Cloning of the PpNHAD1 transporter of Physcomitrella patens, a chloroplast transporter highly conserved in photosynthetic eukaryotic organisms

A cDNA that encodes a transporter from the NHAD family was identified in Physcomitrella patens. Computer-based searches using the amino acid sequence of PpNHAD1 revealed that, in addition to being expressed in flowering plants, highly conserved transporters of this family are expressed in red algae, green algae, mosses, liverworts, and photosynthetic stramenopiles, but not in heterotrophic stramenopiles. A chloroplast transit peptide was detected in PpNHAD1 and in most of the related sequences, indicating that PpNHAD1 is a chloroplast transporter. A PpNHAD1-GFP fusion localized to the chloroplast in Physcomitrella protoplasts, and truncation of the N-terminus of the protein dispersed the fluorescence signal outside the chloroplast. PpNHAD1 did not show functional expression in either yeast or bacterial mutants, but truncated proteins with shorter N-termini, PpNHAD1-1 and PpNHAD1-2, could be functionally expressed in bacteria. PpNHAD1-1 alleviated the Li(+) intolerance of a Na(+)-efflux Escherichia coli mutant at acidic pH values. Both PpNHAD1-1 and PpNHAD1-2 reduced the K(+) requirements of a K(+)-influx E. coli mutant more actively at high pH values. PpNHAD1 seems to be an important transporter that mediates ionic homeostasis in chloroplasts from red algae to flowering plants.     

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.