Beltrami equations with coefficient in the Sobolev space W1,p

We study the removable singularities for solutions to the Beltrami equation ∂f = µ ∂f, where µ is a bounded function, kµk∞ ≤ K−1 K+1 < 1, and such that µ ∈ W1,p for some p ≤ 2. Our results are based on an extended version of the well known Weyl's lemma, asserting that distributional solutions are actually true solutions. Our main result is that quasiconformal mappings with compactly supported Beltrami coefficient µ ∈ W1,p, 2K2 K2+1 < p ≤ 2, preserve compact sets of σ-finite length and vanishing analytic capacity, even though they need not be bilipschitz

Manufacturing traces and pot-forming processes during the Early Neolithic at Cueva de El Toro (Málaga, Spain, 5280-4780 BCE)

Altres ajuts: Acord transformatiu CRUE-CSICJavier Cámara is a predoctoral researcher with a FI-DGR 2017 grant (No.: 00567) funded by Generalitat de Catalunya. The authors wish to thank Dr. L. Gomart (CNRS, UMR 8215 Trajectoires) for her helpful comments and observations to identify the new technologies discovered in the ongoing researches on prehistoric pottery. The authors also wish to thank the comments and criticisms made by anonymous reviewers, which improved the earliest version of the paper.This paper reports the results of forming processes used in pottery manufacture at La Cueva de El Toro (Málaga, Spain) during the Early Neolithic (5280-4780 cal. BCE). La Cueva de El Toro is one of the most important sites of reference on the southern Iberian Peninsula for providing extensive and systematised data on early farming practices. The identification of manufacturing traces on pottery has enabled the assessment of the variability of forming techniques used by the communities of herders that seasonally inhabited the cave during the Early Neolithic. Forming processes were also compared with characteristic features of pottery products (typology, decorations) that are representative of the first pottery production in this area. Furthermore, this study provides new insights into the distribution of the first pot-forming processes in the south of the Iberian Peninsula, which suggest the use of similar techniques to the forming-sequences documented at other Early Neolithic sites (the use of coils and circular patches) and other forming processes (moulding process and the use of discs) which are still unknown in the Western Mediterranean

Two novel missense mutations in the myostatin gene identified in Japanese patients with Duchenne muscular dystrophy

BACKGROUND: Myostatin is a negative regulator of skeletal muscle growth. Truncating mutations in the myostatin gene have been reported to result in gross muscle hypertrophy. Duchenne muscular dystrophy (DMD), the most common lethal muscle wasting disease, is a result of an absence of muscle dystrophin. Although this disorder causes a rather uniform pattern of muscle wasting, afflicted patients display phenotypic variability. We hypothesized that genetic variation in myostatin is a modifier of the DMD phenotype. METHODS: We analyzed 102 Japanese DMD patients for mutations in the myostatin gene. RESULTS: Two polymorphisms that are commonly observed in Western countries, p.55A>T and p.153K>R, were not observed in these Japanese patients. An uncommon polymorphism of p.164E>K was uncovered in four cases; each patient was found to be heterozygous for this polymorphism, which had the highest frequency of the polymorphism observed in the Japanese patients. Remarkably, two patients were found to be heterozygous for one of two novel missense mutations (p.95D>H and p.156L>I). One DMD patient carrying a novel missense mutation of p.95D>H was not phenotypically different from the non-carriers. The other DMD patient was found to carry both a novel mutation (p.156L>I) and a known polymorphism (p.164E>K) in one allele, although his phenotype was not significantly modified. Any nucleotide change creating a target site for micro RNAs was not disclosed in the 3' untranslated region. CONCLUSION: Our results indicate that heterozygous missense mutations including two novel mutations did not produce an apparent increase in muscle strength in Japanese DMD cases, even in a patient carrying two missense mutations

Microarray-Based Approach Identifies Differentially Expressed MicroRNAs in Porcine Sexually Immature and Mature Testes

