Unusual echinoid resting trace records change in the position of the redox boundary (Palaeogene of the Lesser Caucasus in Georgia)

The first recognition of a tracemaker responding to a temporary shift in the redox boundary is recognized. This is recorded by a new trace fossil, Sursumichnus orbicularis igen. et isp. nov., which is established for mound-like structures on the upper surfaces of sandstone beds from the Borjomi Flysch (upper Paleocene–lower Eocene) in the Lesser Caucasus (Georgia). It is connected with the spatangoid echinoid burrow Scolicia de Quatrefages, 1849 and interpreted as a resting trace of the same tracemaker produced after moving up from a deeper position within the sediment. The resting is caused by an episode of unfavourable conditions related to shallowing of the redox boundary. The trace fossil is a component of the Nereites ichnofacies

Browser-based visualization framework Tracer for Outreach & Education

Education & outreach is an important part of HEP experiments. With outreach & education, experiments can have an impact on the public, students and their teachers, as well as policymakers and the media. The tools and methods for visualization enable to represent the detectors’ facilities, explaining their purpose, functionalities, development histories, and participant institutes. In addition, they make it possible to visualize different physical events together with important parameters and plots for physics analyses. 3D visualization and advanced VR (Virtual Reality), AR (Augmented Reality) and MR (Mixed Reality) extensions are the keys for successful outreach & education. This paper describes requirements and methods for the creation of browser-based visualization applications for outreach & education. The visualization framework TRACER is considered as a case study

Revision of the trace fossil Megagrapton Książkiewicz, 1968 with focus on Megagrapton aequale Seilacher, 1977 from the lower Eocene of the Lesser Caucasus in Georgia

Megagrapton Książkiewicz, 1968 is a characteristic deep-sea trace fossil belonging to the group of graphoglyptids and mostly preserved as a network of irregular meshes in hypichnial semirelief. So far, eleven ichnospecies have been distinguished under this ichnogenus, though commonly on weak evidence. The so-far poorly known ichnospecies Megagrapton aequale Seilacher, 1977 is described here on the basis of the numerous, newly discovered specimens from deep-sea siliciclastic deposits of the Bolevani Subsuite (lower Eocene) in the Lesser Caucasus of Georgia, together with other collections and published examples. A neotype of this ichnospecies is designated and the diagnosis emended. M. aequale occurs in lower Cambrian to upper Miocene deep-sea turbiditic deposits, mostly in the Paleogene. It is characterized by relatively small, variable meshes, which have mostly irregular sub-pentagonal, sub-hexagonal or sub-heptagonal shapes that are variable in size and are bordered by curved or straight semicircular ridges. It has been mistaken for Paleodictyon, which forms regular hexagonal nets. Paleodictyon imperfectum Seilacher, 1977 is included in M. aequale as the ichnosubspecies M. a. imperfectum, which is characterized by relatively thin bordering ridges. After critical analysis of all ichnospecies, only M. irregulare Książkiewicz, 1968, M. submontanum (Azpeitia Moros, 1933), and M. aequale are recommended for further use. These are distinguished on the basis of the prevailing morphology of the meshes, irrespective of large differences in morphometric parameters within the ichnospecies. Irredictyon chaos Vialov, 1972 is included in M. irregulare as the ichnosubspecies M. i. chaos, which is characterized by relatively thick bordering ridges. Megagrapton is interpreted as a cast of a subsurface open burrow network with a few connections to the sea floor. The burrows probably functioned as a trap for small organisms (ethological subcategory irretichnia)

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 x 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P &lt; 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology

Association of Rare CYP39A1 Variants with Exfoliation Syndrome Involving the Anterior Chamber of the Eye

IMPORTANCE: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. OBJECTIVE: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. DESIGN, SETTING, AND PARTICIPANTS: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. EXPOSURES: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. MAIN OUTCOMES AND MEASURES: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10(−6). The secondary outcomes included biochemical enzymatic assays and gene expression analyses. RESULTS: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10(−7)). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. CONCLUSIONS AND RELEVANCE: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings

Genetic Association Study Of Exfoliation Syndrome Identifies A Protective Rare Variant At Loxl1 And Five New Susceptibility Loci

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 x 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.Wo