Down's syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse

Aims Cardiac malformations are prevalent in trisomies of human chromosome 21 [Down's syndrome (DS)], affecting normal chamber separation in the developing heart. Efforts to understand the aetiology of these defects have been severely hampered by the absence of an accurate mouse model. Such models have proved challenging to establish because synteny with human chromosome Hsa21 is distributed across three mouse chromosomes. None of those engineered so far accurately models the full range of DS cardiac phenotypes, in particular the profound disruptions resulting from atrioventricular septal defects (AVSDs). Here, we present analysis of the cardiac malformations exhibited by embryos of the transchromosomic mouse line Tc(Hsa21)1TybEmcf (Tc1) which contains more than 90% of chromosome Hsa21 in addition to the normal diploid mouse genome. Methods and results Using high-resolution episcopic microscopy and three-dimensional (3D) modelling, we show that Tc1 embryos exhibit many of the cardiac defects found in DS, including balanced AVSD with single and separate valvar orifices, membranous and muscular ventricular septal defects along with outflow tract and valve leaflet abnormalities. Frequencies of cardiac malformations (ranging from 38 to 55%) are dependent on strain background. In contrast, no comparable cardiac defects were detected in embryos of the more limited mouse trisomy model, Dp(16Cbr1-ORF9)1Rhr (Ts1Rhr), indicating that trisomy of the region syntenic to the Down's syndrome critical region, including the candidate genes DSCAM and DYRK1A, is insufficient to yield DS cardiac abnormalities. Conclusion The Tc1 mouse line provides a suitable model for studying the underlying genetic causes of the DS AVSD cardiac phenotype

Ultra high performance liquid chromatography–tandem mass spectrometry method for cyclosporine a quantification in biological samples and lipid nanosystems

Cyclosporine A (CyA) is an immunosuppressant cyclic undecapeptide used for the prevention of organ transplant rejection and in the treatment of several autoimmune disorders. An ultra high performance liquid chromatography–tandem mass spectrometry method (UHPLC–MS/MS) to quantify CyA in lipid nanosystems and mouse biological matrices (whole blood, kidneys, lungs, spleen, liver, heart, brain, stomach and intestine) was developed and fully validated. Chromatographic separation was performed on an Acquity UPLC® BEH C18 column with a gradient elution consisting of methanol and 2 mM ammonium acetate aqueous solution containing 0.1% formic acid at a flow rate of 0.6 mL/min. Amiodarone was used as internal standard (IS). Retention times of IS and CyA were 0.69 min and 1.09 min, respectively. Mass spectrometer operated in electrospray ionization positive mode (ESI+) and multiple reaction monitoring (MRM) transitions were detected, m/z 1220.69 → 1203.7 for CyA and m/z 646 → 58 for IS. The extraction method from biological samples consisted of a simple protein precipitation with 10% trichloroacetic acid aqueous solution and acetonitrile and 5 μL of supernatant were directly injected into the UHPLC–MS/MS system. Linearity was observed between 0.001 μg/mL–2.5 μg/mL (r ≥ 0.99) in all matrices. The precision expressed in coefficient of variation (CV) was below 11.44% and accuracy in bias ranged from −12.78% to 7.99% including methanol and biological matrices. Recovery in all cases was above 70.54% and some matrix effect was observed. CyA was found to be stable in post-extraction whole blood and liver homogenate samples exposed for 6 h at room temperature and 72 h at 4 °C. The present method was successfully applied for quality control of lipid nanocarriers as well as in vivo studies in BALB/c mice

Exploring Health Science Students’ Notions on Organ Donation and Transplantation: A Multicenter Study

The knowledge acquired during university education about organ donation and transplantation (ODT) decisively influences the information future health professionals transmit. This is important in ODT where the participation of the general public is essential to obtain organs. Objective: To determine notions of Spanish medicine and nursing students on ODT and its relationship with attitude toward ODT. Methods and Design: and design. We conducted a sociologic, multicenter, and observational study. The population for our study consisted of medical and nursing students in Spanish universities. Our database was the Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. Our sample consisted of 9598 medical and 10, 566 nursing students (99% confidence interval; precision of ±1%), stratified by geographic area and year of study. Results: The completion rate for our study was 90%. Only 20% (n=3640) of students thought their notions on ODT were good; 41% (n=7531) thought their notions were normal; 36% (n=6550) thought their notions were scarce. Comparing groups, there were differences between those who believed that their notions on ODT were good (44% nursing vs 56% medical students; P < .000), and those who believed it scarce (54% nursing vs 46% medical students; P < .000). Notions on ODT were related with attitude toward the donation of one''s own organs: those who considered their notions were good were more in favor then those who considered it scarce (88% vs 72%; P < .000). Conclusion: Only 20% of Spanish medical and nursing students thought their notions on ODT were good. Having good knowledge is related to a favorable attitude towards ODT. Receiving specific information on the subject could improve their knowledge about ODT during their training

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements