Distribution of melanopsin positive neurons in pigmented and albino mice: evidence for melanopsin interneurons in the mouse retina.

Here we have studied the population of intrinsically photosensitive retinal ganglion cells (ipRGCs) in adult pigmented and albino mice. Our data show that although pigmented (C57Bl/6) and albino (Swiss) mice have a similar total number of ipRGCs, their distribution is slightly different: while in pigmented mice ipRGCs are more abundant in the temporal retina, in albinos the ipRGCs are more abundant in superior retina. In both strains, ipRGCs are located in the retinal periphery, in the areas of lower Brn3a(+)RGC density. Both strains also contain displaced ipRGCs (d-ipRGCs) in the inner nuclear layer (INL) that account for 14% of total ipRGCs in pigmented mice and 5% in albinos. Tracing from both superior colliculli shows that 98% (pigmented) and 97% (albino) of the total ipRGCs, become retrogradely labeled, while double immunodetection of melanopsin and Brn3a confirms that few ipRGCs express this transcription factor in mice. Rather surprisingly, application of a retrograde tracer to the optic nerve (ON) labels all ipRGCs, except for a sub-population of the d-ipRGCs (14% in pigmented and 28% in albino, respectively) and melanopsin positive cells residing in the ciliary marginal zone (CMZ) of the retina. In the CMZ, between 20% (pigmented) and 24% (albino) of the melanopsin positive cells are unlabeled by the tracer and we suggest that this may be because they fail to send an axon into the ON. As such, this study provides the first evidence for a population of melanopsin interneurons in the mammalian retina

What do rates of deposition of dental cementum tell us? Functional and evolutionary hypotheses in red deer.

Cementum is a bone connective tissue that provides a flexible attachment for the tooth to the alveolar bone in many mammalian species. It does not undergo continuous remodelling, unlike non-dental bone, which combined with its growth pattern of seasonal layering makes this tissue uniquely suitable as a proxy for tracking changes in body repair investment throughout an animal´s life. We tested functional and sexual selection hypotheses on the rate of cementum deposition related to the highly polygynous mating strategy of red deer. We used a sample of 156 first lower molars from wild Scottish red deer of known age between 1 and 17 years old, approximately balanced by sex and age class. Cementum deposition on the inter-radicular pad increased with age at a constant average rate of 0.26 mm per year, with no significant differences between sexes. Cementum deposition was independent of (i) tooth wear, other than that associated with age, and (ii) enamel and dentine micro-hardness. The results partially supported the hypothesis that the main function of cementum is the repositioning of the tooth to maintain opposing teeth in occlusion. However, teeth that had more wear or males´ teeth that had faster rates of tooth wear than those of females did not present the expected higher rates of cementum deposition

Municipal distribution of ovarian cancer mortality in Spain

<p>Abstract</p> <p>Background</p> <p>Spain was the country that registered the greatest increases in ovarian cancer mortality in Europe. This study describes the municipal distribution of ovarian cancer mortality in Spain using spatial models for small-area analysis.</p> <p>Methods</p> <p>Smoothed relative risks of ovarian cancer mortality were obtained, using the Besag, York and Molliè autoregressive spatial model. Standardised mortality ratios, smoothed relative risks, and distribution of the posterior probability of relative risks being greater than 1 were depicted on municipal maps.</p> <p>Results</p> <p>During the study period (1989–1998), 13,869 ovarian cancer deaths were registered in 2,718 Spanish towns, accounting for 4% of all cancer-related deaths among women. The highest relative risks were mainly concentrated in three areas, i.e., the interior of Barcelona and Gerona (north-east Spain), the north of Lugo and Asturias (north-west Spain) and along the Seville-Huelva boundary (in the south-west). Eivissa (Balearic Islands) and El Hierro (Canary Islands) also registered increased risks.</p> <p>Conclusion</p> <p>Well established ovarian cancer risk factors might not contribute significantly to the municipal distribution of ovarian cancer mortality. Environmental and occupational exposures possibly linked to this pattern and prevalent in specific regions, are discussed in this paper. Small-area geographical studies are effective instruments for detecting risk areas that may otherwise remain concealed on a more reduced scale.</p

Designing and evaluation of sodium selenite nanoparticles in vitro to improve selenium absorption in ruminants

Sodium selenite is used to prevent selenium deficiency known as nutritional muscular dystrophy or white muscle disease. In ruminants, selenium supplements are transformed partiality in insoluble form by ruminal microorganisms and its process decrease the selenium absorption in digestive gastrointestinal. However, the objective in this research was focused in encapsulated sodium selenite to be release into of a pH less than four, similarity to an intestinal environment. It was encapsulated by nanoprecipitation and emulsion–evaporation methods, within polymeric nanoparticles. The effect of these methods, polymer proportion (Eudragit RL and RS) and solvent (ethanol and acetone) on the physicochemical (drug entrapment, polidispersity index (PDI) and z potential) and morphological characteristics (particle morphology and particle size) were evaluated. Particle size from each nanoparticles, formulation ranged from 36.64 to 213.86 nm. Particle size, z potential and PDI increased (P ≤ 0.01) when nanoprecipitation and ethanol were used. No significant differences (P > 0.05) were observed when different polymeric proportions were used. Selenium entrapment was 26% when emulsion–evaporation method was used and 78% with nanoprecipitation. Nanoparticles produced by nanoprecipitation were spherical and had a great variation in particle size; on the other hand, nanoparticles produced by emulsion–evaporation were spherical as well as amorphous and presented a homogeneous nanopartcicle size distribution. The release of selenium from nanoparticles was higher in acid pH (less than 4), this condition may represent a better availability of the mineral in the small intestine

