Goat biodiversity in Spain

Goats are located predominantly in the dry Spain specially in Andalusia, Castilla-La Mancha, the Canary Islands, Murcia and Extremadura. In this paper we have analyzed 867 samples of 18 Spanish goat populations from different parts of the Iberian Peninsula (Azpi-Gorri, Blanca de Rasquera, Blanca Andaluza, Blanca Celtibérica, Florida, Malagueña, Murciano-Granadina, Negra Serrana, Payoya and Retinta) and the Balearic (Ibicenca, Mallorquina and Formentera goat) and Canarian Archipelagos (Ajuí, Majorera, Palmera, Tenerife North and Tenerife South). Twenty-three microsatellites have been amplified and the within-breed genetic variation has been calculated through the analysis of the mean number of alleles, heterozygosity and FIS The values of expected heterozygosity (He) per breed ranged from 0.524 to 0.721 in Palmera and Florida, respectively, while the observed heterozygosity (Ho) ranged between 0.515 and 0.705 in Palmera and Retinta, respectively. Goat genetic diversity in Spain is very high, with a mean number of alleles, expected and observed heterozigosities across the breeds of 7.04, 0.668 and 0.621, respectively.La especie caprina se localiza predominantemente en la España seca con gran protagonismo de Andalucía, Castilla-La Mancha, Canarias, Murcia y Extremadura. En este trabajo se analizan 867 muestras de 18 poblaciones caprinas españolas provenientes de diferentes zonas de la Península Ibérica (Azpi-Gorri, Blanca de Rasquera, Blanca Andaluza, Blanca Celtibérica, Florida, Malagueña, Murciano-Granadina, Negra Serrana, Payoya y Retinta) y de los archipiélagos Balear (Ibicenca, Mallorquina y cabra de Formentera) y Canario (Ajuí, Majorera, Palmera, Tinerfeña del Norte y Tinerfeña del Sur). Se amplifican 23 microsatélites de ADN y se determina la variación genética de las razas mediante el análisis del número medio de alelos, la heterocigosis, y el estadístico FIS. Los valores de heterocigosis esperada (He) oscilan entre 0,524 en la raza Palmera y 0,721 en la Florida mientras que la heterocigosis observada (Ho) fluctúa entre 0,515 en la Palmera y 0,705 en la Retinta. En España existe una diversidad genética caprina elevada con valores de número medio de alelos, heterocigosis esperada y observada para todas las razas de 7,04, 0,668 y 0,621 respectivamente

Adenomas hipofisarios no funcionantes: valoración de la invasión, persistencia, recurrencia y del índice de proliferación celular Ki-67

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Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK

The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segureña) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150–154 Mb), Oar6 (4–49 Mb) and Oar13 (68–74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection.Publishe

Associations between pig adiponectin (ADIPOQ) genotype and serum lipid levels are modulated by age-specific modifiers

The adiponectin (ADIPOQ) locus is a positional and functional candidate gene for 2 porcine chromosome 13 (SSC13) QTL influencing cholesterol (CHOL) and low-density lipoprotein (LDL) concentrations in 190-d-old pigs. By sequencing 2.37 kb of the pig ADIPOQ cDNA, we have identified 1 c.*1512G > T 3′ untranslated region polymorphism that has been genotyped in a Duroc pig commercial population with records for serum lipid levels at 45 and 190 d of age. Statistical analysis of the data have revealed significant associations between the ADIPOQ genotype and CHOL (P = 0.0040) and LDL (P = 0.0011) concentrations at 190 d but not at 45 d. In family 3, most of the SSC13 QTL effects on LDL levels at 190 d were explained by the ADIPOQ genotype. We also found an association with triglyceride levels at 45 d (P = 0.0060) but not at 190 d. Measurement of allelic mRNA imbalance demonstrated that the G and T alleles are expressed at very similar levels at muscle and fat tissues, indicating that the c.*1512G > T polymorphism does not affect transcript abundance. As a whole, results obtained in the current work as well as previous data gathered in humans and pigs provide[AU: please confirm change] evidence that the magnitude of associations between blood lipid phenotypes and candidate loci genotypes may vary depending on the age of the individual, therefore suggesting the existence of dynamic genotype × environment interactions changing on a temporal scaleThis work has been funded by grants AGL2007-66707-C02, AGL2010- 22208-C02-01, and AGL2010-22208-C02-02 (Ministerio de Ciencia e Innovación) and CSD 2007-00036 (Ministerio de Ciencia e Innovación, Consolider Ingenio 2010 Program). The authors are indebted to Selección Batallé S.A. for providing the animal material and for their cooperation in the experimental protocol. D. Gallardo and C. Melo were funded with fellowships from the Universitat Autònoma de Barcelona and the Instituto Agronómico Mediterráneo, respectively. A. Zidi received a contractual grant under the framework of CSD 2007-0003

Grey matter atrophy is associated with disability increase in natalizumab-treated patients

