Estudio mineralógico de los granates de la Unidad de Fuente Piedra (Sierra Nevada, Cordilleras Béticas)

The Fuente Piedra Unit Includes garnet-bearing metape- liks. The mineralogical sIcibdy of garnets reveals a shift to the alniandine end of the Al-Sp-Pyr. series in imreasing con- ditions of metamorphism.

Self-Assembly Behavior of Amphiphilic Janus Dendrimers in Water: A Combined Experimental and Coarse-Grained Molecular Dynamics Simulation Approach

Indexación: Scopus.Acknowledgments: M.E.E.G. thank the Ph. D. scholarship (251115) from CONACyT. The authors would like to thank: Luis Elizalde-Herrera (CIQA) for his help running the NMR spectra; Gloria Macedo-Raygoza and Miguel J. Beltrán-García (UAG), for their help in the measuring of MALDI-TOF mass spectra; and Maricela Rodríguez-Nieto and Jorge Luis Menchaca (UANL), for their help with the AFM measurements. FDGN thanks to the USA Air Force Office of Scientific Research Awards.Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with hydrophilic and hydrophobic components that self-assemble in water to form a variety of morphologies, including vesicles analogous to liposomes with potential pharmaceutical and medical application. To date, the self-assembly of JDs has not been fully investigated thus it is important to gain insight into its mechanism and dependence on JDs’ molecular structure. In this study, the aggregation behavior in water of a second-generation bis-MPA JD was evaluated using experimental and computational methods. Dispersions of JDs in water were carried out using the thin-film hydration and ethanol injection methods. Resulting assemblies were characterized by dynamic light scattering, confocal microscopy, and atomic force microscopy. Furthermore, a coarse-grained molecular dynamics (CG-MD) simulation was performed to study the mechanism of JDs aggregation. The obtaining of assemblies in water with no interdigitated bilayers was confirmed by the experimental characterization and CG-MD simulation. Assemblies with dendrimersome characteristics were obtained using the ethanol injection method. The results of this study establish a relationship between the molecular structure of the JD and the properties of its aggregates in water. Thus, our findings could be relevant for the design of novel JDs with tailored assemblies suitable for drug delivery systems. © 2018 by the authors.https://www.mdpi.com/1420-3049/23/4/96

Impact of concurrent pregnancy and lactation on maternal nestbuilding, estradiol and progesterone concentrations in rabbits

[EN] We evaluated the impact of concurrent pregnancy and lactation on: nest-building (i.e., digging, straw-carrying, hair-pulling), food intake, milk output, body weight, and the concentration of estradiol and progesterone in blood. Digging was lower in pregnant-lactating (PL) rabbits, compared with pregnant-only (PO) does, on 21-23 d (52±64 vs. 104±86 g, respectively; mean±SD; P<0.05). Straw-carrying was also reduced in PL does on 24-26 d (9±27 vs. 79±94 g; P<0.005), 27-29 (27±56 vs. 99±77 g; P<0.005), and in the total amount of material introduced into the nest box (132±167 vs. 286±217 g; P<0.02). Hair-pulling was expressed by practically all animals. Food intake declined in PO does on the three days preceding parturition (P<0.01) and increased markedly during lactation; this increase was much larger in PL than in lactating-only (LO) rabbits (P<0.01). Milk output was similar between PL and LO does during the first 21 d of lactation but a marked decline in this parameter occurred in PL does from then until 30 d. The differences in nest-building between PL and PO rabbits may be related to the concentrations of estradiol and progesterone on specific days of pregnancy. PL does showed significantly higher estradiol levels than PO animals on pregnancy 1 d (33±13 vs. 23±4 pg/mL; P<0.02) and 21 (34±19 vs. 24±6 pg/mL; P<0.05) and also higher levels of progesterone on pregnancy 1 d (4±5 vs. 1±2 ng/mL; P<0.05). However, PL rabbits had lower levels of progesterone on 7 d (6±3 vs. 9±2 ng/mL; P<0.02) and 14 d (8±3 vs. 11±3 ng/mL; P<0.005) than PO does. Our results indicate that the unique endocrine milieu of PL rabbits has a direct bearing on specific behavioral and physiological phenomena that impact productivity on the farm.González-Mariscal, G.; Gallegos, J.; Sierra-Ramírez, A.; Garza Flores, J. (2009). Impact of concurrent pregnancy and lactation on maternal nestbuilding, estradiol and progesterone concentrations in rabbits. World Rabbit Science. 17(3):145-152. doi:10.4995/wrs.2009.65414515217

