Are Entry Criteria for Cataract Surgery Justified?

Purpose

The German Ophthalmological Society (GOS) recently proposed surgical entry criteria, i.e. 300 cataract surgeries. We herein correlate the surgical hands-on experience with the risk of posterior capsule ruptures in order to assess whether this number is appropriate.

Methods

We identified all cataract operations that had been performed at the University Eye Hospital Freiburg since 1995. For each surgeon, we assigned a running number to his/her procedures in the order they had been performed. Thereafter, we excluded all combined procedures and the second eyes. We then selected the 5475 surgical reports between November 2008 and November 2012 for detailed review. We additionally classified each surgery into low- vs. high- à priori risk for posterior capsule ruptures. We fitted a multifactorial logistic regression model to assess the GOS recommendation of 300 surgeries under supervision. In the low-risk group, we additionally visualized the ''typical'' learning curve by plotting the posterior capsule ruptures against the respective rank numbers.

Results

The odds ratio for posterior capsule ruptures of ''learning-mode'' (one of the respective surgeon''s 300 first procedures) vs. the non-learning-mode was 3.8 (p<0.0001). By contrast, classification into the low-risk group lowered the risk of posterior capsule ruptures three fold (p<0.0001). According to the low-risk plot, the surgeons started with a complication rate of 4% and continuously improved towards 0.5% after 1500 operations. Thereafter, the rate increased again and stabilized around one percent.

Conclusion

The learning curve with respect to posterior capsule ruptures is surprisingly flat. The GOS entry criterion of 300 cataract procedures is therefore most likely justified. Careful selection of low-risk patients for the training surgeons may help in reducing the rate of posterior capsule ruptures during training.     

Species’ Geographic Distributions Through Time: Playing Catch-up with Changing Climates

Species?? ranges are often treated as a fixed characteristic, rather than a fluid, ever-changing manifestation of their ecological requirements and dispersal abilities. Paleontologists generally have had a better appreciation of the changeable nature of species?? ranges than neontologists, but each perspective can improve by appreciating the other. Here, we provide an overview of paleontological and neontological perspectives on species?? geographic distributions, focusing on what can be learned about historical variations in distributions. In particular, we focus on enriching the field of phylogeography with a more explicit view of geography, taking into account variation through time in the geographic distribution of different environments, effectively integrating information from the fossil record, molecular genetics, and paleoclimatology. The cross-disciplinary view that would result offers novel perspectives on biogeography and macroevolution.     

αA-Crystallin-Derived Mini-Chaperone Modulates Stability and Function of Cataract Causing αAG98R-Crystallin

Background

A substitution mutation in human αA-crystallin (αAG98R) is associated with autosomal dominant cataract. The recombinant mutant αAG98R protein exhibits altered structure, substrate-dependent chaperone activity, impaired oligomer stability and aggregation on prolonged incubation at 37°C. Our previous studies have shown that αA-crystallin–derived mini-chaperone (DFVIFLDVKHFSPEDLTVK) functions like a molecular chaperone by suppressing the aggregation of denaturing proteins. The present study was undertaken to determine the effect of αA-crystallin–derived mini-chaperone on the stability and chaperone activity of αAG98R-crystallin.

Methodology/Principal Findings

Recombinant αAG98R was incubated in presence and absence of mini-chaperone and analyzed by chromatographic and spectrometric methods. Transmission electron microscope was used to examine the effect of mini-chaperone on the aggregation propensity of mutant protein. Mini-chaperone containing photoactive benzoylphenylalanine was used to confirm the interaction of mini-chaperone with αAG98R. The rescuing of chaperone activity in mutantα-crystallin (αAG98R) by mini-chaperone was confirmed by chaperone assays. We found that the addition of the mini-chaperone during incubation of αAG98R protected the mutant crystallin from forming larger aggregates that precipitate with time. The mini-chaperone-stabilized αAG98R displayed chaperone activity comparable to that of wild-type αA-crystallin. The complexes formed between mini-αA–αAG98R complex and ADH were more stable than the complexes formed between αAG98R and ADH. Western-blotting and mass spectrometry confirmed the binding of mini-chaperone to mutant crystallin.

Conclusion/Significance

These results demonstrate that mini-chaperone stabilizes the mutant αA-crystallin and modulates the chaperone activity of αAG98R. These findings aid in our understanding of how to design peptide chaperones that can be used to stabilize mutant αA-crystallins and preserve the chaperone function.     

Geographic distributions of homosporous ferns: does dispersal obscure evidence of vicariance?

The central problem in biogeography is that interactions between different processes result in the formation of historical patterns, such that it is difficult to discriminate the relative roles of vicariance and dispersal. Ferns are distributed by small wind-dispersed propagules that are produced in very large numbers and capable of dispersing thousands of kilometers. Thus, most taxon distributions in ferns are assumed to be a function of dispersal rather than vicariance. Here, we review some case examples that provide good evidence for vicariance and dispersal in ferns. We then ask whether dispersal is so extensive in ferns that vicariance is no longer detectable in most cases. Although we think that too few studies have been carried out to make generalizations at this stage, we outline the criteria for an effective research programme that can address this issue. Phylogenetic and distributional data are needed, not only because they are lacking in an evolutionarily important group of organisms, but also because data from ferns and other cryptogams are likely to be crucial in making broad biogeographic statements.     

Geographic origin of the Y Chromosomes in “old” inbred strains of mice

Six distinct Y Chromosomes (Chr) were identified among 39 standard inbred strains of mice with five probes that identified Y Chr-specific restriction fragments on Southern blots. Three Y Chr types, distributed among 31 strains, were of Asian Mus musculus origin. The remaining three Y Chr types, distributed among eight strains, were of M. domesticus origin. The Asian source of the M. musculus Y Chr was confirmed by determining the DNA sequence of 221 bp from an open reading frame within the Sry (sex determining region Y) gene (Gubbay et al., Nature 346 245–250, 1990) in three inbred strains (C57BL/6J, AKR/J, and SWR/J) and comparing the sequence to the homologous sequences derived from wild caught European and Asian M. musculus males. These data indicate that a minimum of six male mice contributed to the formation of the old inbred strains.     

Molecular Evolution of PvMSP3α Block II in Plasmodium vivax from Diverse Geographic Origins

Block II of Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is conserved and has been proposed as a potential candidate for a malaria vaccine. The present study aimed to compare sequence diversity in PvMSP3a block II at a local microgeographic scale in a village as well as from larger geographic regions (countries and worldwide). Blood samples were collected from asymptomatic carriers of P. vivax in a village at the western border of Thailand and PvMSP3α was amplified and sequenced. For population genetic analysis, 237 PvMSP3α block II sequences from eleven P. vivax endemic countries were analyzed. PvMSP3α sequences from 20 village-level samples revealed two length variant types with one type containing a large deletion in block I. In contrast, block II was relatively conserved; especially, some non-synonymous mutations were extensively shared among 11 parasite populations. However, the majority of the low-frequency synonymous variations were population specific. The conserved pattern of nucleotide diversity in block II sequences was probably due to functional/structural constraints, which were further supported by the tests of neutrality. Notably, a small region in block II that encodes a predicted B cell epitope was highly polymorphic and showed signs of balancing selection, signifying that this region might be influenced by the immune selection and may serve as a starting point for designing multi-antigen/stage epitope based vaccines against this parasite.     

Dynamic Geographic Personal Data – New Opportunity and Challenge Introduced by the Location-Aware Mobile Networks

A new generation of mobile terminals, communicators and smartphones, designed for general public, are emerging from the mobile phone revolution. Their distinctive features include enhanced data capabilities and the ability to locate the user. These features make these new types of applications, location-based and location-aware services, suitable for mobile users. In addition to location-based information access they also provide excellent means for data collection about the mobile users themselves, yielding valuable dynamic and geographic personal data. This type of data has never been available to such an extent before. Availability of such data would result in new opportunities for potential users: in commerce, in the public sector and even for private use. It is also a great challenge to the information systems: in data collection, management and analysis. Privacy protection is maybe the most serious problem to be found in this context. The objective of this paper is to present the opportunities and challenges provided by dynamic geographic personal data in the context of emerging location-aware mobile networks. Here a new service is outlined in parallel with existing and planned location-based services. The new service, designed for collecting, managing and releasing dynamic geographic population data, is called Dynamic Geographic Data Service (DGDS).     

