CEMIP ( HYBID , KIAA1199 ): structure, function and expression in health and disease

CEMIP (cell migration-inducing protein), also known as KIAA1199 or HYBID, is a protein involved in the depolymerisation of hyaluronic acid (HA), a major glycosaminoglycan component of the extracellular matrix. CEMIP was originally described in patients affected by nonsyndromic hearing loss and has subsequently been shown to play a key role in tumour initiation and progression, as well as arthritis, atherosclerosis and idiopathic pulmonary fibrosis. Despite the vast literature associating CEMIP with these diseases, its biology remains elusive. The present review article summarises all the major scientific evidence regarding its structure, function, role and expression, and attempts to cast light on a protein that modulates EMT, fibrosis and tissue inflammation, an unmet key aspect in several inflammatory disease conditions

Differential expression of paralog RNA binding proteins establishes a dynamic splicing program required for normal cerebral cortex development

: sam68 and SLM2 are paralog RNA binding proteins (RBPs) expressed in the cerebral cortex and display similar splicing activities. however, their relative functions during cortical development are unknown. we found that these RBPs exhibit an opposite expression pattern during development. sam68 expression declines postnatally while SLM2 increases after birth, and this developmental pattern is reinforced by hierarchical control of sam68 expression by SLM2. analysis of sam68:Slm2 double knockout (Sam68:Slm2dko) mice revealed hundreds of exons that respond to joint depletion of these proteins. moreover, parallel analysis of single and double knockout cortices indicated that exons regulated mainly by SLM2 are characterized by a dynamic splicing pattern during development, whereas sam68-dependent exons are spliced at relatively constant rates. dynamic splicing of SLM2-sensitive exons is completely suppressed in the sam68:Slm2dko developing cortex. sam68:Slm2dko mice die perinatally with defects in neurogenesis and in neuronal differentiation, and develop a hydrocephalus, consistent with splicing alterations in genes related to these biological processes. thus, our study reveals that developmental control of separate sam68 and Slm2 paralog genes encoding homologous RBPs enables the orchestration of a dynamic splicing program needed for brain development and viability, while ensuring a robust redundant mechanism that supports proper cortical development

Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein

Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2´ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice expressing human ACE2 against infection when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants

Extending in vitro digestion models to specific human populations: Perspectives, practical tools and bio-relevant information

[EN] Background In vitro digestion models show great promise in facilitating the rationale design of foods. This paper provides a look into the current state of the art and outlines possible future paths for developments of digestion models recreating the diverse physiological conditions of specific groups of the human population. Scope and approach Based on a collective effort of experts, this paper outlines considerations and parameters needed for development of new in vitro digestion models, e.g. gastric pH, enzymatic activities, gastric emptying rate and more. These and other parameters are detrimental to the adequate development of in vitro models that enable deeper insight into matters of food luminal breakdown as well as nutrient and nutraceutical bioaccessibility. Subsequently, we present an overview of some new and emerging in vitro digestion models mirroring the gastro-intestinal conditions of infants, the elderly and patients of cystic fibrosis or gastric bypass surgery. Key findings and conclusions This paper calls for synchronization, harmonization and validation of potential developments in in vitro digestion models that would greatly facilitate manufacturing of foods tailored or even personalized, to a certain extent, to various strata of the human population.Shani-Levi, C.; Alvito, P.; Andrés Grau, AM.; Assunção, R.; Barbera, R.; Blanquet-Diot, S.; Bourlieu, C.... (2017). Extending in vitro digestion models to specific human populations: Perspectives, practical tools and bio-relevant information. Trends in Food Science & Technology. 60:52-63. https://doi.org/10.1016/j.tifs.2016.10.017S52636

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Caratterizzazione preliminare di Tmx5, una proteina transmembrana di tipo I della famiglia delle disolfuro isomerasi (PDI)

Tato diplomová práce se zabývá porovnáním didaktické vybavenosti učebnic chemie pro základní školy v České republice. První část práce je věnována teorii učebnic a jejich výzkumu. V další části se autorka věnuje komparaci učebnic z pohledu dvou metod: míry didaktické vybavenosti a stanovování didaktických kritérií. Učebnice chemie pro základní školy v České republice jsou dle výsledků této práce dobře didakticky vybavené. Analyzované učebnice obsahují podobné strukturní prvky. Mezi nejlépe didakticky vybavenými učebnicemi (učebnice nakladatelství Nová škola, Fraus) a těmi s nejnižšími výsledky (učebnice nakladatelství Taktik) byly nalezeny jen malé rozdíly, přestože doba, která uplynula mezi vydáním nejnovější a nejstarší učebnice činí více než 25 let. Z důvodu homogenity výsledků, a s ní spojenou nižší možností učebnice srovnávat, byla dále aplikována metoda stanovování didaktických kritérií. Ta sice nenabízí absolutní určení toho, která z učebnic je nejvhodnější pro výuku, zato předkládá další náhled na hodnocené učebnice, např. z hlediska otázek a úkolů, obrazů či pokusů, které mohou vypovídat o kvalitě učebnic. Nejlépe vybavené učebnice jsou první díly učebnic nakladatelství Fraus a Základy chemie. Naopak nejnižší vybaveností disponují druhé díly učebnic nakladatelství Taktik a Základy...This thesis deals with the comparison of didactical equipment of Chemistry Textbooks for Basic Schools in the Czech Republic. The first part of the thesis is dedicated to the theory of textbooks and their research within it. The next part, which includes comparison of the textbooks, is pursued by the author from the perspective of two methods: the first being The Degree of Didactical Equipment and the second one The Determination of Didactical Criterion. According to the results of this thesis, the Chemistry Textbooks for Basic Schools in the Czech Republic are alike in its didactical equipment. There are similar structural components in each analysed textbook. There were found only small differences between the best didactically equipped textbooks (the textbooks of the publishers Nová škola and Fraus) and those with the lowest outcome (the textbooks of the publisher Taktik), although the time period between publishing the newest and the oldest textbook is more than 25 years. Due to homogeneity of the results and therefore lower possibility of comparing textbooks the method of the Determination of Didactical Criterion was applied. The method does not offer the final account of the most suitable textbook for school education but it presents different view of analysed textbooks, for example the...Katedra chemie a didaktiky chemiePedagogická fakultaFaculty of Educatio