julilili42/papers huggingface dataset:
The Molybdenum isotope subduction recycling conundrum: A case study from the Tongan subduction zone, Western Alps and Alpine Corsica
2021-04-16

Molybdenum isotopes have emerged as novel tracers for high-temperature igneous and metamorphic processes. The debate remains to what extent different subducted slab lithologies, such as oceanic crust and marine sediments, contribute to the Mo isotope signature of arc magmas and, hence, exert different controls on the terrestrial Mo cycle. Here we investigate Mo isotope systematics from input to output at the Tongan subduction zone: Arc lavas from different Tongan islands, pelagic sediments and altered oceanic crust (AOC) samples from DSDP site 595/596 on the subducting Pacific plate. For complementary insights into the fate of Mo and its isotopic signatures during prograde subduction metamorphism, we also present data of metasediments and variably altered AOC-type eclogites from the Zermatt-Saas ophiolite, Switzerland and Italy, and the Schistes Lustrés Complex in Alpine Corsica. Manganese oxide-rich pelagic sediments from DSDP site 595/596 show variable, depth-dependent Mo/Mn ratios and Mo isotope compositions controlled by diagenetic reactions. As subducted equivalents, Mn-rich eclogitic metapelites display lower Mo contents and δ98/95Mo ratios compared to their non-subducted protolith. This indicates prominent loss of Mo along with isotope fractionation during early subduction metamorphism. In comparison to unaltered MORB, low temperature seafloor alteration has shifted Mo/Ce and δ98/95Mo in studied AOC samples towards lower ratios, in the range of most mafic eclogites published so far. However, some mafic eclogites show even lower Mo/Ce and δ98/95Mo ratios compared to AOC, likely due to fluid-related Mo loss upon early subduction and preferential incorporation of light Mo into residual rutile. Our data document a prominent loss of isotopically heavy Mo before and upon early subduction metamorphism at shallow depths in the forearc region. Moreover, when prograde rutile crystallizes at ~30 km depth, it fixes the largest fraction of Mo in the subducting material. This creates an "arc Mo-conundrum" as devolatization of the slab at subarc depths is not able to account for the fluid-mobile Mo source responsible for observed higher Mo/Ce and δ98/95Mo in Tongan arc lavas compared to the mantle. As an alternative scenario, Mo mobilization by slab-derived aqueous fluids during the early stages of subduction into the forearc mantle produces serpentinites enriched in Mo with a possible heavy Mo isotopic signature. Mechanical transport and devolatization of forearc serpentinites at subarc regions is a plausible alternative recycling process accounting for the observed Mo systematics in Tongan arc lavas. This is supported by positive covariations of Mo/Ce and δ98/95Mo with elements such as As, Sb, and Cs, which are thought to be mostly released from the subducting material during early stages of subduction. We propose that a multi-stage recycling of metasomatized forearc mantle can be an important process in recycling of Mo and possibly other elements.
Genome-wide analysis of plant miRNA action clarifies levels of regulatory dynamics across developmental contexts
2021-04-16

Development of complex organisms requires the delicate and dynamic spatiotemporal regulation of gene expression. Central to this are microRNAs (miRNAs). These mobile small RNAs offer specificity in conveying positional information and versatility in patterning the outcomes of gene expression. However, the parameters that shape miRNA output during development are still to be clarified. Here, we address this question on a genome-wide scale, using the maize shoot apex as a model. We show that patterns and levels of miRNA accumulation are largely determined at the transcriptional level, but are finessed post-transcriptionally in a tissue-dependent manner. The stem cell environments of the shoot apical meristem and vasculature appear particularly liable to this. Tissue-specific effects are also apparent at the level of target repression, with target cleavage products in the vasculature exceeding those of other tissues. Our results argue against a clearance mode of regulation purely at the level of transcript cleavage, leading us to propose that transcript cleavage provides a baseline level of target repression, onto which miRNA-driven translational repression can act to toggle the mode of target regulation between clearance and rheostat. Our data show how the inherent complexities of miRNA pathways allow the accumulation and activity of these small RNAs to be tailored in space and time to bring about the gene expression versatility needed during development.
Association of low birth weight and polyparasitic infection during pregnancy in Lambaréné, Gabon
2021-04-16

