Scleral fixation of a novel modified, injected canine intraocular lens by haptic capture, in 17 dogs.

INTRODUCTION: The aims of lens removal surgery are to re-establish or preserve both a clear visual axis and emmetropic vision. Trans-scleral intraocular lens (IOL) fixation has been described in cases where lens capsule instability precludes the insertion of a prosthetic intraocular lens into the lens capsule. Previous techniques have necessitated enlargement of the corneal incision to accommodate either a rigid polymethylmethacrylate IOL or an acrylic foldable IOL inserted using forceps. This paper reports the modification of an endocapsular IOL to be used as an injectable suture-fixated IOL introduced through a 2.8 mm corneal incision. MATERIALS AND METHODS: All cases underwent lens extraction by phacoemulsification followed by removal of the unstable lens capsule. A PFI X4 IOL (Medicontur) was modified to create four open-loop haptics. The IOL was injected into the anterior chamber, each haptic was captured in a loop of suture introduced ab externo, and the lens was sutured with four-point fixation. RESULTS: The results from 20 eyes in 17 dogs are reported. Over an average follow-up time of 14.5 months, vision was retained in 16/20 eyes. Vision was lost in four eyes due to corneal ulceration and ocular hypertension (1/20), retinal detachment (2/20), and Progressive Retinal Atrophy (1/20). CONCLUSIONS: The modified PFI X4 proved suitable for injection and scleral fixation through a 2.8 mm corneal incision, with a success rate comparable to previously published techniques.

Supporting a Healthier Takeaway Meal Choice: Creating a Universal Health Rating for Online Takeaway Fast-Food Outlets.

Digital food ordering platforms are used by millions across the world and provide easy access to takeaway fast-food that is broadly, though not exclusively, characterised as energy dense and nutrient poor. Outlets are routinely rated for hygiene, but not for their healthiness. Nutritional information is mandatory in pre-packaged foods, with many companies voluntarily using traffic light labels to support making healthier choices. We wanted to identify a feasible universal method to objectively score takeaway fast-food outlets listed on Just Eat that could provide users with an accessible rating that can infer an outlet's 'healthiness'. Using a sample of takeaway outlets listed on Just Eat, we obtained four complete assessments by nutrition researchers of each outlet's healthiness to create a cumulative score that ranged from 4 to 12. We then identified and manually extracted nutritional attributes from each outlet's digital menu, e.g., number of vegetables that have the potential to be numerated. Using generalized linear modelling we identified which attributes were linear predictors of an outlet's healthiness assessment from nutritional researchers. The availability of water, salad, and the diversity of vegetables were positively associated with academic researchers' assessment of an outlet's healthiness, whereas the availability of chips, desserts, and multiple meal sizes were negatively associated. This study shows promise for the feasibility of an objective measure of healthiness that could be applied to all outlet listings on Just Eat and other digital food outlet aggregation platforms. However, further research is required to assess the metric's validity, its desirability and value to users, and ultimately its potential influence on food choice behaviour.

Taxonomy and nomenclature of the polymorphic European high mountain species Androsace vitaliana (L.) Lapeyr. (Primulaceae).

Androsace vitaliana (syn. Vitaliana primuliflora; Primulaceae) has been subject to several taxonomic treatments, whose conclusions ranged from a single species with numerous infraspecific taxa to several species usually without infraspecific taxa. Here, following molecular investigation, several taxonomic changes are made. A single species with the following infraspecific taxa is recognized: subsp. vitaliana (Pyrenees), subsp. cinerea (south-western Alps), subsp. lepontina (Pennine Alps), subsp. sesleri (south-eastern Alps), subsp. praetutiana (Apennines) and subsp. assoana (Iberian Peninsula excluding the Pyrenees), the last of which is divided into the four allopatrically distributed varieties assoana, centriberica, flosjugorum and nevadensis. Contrary to some previous assertions, all taxa are allopatric and, especially for subspp. vitaliana, cinerea and lepontina, where clear diagnostic characters are lacking, they can best be determined by their geographic origin.

Achromatopsia in three sibling Labrador Retrievers in the UK.

Achromatopsia was identified in three Labrador Retriever littermates. The dogs demonstrated day blindness, negotiating obstacles under low-light conditions, but apparently blind when outdoors. One of the dogs presented with immature bilateral diffuse posterior cortical cataracts and clinical signs of day blindness became apparent following cataract extraction surgery. Electroretinography demonstrated an absence of a cone photoreceptor response to a bright stimulus and a flicker response of 30 Hz in all three dogs. No fundic lesions have been apparent ophthalmoscopically in any of the dogs as the initial presentation of each case. No abnormalities were detected with DNA screening for known mutations of the CNGB3 gene in any of the dogs.

Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

An ecohydraulic model to identify and monitor Moapa dace habitat.

Moapa dace (Moapa coriacea) is a critically endangered thermophilic minnow native to the Muddy River ecosystem in southeastern Nevada, USA. Restricted to temperatures between 26.0 and 32.0 °C, these fish are constrained to the upper two km of the Muddy River and several small tributaries fed by warm springs. Habitat alterations, nonnative species invasion, and water withdrawals during the 20th century resulted in a drastic decline in the dace population and in 1979 the Moapa Valley National Wildlife Refuge (Refuge) was created to protect them. The goal of our study was to determine the potential effects of reduced surface flows that might result from groundwater pumping or water diversions on Moapa dace habitat inside the Refuge. We accomplished our goal in several steps. First, we conducted snorkel surveys to determine the locations of Moapa dace on three warm-spring tributaries of the Muddy River. Second, we conducted hydraulic simulations over a range of flows with a two-dimensional hydrodynamic model. Third, we developed a set of Moapa dace habitat models with logistic regression and a geographic information system. Fourth, we estimated Moapa dace habitat over a range of flows (plus or minus 30% of base flow). Our spatially explicit habitat models achieved classification accuracies between 85% and 91%, depending on the snorkel survey and creek. Water depth was the most significant covariate in our models, followed by substrate, Froude number, velocity, and water temperature. Hydraulic simulations showed 2-11% gains in dace habitat when flows were increased by 30%, and 8-32% losses when flows were reduced by 30%. To ensure the health and survival of Moapa dace and the Muddy River ecosystem, groundwater and surface-water withdrawals and diversions need to be carefully monitored, while fully implementing a proactive conservation strategy.

Dynamics of drift, gene flow, and selection during speciation in Silene.

The mechanics of speciation with gene flow are still unclear. Disparity among genes in population differentiation (F(ST)) between diverging species is often interpreted as evidence for semipermeable species boundaries, with selection preventing "key" genes from introgressing despite ongoing gene flow. However, F(ST) can remain high before it reaches equilibrium between the lineage sorting of species divergence and the homogenizing effects of gene flow (via secondary contact). Thus, when interpreting F(ST), the dynamics of drift, gene flow, and selection need to be taken into account. We illustrate this view with a multigenic analyses of gene flow and selection in three closely related Silene species, S. latifolia, S. dioica, and S. diclinis. We report that although S. diclinis appears to have evolved in allopatry, isolation with (bidirectional) gene flow between S. latifolia and S. dioica is likely, perhaps as a result of parapatric speciation followed by more extensive sympatry. Interestingly, we detected the signatures of apparently independent instances of positive selection at the same locus in S. latifolia and S. dioica. Despite gene flow between the species, the adaptive alleles have not crossed the species boundary, suggesting that this gene has independently undergone species-specific (diversifying or parallel) selection.

Positive selection differs between protein secondary structure elements in Drosophila.

Different protein secondary structure elements have different physicochemical properties and roles in the protein, which may determine their evolutionary flexibility. However, it is not clear to what extent protein structure affects the way Darwinian selection acts at the amino acid level. Using phylogeny-based likelihood tests for positive selection, we have examined the relationship between protein secondary structure and selection across six species of Drosophila. We find that amino acids that form disordered regions, such as random coils, are far more likely to be under positive selection than expected from their proportion in the proteins, and residues in helices and beta-structures are subject to less positive selection than predicted. In addition, it appears that sites undergoing positive selection are more likely than expected to occur close to one another in the protein sequence. Finally, on a genome-wide scale, we have determined that positively selected sites are found more frequently toward the gene ends. Our results demonstrate that protein structures with a greater degree of organization and strong hydrophobicity, represented here as helices and beta-structures, are less tolerant to molecular adaptation than disordered, hydrophilic regions, across a diverse set of proteins.

Genome wide analyses reveal little evidence for adaptive evolution in many plant species.