“Male effect” and “temporary weaning” in synchronization of post-partum ovarian activity in Pelibuey ewes

To evaluate the response of the “male effect” and “temporary weaning” on the synchronization of post-partum ovarian activity in Pelibuey ewes, an experiment was carried out using 78 Pelibuey ewes with suckling lambs. The ewes were separated from their offspring for 48 hours and randomly assigned to one of four treatments derived from the arrangement of two factors, “male effect” and “temporary weaning”, each at two levels. Treatments were: T1 (n = 20) control ewes, without “male effect” and without “temporary weaning”); T2 (n = 19) ewes without “male effect” and with “temporary weaning”; T3 (n = 20) ewes with “male effect” and without “temporary weaning”; and T4 (n = 19), ewes with “male effect” and with “temporary weaning”. The response to oestrus, return to oestrus, gestation rate and lambing rate were analysed using logistic regression. The onset of oestrus was analysed using survival curves. No significant differences were found for lambing rate and prolificacy among treatments. “Temporary weaning” (T2) and “male effect” (T3) did not influence the response to oestrus, rate and duration of return to oestrus, or gestation rate and fertility, and was similar to the control group (T1). The interaction of “male effect” with “temporary weaning” (T4) increased the response to oestrus, reduced the rate and duration of return to oestrus, and the gestation rate, but increased fertility. Synchronizing post-partum ovarian activity with “male effect” and “temporary weaning” reduces the onset of oestrus and the rate of return to oestrus, but increases the response to oestrus and fecundity in Pelibuey ewes.Keywords: Biostimulation, progestogens, prolificacy, prostaglandins, sucklin

Ellagic Acid Recovery by Solid State Fermentation of Pomegranate Wastes by Aspergillus niger and Saccharomyces cerevisiae : a Comparison

Abstract: Fermentation in solid state culture (SSC) has been the focus of increasing interest because of its potential for industrial applications. In previous studies SSC of pomegranate wastes by Aspergillus niger has been extensively developed and optimized for the recovery of ellagic acid (EA), a high value bioactive. In this study we comparatively investigated the SSC of powdered pomegranate husks by A. niger and Saccharomyces cerevisiae and evaluated the recovery yields of EA by an ultrasound and microwave-assisted 7:3 water/ethanol extraction. Surprisingly enough, the yields obtained by S. cerevisiae fermentation (4% w/w) were found 5-fold higher than those of the A. niger fermented material, with a 10-fold increase with respect to the unfermented material. The EA origin was traced by HPLC analysis that showed a significant decrease in the levels of punicalagin isomers and granatin B and formation of punicalin following fermentation. Other extraction conditions that could warrant a complete solubilization of EA were evaluated. Using a 1:100 solid to solvent ratio and DMSO as the solvent, EA was obtained in 4% yields from S. cerevisiae fermented husks at a high purity degree. Hydrolytic treatment of S. cerevisiae fermented pomegranate husks aorded a material freed of the polysaccharides components that gave recovery yields of EA up to 12% w/w

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

Acessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition

PPARGC1A gene promoter methylation as a biomarker of insulin secretion and sensitivity in response to glucose challenges

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects. Methods: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants. Results: We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / +, KINSSHIP/KINSSHIP, LoF/ +, LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation. Conclusions: Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.</p

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects. Methods: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants. Results: We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / +, KINSSHIP/KINSSHIP, LoF/ +, LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation. Conclusions: Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.</p