The molecular phylogeny of eph receptors and ephrin ligands

<p>Abstract</p> <p>Background</p> <p>The tissue distributions and functions of Eph receptors and their ephrin ligands have been well studied, however less is known about their evolutionary history. We have undertaken a phylogenetic analysis of Eph receptors and ephrins from a number of invertebrate and vertebrate species.</p> <p>Results</p> <p>Our findings indicate that Eph receptors form three major clades: one comprised of non-chordate and cephalochordate Eph receptors, a second comprised of urochordate Eph receptors, and a third comprised of vertebrate Eph receptors. Ephrins, on the other hand, fall into either a clade made up of the non-chordate and cephalochordate ephrins plus the urochordate and vertebrate ephrin-Bs or a clade made up of the urochordate and vertebrate ephrin-As.</p> <p>Conclusion</p> <p>We have concluded that Eph receptors and ephrins diverged into A and B-types at different points in their evolutionary history, such that primitive chordates likely possessed an ancestral ephrin-A and an ancestral ephrin-B, but only a single Eph receptor. Furthermore, ephrin-As appear to have arisen in the common ancestor of urochordates and vertebrates, whereas ephrin-Bs have a more ancient bilaterian origin. Ancestral ephrin-B-like ligands had transmembrane domains; as GPI anchors appear to have arisen or been lost at least 3 times.</p

Dehydration of subducting slow-spread oceanic lithosphere in the Lesser Antilles

Subducting slabs carry water into the mantle and are a major gateway in the global geochemical water cycle. Fluid transport and release can be constrained with seismological data. Here we use joint active-source/local-earthquake seismic tomography to derive unprecedented constraints on multi-stage fluid release from subducting slow-spread oceanic lithosphere. We image the low P-wave velocity crustal layer on the slab top and show that it disappears beneath 60–100 km depth, marking the depth of dehydration metamorphism and eclogitization. Clustering of seismicity at 120–160 km depth suggests that the slab’s mantle dehydrates beneath the volcanic arc, and may be the main source of fluids triggering arc magma generation. Lateral variations in seismic properties on the slab surface suggest that serpentinized peridotite exhumed in tectonized slow-spread crust near fracture zones may increase water transport to sub-arc depths. This results in heterogeneous water release and directly impacts earthquakes generation and mantle wedge dynamics

Short term non-invasive ventilation post-surgery improves arterial blood-gases in obese subjects compared to supplemental oxygen delivery - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>In the immediate postoperative period, obese patients are more likely to exhibit hypoxaemia due to atelectasis and impaired respiratory mechanics, changes which can be attenuated by non-invasive ventilation (NIV). The aim of the study was to evaluate the duration of any effects of early initiation of short term pressure support NIV vs. traditional oxygen delivery via venturi mask in obese patients during their stay in the PACU.</p> <p>Methods</p> <p>After ethics committee approval and informed consent, we prospectively studied 60 obese patients (BMI 30-45) undergoing minor peripheral surgery. Half were randomly assigned to receive short term NIV during their PACU stay, while the others received routine treatment (supplemental oxygen via venturi mask). Premedication, general anaesthesia and respiratory settings were standardized. We measured arterial oxygen saturation by pulse oximetry and blood gas analysis on air breathing. Inspiratory and expiratory lung function was measured preoperatively (baseline) and at 10 min, 1 h, 2 h, 6 h and 24 h after extubation, with the patient supine, in a 30 degrees head-up position. The two groups were compared using repeated-measure analysis of variance (ANOVA) and t-test analysis. Statistical significance was considered to be P < 0.05.</p> <p>Results</p> <p>There were no differences at the first assessment. During the PACU stay, pulmonary function in the NIV group was significantly better than in the controls (p < 0.0001). Blood gases and the alveolar to arterial oxygen partial pressure difference were also better (p < 0.03), but with the addition that overall improvements are of questionable clinical relevance. These effects persisted for at least 24 hours after surgery (p < 0.05).</p> <p>Conclusion</p> <p>Early initiation of short term NIV during in the PACU promotes more rapid recovery of postoperative lung function and oxygenation in the obese. The effect lasted 24 hours after discontinuation of NIV. Patient selection is necessary in order to establish clinically relevant improvements.</p> <p>Trial Registration#</p> <p>DRKS00000751; <url>http://www.germanctr.de</url></p