Geographic variability of ecological niches of plant species: are competition and stress relevant?

A species’ niche position may differ strongly between geographic regions, for instance due to the effect of competitors or ecophysiological stress. However, it is unclear whether such strong geographic niche variation is the rule or the exception. We compared the niche positions of plant species between central England and eastern central Europe (as available from the literature), using phylogenetically independent contrasts. We found that most species occupied similar niche positions in both regions. More importantly, we found that niche variation was not higher in species susceptible to competitive displacement. Nor was niche variation higher in species that reach the edge of their range and thus suffer ecophysiological stress. We suggest that although these species might be easily displaced in their position along a niche axis, they may only be displaced over a short distance. Overall, ecological mechanisms that cause niche variation at the local scale may be much less relevant at the geographic scale.     

Geographic variation of genetic and behavioral traits in northern and southern tüngara frogs

We use a combination of microsatellite marker analysis and mate-choice behavior experiments to assess patterns of reproductive isolation of the túngara frog Physalaemus pustulosus along a 550-km transect of 25 populations in Costa Rica and Panama. Earlier studies using allozymes and mitochondrial DNA defined two genetic groups of túngara frogs, one ranging from Mexico to northern Costa Rica (northern group), the second ranging from Panama to northern South America (southern group). Our more fine-scale survey also shows that the northern and southern túngara frogs are genetically different and geographically separated by a gap in the distribution in central Pacific Costa Rica. Genetic differences among populations are highly correlated with geographic distances. Temporal call parameters differed among populations as well as between genetic groups. Differences in calls were explained better by geographic distance than by genetic distance. Phonotaxis experiments showed that females preferred calls of males from their own populations over calls of males from other populations in about two-thirds to three-fourths of the contrasts tested. In mating experiments, females and males from the same group and females from the north with males from the south produced nests and tadpoles. In contrast, females from the south did not produce nests or tadpoles with males from the north. Thus, northern and southern túngara frogs have diverged both genetically and bioacoustically. There is evidence for some prezygotic isolation due to differences in mate recognition and fertilization success, but such isolation is hardly complete. Our results support the general observation that significant differences in sexual signals are often not correlated with strong genetic differentiation.     

UPR Activation and the Down–Regulation of α-Crystallin in Human High Myopia-Related Cataract Lens Epithelium

Purpose

To investigate the expression of αA- and αB-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia-related cataracts.

Methods and Materials

The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent ≥-10.00 diopters) and age-related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of α-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of α-crystallin, GRP78, p-IRE1α, p-eIF2α and ATF6.

Results

In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of αA- and αB-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control.

Conclusion

These results suggest the significant loss of soluble α-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract.     

Genetic Heterogeneity of the β-Globin Gene in Various Geographic Populations of Yunnan in Southwestern China

Objectives

The aim of this study was to investigate the geographic distribution of β-globin gene mutations in different ethnic groups in Yunnan province.

Methods

From 2004 to 2014, 1,441 subjects with hemoglobin disorders, identified by PCR-reverse dot blot and DNA sequencing, were studied according to ethnicity and geographic origin. Haplotypes were examined among 41 unrelated thalassemia chromosomes.

Results

Eighteen β-thalassemia mutations and seven hemoglobin variants were identified for 1,616 alleles in 22 different ethnic groups from all 16 prefecture-level divisions of Yunnan. The prevalence of β-thalassemia was heterogeneous and regionally specific. CD 41-42 (-TCTT) was the most prevalent mutation in the populations of northeastern Yunnan. CD 17 (A>T) was the most common mutation in the populations of southeastern Yunnan, especially for the Zhuang minority, whereas Hb E (CD 26, G>A) was the most prevalent mutation in populations of southwestern Yunnan, especially for the Dai minority. Among the seven types of haplotypes identified, CD 17 (A>T) was mainly linked to haplotype VII (+ - - - - - +) and IVS-II-654 (C>T) was only linked to haplotype I (+ - - - - + +).