Background: Brain volume loss (BVL) is a key outcome in multiple sclerosis (MS) trials. Natalizumab is highly effective on inflammation with moderate impact on atrophy. Objective: To explore BVL in patients receiving natalizumab with an emphasis on grey matter (GM). Methods: We performed a retrospective post hoc analysis of BVL in 38 patients receiving natalizumab for 3 years using longitudinal voxel-based morphometry (VBM) and FreeSurfer. Results: Significant BVL was observed during first year: brain parenchymal fraction (BPF): −1.12% (p  right fronto-parietal cortex, right > left hippocampus and left caudate. FreeSurfer showed significant volume losses in subcortical GM, brainstem and cerebellum, and cortical thinning in the left insula. In the second year, only WMF decrease (−0.6%; p = 0.015) was observed with no VBM changes, although FreeSurfer detected significant volume loss in thalamus, hippocampus and cerebellum. Baseline gadolinium enhancement influenced WMF and BPF changes during the first year, but not GMF. Patients with confirmed Expanded Disability Status Scale (EDSS) worsening at 3 years had lower baseline GMF and left thalamus volume and greater BVL over follow-up. Conclusion: BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability

Brain atrophy 15 years after CIS: Baseline and follow-up clinico-radiological correlations

BACKGROUND: Brain atrophy in multiple sclerosis (MS) patients is present since the very early stages of the disease and it has been related to long-term disability. OBJECTIVE: To estimate brain volume (BV) at 15 years after a clinically isolated syndrome (CIS) and to evaluate its relationship with disease outcomes. METHODS: From a prospective cohort including patients presenting with a CIS, 54 patients with a brain magnetic resonance imaging (MRI) performed 15 years after CIS were included. Brain parenchymal fraction (BPF), grey matter fraction (GMF) and white matter fraction (WMF) at 15-year follow-up were obtained. Regression analyses were conducted to predict BV loss and reaching an Expanded Disability Status Scale (EDSS) of 3.0 in that 15-year period. RESULTS: In multivariable analyses, lower values of BPF and WMF were significantly associated with being male, presenting 3–4 Barkhof criteria at baseline, presenting a second relapse, and with a decision to start treatment. In the multivariable logistic regression analysis, only lower GMF was associated with a greater risk of reaching EDSS 3.0 (odds ratio (OR) = 0.24, p = 0.028). CONCLUSION: Lower BPF and WMF 15 years after CIS are associated with previous markers of inflammatory disease. Lower GMF 15 years after a CIS is associated with an increased risk of reaching an EDSS of 3.0

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study.

BACKGROUNG: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. OBJECTIVE: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. METHODS: In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. RESULTS: There was a significant increase in INL volume in eyes with new MSON during the study (N = 61/1562, β = 0.01 mm(3), p < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005, p = .025). INL volume was independent of disease progression (β = 0.002 mm(3), p = .474). CONCLUSION: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials

The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS

OBJECTIVE: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. METHODS: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). RESULTS: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28–95) versus 7 (1–19) and 3 (1–24) versus 0 (0–1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. CONCLUSION: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS

Catalonia rescaling Spain : is it feasible to accommodate its "stateless citizenship"?

The Spanish nation-state is gradually being rescaled by Catalonia's “secession crisis.” Recently and dramatically, in the aftermath of the “illegal” and “constitutive referendum” that took place on 1 October 2017, 2,286,217 Catalan citizens attempted to exercise the “right to decide” to ultimately become “stateless citizens.” This paper examines this rescaling process that has been forming in Barcelona since 10 July 2010 when 1 million Catalan citizens marched to claim their “right to decide” on secession. This paper concludes that, at present, it is not feasible for the Spanish nation-state to accommodate Catalonia's “stateless citizenship.”

Disability progression markers over 6-12 years in interferon-beta-treated multiple sclerosis patients

Objective: To investigate the association between activity during interferon-beta (IFNβ) therapy and disability outcomes in patients with relapsing–remitting multiple sclerosis (RRMS). Methods: A longitudinal study based on two previously described cohorts of IFNβ-treated RRMS patients was conducted. Patients were classified according to clinical activity after 2 years (clinical cohort) or to clinical and radiological activity after 1 year (magnetic resonance imaging (MRI) cohort). Multivariate Cox models were calculated for early disease activity predicting long-term disability. Results: A total of 516 patients from two different cohorts were included in the analyses. Persistent clinical disease activity during the first 2 years of therapy predicted severe long-term disability (clinical cohort). In the MRI cohort, modified Rio score and no or minimal evidence of disease activity (NEDA/MEDA) did not identify patients with risk of Expanded Disability Status Scale (EDSS) worsening. However, a Rio score ≥ 2 (hazard ratio (HR): 3.3, 95% confidence interval (CI): 1.7–6.4); ≥3 new T2 lesions (HR: 2.9, 95% CI: 1.5–5.6); or ≥2 Gd-enhancing lesions (HR: 2.1, 95% CI: 1.1–4) were able to identify patients with EDSS worsening. Conclusion: Although early activity during IFNβ therapy is associated with poor long-term outcomes, minimal degree of activity does not seem to be predictive of EDSS worsening over 6.7-year mean follow-up