The relative contribution of advantageous and neutral mutations to the evolutionary process is a central problem in evolutionary biology. Current estimates suggest that whereas Drosophila, mice, and bacteria have undergone extensive adaptive evolution, hominids show little or no evidence of adaptive evolution in protein-coding sequences. This may be a consequence of differences in effective population size. To study the matter further, we have investigated whether plants show evidence of adaptive evolution using an extension of the McDonald-Kreitman test that explicitly models slightly deleterious mutations by estimating the distribution of fitness effects of new mutations. We apply this method to data from nine pairs of species. Altogether more than 2,400 loci with an average length of approximately 280 nucleotides were analyzed. We observe very similar results in all species; we find little evidence of adaptive amino acid substitution in any comparison except sunflowers. This may be because many plant species have modest effective population sizes.

Bayesian hypothesis testing supports long-distance Pleistocene migrations in a European high mountain plant (Androsace vitaliana, Primulaceae).

Colonization of the south-western European mountain ranges is suggested to have predominantly progressed from the Iberian Peninsula eastwards, but this hypothesis has never been tested in a statistical framework. Here, we test this hypothesis using Androsace vitaliana, a high elevation species with eight mostly allopatric subspecies, which is widely but disjunctly distributed across all major south-western European mountain ranges. To this end, we use plastid and nuclear sequence data as well as fingerprint (amplified fragment length polymorphisms) data and employ Bayesian methods, which allow co-estimation of genealogy and divergence times using explicit demographic models, as well as hypothesis testing via Bayes factors. Irrespective of the ambiguity concerning where A. vitaliana started to diversify -- both the Alps and the mountain ranges of the Iberian Peninsula outside the Pyrenees were possible -- colonization routes were not simply unidirectional, but involved Pleistocene connections between the Alps and mountain ranges of the Iberian Peninsula bypassing the interjacent Pyrenees via long-distance dispersal. In contrast, the species' post-glacial history is shaped by regional gene pool homogenization resulting in the genetic pattern showing good congruence with geographical proximity in agreement with a vicariance model, but only partly supporting current taxonomy.

Reciprocal Pleistocene origin and postglacial range formation of an allopolyploid and its sympatric ancestors (Androsace adfinis group, Primulaceae).

The biogeographic history of polyploids and their lower-ploid ancestors is an important feature to achieve a better understanding of polyploid evolution. This is exemplified here using the ecologically congruent members of the Androsace adfinis group (Primulaceae) endemic to the southwestern European Alps. Employing relative genome size, AFLP fingerprint and chloroplast sequence haplotype data, we show that Androsace brigantiaca is a recent (probably no more than 0.2 million years) allopolyploid derivative of the geographically close A. adfinis and A. puberula, which formed reciprocally in a comparatively restricted area in the southern Southwestern Alps. Bayesian admixture analysis--also of artificial additive AFLP profiles--shows that the nuclear genome of A. brigantiaca is significantly biased towards the puberula-genome irrespective of maternal parentage. Nevertheless, there is no evidence for genetic interaction (hybridization, introgression) of A. brigantiaca with either of its ancestors, including the widely sympatric A. puberula. Sympatry might be facilitated by ecological displacement on a local scale or might be a transitory phase on the way to competitive replacement via, for instance, polyploid superiority.

Traces of ancient range shifts in a mountain plant group (Androsace halleri complex, Primulaceae).

Phylogeographical studies frequently detect range shifts, both expansions (including long-distance dispersal) and contractions (including vicariance), in the studied taxa. These processes are usually inferred from the patterns and distribution of genetic variation, with the potential pitfall that different historical processes may result in similar genetic patterns. Using a combination of DNA sequence data from the plastid genome, AFLP fingerprinting, and rigorous phylogenetic and coalescence-based hypothesis testing, we show that Androsace halleri (currently distributed disjunctly in the northwestern Iberian Cordillera Cantábrica, the eastern Pyrenees, and the French Massif Central and Vosges), or its ancestor, was once more widely distributed in the Pyrenees. While there, it hybridized with Androsace laggeri and Androsace pyrenaica, both of which are currently allopatric with A. halleri. The common ancestor of A. halleri and the north Iberian local endemic Androsace rioxana probably existed in the north Iberian mountain ranges with subsequent range expansion (to the French mountain ranges of the Massif Central and the Vosges) and allopatric speciation (A. rioxana, A. halleri in the eastern Pyrenees, A. halleri elsewhere). We have thus been able to use the reticulate evolution in this species group to help elucidate its phylogeographical history, including evidence of range contraction.