Abstract Objective To report the prevalence of polyparasitism during pregnancy in the Lambaréné region of Gabon and its association with newborn birth weight. Method Pregnant women in their third trimester were recruited in a prospective study between November 2011 and March 2015. Parasite infection status was assessed microscopically in stool, urine and blood samples. Maternal demographic and obstetrical characteristics and newborns anthropometric data were collected. Multivariable logistic regression was used to assess the association between low birth weight and polyparasitism. Results 678 of 927 pregnant women were included for analysis with mean age (SD) of 25 (6.8) years. The analysis showed that 69% (468/678) were infected with at least one parasite ( Plasmodium spp ., Schistosoma spp ., soil‐transmitted helminths, filarial infections). This comprised of 38% with monoparasitism and 31% polyparasitism. The proportion of newborn babies with a weight below 2500 g (LBW) in our study was 21% (142/678). Compared to pregnant women without infection, women with monoparasitic infection had adjusted Odds Ratio confidence interval 95% CI (aOR [95%CI]) of 1.6 [0.95–2.73], those with two parasites had aOR 95%CI of 2.63 [1.51–4.62], and those with more than two parasites had aOR of 5.08 [2.5–10.38] for delivering a newborn with low birth weight. Conclusion In Lambaréné, an endemic area for multiple parasite infections, there is a high prevalence of polyparasitism in pregnant women. Polyparasitism is associated with low birth weight. Therefore, there is an urgent need for active screening and treatment of parasite infections in pregnant women to assess the potential public health benefit of such interventions.
Quantifying Stabilized Phase Purity in Formamidinium-Based Multiple-Cation Hybrid Perovskites
2021-04-16

A promising approach for the production of highly efficient and stable hybrid perovskite solar cells is employing mixed-ion materials. Remarkable performances have been reached by materials comprising a stabilized mixture of methylammonium (MA(+)) and formamidinium (FA(+)) as a monovalent cation. We compare and quantify the methods of stabilizing FA(-) based perovskites involving the additional blending of the smaller inorganic cations cesium (Cs+) and rubidium (Rb+), which can lead to an improvement in phase purity of black cubic perovskite modification. Even under excess lead iodide conditions, the presence of a separate PbI2 phase as well as hexagonal phases, which are very common for formamidinium-containing perovskites, can be drastically reduced or even completely prevented. In this aspect, adding both Cs+ and Rb+ showed greater effectivity than only adding Cs+, enabling an increase in the percentage of the cubic phase within the material from 45% in the double-cation FA:MA mixture to 97.8% in the quadruple composition. The impact of admixing inorganic cations on the perovskite crystal structure resulted in enlarged homogeneous crystallite sizes and a less pronounced orientational order and indicated also minor modifications of unit cell sizes. Finally, we discuss the impact of the phase purity on charge-carrier recombination dynamics and solar cell performance.
Cortical and subcortical gray matter changes in patients with chronic tinnitus sustaining after vestibular schwannoma surgery
2021-04-16

Abstract Tinnitus is attributed to partial sensory deafferentation resulting in a central maladaptive neuroplasticity. Unfortunately, the agent of deafferentation is usually unknown or irreversible. In patients with unilateral vestibular schwannoma (VS), however, the auditory nerve is affected by a benign tumor. Hence, removal of the tumor can cease the tinnitus. In turn, sustaining complaints after surgery indicate cortical neuroplasticity. The present study is a cross sectional study which aims to track cortical structural changes by surface-based morphometry in 46 VS patients with sustained (i.e. centralized) or ceased (i.e. peripheral) tinnitus after surgery. A volumetric analysis of cortical and subcortical gray matter (GM) anatomy was performed on preoperative high-resolution MRI and related to the presence of hearing impairment, pre- and/or postoperative tinnitus. Patients with sustained (i.e. chronic) tinnitus showed an increased GM volume of the bilateral caudate nucleus, the contralateral superior colliculus, the middle frontal and middle temporal gyrus, the fusiform gyrus as well as the ipsilateral pars orbitalis when compared to those patients in whom tinnitus ceased postoperatively. Chronic tinnitus in VS patients is associated with characteristic structural changes in frontal, temporal and subcortical areas. Notably, a significant GM change of the caudate nucleus was detected providing further support for the striatal gaiting model of tinnitus.
No association of genetic variants in TLR4, TNF-α, IL10, IFN-γ, and IL37 in cytomegalovirus-positive renal allograft recipients with active CMV infection—Subanalysis of the prospective randomised VIPP study
2021-04-16