MicroRNAs (miRNAs) are short non-coding RNA molecules which are proved to be involved in mammalian spermatogenesis. Their expression and function in the porcine germ cells are not fully understood.We employed a miRNA microarray containing 1260 unique miRNA probes to evaluate the miRNA expression patterns between sexually immature (60-day) and mature (180-day) pig testes. One hundred and twenty nine miRNAs representing 164 reporter miRNAs were expressed differently (p<0.1). Fifty one miRNAs were significantly up-regulated and 78 miRNAs were down-regulated in mature testes. Nine of these differentially expressed miRNAs were validated using quantitative RT-PCR assay. Totally 15,919 putative miRNA-target sites were detected by using RNA22 method to align 445 NCBI pig cDNA sequences with these 129 differentially expressed miRNAs, and seven putative target genes involved in spermatogenesis including DAZL, RNF4 gene were simply confirmed by quantitative RT-PCR.Overall, the results of this study indicated specific miRNAs expression in porcine testes and suggested that miRNAs had a role in regulating spermatogenesis

Genome-Wide Association Study Singles Out SCD and LEPR as the Two Main Loci Influencing Intramuscular Fat Content and Fatty Acid Composition in Duroc Pigs

[EN] Intramuscular fat (IMF) content and fatty acid composition affect the organoleptic quality and nutritional value of pork. A genome-wide association study was performed on 138 Duroc pigs genotyped with a 60k SNP chip to detect biologically relevant genomic variants influencing fat content and composition. Despite the limited sample size, the genome-wide association study was powerful enough to detect the association between fatty acid composition and a known haplotypic variant in SCD (SSC14) and to reveal an association of IMF and fatty acid composition in the LEPR region (SSC6). The association of LEPR was later validated with an independent set of 853 pigs using a candidate quantitative trait nucleotide. The SCD gene is responsible for the biosynthesis of oleic acid (C18:1) from stearic acid. This locus affected the stearic to oleic desaturation index (C18:1/C18:0), C18: 1, and saturated (SFA) and monounsaturated (MUFA) fatty acids content. These effects were consistently detected in gluteus medius, longissimus dorsi, and subcutaneous fat. The association of LEPR with fatty acid composition was detected only in muscle and was, at least in part, a consequence of its effect on IMF content, with increased IMF resulting in more SFA, less polyunsaturated fatty acids (PUFA), and greater SFA/PUFA ratio. Marker substitution effects estimated with a subset of 65 animals were used to predict the genomic estimated breeding values of 70 animals born 7 years later. Although predictions with the whole SNP chip information were in relatively high correlation with observed SFA, MUFA, and C18: 1/C18: 0 (0.48-0.60), IMF content and composition were in general better predicted by using only SNPs at the SCD and LEPR loci, in which case the correlation between predicted and observed values was in the range of 0.36 to 0.54 for all traits. Results indicate that markers in the SCD and LEPR genes can be useful to select for optimum fatty acid profiles of pork.This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO; grants AGL2012-33529 and AGL2015-65846-R).Ros-Freixedes, R.; Gol, S.; Pena, R.; Tor, M.; Ibañez Escriche, N.; Dekkers, J.; Estany, J. (2016). Genome-Wide Association Study Singles Out SCD and LEPR as the Two Main Loci Influencing Intramuscular Fat Content and Fatty Acid Composition in Duroc Pigs. PLoS ONE. 11(3). https://doi.org/10.1371/journal.pone.0152496S113Cameron, N. ., Enser, M., Nute, G. ., Whittington, F. ., Penman, J. ., Fisken, A. ., … Wood, J. . (2000). Genotype with nutrition interaction on fatty acid composition of intramuscular fat and the relationship with flavour of pig meat. Meat Science, 55(2), 187-195. doi:10.1016/s0309-1740(99)00142-4Christophersen, O. A., & Haug, A. (2011). Animal products, diseases and drugs: a plea for better integration between agricultural sciences, human nutrition and human pharmacology. Lipids in Health and Disease, 10(1), 16. doi:10.1186/1476-511x-10-16Ntawubizi, M., Colman, E., Janssens, S., Raes, K., Buys, N., & De Smet, S. (2010). Genetic parameters for intramuscular fatty acid composition and metabolism in pigs1. Journal of Animal Science, 88(4), 1286-1294. doi:10.2527/jas.2009-2355Ros-Freixedes, R., Reixach, J., Tor, M., & Estany, J. (2012). Expected genetic response for oleic acid content in pork1. Journal of Animal Science, 90(12), 4230-4238. doi:10.2527/jas.2011-5063Clop, A., Ovilo, C., Perez-Enciso, M., Cercos, A., Tomas, A., Fernandez, A., … Noguera, J. L. (2003). Detection of QTL affecting fatty acid composition in the pig. Mammalian Genome, 14(9), 650-656. doi:10.1007/s00335-002-2210-7Kim, Y., Kong, M., Nam, Y. J., & Lee, C. (2006). A Quantitative Trait Locus for Oleic Fatty Acid Content on Sus scrofa Chromosome 7. Journal of Heredity, 97(5), 535-537. doi:10.1093/jhered/esl026Sanchez, M.-P., Iannuccelli, N., Basso, B., Bidanel, J.-P., Billon, Y., Gandemer, G., … Le Roy, P. (2007). Identification of QTL with effects on intramuscular fat content and fatty acid composition in a Duroc × Large White cross. BMC Genetics, 8(1), 55. doi:10.1186/1471-2156-8-55Guo, T., Ren, J., Yang, K., Ma, J., Zhang, Z., & Huang, L. (2009). Quantitative trait loci for fatty acid composition in longissimus dorsi and abdominal fat: results from a White Duroc × Erhualian intercross F2population. Animal Genetics, 40(2), 185-191. doi:10.1111/j.1365-2052.2008.01819.xC.M. Dekkers, J. (2012). Application of Genomics Tools to Animal Breeding. Current Genomics, 13(3), 207-212. doi:10.2174/138920212800543057Uemoto, Y., Nakano, H., Kikuchi, T., Sato, S., Ishida, M., Shibata, T., … Suzuki, K. (2011). Fine mapping of porcine SSC14 QTL and SCD gene effects on fatty acid composition and melting point of fat in a Duroc purebred population. Animal Genetics, 43(2), 225-228. doi:10.1111/j.1365-2052.2011.02236.xUemoto, Y., Soma, Y., Sato, S., Ishida, M., Shibata, T., Kadowaki, H., … Suzuki, K. (2011). Genome-wide mapping for fatty acid composition and melting point of fat in a purebred Duroc pig population. Animal Genetics, 43(1), 27-34. doi:10.1111/j.1365-2052.2011.02218.xEstany, J., Ros-Freixedes, R., Tor, M., & Pena, R. N. (2014). A Functional Variant in the Stearoyl-CoA Desaturase Gene Promoter Enhances Fatty Acid Desaturation in Pork. PLoS ONE, 9(1), e86177. doi:10.1371/journal.pone.0086177Ramayo-Caldas, Y., Mercadé, A., Castelló, A., Yang, B., Rodríguez, C., Alves, E., … Folch, J. M. (2012). Genome-wide association study for intramuscular fatty acid composition in an Iberian × Landrace cross1. Journal of Animal Science, 90(9), 2883-2893. doi:10.2527/jas.2011-4900Muñoz, M., Rodríguez, M. C., Alves, E., Folch, J. M., Ibañez-Escriche, N., Silió, L., & Fernández, A. I. (2013). Genome-wide analysis of porcine backfat and intramuscular fat fatty acid composition using high-density genotyping and expression data. BMC Genomics, 14(1), 845. doi:10.1186/1471-2164-14-845Yang, B., Zhang, W., Zhang, Z., Fan, Y., Xie, X., Ai, H., … Ren, J. (2013). Genome-Wide Association Analyses for Fatty Acid Composition in Porcine Muscle and Abdominal Fat Tissues. PLoS ONE, 8(6), e65554. doi:10.1371/journal.pone.0065554Zhang, W., Zhang, J., Cui, L., Ma, J., Chen, C., Ai, H., … Yang, B. (2016). Genetic architecture of fatty acid composition in the longissimus dorsi muscle revealed by genome-wide association studies on diverse pig populations. Genetics Selection Evolution, 48(1). doi:10.1186/s12711-016-0184-2Kim, E.-S., Ros-Freixedes, R., Pena, R. N., Baas, T. J., Estany, J., & Rothschild, M. F. (2015). Identification of signatures of selection for intramuscular fat and backfat thickness in two Duroc populations1. Journal of Animal Science, 93(7), 3292-3302. doi:10.2527/jas.2015-8879Bosch, L., Tor, M., Reixach, J., & Estany, J. (2009). Estimating intramuscular fat content and fatty acid composition in live and post-mortem samples in pigs. Meat Science, 82(4), 432-437. doi:10.1016/j.meatsci.2009.02.013AOAC. 1997. Supplement to AOAC Official Method 996.06: Fat (total, saturated, and monounsaturated) in foods hydrolytic extraction gas chromatographic method. Page 18 in Official Methods of Analysis (16th ed). Association of Official Analytical Chemists, Arlington, VA.ÓVILO, C., FERNÁNDEZ, A., NOGUERA, J. L., BARRAGÁN, C., LETÓN, R., RODRÍGUEZ, C., … TORO, M. (2005). Fine mapping of porcine chromosome 6 QTL and LEPR effects on body composition in multiple generations of an Iberian by Landrace intercross. Genetical Research, 85(1), 57-67. doi:10.1017/s0016672305007330Amills, M., Villalba, D., Tor, M., Mercad, A., Gallardo, D., Cabrera, B., … Estany, J. (2008). Plasma leptin levels in pigs with different leptin and leptin receptor genotypes. Journal of Animal Breeding and Genetics, 125(4), 228-233. doi:10.1111/j.1439-0388.2007.00715.xPurcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., … Sham, P. C. (2007). PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. The American Journal of Human Genetics, 81(3), 559-575. doi:10.1086/519795Bouwman, A. C., Janss, L. L., & Heuven, H. C. (2011). A Bayesian approach to detect QTL affecting a simulated binary and quantitative trait. BMC Proceedings, 5(S3). doi:10.1186/1753-6561-5-s3-s4Legarra, A., Croiseau, P., Sanchez, M., Teyssèdre, S., Sallé, G., Allais, S., … Elsen, J.-M. (2015). A comparison of methods for whole-genome QTL mapping using dense markers in four livestock species. Genetics Selection Evolution, 47(1), 6. doi:10.1186/s12711-015-0087-7Kass, R. E., & Raftery, A. E. (1995). Bayes Factors. Journal of the American Statistical Association, 90(430), 773-795. doi:10.1080/01621459.1995.10476572Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2004). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics, 21(2), 263-265. doi:10.1093/bioinformatics/bth457Wolc, A., Arango, J., Settar, P., Fulton, J. E., O’Sullivan, N. P., Preisinger, R., … Dekkers, J. C. M. (2012). Genome-wide association analysis and genetic architecture of egg weight and egg uniformity in layer chickens. Animal Genetics, 43, 87-96. doi:10.1111/j.1365-2052.2012.02381.xChen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G., … Ma’ayan, A. (2013). Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics, 14(1), 128. doi:10.1186/1471-2105-14-128Rabbit programme. 2012. Available from: http://www.dcam.upv.es/dcia/ablasco/Programas/THE%20PROGRAM%20Rabbit.pdfHu, Z.-L., Park, C. A., & Reecy, J. M. (2015). Developmental progress and current status of the Animal QTLdb. Nucleic Acids Research, 44(D1), D827-D833. doi:10.1093/nar/gkv1233Óvilo, C., Fernández, A., Fernández, A. I., Folch, J. M., Varona, L., Benítez, R., … Silió, L. (2010). Hypothalamic expression of porcine leptin receptor (LEPR), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript (CART) genes is influenced by LEPR genotype. Mammalian Genome, 21(11-12), 583-591. doi:10.1007/s00335-010-9307-1Muñoz, G., Alcázar, E., Fernández, A., Barragán, C., Carrasco, A., de Pedro, E., … Rodríguez, M. C. (2011). Effects of porcine MC4R and LEPR polymorphisms, gender and Duroc sire line on economic traits in Duroc×Iberian crossbred pigs. Meat Science, 88(1), 169-173. doi:10.1016/j.meatsci.2010.12.018Galve, A., Burgos, C., Silió, L., Varona, L., Rodríguez, C., Ovilo, C., & López-Buesa, P. (2012). The effects of leptin receptor (LEPR) and melanocortin-4 receptor (MC4R) polymorphisms on fat content, fat distribution and fat composition in a Duroc×Landrace/Large White cross. Livestock Science, 145(1-3), 145-152. doi:10.1016/j.livsci.2012.01.010UEMOTO, Y., KIKUCHI, T., NAKANO, H., SATO, S., SHIBATA, T., KADOWAKI, H., … SUZUKI, K. (2011). Effects of porcine leptin receptor gene polymorphisms on backfat thickness, fat area ratios by image analysis, and serum leptin concentrations in a Duroc purebred population. Animal Science Journal, 83(5), 375-385. doi:10.1111/j.1740-0929.2011.00963.xHirose, K., Ito, T., Fukawa, K., Arakawa, A., Mikawa, S., Hayashi, Y., & Tanaka, K. (2013). Evaluation of effects of multiple candidate genes (LEP,LEPR,MC4R,PIK3C3, andVRTN) on production traits in Duroc pigs. Animal Science Journal, 85(3), 198-206. doi:10.1111/asj.12134López-Buesa, P., Burgos, C., Galve, A., & Varona, L. (2013). Joint analysis of additive, dominant and first-order epistatic effects of four genes (IGF2,MC4R,PRKAG3andLEPR) with known effects on fat content and fat distribution in pigs. Animal Genetics, 45(1), 133-137. doi:10.1111/age.12091Mackowski, M., Szymoniak, K., Szydlowski, M., Kamyczek, M., Eckert, R., Rozycki, M., & Switonski, M. (2005). Missense mutations in exon 4 of the porcine LEPR gene encoding extracellular domain and their association with fatness traits. Animal Genetics, 36(2), 135-137. doi:10.1111/j.1365-2052.2005.01247.xLi, X., Kim, S.-W., Choi, J.-S., Lee, Y.-M., Lee, C.-K., Choi, B.-H., … Kim, K.-S. (2010). Investigation of porcine FABP3 and LEPR gene polymorphisms and mRNA expression for variation in intramuscular fat content. Molecular Biology Reports, 37(8), 3931-3939. doi:10.1007/s11033-010-0050-1Tyra, M., & Ropka-Molik, K. (2011). Effect of the FABP3 and LEPR gene polymorphisms and expression levels on intramuscular fat (IMF) content and fat cover degree in pigs. Livestock Science, 142(1-3), 114-120. doi:10.1016/j.livsci.2011.07.003Muraoka, O., Xu, B., Tsurumaki, T., Akira, S., Yamaguchi, T., & Higuchi, H. (2003). Leptin-induced transactivation of NPY gene promoter mediated by JAK1, JAK2 and STAT3 in the neural cell lines. Neurochemistry International, 42(7), 591-601. doi:10.1016/s0197-0186(02)00160-2Wood, J. D., Enser, M., Fisher, A. V., Nute, G. R., Sheard, P. R., Richardson, R. I., … Whittington, F. M. (2008). Fat deposition, fatty acid composition and meat quality: A review. Meat Science, 78(4), 343-358. doi:10.1016/j.meatsci.2007.07.019Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., … Guy-Grand, B. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature, 392(6674), 398-401. doi:10.1038/32911Dubern, B., & Clement, K. (2012). Leptin and leptin receptor-related monogenic obesity. Biochimie, 94(10), 2111-2115. doi:10.1016/j.biochi.2012.05.010Lim, K.-S., Kim, J.-M., Lee, E.-A., Choe, J.-H., & Hong, K.-C. (2014). A Candidate Single Nucleotide Polymorphism in the 3′ Untranslated Region of Stearoyl-CoA Desaturase Gene for Fatness Quality and the Gene Expression in Berkshire Pigs. Asian-Australasian Journal of Animal Sciences, 28(2), 151-157. doi:10.5713/ajas.14.0529Saatchi, M., Garrick, D. J., Tait, R. G., Mayes, M. S., Drewnoski, M., Schoonmaker, J., … Reecy, J. M. (2013). Genome-wide association and prediction of direct genomic breeding values for composition of fatty acids in Angus beef cattlea. BMC Genomics, 14(1). doi:10.1186/1471-2164-14-730Chen, L., Ekine-Dzivenu, C., Vinsky, M., Basarab, J., Aalhus, J., Dugan, M. E. R., … Li, C. (2015). Genome-wide association and genomic prediction of breeding values for fatty acid composition in subcutaneous adipose and longissimus lumborum muscle of beef cattle. BMC Genetics, 16(1). doi:10.1186/s12863-015-0290-