A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5′UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA–binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1–null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

A new classification of earthquake-induced landslide event sizes based on seismotectonic, topographic, climatic and geologic factors

Background This paper reviews the classical and some particular factors contributing to earthquake-triggered landslide activity. This analysis should help predict more accurately landslide event sizes, both in terms of potential numbers and affected area. It also highlights that some occurrences, especially those very far from the hypocentre/activated fault, cannot be predicted by state-of-the-art methods. Particular attention will be paid to the effects of deep focal earthquakes in Central Asia and to other extremely distant landslide activations in other regions of the world (e.g. Saguenay earthquake 1988, Canada). Results The classification of seismically induced landslides and the related ‘event sizes’ is based on five main factors: ‘Intensity’, ‘Fault factor’, ‘Topographic energy’, ‘Climatic background conditions’, ‘Lithological factor’. Most of these data were extracted from papers, but topographic inputs were checked by analyzing the affected region in Google Earth. The combination and relative weight of the factors was tested through comparison with well documented events and complemented by our studies of earthquake-triggered landslides in Central Asia. The highest relative weight (6) was attributed to the ‘Fault factor’; the other factors all received a smaller relative weight (2–4). The high weight of the ‘Fault factor’ (based on the location in/outside the mountain range, the fault type and length) is strongly constrained by the importance of the Wenchuan earthquake that, for example, triggered far more landslides in 2008 than the Nepal earthquake in 2015: the main difference is that the fault activated by the Wenchuan earthquake created an extensive surface rupture within the Longmenshan Range marked by a very high topographic energy while the one activated by the Nepal earthquake ruptured the surface in the frontal part of the Himalayas where the slopes are less steep and high. Finally, the calibrated factor combination was applied to almost 100 other earthquake events for which some landslide information was available. This comparison revealed the ability of the classification to provide a reasonable estimate of the number of triggered landslides and of the size of the affected area. According to this prediction, the most severe earthquake-triggered landslide event of the last one hundred years would actually be the Wenchuan earthquake in 2008 followed by the 1950 Assam earthquake in India – considering that the dominating role of the Wenchuan earthquake data (including the availability of a complete landslide inventory) for the weighting of the factors strongly influences and may even bias this result. The strongest landslide impacts on human life in recent history were caused by the Haiyuan-Gansu earthquake in 1920 – ranked as third most severe event according to our classification: its size is due to a combination of high shaking intensity, an important ‘Fault factor’ and the extreme susceptibility of the regional loess cover to slope failure, while the surface morphology of the affected area is much smoother than the one affected by the Wenchuan 2008 or the Nepal 2015 earthquakes. Conclusions The main goal of the classification of earthquake-triggered landslide events is to help improve total seismic hazard assessment over short and longer terms. Considering the general performance of the classification-prediction, it can be seen that the prediction either fits or overestimates the known/observed number of triggered landslides for a series of earthquakes, while it often underestimates the size of the affected area. For several events (especially the older ones), the overestimation of the number of landslides can be partly explained by the incompleteness of the published catalogues. The underestimation of the extension of the area, however, is real – as some particularities cannot be taken into account by such a general approach: notably, we used the same seismic intensity attenuation for all events, while attenuation laws are dependent on regional tectonic and geological conditions. In this regard, it is likely that the far-distant triggering of landslides, e.g., by the 1988 Saguenay earthquake (and the related extreme extension of affected area) is due to a very low attenuation of seismic energy within the North American plate. Far-distant triggering of landslides in Central Asia can be explained by the susceptibility of slopes covered by thick soft soils to failure under the effect of low-frequency shaking induced by distant earthquakes, especially by the deep focal earthquakes in the Pamir – Hindukush seismic region. Such deep focal and high magnitude (> > 7) earthquakes are also found in Europe, first of all in the Vrancea region (Romania). For this area as well as for the South Tien Shan we computed possible landslide event sizes related to some future earthquake scenarios