Conclusion

Our data underline the heterogeneity of β-globin gene mutations in Yunnan. This distribution of β-globin mutations in the geographic regions and ethnic populations provided a detailed ethnic basis and evolutionary view of humans in southern China, which will be beneficial for genetic counseling and prevention strategies.     

Geographic Variation in Populations of Microcebus murinus in Madagascar: Resource Seasonality or Bergmann's Rule?

Gray mouse lemurs (Microcebus murinus) occur in western Madagascar from the evergreen littoral rain forests at the southern tip of the island to the seasonal dry deciduous forests of the west and northwest. The wide geographic distribution allows researchers to investigate whether ecogeographic variations reflect adaptations to ambient temperatures, as a proxy for constraints of thermoregulation, or to rainfall, as a proxy of food availability. We compared body mass, number of litters/yr, and longevity for 3 populations: 1 from the evergreen littoral rain forest of the south (Mandena: annual mean temperature 23°C, 1600 mm rain/yr), 1 from the dry deciduous forest of the west (Kirindy/CFPF: 25°C, 800 mm), and 1 from the dry deciduous forest of northwestern Madagascar (Ampijoroa: 27°C, 1200 mm). Body mass decreases with increasing ambient temperature from south to north (Mandena > Kirindy/CFPF > Ampijoroa). The number of litters/yr was highest in the littoral rain forest (2 or 3 litters/yr) and decreased with decreasing rainfall (Mandena > Ampijoroa > Kirindy/CFPF). Life expectancy is lowest in the littoral forest (13% recaptures of mouse lemurs between years) and high (ca. 30–40% recaptures between years) in the dry forests (Mandena < Kirindy/CFPF and Ampijoroa). We postulate that constraints of thermoregulation result in the latitudinal gradient of body mass. Reduced resource productivity or seasonality is reflected in differences in reproductive rates, which seemed to be traded off against longevity. Thus body mass, longevity, and reproductive parameters respond differently to ambient conditions.     

What Story Does Geographic Separation of Insular Bats Tell? A Case Study on Sardinian Rhinolophids

Competition may lead to changes in a species’ environmental niche in areas of sympatry and shifts in the niche of weaker competitors to occupy areas where stronger ones are rarer. Although mainland Mediterranean (Rhinolophus euryale) and Mehely’s (R. mehelyi) horseshoe bats mitigate competition by habitat partitioning, this may not be true on resource-limited systems such as islands. We hypothesize that Sardinian R. euryale (SAR) have a distinct ecological niche suited to persist in the south of Sardinia where R. mehelyi is rarer. Assuming that SAR originated from other Italian populations (PES) – mostly allopatric with R. mehelyi – once on Sardinia the former may have undergone niche displacement driven by R. mehelyi. Alternatively, its niche could have been inherited from a Maghrebian source population. We: a) generated Maxent Species Distribution Models (SDM) for Sardinian populations; b) calibrated a model with PES occurrences and projected it to Sardinia to see whether PES niche would increase R. euryale’s sympatry with R. mehelyi; and c) tested for niche similarity between R. mehelyi and PES, PES and SAR, and R. mehelyi and SAR. Finally we predicted R. euryale’s range in Northern Africa both in the present and during the Last Glacial Maximum (LGM) by calibrating SDMs respectively with SAR and PES occurrences and projecting them to the Maghreb. R. mehelyi and PES showed niche similarity potentially leading to competition. According to PES’ niche, R. euryale would show a larger sympatry with R. mehelyi on Sardinia than according to SAR niche. Such niches have null similarity. The current and LGM Maghrebian ranges of R. euryale were predicted to be wide according to SAR’s niche, negligible according to PES’ niche. SAR’s niche allows R. euryale to persist where R. mehelyi is rarer and competition probably mild. Possible explanations may be competition-driven niche displacement or Maghrebian origin.     