Evidence for natural antisense transcript-mediated inhibition of microRNA function

MicroRNAs (miRNAs) have the potential to regulate diverse sets of mRNA targets. In addition, mammalian genomes contain numerous natural antisense transcripts, most of which appear to be non-protein-coding RNAs (ncRNAs). We have recently identified and characterized a highly conserved non-coding antisense transcript for beta-secretase-1 (BACE1), a critical enzyme in Alzheimer's disease pathophysiology. The BACE1-antisense transcript is markedly up-regulated in brain samples from Alzheimer's disease patients and promotes the stability of the (sense) BACE1 transcript. We report here that BACE1-antisense prevents miRNA-induced repression of BACE1 mRNA by masking the binding site for miR-485-5p. Indeed, miR-485-5p and BACE1-antisense compete for binding within the same region in the open reading frame of the BACE1 mRNA. We observed opposing effects of BACE1-antisense and miR-485-5p on BACE1 protein in vitro and showed that Locked Nucleic Acid-antimiR mediated knockdown of miR-485-5p as well as BACE1-antisense over-expression can prevent the miRNA-induced BACE1 suppression. We found that the expression of BACE1-antisense as well as miR-485-5p are dysregulated in RNA samples from Alzheimer's disease subjects compared to control individuals. Our data demonstrate an interface between two distinct groups of regulatory RNAs in the computation of BACE1 gene expression. Moreover, bioinformatics analyses revealed a theoretical basis for many other potential interactions between natural antisense transcripts and miRNAs at the binding sites of the latter

