Investigation of the Stock Structure of Atlantic Walrus (Odobenus rosmarus rosmarus) in Canada and Greenland Using Dental Pb Isotopes Derived from Local Geochemical Environments

The chemical composition of animal tissues such as teeth appears to reflect an individual's exposure to its geochemical environment. In this study, the lead (Pb) isotope composition of dental cementum was used to investigate the stock structure of Atlantic walrus (Odobenus rosmarus rosmarus) in the Canadian Arctic and Greenland. The 12 communities providing walrus samples for this study represent most of the Canadian and Greenlandic villages where walrus still form an important part of the traditional Inuit diet. Significant differences between locations in mean Pb isotope ratios and the limited overlap of the ranges of values indicate that each village harvested walrus herds that exploited substantially different geological/geographical habitats. This geographic segregation based on isotopic signatures suggests that most walrus stocks (i.e., the groups of walrus that interact with hunters at each community) are more localized in their range than previously thought. 208Pb/207Pb and 208Pb/204Pb were the most important stock discriminators, reflecting the influence of local geological Th/U composition (i.e., 208Pb) on Pb isotope composition in walrus teeth. 204Pb-based isotope ratios in walrus were consistently higher (more radiogenic) and more homogeneous than those in regional terrestrial bedrock, a difference probably due to selective leaching of radiogenic Pb from mineral phases into seawater and mixing during weathering and transport. Dental Pb isotope signatures may have widespread application to stock discrimination of other coastal marine mammal species.La composition chimique de tissus animaux tels que les dents semble refléter l'exposition d'un individu à son milieu géochimique. Pour la présente étude, on a utilisé la composition isotopique du plomb (Pb) contenu dans le cément pour examiner la structure du stock du morse de l'Atlantique (Odobenus rosmarus rosmarus) dans l'Arctique canadien et le Groenland. Les 12 communautés qui ont fourni les échantillons de morse pour ce projet représentent la majorité des villages canadiens et groenlandais où le morse constitue toujours une grande partie du régime alimentaire traditionnel des Inuits. Des différences marquées entre les sites dans la moyenne des rapports isotopiques du Pb et le faible recoupement des gammes de valeurs révèlent que chaque village prélevait des morses au sein de troupeaux qui exploitaient des habitats géologiques/géographiques bien distincts. Cette ségrégation géographique fondée sur des signatures isotopiques suggère que la plupart des stocks de morses (c.-à-d. le groupe de morses qui interagit avec les chasseurs dans chaque communauté) sont plus localisés dans leur territoire qu'on ne le pensait auparavant. 208Pb/207Pb et 208Pb/204Pb étaient les grands caractères discriminants des stocks, reflétant l'influence de la composition géologique locale Th/U (c-à-d. 208Pb) sur la composition isotopique du Pb dans les dents du morse. Les rapports isotopiques fondés sur 204Pb étaient constamment plus élevés (plus radiogéniques) et plus homogènes que ceux du substratum terrestre, la différence étant probablement due à la lixiviation sélective du Pb radiogénique passant des phases minérales dans l'eau de mer et à son mélange durant la météorisation et le transport. Les signatures isotopiques du plomb dentaire peuvent avoir de vastes applications dans la discrimination des stocks d'autres espèces de mammifères marins côtiers

Ground State H-Atom in Born-Infeld Theory

Within the context of Born-Infeld (BI) nonlinear electrodynamics (NED) we revisit the non-relativistic, spinless H-atom. The pair potential computed from the Born-Infeld equations is approximated by the Morse type potential with remarkable fit over the critical region where the convergence of both the short and long distance expansions slows down dramatically. The Morse potential is employed to determine both the ground state energy of the electron and the BI parameter.Comment: 4 pages, 1 figure, final version to appear in Foundation of Physic

Lorentz Invariant Superluminal Tunneling

It is shown that superluminal optical signalling is possible without violating Lorentz invariance and causality via tunneling through photonic band gaps in inhomogeneous dielectrics of a special kind.Comment: 10 pages revtex, no figure, more discussions added, submitted to Phys. Rev.

Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290

Contains fulltext : 108895.pdf (publisher's version ) (Open Access)PURPOSE: This study investigated the centrosomal protein, 290-KD (CEP290) associated genotype and ocular and extra-ocular phenotype in 18 patients with Leber congenital amaurosis (LCA). METHODS: Eighteen patients with LCA from 14 families with mutations in the CEP290 gene were identified with sequencing or with heteroduplex analysis. Ophthalmic examinations were performed on all patients. Scans of the central nervous system were reassessed in three patients and obtained in two. Renal function was evaluated in all patients. Ultrasonography of the kidneys was performed in six patients. RESULTS: Eight patients (from five families) carried the c.2991+1655A>G mutation homozygously. Nine solitary patients carried this variant combined with a nonsense, frameshift, or splice site mutation on the second allele. One new nonsense mutation was identified: c.1078C>T. Fourteen patients (from 12 families) had been completely blind from birth or had light perception. The best-recorded visual acuity was 20/200. Peripheral fundus changes appeared to be progressive with a relatively preserved posterior pole. Novel ophthalmic features for the CEP290 phenotype were Coats-like exudative vasculopathy in two patients, a small chorioretinal coloboma in one patient, and well defined, small, atrophic spots at the level of the retinal pigment epithelium causing a dot-like appearance in five patients. Some CEP290 patients exhibited systemic abnormalities. We found abnormal proprioception in two patients and mild mental retardation in one. One patient was infertile due to immobile spermatozoa. No renal abnormalities were detected. CONCLUSIONS: CEP290-associated LCA has a severe, progressive, and clinically identifiable phenotype. Distinct extra-ocular findings were noted, which may be attributed to ciliary dysfunction

New diagnostic and treatment strategies in renal artery stenosis: a promising pursuit or disappointment foretold?

