Local synthesis of sex hormones:are there consequences for the ocular surface and dry eye?

Sex hormones are associated with the physiology and pathophysiology of almost all organs in the body, as well as most diseases. Interest in the associations between sex hormones and ocular tissues has increased in recent years. Androgens may have a positive effect on dry eye, whereas the effects of oestrogen on ocular conditions remain unclear. Intracrinology, the local synthesis and metabolism of hormones that is unique to humans, is of relevance to the eye and may help to explain why studies of the relationship between oestrogens and dry eye signs and symptoms are inconclusive. Knowledge of the pathways of hormone formation and metabolism is crucial to understanding the pathogenesis of ocular disease including dry eye. This review examines the mechanisms of steroidal sex hormone biosynthesis and reviews the significance of locally produced sex hormones, with a focus on ocular surface tissues. Much of the current literature is based on animal studies, which may not be transferable to humans due to the absence of intracrine production in animals. A large proportion of the human studies investigate systemic hormone levels rather than local levels. There is subsequently a need for additional studies to provide a better understanding of the local production of sex hormones within the human eye and ocular surface and to clarify the relationships between ocular levels of sex hormones and conditions including dry eye

Blink rate measured in situ decreases while reading from printed text or digital devices, regardless of task duration, difficulty or viewing distance

Purpose: To compare blinking measured in situ during various tasks and examine relationships with ocular surface symptoms. The day-to-day repeatability of the blink rate and interblink interval was assessed

Detailed clay mineralogy of the TriassicJurassic boundary section at Kendlbachgraben (Northern Calcareous Alps, Austria)

The Triassic-Jurassic boundary (TJB) is marked by one of the five largest Phanerozoic mass extinctions. To constrain existing models for TJB events, we obtained a stratigraphically highly resolved dataset from a marine section at Kendlbachgraben, Austria. The topmost Triassic Ko¨ssen Formation contains low to medium-charged smectite and vermiculite as alteration products of mafic-ultramafic minerals. The clay minerals in the boundary mudstone are kaolinite 5 illite + muscovite >> smectite > chlorite. Predominant kaolinite suggests humid climate and abundant terrigenous input. In the lowermost Jurassic, the clay mineral pattern changes to illite + muscovite >> kaolinite >> smectite, which reflects change to less humid and more moderate climate. The topmost Ko¨ssen Formation also contains clay spherules. Their composition, shape and size indicate that they are alteration products of airborne volcanic glass droplets solidified in the air, settled in the sea and altered rapidly with negligible transport in terrestrial or marine environments. Our data are consistent with sudden climatic change at the TJB, as a result of large-scale volcanic activity of the Central Atlantic Magmatic Province which produced distal airfall volcanic ash

Atomistic QM/MM simulations of the strength of covalent interfaces in carbon nanotube–polymer composites

We investigate the failure of carbon-nanotube/polymer composites by using a recently-developed hybrid quantum-mechanical/molecular-mechanical (QM/MM) approach to simulate nanotube pull-out from a cross-linked polyethene matrix. Our study focuses on the strength and failure modes of covalently-bonded nanotube–polymer interfaces based on amine, carbene and carboxyl functional groups and a [2+1] cycloaddition. We find that the choice of the functional group linking the polymer matrix to the nanotube determines the effective strength of the interface, which can be increased by up to 50% (up to the limit dictated by the strength of the polymer backbone itself) by choosing groups with higher interfacial binding energy. We rank the functional groups presented in this work based on the strength of the resulting interface and suggest broad guidelines for the rational design of nanotube functionalisation for nanotube–polymer composites

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

SUBARU prime focus spectrograph: integration, testing and performance for the first spectrograph

The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and Redshifts (SuMIRe) project for Subaru telescope consists in four identical spectrographs fed by 600 fibers each. Each spectrograph is composed by an optical entrance unit that creates a collimated beam and distributes the light to three channels, two visibles and one near infrared. This paper presents the on-going effort for the tests & integration process for the first spectrograph channel: we have developed a detailed Assembly Integration and Test (AIT) plan, as well as the methods, detailed processes and I&T tools. We describe the tools we designed to assemble the parts and to test the performance of the spectrograph. We also report on the thermal acceptance tests we performed on the first visible camera unit. We also report on and discuss the technical difficulties that did appear during this integration phase. Finally, we detail the important logistic process that is require to transport the components from other country to Marseille

Fast automated placement of polar hydrogen atoms in protein-ligand complexes

<p>Abstract</p> <p>Background</p> <p>Hydrogen bonds play a major role in the stabilization of protein-ligand complexes. The ability of a functional group to form them depends on the position of its hydrogen atoms. An accurate knowledge of the positions of hydrogen atoms in proteins is therefore important to correctly identify hydrogen bonds and their properties. The high mobility of hydrogen atoms introduces several degrees of freedom: Tautomeric states, where a hydrogen atom alters its binding partner, torsional changes where the position of the hydrogen atom is rotated around the last heavy-atom bond in a residue, and protonation states, where the number of hydrogen atoms at a functional group may change. Also, side-chain flips in glutamine and asparagine and histidine residues, which are common crystallographic ambiguities must be identified before structure-based calculations can be conducted.</p> <p>Results</p> <p>We have implemented a method to determine the most probable hydrogen atom positions in a given protein-ligand complex. Optimality of hydrogen bond geometries is determined by an empirical scoring function which is used in molecular docking. This allows to evaluate protein-ligand interactions with an established model. Also, our method allows to resolve common crystallographic ambiguities such as as flipped amide groups and histidine residues. To ensure high speed, we make use of a dynamic programming approach.</p> <p>Conclusion</p> <p>Our results were checked against selected high-resolution structures from an external dataset, for which the positions of the hydrogen atoms have been validated manually. The quality of our results is comparable to that of other programs, with the advantage of being fast enough to be applied on-the-fly for interactive usage or during score evaluation.</p

Smell and taste changes are early indicators of the COVID-19 pandemic and political decision effectiveness

In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201