Cryptic Patterning of Avian Skin Confers a Developmental Facility for Loss of Neck Feathering

Vertebrate skin is characterized by its patterned array of appendages, whether feathers, hairs, or scales. In avian skin the distribution of feathers occurs on two distinct spatial levels. Grouping of feathers within discrete tracts, with bare skin lying between the tracts, is termed the macropattern, while the smaller scale periodic spacing between individual feathers is referred to as the micropattern. The degree of integration between the patterning mechanisms that operate on these two scales during development and the mechanisms underlying the remarkable evolvability of skin macropatterns are unknown. A striking example of macropattern variation is the convergent loss of neck feathering in multiple species, a trait associated with heat tolerance in both wild and domestic birds. In chicken, a mutation called Naked neck is characterized by a reduction of body feathering and completely bare neck. Here we perform genetic fine mapping of the causative region and identify a large insertion associated with the Naked neck trait. A strong candidate gene in the critical interval, BMP12/GDF7, displays markedly elevated expression in Naked neck embryonic skin due to a cis-regulatory effect of the causative mutation. BMP family members inhibit embryonic feather formation by acting in a reaction-diffusion mechanism, and we find that selective production of retinoic acid by neck skin potentiates BMP signaling, making neck skin more sensitive than body skin to suppression of feather development. This selective production of retinoic acid by neck skin constitutes a cryptic pattern as its effects on feathering are not revealed until gross BMP levels are altered. This developmental modularity of neck and body skin allows simple quantitative changes in BMP levels to produce a sparsely feathered or bare neck while maintaining robust feather patterning on the body