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies

Generalized Global Defect Solutions

We investigate the presence of defect structures in generalized models described by real scalar field in $(1,1)$ space-time dimensions. We work with two distinct generalizations, one in the form of a product of functions of the field and its derivative, and the other as a sum. We search for static solutions and study the corresponding linear stability on general grounds. We illustrate the results with several examples, where we find stable defect structures of modified profile. In particular, we show how the new defect solutions may give rise to evolutions not present in the standard scenario in higher spatial dimensions.Comment: RevTex, 10 pages, 2 figures; version to appear in EPJ

Stargardt disease:monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry

PURPOSE: To assess the incidence of Stargardt disease (STGD1) and to evaluate demographics of incident cases. METHODS: For this retrospective cohort study, demographic, clinical and genetic data of patients with a clinical diagnosis of STGD1 were registered between September 2010 and January 2020 in a nationwide disease registry. Annual incidence (2014-2018) and point prevalence (2018) were assessed on the basis of this registry. RESULTS: A total of 800 patients were registered, 56% were female and 83% were of European ancestry. The incidence was 1.67-1.95:1,000,000 per year and the point prevalence in 2018 was approximately 1:22,000-1:19,000 (with and without 10% of potentially unregistered cases). Age at onset was associated with sex (p = 0.027, Fisher's exact); 1.9x more women than men were observed (140 versus 74) amongst patients with an age at onset between 10 and 19 years, while the sex ratio in other age-at-onset categories approximated one. Late-onset STGD1 (≥45 years) constituted 33% of the diagnoses in 2014-2018 compared to 19% in 2004-2008. Diagnostic delay (≥2 years between the first documentation of macular abnormalities and diagnosis) was associated with older age of onset (p = 0.001, Mann-Whitney). Misdiagnosis for age-related macular degeneration (22%) and incidental STGD1 findings (14%) was common in patients with late-onset STGD1. CONCLUSION: The observed prevalence of STGD1 in real-world data was lower than expected on the basis of population ABCA4 allele frequencies. Late-onset STGD1 was more frequently diagnosed in recent years, likely due to higher awareness of its phenotype. In this pretherapeutic era, mis- and underdiagnosis of especially late-onset STGD1 and the role of sex in STGD1 should receive special attention

Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy

Exome sequencing revealed a homozygous missense mutation (c.317C>G [p.Arg106Pro]) in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations (c.199_201del [p.Gln67del] and c.810+1G>T) in an unrelated person with cone-rod dystrophy. Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.Gln67del variant forms of POC1B. Morpholino-oligonucleotide-induced knockdown of poc1b translation in zebrafish resulted in a dose-dependent small-eye phenotype, impaired optokinetic responses, and decreased length of photoreceptor outer segments. These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs. Yeast two-hybrid screening of a human retinal cDNA library revealed FAM161A as a binary interaction partner of POC1B. This was confirmed in coimmunoprecipitation and colocalization assays, which both showed loss of FAM161A interaction with p.Arg106Pro and p.Gln67del variant forms of POC1B. FAM161A was previously implicated in autosomal-recessive retinitis pigmentosa and shown to be located at the base of the photoreceptor connecting cilium, where it interacts with several other ciliopathy-associated proteins. Altogether, this study demonstrates that POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors

Whole genome sequencing for USH2A-associated disease reveals several pathogenic deep-intronic variants that are amenable to splice correction

A significant number of individuals with a rare disorder such as Usher syndrome (USH) and (non-)syndromic autosomal recessive retinitis pigmentosa (arRP) remain genetically unexplained. Therefore, we assessed subjects suspected of USH2A-associated disease and no or mono-allelic USH2A variants using whole genome sequencing (WGS) followed by an improved pipeline for variant interpretation to provide a conclusive diagnosis. One hundred subjects were screened using WGS to identify causative variants in USH2A or other USH/arRP-associated genes. In addition to the existing variant interpretation pipeline, a particular focus was put on assessing splice-affecting properties of variants, both in silico and in vitro. Also structural variants were extensively addressed. For variants resulting in pseudoexon inclusion, we designed and evaluated antisense oligonucleotides (AONs) using minigene splice assays and patient-derived photoreceptor precursor cells. Biallelic variants were identified in 49 of 100 subjects, including novel splice-affecting variants and structural variants, in USH2A or arRP/USH-associated genes. Thirteen variants were shown to affect USH2A pre-mRNA splicing, including four deep-intronic USH2A variants resulting in pseudoexon inclusion, which could be corrected upon AON treatment. We have shown that WGS, combined with a thorough variant interpretation pipeline focused on assessing pre-mRNA splicing defects and structural variants, is a powerful method to provide subjects with a rare genetic condition, a (likely) conclusive genetic diagnosis. This is essential for the development of future personalized treatments and for patients to be eligible for such treatments.</p