Geographic patterns in fruit colour diversity: do leaves constrain the colour of fleshy fruits?

We tested for geographic patterns in fruit colour diversity. Fruit colours are thought to promote detection by seed dispersers. Because seed dispersers differ in their spectral sensitivities, we predicted that fruit colour diversity would be higher in regions with higher seed disperser diversity (i.e. the tropics). We collected reflectance data on 232 fruiting plant species and their natural backgrounds in seven localities in Europe, North and South America, and analysed fruit colour diversity according to the visual system of birds—the primary consumer types of these fruits. We found no evidence that fruit colours are either more conspicuous or more diverse in tropical areas characterised by higher seed disperser diversity. Instead, fruit colour diversity was lowest in central Brazil, suggesting that fruit colours may be more diverse in temperate regions. Although we found little evidence for geographic variation in fruit hues, the spectral properties of fruits were positively associated with the spectral properties of backgrounds. This result implies that fruit colours may be influenced by selection on the reflectance properties of leaves, thus constraining the evolution of fruit colour. Overall, the results suggest that fruit colours in the tropics are neither more diverse nor more conspicuous than temperate fruits, and that fruit colours may be influenced by correlated selection on leaf reflectance properties. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Geographic limitations in the movement of Deep‐Draft tankers between the Indian and pacific oceans

Abstract

The need to move increasing volumes of petroleum over long distances has stimulated the construction of a large fleet of tankers of unprecedented dimensions. The extraordinarily deep drafts of these ships have necessitated a reevaluation of the extent of navigable ocean. Because some major shipping lanes are closed to their movement, alternative routes have developed. For this study, hydrographic charts of the passages between the Indian and Pacific oceans were examined in detail and special purpose maps were constructed. The patterns illustrate the categories of negative ocean, open ocean, and ocean conditional for the movement of deep‐draft ships. Actual and potential routeways for deep‐draft ships past Southeast Asia are identified and the limitations of the Malacca/Singapore straits are described in greater detail.     

��-Catenin Is Genetically and Biologically Associated with Cortical Cataract and Future Alzheimer-Related Structural and Functional Brain Changes

Multiple lines of evidence suggest that specific subtypes of age-related cataract (ARC) and Alzheimer disease (AD) are related etiologically. To identify shared genetic factors for ARC and AD, we estimated co-heritability of quantitative measures of cataract subtypes with AD-related brain MRI traits among 1,249 members of the Framingham Eye Study who had a brain MRI scan approximately ten years after the eye exam. Cortical cataract (CC) was found to be co-heritable with future development of AD and with several MRI traits, especially temporal horn volume (THV, ρ = 0.24, P<10⁻⁴). A genome-wide association study using 187,657 single nucleotide polymorphisms (SNPs) for the bivariate outcome of CC and THV identified genome-wide significant association with CTNND2 SNPs rs17183619, rs13155993 and rs13170756 (P<2.6×10⁻⁷). These SNPs were also significantly associated with bivariate outcomes of CC and scores on several highly heritable neuropsychological tests (5.7×10⁻⁹≤P<3.7×10⁻⁶). Statistical interaction was demonstrated between rs17183619 and APP SNP rs2096488 on CC (P = 0.0015) and CC-THV (P = 0.038). A rare CTNND2 missense mutation (G810R) 249 base pairs from rs17183619 altered δ-catenin localization and increased secreted amyloid-β_1–42 in neuronal cell culture. Immunohistopathological analysis of lens tissue obtained from two autopsy-confirmed AD subjects and two non-AD controls revealed elevated expression of δ-catenin in epithelial and cortical regions of lenses from AD subjects compared to controls. Our findings suggest that genetic variation in delta catenin may underlie both cortical lens opacities in mid-life and subsequent MRI and cognitive changes that presage the development of AD.     

Do hotspots fall within protected areas? A Geographic Approach to Planning analysis of regional freshwater biodiversity

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