Interacción entre clima y ocupación humana en la configuración del paisaje vegetal del Parque Nacional de Aigüestortes i Estany de Sant Maurici a lo largo de los últimos 15.000 años

The vegetation of the National Park of Aigüestortes i Estany de St Maurici is the result of an interaction between climate, plant community dynamics and the human occupation of the territory. The OCUPAproject aimed to reconstruct this interaction across the last millennia combining methods from palaeoecology and archaeology. The study focused primarily on the Sant Nicolau valley and built on the multidisciplinary analysis of the sedimentary archive of two lakes (Llebreta and Redó) and a number of archaeological sites located in shelters and outdoors. There is archaeological evidence of human presencesince 9000 yr cal BP, and a continuous record since 7500 yr cal BP. At early stages, humans transformed the surroundings of the shelters occupied and lithic tools indicate contacts with locations far away (i.e.,the Ebro plains). Since more than 3000 years ago, there has been human impact on the vegetation withoutinterruption until present. Initially, the impacts were mostly related to livestock: use of fire to open grazing lands, soil erosion and, during the medieval period, forestry and eutrophication of lakes. The agriculture impact in the lower part of the valley (e.g., Llebreta) occurred about 2100 yr ago, although some cereal grains and tools for harvesting have been found for the Neolithic. In the medieval period, the impact was higher than during the last centuries. In general, the changes in the human land use approximately follow the major changes in climate, but the specific causal link is likely related to the social and cultural dynamics of a broader territory since the Neolithic

Histological and transcriptome-wide level characteristics of fetal myofiber hyperplasia during the second half of gestation in Texel and Ujumqin sheep

<p>Abstract</p> <p>Background</p> <p>Whether myofibers increase with a pulsed-wave mode at particular developmental stages or whether they augment evenly across developmental stages in large mammals is unclear. Additionally, the molecular mechanisms of myostatin in myofiber hyperplasia at the fetal stage in sheep remain unknown. Using the first specialized transcriptome-wide sheep oligo DNA microarray and histological methods, we investigated the gene expression profile and histological characteristics of developing fetal ovine longissimus muscle in Texel sheep (high muscle and low fat), as a myostatin model of natural mutation, and Ujumqin sheep (low muscle and high fat). Fetal skeletal muscles were sampled at 70, 85, 100, 120, and 135 d of gestation.</p> <p>Results</p> <p>Myofiber number increased sharply with a pulsed-wave mode at certain developmental stages but was not augmented evenly across developmental stages in fetal sheep. The surges in myofiber hyperplasia occurred at 85 and 120 d in Texel sheep, whereas a unique proliferative surge appeared at 100 d in Ujumqin sheep. Analysis of the microarray demonstrated that immune and hematological systems' development and function, lipid metabolism, and cell communication were the biological functions that were most differentially expressed between Texel and Ujumqin sheep during muscle development. Pathways associated with myogenesis and the proliferation of myoblasts, such as calcium signaling, chemokine (C-X-C motif) receptor 4 signaling, and vascular endothelial growth factor signaling, were affected significantly at specific fetal stages, which underpinned fetal myofiber hyperplasia and postnatal muscle hypertrophy. Moreover, we identified some differentially expressed genes between the two breeds that could be potential myostatin targets for further investigation.</p> <p>Conclusions</p> <p>Proliferation of myofibers proceeded in a pulsed-wave mode at particular fetal stages in the sheep. The myostatin mutation changed the gene expression pattern in skeletal muscle at a transcriptome-wide level, resulting in variation in myofiber phenotype between Texel and Ujumqin sheep during the second half of gestation. Our findings provide a novel and dynamic description of the effect of myostatin on skeletal muscle development, which contributes to understanding the biology of muscle development in large mammals.</p

Activin signaling as an emerging target for therapeutic interventions

After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-β, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-β ligands, and control the signaling and availability of ligands