Background Cytomegalovirus (CMV) infection is amongst the most important factors complicating solid organ transplantation. In a large prospective randomized clinical trial, valganciclovir prophylaxis reduced the occurrence of CMV infection and disease compared with preemptive therapy in CMV-positive renal allograft recipients (VIPP study; NCT00372229). Here, we present a subanalysis of the VIPP study, investigating single nucleotide polymorphisms (SNPs) in immune-response-related genes and their association with active CMV infection, CMV disease, graft loss or death, rejection, infections, and leukopenia. Methods Based on literature research ten SNPs were analyzed for TLR4 , three for IFN-γ , six for IL10 , nine for IL37 , and two for TNF-α . An asymptotic independence test (Cochran-Armitage trend test) was used to examine associations between SNPs and the occurrence of CMV infection or other negative outcomes. Statistical significance was defined as p&lt;0.05 and Bonferroni correction for multiple testing was performed. Results SNPs were analyzed on 116 blood samples. No associations were found between the analyzed SNPs and the occurrence of CMV infection, rejection and leukopenia in all patients. For IL37 rs2723186, an association with CMV disease (p = 0.0499), for IL10 rs1800872, with graft loss or death (p = 0.0207) and for IL10 rs3024496, with infections (p = 0.0258) was observed in all patients, however did not hold true after correction for multiple testing. Conclusion The study did not reveal significant associations between the analyzed SNPs and the occurrence of negative outcomes in CMV-positive renal transplant recipients after correction for multiple testing. The results of this association analysis may be of use in guiding future research efforts.
Specific heterozygous frameshift variants in hnRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy
2021-04-16

Summary RNA-binding proteins (RBPs) are essential for post-transcriptional regulation and processing of RNAs. Pathogenic missense variants in RBPs underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy, distal myopathy, and Paget’s disease of the bone. Here, we present ten independent families with a severe, progressive, early-onset muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD), caused by heterozygous frameshift variants in the prion-like domain of hnRNPA2B1 . We found that in contrast with the previously reported missense variants, the frameshift hnRNPA2B1 variants do not promote, but rather decelerate the fibrillization of the protein. Importantly, the frameshift variants harbor altered nuclear-localization sequences and exhibit reduced affinity for the nuclear-import receptor, Karyopherin-β2, which promotes their cytoplasmic accumulation in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with hnRNPA2B1 to include a severe, early-onset disease reminiscent of OPMD, caused by a distinct class of frameshift variants that alter its nucleocytoplasmic transport dynamics.
How To Handle Disaster? – Evaluation of a Course for Disaster Medicine and Humanitarian Assistance for Undergraduate Medical Students
2021-04-16

Abstract Background: Disaster medicine is a component of the German medical education since 2003. However, studies have shown some inconsistencies within the implementation of the national curriculum, and limits with the number of students trained over the years. Facing the SARS-CoV-2 pandemic and other disasters, it became much more important to train medical students in disaster medicine on a coordinated basis. Methods: The University Clinic for Anaesthesiology and Intensive Care Medicine in Tübingen, Germany, expanded the existing curriculum of undergraduate disaster medicine training with fundamentals of humanitarian medicine, integrating the experience with distance learning, interactive teaching and simulation sessions. Survey tools were used to assess participants’ previous experiences and interest in the field of disaster medicine, to compare the self-reported degree of knowledge before and after training, and the programme’s quality evaluation. A mandatory pre- and post-test of knowledge was also administered to evaluate learner outcomes. The prospective and cross-sectional study evaluates the pilot course Disaster Medicine and Humanitarian Assistance carried out for third-, fourth- and fifth- year medical students over five semesters during the period between 2018 and 2020. Results: Data was collected from 107 students over five training sessions. Out of a sample of 82 students, the subjective perception of knowledge increased after the course (t [81] = 24.426, p &lt; .001), alongside with the interest in engaging in the field of disaster medicine (t[81 ] = 7.031, p &lt; .001). 102 students entered the mandatory knowledge assessment, with the rate of correct answers passing from 73.27% in the pre-test to 95.23% in the post-test ( t [101] = 18.939, p &lt; .001). The 93.46% of the medical students ( N = 100) graded the training received with an excellent overall score (1.01 out of 6). Discussion: The study indicates a significant increase in students’ understanding of disaster medicine through the use of both subjective and objective measures, as well as an increase interest in the field of disaster and humanitarian medicine. The educational programme appears to address the deficiencies documented in previous studies, and possible adaptation with virtual reality approaches could expand access to a larger audience. Conclusion: The programme offers an effective and comprehensive tool to address the urgent need of quality education for medical students, suggesting integrated strategies to implement disaster medicine training.
A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes
2021-04-16

Abstract Three-dimensional cell technologies as pre-clinical models are emerging tools for mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neural tissues. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human induced pluripotent stem cell–derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.
Epigenetics and the success of invasive plants
2021-04-17

