ‘omic’ procedures based in liquid chromatography coupled with mass spectrometry (LC-MS) data files. These tissues were chosen as they are often target tissues following environmental exposure. Marked alterations in lipid species are noted in all three tissues. To further explore CBN-induced brain alterations, Raman microspectroscopy analysis of lipid extracts was conducted. Marked lipid alterations are observed with males responding differently to females; in addition, there also appears to be consistent elevations in global genomic methylation. This latter observation is most profound in female zebrafish brain tissues post-exposure to short MWCNTs or SWCNTs (P < 0.05). This study demonstrates that even at low levels, CBNs are capable of inducing significant cellular and genomic modifications in a range of tissues. Such alterations could result in modified susceptibility to other influences such as environmental exposures, pathology and, in the case of brain, developmental alterations

    A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

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    Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

    A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

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    Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

    Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host: implications for exosome stability and biology

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    Extracellular vesicles (EVs) mediate communication between cells and organisms across all 3 kingdoms of life. Several reports have demonstrated that EVs can transfer molecules between phylogenetically diverse species and can be used by parasites to alter the properties of the host environment. Whilst the concept of vesicle secretion and uptake is broad reaching, the molecular composition of these complexes is expected to be diverse based on the physiology and environmental niche of different organisms. Exosomes are one class of EVs originally defined based on their endocytic origin, as these derive from multivesicular bodies that then fuse with the plasma membrane releasing them into the extracellular environment. The term exosome has also been used to describe any small EVs recovered by high-speed ultracentrifugation, irrespective of origin since this is not always well characterized. Here, we use comparative global lipidomic analysis to examine the composition of EVs, which we term exosomes, that are secreted by the gastrointestinal nematode, Heligmosomoides polygyrus, in relation to exosomes secreted by cells of its murine host. Ultra-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS) analysis reveals a 9- to 62-fold enrichment of plasmalogens, as well as other classes of ether glycerophospholipids, along with a relative lack of cholesterol and sphingomyelin (SM) in the nematode exosomes compared with those secreted by murine cells. Biophysical analyses of the membrane dynamics of these exosomes demonstrate increased rigidity in those from the nematode, and parallel studies with synthetic vesicles support a role of plasmalogens in stabilizing the membrane structure. These results suggest that nematodes can maintain exosome membrane structure and integrity through increased plasmalogens, compensating for diminished levels of other lipids, including cholesterol and SM. This work also illuminates the prevalence of plasmalogens in some EVs, which has not been widely reported and could have implications for the biochemical or immunomodulatory properties of EVs. Further comparative analyses such as those described here will shed light on diversity in the molecular properties of EVs that enable them to function in cross-species communication

    Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial

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    Abstract Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naïve) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.</jats:p

    Diagnosis, monitoring and prevention of exposure-related non-communicable diseases in the living and working environment: DiMoPEx-project is designed to determine the impacts of environmental exposure on human health

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    La religión de los Vascones. Una mirada comparativa. Concomitancias y diferencias con la de sus vecinos

    No full text
    Comparing the religious beliefs of the Vascons with those of the peoples bordering (vardulos, autrigones, berones, celtiberos and aquitanos) we can state that: a) The Vascons owned quite distinctive and particular beliefs, rather peculiar because their etymology cannot be explained under Indo-European basis and they seem to refer to nature forces or to certain totemic animals, b) According to linguistics the Vascons are closely connected with their northern neighbours; despite unavoidable caution upon etymological interpre- tations, just both of them agree on having gods regarding to nature forces with an “euskaro” name. This is not the same for the rest of the surrounding peoples whose deities can be explained into the Indo-European sphere according to function and etymology. And, c) The native inhabitants of the land are, under sociological terms, those who have preserved these beliefs even in an already romanized background. On the whole, the Hispanic peoples adopted Latin structures and onomastics, though in most cases their autochthonous origin can be traced. These indigenous features are more clearly marked in the peoples from Aquitaine; only one third of them followed the Roman pattern for structures and onomastics.La comparación de las creencias religiosas de los vascones con las de sus vecinos (várdulos, caristos, autrigones, berones, celtíberos y aquitanos) constata: a) que los vascones tuvieron unas creencias peculiares y distintivas: peculiares, porque su etimología no tiene explicación por el indoeuropeo y parecen referirse a fuerzas naturales o a ciertos animales totémicos; b) que lingüísticamente se relacionan estrechamente con sus vecinos septentrionales, ya que ambos pueblos, a pesar de las cautelas insoslayables sobre las interpretaciones etimológicas, coinciden en exclusiva en tener dioses de nombre “éuskaro”, relacionados, además, con las fuerzas de la naturaleza. Muy distinto es el caso de los demás vecinos, cuyas divinidades se explican, tanto etimológica como funcionalmente, en el ámbito indoeuropeo: c) que, sociológicamente, son los autóctonos los que han conservado estas creencias, incluso en un ambiente ya romanizado. Los pueblos hispánicos han adoptado, de forma casi generalizada, la estructura y onomástica latina, pero dejan percibir su origen autóctono en la mayoría de los casos. Los aquitanos presentan un indigenismo mucho más acusado: tan solo un tercio ha adoptado la estructura y onomástica romana

    A longitudinal study of queen health in honey bees reveals tissue specific response to seasonal changes and pathogen pressure

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    Abstract The health of honey bee queens is crucial for colony success, particularly during stressful periods like overwintering. To accompany a previous longitudinal study of colony and worker health, we explored niche-specific gut microbiota, host gene expression, and pathogen prevalence in honey bee queens overwintering in a warm southern climate. We found differential gene expression and bacterial abundance with respect to various pathogens throughout the season. Biologically older queens had larger microbiotas, particularly enriched in Bombella and Bifidobacterium. Both Deformed Wing Virus A and B subtypes were highest in the fat body tissue in January, correlating with colony Varroa levels, and Deformed Wing Virus titers in workers. High viral titers in queens were associated with decreased vitellogenin expression, suggesting a potential trade-off between immune function and reproductive capacity. Additionally, we found a complex and dynamic relationship between these viral loads and immune gene expression, indicating a possible breakdown in the coordinated immune response as the season progressed. Our study also revealed a potential link between Nosema and Melissococcus plutonius infections in queens, demonstrating that seasonal opportunism is not confined to just workers. Overall, our findings highlight the intricate interplay between pathogens, metabolic state, and immune response in honey bee queens. Combined with worker and colony-level metrics from the same colonies, our findings illustrate the social aspect of queen health and resilience over the winter dearth
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