bluuebunny/crossref_metadata_2025 huggingface dataset:
Faktorielle und kriteriale Validität von BiSpra 2 – 4
Authors: Heppt Birgit , Volodina Anna , Eglinsky Jenny , Stanat Petra , Weinert Sabine
Published: November 2020

Zusammenfassung. Bildungssprachliche Kompetenzen sind für den Schulerfolg unabdingbar. Jedoch mangelt es bisher an validen Instrumenten zu ihrer Erfassung. Im vorliegenden Beitrag stellen wir das Testinstrument BiSpra 2 – 4 vor, mit dem sich verschiedene Facetten des Verständnisses von Bildungssprache bei Grundschulkindern der Klassenstufen 2 bis 4 bestimmen lassen. Anschließend werden Ergebnisse aus zwei Validierungsstudien berichtet. Studie 1 ( N = 3 658 Grundschulkinder) dient der Überprüfung der faktoriellen Validität von BiSpra 2 – 4. In Studie 2 ( N = 714 Grundschulkinder) wird die kriteriale Validität anhand von Zusammenhängen mit zeitgleich und zeitversetzt erhobenen schulischen Leistungstests betrachtet. Konfirmatorische Faktorenanalysen bestätigen die theoretisch angenommene dreifaktorielle Struktur von BiSpra 2 – 4. Korrelativ zeigen sich zudem positive Zusammenhänge zwischen den Untertests von BiSpra 2 – 4 mit dem Leseverständnis, den arithmetischen Fertigkeiten und dem mathematischen Problemlösen. Auch unter Kontrolle eher allgemeiner Wortschatzkenntnisse und des Satzverständnisses bestehen signifikante Korrelationen mit den Testleistungen in den Schulleistungstests, was auf die kriteriale Validität von BiSpra 2 – 4 hinweist.
Vergleich von Intelligenztestleistungen bei monolingualen und bilingualen Kindern und Jugendlichen in den Intelligence and Development Scales–2 (IDS-2)
Authors: Schweizer Florine , Grieder Silvia , Bünger Anette , Grob Alexander
Published: November 2020

Zusammenfassung. Die Studie untersucht Mittelwertdifferenzen bei Monolingualen und Bilingualen in der allgemeinen Intelligenz sowie 7 Faktoren mit je 2 Untertests mit den Intelligence and Development Scales-2 (IDS-2; Grob & Hagmann-von Arx, 2018 ). Die Stichprobe besteht aus je 132 gepaarten monolingualen, simultan bilingualen und sukzessiv bilingualen Kindern und Jugendlichen der Normierungs- und Validierungsstichprobe ( MAlter = 12.34, SDAlter = 4.44; 48 % Jungen). In einer einfaktoriellen Varianzanalyse wurde in der allgemeinen Intelligenz 5 – 7 %, im Langzeitgedächtnis 3 % und im Denken Verbal 11 % der Varianz durch die Gruppenzugehörigkeit erklärt: Die sukzessiv Bilingualen erzielten in der allgemeinen Intelligenz, im verbalen Langzeitgedächtnis und im verbalen Denken niedrigere Werte als die Monolingualen und teilweise auch als die simultan Bilingualen, während die Unterschiede zwischen simultan Bilingualen und Monolingualen nicht bedeutsam waren. Die Befunde implizieren, dass ein möglicher sprachlicher Nachteil für Personen mit fremdsprachigem Hintergrund bei der Interpretation der Intelligenz-Testergebnisse in den IDS-2 berücksichtigt werden muss.
Serious Suicide Attempts and Risk of Suicide Death
Authors: Prabhakar Deepak , Peterson Edward L. , Hu Yong , Chawa Simran , Rossom Rebecca C. , Lynch Frances L. , Lu Christine Y. , Waitzfelder Beth E. , Owen-Smith Ashli A. , Williams L. Keoki , Beck Arne , Simon Gregory E. , Ahmedani Brian K.
Published: November 2020

Abstract. Background: In the US, more than one million people attempt suicide each year. History of suicide attempt is a significant risk factor for death by suicide; however, there is a paucity of data from the US general population on this relationship. Aim: The objective of this study was to examine suicide attempts needing medical attention as a risk for suicide death. Method: We conducted a case–control study involving eight US healthcare systems. A total of 2,674 individuals who died by suicide from 2000 to 2013 were matched to 267,400 individuals by year and location. