Identifying native animals in crossbred populations: the case of the Sardinian goat population

The aim of this work was to develop a strategy for using a genetic analysis for identifying native animals in regions where local breeds have been crossed with improved breeds and then compare that strategy to the overall morphology and breeding histories of the herds for identifying these animals. The experiment included the Sardinian goat population, which is a crossbred of native animals with the Maltese breed. Whole herds were assigned to Maltese (five herds; 49 animals), crossbred (18 herds; 117 animals) or Sardinian (12 herds; 164 animals) groups. For the genetic analysis, genotypes of 22 microsatellites were determined on 330 animals, and basic measurements of genetic diversity were calculated. Genetic variability in the microsatellites was different in the three groups. High positive F _IS showed that inbreeding existed in the subpopulations. The index of genetic differentiation, Nei's standard genetic distance and Reynolds' genetic distance were calculated and found to be significantly different between the three groups. The Sardinian and Maltese groups were the most distant whereas the crossbred group was closer to the Sardinian group. The proportion of the genome derived from two ancestral populations (native Sardinian and Maltese) was assessed using the structure software. Animals were assigned to three clusters on the basis of native Sardinian thresholds. A good correspondence between the empirical (morphology and breeding histories) and the objective genetic analysis was found. Both approaches indicate the presence of three different subpopulations in the Sardinian goat population.     

Quinazolinones as γ-secretase modulators

Synthesis, SAR and evaluation of styrenyl quinazolinones as novel gamma secretase modulators are presented in this communication. Starting from literature and in-house leads we evaluated a range of quinazolinones which showed good modulation of γ-secretase activity.     

Intra‐specific variability and plasticity influence potential tree species distributions under climate change

Aim To assess the effect of local adaptation and phenotypic plasticity on the potential distribution of species under future climate changes. Trees may be adapted to specific climatic conditions; however, species range predictions have classically been assessed by species distribution models (SDMs) that do not account for intra‐specific genetic variability and phenotypic plasticity, because SDMs rely on the assumption that species respond homogeneously to climate change across their range, i.e. a species is equally adapted throughout its range, and all species are equally plastic. These assumptions could cause SDMs to exaggerate or underestimate species at risk under future climate change. Location The Iberian Peninsula. Methods Species distributions are predicted by integrating experimental data and modelling techniques. We incorporate plasticity and local adaptation into a SDM by calibrating models of tree survivorship with adaptive traits in provenance trials. Phenotypic plasticity was incorporated by calibrating our model with a climatic index that provides a measure of the differences between sites and provenances. Results We present a new modelling approach that is easy to implement and makes use of existing tree provenance trials to predict species distribution models under global warming. Our results indicate that the incorporation of intra‐population genetic diversity and phenotypic plasticity in SDMs significantly altered their outcome. In comparing species range predictions, the decrease in area occupancy under global warming conditions is smaller when considering our survival–adaptation model than that predicted by a ‘classical SDM’ calibrated with presence–absence data. These differences in survivorship are due to both local adaptation and plasticity. Differences due to the use of experimental data in the model calibration are also expressed in our results: we incorporate a null model that uses survival data from all provenances together. This model always predicts less reduction in area occupancy for both species than the SDM calibrated with presence–absence. Main conclusions We reaffirm the importance of considering adaptive traits when predicting species distributions and avoiding the use of occurrence data as a predictive variable. In light of these recommendations, we advise that existing predictions of future species distributions and their component populations must be reconsidered.     

Tissue-specificity of insulin action and resistance

Insulin resistance is the most important pathophysiological feature in many pre-diabetic states. Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion by pancreatic beta cells. The creation of monogenic or polygenic genetically manipulated mice models in a tissue-specific manner was of great help to elucidate the tissue-specificity of insulin action and its contribution to the overall insulin resistance. However, complete understanding of the molecular bases of the insulin action and resistance requires the identification of the intracellular pathways that regulate insulin-stimulated proliferation, differentiation and metabolism. Accordingly, cell lines derived from insulin target tissues such as brown adipose tissue, liver and beta islets lacking insulin receptors or sensitive candidate genes such as IRS-1, IRS-2, IRS-3, IR and PTP1B were developed. Indeed, these cell lines have been also very useful to understand the tissue-specificity of insulin action and inaction.     

An objective scatter index based on double-pass retinal images of a point source to classify cataracts

Purpose

To propose a new objective scatter index (OSI) based in the analysis of double-pass images of a point source to rank and classify cataract patients. This classification scheme is compared with a current subjective system.

Methods

We selected a population including a group of normal young eyes as control and patients diagnosed with cataract (grades NO2, NO3 and NO4) according to the Lens Opacities Classification System (LOCS III). For each eye, we recorded double-pass retinal images of a point source. In each patient, we determined an objective scatter index (OSI) as the ratio of the intensity at an eccentric location in the image and the central part. This index provides information on the relevant forward scatter affecting vision. Since the double-pass retinal images are affected by both ocular aberrations and intraocular scattering, an analysis was performed to show the ranges of contributions of aberrations to the OSI.

Results

We used the OSI values to classify each eye according to the degree of scatter. The young normal eyes of the control group had OSI values below 1, while the OSI for subjects in LOCS grade II were around 1 to 2. The use of the objective index showed some of the weakness of subjective classification schemes. In particular, several subjects initially classified independently as grade NO2 or NO3 had similar OSI values, and in some cases even higher than subjects classified as grade NO4. A new classification scheme based in OSI is proposed.

Conclusions

We introduced an objective index based in the analysis of double-pass retinal images to classify cataract patients. The method is robust and fully based in objective measurements; i.e., not depending on subjective decisions. This procedure could be used in combination with standard current methods to improve cataract patient surgery scheduling.     

Molecular characterization of the region 7q22.1 in splenic marginal zone lymphomas

Splenic marginal zone lymphomas (SMZL) are an uncommon type of B-cell non-Hodgkin's lymphoma (NHL-B) in which no specific chromosomal translocations have been described. In contrast, the most frequent cytogenetic abnormality is the loss of the long arm of chromosome 7 (7q). Previous reports have located this loss in the 7q32 region. In order to better characterize the genomic imbalances in SMZL, molecular studies were carried out in 73 patients with SMZL. To gain insight into the mapping at 7q a tiling array was also used. The results confirmed the loss of 7q as the most frequent change. In addition, several abnormalities, including 4q22.1, 1q21.3-q22, 6q25.3, 20q13.33, 3q28, 2q23.3-q24.1 and 17p13, were also present. A loss of 7q22.1 at 99925039-101348479 bp was observed in half of the cases. The region of 7q22.1 has not previously been characterised in SMZL. Our results confirmed the presence of a new region of loss on chromosome 7 in these NHL.