New Tools for Embryo Selection: Comprehensive Chromosome Screening by Array Comparative Genomic Hybridization

The objective of this study was to evaluate the usefulness of comprehensive chromosome screening (CCS) using array comparative genomic hybridization (aCGH). The study included 1420 CCS cycles for recurrent miscarriage (n = 203); repetitive implantation failure (n = 188); severe male factor (n = 116); previous trisomic pregnancy (n = 33); and advanced maternal age (n = 880). CCS was performed in cycles with fresh oocytes and embryos (n = 774); mixed cycles with fresh and vitrified oocytes (n = 320); mixed cycles with fresh and vitrified day-2 embryos (n = 235); and mixed cycles with fresh and vitrified day-3 embryos (n = 91). Day-3 embryo biopsy was performed and analyzed by aCGH followed by day-5 embryo transfer. Consistent implantation (range: 40.5–54.2%) and pregnancy rates per transfer (range: 46.0–62.9%) were obtained for all the indications and independently of the origin of the oocytes or embryos. However, a lower delivery rate per cycle was achieved in women aged over 40 years (18.1%) due to the higher percentage of aneuploid embryos (85.3%) and lower number of cycles with at least one euploid embryo available per transfer (40.3%). We concluded that aneuploidy is one of the major factors which affect embryo implantation

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p> <p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p> <p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p> <p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p&gt

Heating and cooling challenges for electric vehicles: A comprehensive experimental study

An efficient mobile air conditioning (MAC) system using a safe and climate-friendly refrigerant is necessary for human comfort, increases the vehicle's energy performance, and reduces fuel/electricity consumption. In the current work, we perform a drop-in experimental comparison for low GWP alternatives to R134a in reversible MAC systems. The study compares two lower global warming potential (GWP) refrigerants, R456A, a non-flammable refrigerant for R134a direct MAC replacement, and R1234yf, an ultra-low GWP and mild flammable refrigerant that is the standard for new MAC systems. The system's operational and energy performance is investigated, simulating a wide range of indoor and outdoor steady-state conditions. The measurements are recorded operating a fully monitored vapour compression test rig with secondary circuits to set the target conditions. In the heating mode (heat pump), the evaporation temperatures are set at −10 ℃, −5 ℃, and 0 ℃, and condensation temperatures at 40 ℃, 50 ℃, and 60 ℃. In cooling mode (air conditioning), the condensation temperatures are 37.5 ℃, 45 ℃, and 52.5 ℃ and are combined with evaporation temperatures of −7.5 ℃, 0 ℃, and 7.5 ℃. In the heating mode, R456A presented a competitive COP to R134a with a reduction of less than 5%, more remarkable at lower evaporation temperatures. In the cooling mode, R456A showed the lowest COP at a low condensation temperature. R456A and R1234yf COP are comparable at a higher condensation temperature, which suits the T3 climate conditions.Funding for open access charge: CRUE-Universitat Jaume

Comprehensive experimental evaluation of R1234yf-based low GWP working fluids for refrigeration and heat pumps

This work presents an experimental comparison for low GWP refrigerants used in vapour compression cooling and heating systems. The study compares three lower global warming potential (GWP) refrigerants (R513A, R516A, and R1234yf) as drop-in refrigerants to replace the hydrofluorocarbon (HFC) R134a. Measurements are taken from a test rig at different steady-state conditions: for the cooling mode, the evaporating temperature is −5 °C, −10 °C and −15 °C, and is combined with two condensing temperatures (32.5 °C and 40 °C), and different internal heat exchanger (IHX) effectiveness. Besides, in the heating mode, the evaporating temperature is 7.5, 15 and 22.5 °C with five condensing temperatures (55 °C to 75 °C, step of 5 °C). In the cooling mode, R513A presented the highest system COP amongst the low GWP alternatives, increasing up to 8%. R516A shows the lowest system COP at the highest evaporation temperature; however, it exhibits the highest COP and capacity at the lowest evaporation temperature. The IHX positively influences the refrigerating effect for all adopted refrigerants. Regarding the heating mode, R513A presents the highest heating capacity with an average 3% increase, whereas R516A shows the lowest results. R513A shows comparable COP to R134a, especially at higher evaporating temperatures.Funding for open access charge: CRUE-Universitat Jaume

Experimental evaluation of the azeotropic mixture R516A as an R134A drop-in alternative for moderately high-temperature heat pumps

The moderately high-temperature heat pump (MHTHP) is a market with a great potential to reduce greenhouse gas emissions from the heating sector. However, future proof MHTHPs cannot be based on hydrofluorocarbons with high global warming potential (GWP). Fourth-generation refrigerants with GWP below 150 are required. This work experimentally investigates the new azeotropic mixture R516A as a drop-in alternative to R134a, with a low GWP (142). Measurements are taken from a test rig at different steady-state operating conditions. The evaporating temperature is 7.5 ºC, 15 ºC and 22.5 ºC, and condensing temperature varies between 55 ºC and 75 ºC, at steps of 5 ºC. R516A presents a lower discharge temperature (average reduction of 7 ºC), which provides a safer operation for the compressor and increases its lifespan. R516A heating capacity reduction is 13.5% on average, with a reduced heating effect and comparable compressor power consumption. R516A shows a 12% COP reduction at higher evaporating temperatures

Experimental drop-in comparison of R516A and R134A for water-to-water refrigeration applications

R134a is still one of the most used hydrofluorocarbons (HFCs) in refrigeration and air conditioning applications. However, it should be phased out in the coming years because of its high global warming potential (GWP). The refrigeration sector needs to find as soon as possible technically suitable alternative refrigerants. R516A is a promising azeotropic mixture at medium-low temperatures. The operational and energetic performance of the lower GWP refrigerant R516A is analysed as a drop-in replacement to R134a. Experimental measurements are taken from in vapour compression test rig at several steady-state refrigeration conditions. The evaporating temperature is -5 ºC, -10 ºC and -15 ºC, and is combined with 32.5 ºC condensing temperature, considering the effect of the internal heat exchanger (IHX) effectiveness. R516A presents a good performance in terms of refrigerating effect and cooling capacity. R516A coefficient of performance (COP) is higher than R134a at the evaporating temperature of -15 ºC

Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease

Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding

Abstract Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection

Complement component 3 (C3) expression in the hippocampus after excitotoxic injury: role of C/EBPβ

[Background] The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor implicated in the control of proliferation, differentiation, and inflammatory processes mainly in adipose tissue and liver; although more recent results have revealed an important role for this transcription factor in the brain. Previous studies from our laboratory indicated that CCAAT/enhancer-binding protein β is implicated in inflammatory process and brain injury, since mice lacking this gene were less susceptible to kainic acid-induced injury. More recently, we have shown that the complement component 3 gene (C3) is a downstream target of CCAAT/enhancer-binding protein β and it could be a mediator of the proinflammatory effects of this transcription factor in neural cells.[Methods] Adult male Wistar rats (8–12 weeks old) were used throughout the study. C/EBPβ+/+ and C/EBPβ–/– mice were generated from heterozygous breeding pairs. Animals were injected or not with kainic acid, brains removed, and brain slices containing the hippocampus analyzed for the expression of both CCAAT/enhancer-binding protein β and C3.[Results] In the present work, we have further extended these studies and show that CCAAT/enhancer-binding protein β and C3 co-express in the CA1 and CA3 regions of the hippocampus after an excitotoxic injury. Studies using CCAAT/enhancer-binding protein β knockout mice demonstrate a marked reduction in C3 expression after kainic acid injection in these animals, suggesting that indeed this protein is regulated by C/EBPβ in the hippocampus in vivo.[Conclusions] Altogether these results suggest that CCAAT/enhancer-binding protein β could regulate brain disorders, in which excitotoxic and inflammatory processes are involved, at least in part through the direct regulation of C3.This work was supported by MINECO, Grant SAF2014-52940-R and partially financed with FEDER funds. CIBERNED is funded by the Instituto de Salud Carlos III. JAM-G was supported by CIBERNED. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

La dhimma o el estatuto legal de los protegidos en la expansión islámica. Su evolución

La dhimma fue un instrumento determinante en la expansión islámica, tratándose de un acuerdo de protección de base coránica para con la “gente del Libro”, que permitió una coexistencia con las comunidades monoteístas autóctonas. Estas gozaron de ciertos privilegios, aunque con unas exigencias y limitaciones vinculadas inherentemente al contexto político en el que se desarrollaron. La situación legal de los protegidos fue, pues, muy dispar en cada una de las etapas y de las regiones de la conquista, deviniendo la dhimma una institución que caló en el comportamiento de la totalidad de la sociedad