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7473G>A (p.=) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of 3 mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that 4 of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease.info:eu-repo/semantics/publishedVersio

Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster

Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we report the results of two independent inbreeding experiments carried out with two different populations of Drosophila melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but also among segregating alleles in natural populationsWe acknowledge the support by Uvigo Marine Research Centre funded by the “Excellence in Research (INUGA)” Programme from the Regional Council of Culture, Education and Universities, with co-funding from the European Union through the ERDF Operational Programme Galicia 2014-2020. This work was funded by Agencia Estatal de Investigación (AEI) (CGL2016-75904-C2-1-P), Xunta de Galicia (ED431C 2016-037) and Fondos Feder: “Unha maneira de facer Europa.” SD was founded by a predoctoral (FPI) grant from Ministerio de Economía y Competitividad, SpainS

High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

<p>Abstract</p> <p>Background</p> <p>The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory.</p> <p>Methods</p> <p>We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls.</p> <p>Results</p> <p>HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; <it>p </it>= 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, <it>p </it>= 0.00001).</p> <p>Conclusion</p> <p>Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA typing has been performed in order to try to establish an association with malignancy.</p

Anthropic resource exploitation and use of the territory at the onset of social complexity in the Neolithic-Chalcolithic Western Pyrenees: a multi-isotope approach

Carbon (δ13C) and nitrogen (δ15N) stable isotope analyses from bone collagen provide information about the dietary protein input, while strontium isotopes (87Sr/86Sr) from tooth enamel give us data about provenance and potential territorial mobility of past populations. To date, isotopic results on the prehistory of the Western Pyrenees are scarce. In this article, we report human and faunal values of the mentioned isotopes from the Early-Middle Neolithic site of Fuente Hoz (Anuntzeta) and the Late Neolithic/Early Chalcolithic site of Kurtzebide (Letona, Zigoitia). The main objectives of this work are to analyze the dietary and territorial mobility patterns of these populations. Furthermore, as an additional aim, we will try to discuss social ranking based on the isotope data and existing literature on this topic in the region of study. Our results show that, based on the bioavailable Sr values, both purported local and non-local humans were buried together at the sites. Additionally, they suggest similar resource consumption based on C3 terrestrial resources (i.e. ovicaprids, bovids, and suids) as the main part of the protein input. Overall, this study sheds light on how individuals from different backgrounds were still buried together and shared the same dietary lifestyle at a time in the Prehistory of Iberia when social complexities started to appear

Municipal distribution of breast cancer mortality among women in Spain

<p>Abstract</p> <p>Background</p> <p>Spain has one of the lowest rates of breast cancer in Europe, though estimated incidence has risen substantially in recent decades. Some years ago, the Spanish Cancer Mortality Atlas showed Spain as having a heterogeneous distribution of breast cancer mortality at a provincial level. This paper describes the municipal distribution of breast cancer mortality in Spain and its relationship with socio-economic indicators.</p> <p>Methods</p> <p>Breast cancer mortality was modelled using the Besag-York-Molliè autoregressive spatial model, including socio-economic level, rurality and percentage of population over 64 years of age as surrogates of reproductive and lifestyle risk factors. Municipal relative risks (RRs) were independently estimated for women aged under 50 years and for those aged 50 years and over. Maps were plotted depicting smoothed RR estimates and the distribution of the posterior probability of RR>1.</p> <p>Results</p> <p>In women aged 50 years and over, mortality increased with socio-economic level, and was lower in rural areas and municipalities with higher proportion of old persons. Among women aged under 50 years, rurality was the only statistically significant explanatory variable.</p> <p>For women older than 49 years, the highest relative risks were mainly registered for municipalities located in the Canary Islands, Balearic Islands, the Mediterranean coast of Catalonia and Valencia, plus others around the Ebro River. In premenopausal women, the pattern was similar but tended to be more homogeneous. In mainland Spain, a group of municipalities with high RRs were located in Andalusia, near the left bank of the Guadalquivir River.</p> <p>Conclusion</p> <p>As previously observed in other contexts, mortality rates are positively related with socio-economic status and negatively associated with rurality and the presence of a higher proportion of people over age 64 years. Taken together, these variables represent the influence of lifestyle factors which have determined the increase in breast cancer frequency over recent decades. The results for the younger group of women suggest an attenuation of the socio-economic gradient in breast cancer mortality in Spain. The geographical variation essentially suggests the influence of other environmental variables, yet the descriptive nature of this study does not allow for the main determinants to be established.</p