Quantitative Fundus Autofluorescence and Optical Coherence Tomography in ABCA4 Carriers

PURPOSE. To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus autofluorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort. METHODS. Seventy-five individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9-82 years) were recruited as family members of affected patients from 46 unrelated families. For comparison, 57 affected family members with biallelic ABCA4 mutations (mean age, 23.4 years; range, 6-67 years) and two noncarrier siblings were also enrolled. Autofluorescence images (308, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Horizontal SD-OCT scans through the fovea were obtained and the thicknesses of the outer retinal layers were measured. RESULTS. In 60 of 65 carriers of ABCA4 mutations (age range, 9-60), qAF levels were within normal limits (95% confidence level) observed for healthy noncarrier subjects, while qAF levels of affected family members were significantly increased. Perifoveal fleck-like abnormalities were observed in fundus AF images in four carriers, and corresponding changes were detected in the outer retinal layers in SD-OCT scans. Thicknesses of the outer retinal layers were within the normal range. CONCLUSIONS. With few exceptions, individuals heterozygous for ABCA4 mutations and between the ages of 9 and 60 years do not present with elevated qAF. In a small number of carriers, perifoveal fleck-like changes were visible

Risks to Birds Traded for African Traditional Medicine: A Quantitative Assessment

Few regional or continent-wide assessments of bird use for traditional medicine have been attempted anywhere in the world. Africa has the highest known diversity of bird species used for this purpose. This study assesses the vulnerability of 354 bird species used for traditional medicine in 25 African countries, from 205 genera, 70 families, and 25 orders. The orders most represented were Passeriformes (107 species), Falconiformes (45 species), and Coraciiformes (24 species), and the families Accipitridae (37 species), Ardeidae (15 species), and Bucerotidae (12 species). The Barn owl (Tyto alba) was the most widely sold species (seven countries). The similarity of avifaunal orders traded is high (analogous to ‘‘morphospecies’’, and using Sørensen’s index), which suggests opportunities for a common understanding of cultural factors driving demand. The highest similarity was between bird orders sold in markets of Benin vs. Burkina Faso (90%), but even bird orders sold in two geographically separated countries (Benin vs. South Africa and Nigeria vs. South Africa) were 87% and 81% similar, respectively. Rabinowitz’s ‘‘7 forms of rarity’’ model, used to group species according to commonness or rarity, indicated that 24% of traded bird species are very common, locally abundant in several habitats, and occur over a large geographical area, but 10% are rare, occur in low numbers in specific habitats, and over a small geographical area. The order with the highest proportion of rare species was the Musophagiformes. An analysis of species mass (as a proxy for size) indicated that large and/or conspicuous species tend to be targeted by harvesters for the traditional medicine trade. Furthermore, based on cluster analyses for species groups of similar risk, vultures, hornbills, and other large avifauna, such as bustards, are most threatened by selective harvesting and should be prioritised for conservation action.University of the Witwatersrand SPARC Prestigious and URC Postdoctoral Fellowships; National Research Foundatio

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Algal richness and life-history strategies are influenced by hydrology and phosphorus in two major subtropical wetlands

We explored controls of algal taxon richness (hereafter richness) in complex and hydrologically dynamic flood-pulsed wetlands by comparing results from independent studies in two globally important subtropical wetlands: the Okavango Delta (Botswana) and the Florida Everglades (U.S.A.). In both wetlands, the flood pulse hydrology is regulated by distinct wet and dry seasons, and creates floodplain landscapes with heterogeneous habitats; algal growth is limited by phosphorus (P); and water uses threaten ecosystem function. To inform future comparisons of algal richness and distribution patterns, we assessed the role of hydrology and P as key controls of richness, and identified indicator taxa of desiccation disturbance and P scarcity in these wetlands under increasing hydrological, nutrient, and habitat changes. We used the intermediate disturbance hypothesis, and the species-energy theory to explain algal richness patterns, and the competitive, stress-tolerant, ruderal (CSR) framework to classify indicator taxa. We collected algal samples, environmental data and information expected to influence community structure (water depth, relative depth change, P concentrations, hydroperiod and habitat type) over several years at sites representing a broad range of environmental characteristics. To account for sample size differences, we estimated algal richness by determining the asymptote of taxon accumulation curves. Using multiple regression analysis, we assessed if and how water depth, depth change, P, hydroperiod, and habitat type influence richness within each wetland. We then compared the strength of the relationships between these controlling features and richness between wetlands. Using indicator species analysis on relative abundance data, we classified C, S and R indicator taxa associated with shorter/longer hydroperiod, and lower/higher P concentrations. In either wetland, we did not observe the negative unimodal relationship between site-specific richness and water depth change that was expected following the intermediate disturbance hypothesis. It is possible that this relationship exists at more highly resolved temporal scales than the semi-annual to annual scales hypothesised here. However, as nutrient flows and algal habitats depend on these wetlands\u27 flood pulse, maintaining the Okavango\u27s natural pulse, and increasing freshwater flow in the Everglades would help protect these wetlands\u27 algal diversity. Chlorophyta richness (Okavango), and total, Bacillariophyta, Chlorophyta and cyanobacteria richness (Everglades) increased with higher P concentrations, as per species-energy theory. In the Okavango, we classified 6 C and 49 R indicator taxa (e.g. many planktonic Chlorophyta), and in the Everglades, 15 C, 1 S and 9 R taxa (e.g. benthic Bacillariophyta and planktonic/benthic Chlorophyta), and one stress- and disturbance-tolerant cyanobacterium species. Our results offer baseline information for future comparisons of richness, and abundance of C, S and R indicator taxa in subtropical wetlands; this can be used to quantify how algal communities may respond to potential changes in hydrology and P due to water diversion, anthropogenic nutrient loads, and climate change. Examining microhabitat heterogeneity, nitrogen and light availability, and grazing pressure in such wetlands would further illuminate patch-scale controls of richness and life-history strategy distribution in algal communities