Biological invasions impose ecological and economic problems on a global scale, but also provide extraordinary opportunities for studying contemporary evolution. It is critical to understand the evolutionary processes that underly invasion success in order to successfully manage existing invaders, and to prevent future invasions. As successful invasive species sometimes are suspected to rapidly adjust to their new environments in spite of very low genetic diversity, we are obliged to re-evaluate genomic-level processes that translate into phenotypic diversity. In this paper, we review work that supports the idea that trait variation, within and among invasive populations, can be created through epigenetic or other non-genetic processes, particularly in clonal invaders where somatic changes can persist indefinitely. We consider several processes that have been implicated as adaptive in invasion success, focusing on various forms of ‘genomic shock’ resulting from exposure to environmental stress, hybridization and whole-genome duplication (polyploidy), and leading to various patterns of gene expression re-programming and epigenetic changes that contribute to phenotypic variation or even novelty. These mechanisms can contribute to transgressive phenotypes, including hybrid vigour and novel traits, and may thus help to understand the huge successes of some plant invaders, especially those that are genetically impoverished. This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’
Middle and Late Devonian paleogeography of the eastern Anti-Atlas (Morocco)
2021-04-17

Abstract The eastern Anti-Atlas of Morocco represents one of the most completely exposed and perfectly documented biostratigraphic records of the entire Devonian worldwide. Paleogeographically it is clearly differentiated into shallow basins, pelagic platforms, and land areas which are newly defined and illustrated, one from the top of the Middle Devonian, the other from the middle Famennian as two of the most characteristic intervals. The dominant paleogeographic feature is the T-shaped Tafilalt Platform which, in spite of common unconformities and hiatuses, provides the best-documented biostratigraphic record through the entire Devonian. The westernmost termination of this platform was emerged during most of the Devonian (and locally even earlier) and became only flooded again by the Tournaisian transgression. In contrast to previous interpretations, this area is considered as autochthonous. In the Mader Basin subsidence was up to one hundred times higher with respect to the adjacent platforms, but water depth during the Middle Devonian to middle Famennian interval generally remained above storm-wave base. Devonian rocks are only patchily and incompletely preserved on the Mader Platform, which can be considered as an intermittently flooded peninsula connected to the Lower Paleozoic farther west. The major paleotectonic element of the entire area is the Great Anti-Atlas Fault, a sinistral strike-slip fault, which sharply confines the above-mentioned realms in the south.
Olinciguat, a stimulator of soluble guanylyl cyclase, attenuates inflammation, vaso‐occlusion and nephropathy in mouse models of sickle cell disease
2021-04-17

Background and Purpose Reduced bioavailability of NO, a hallmark of sickle cell disease (SCD), contributes to intravascular inflammation, vasoconstriction, vaso‐occlusion and organ damage observed in SCD patients. Soluble guanylyl cyclase (sGC) catalyses synthesis of cGMP in response to NO. cGMP‐amplifying agents, including NO donors and phosphodiesterase 9 inhibitors, alleviate TNFα‐induced inflammation in wild‐type C57BL/6 mice and in ‘humanised’ mouse models of SCD. Experimental Approach Effects of the sGC stimulator olinciguat on intravascular inflammation and renal injury were studied in acute (C57BL6 and Berkeley mice) and chronic (Townes mice) mouse models of TNFα‐induced and systemic inflammation associated with SCD. Key Results Acute treatment with olinciguat attenuated increases in plasma biomarkers of endothelial cell activation and leukocyte‐endothelial cell interactions in TNFα‐challenged mice. Co‐treatment with hydroxyurea, an FDA‐approved SCD therapeutic agent, further augmented the anti‐inflammatory effect of olinciguat. In the Berkeley mouse model of TNFα‐induced vaso‐occlusive crisis, a single dose of olinciguat attenuated leukocyte‐endothelial cell interactions, improved blood flow and prolonged survival time compared to vehicle‐treated mice. In Townes SCD mice, plasma biomarkers of inflammation and endothelial cell activation were lower in olinciguat‐ than in vehicle‐treated mice. In addition, kidney mass, water consumption, 24‐h urine excretion, plasma levels of cystatin C and urinary excretion of N‐acetyl‐β‐d‐glucosaminidase and neutrophil gelatinase‐associated lipocalin were lower in Townes mice treated with olinciguat than in vehicle‐treated mice. Conclusion and Implications Our results suggest that the sGC stimulator olinciguat attenuates inflammation, vaso‐occlusion and kidney injury in mouse models of SCD and systemic inflammation.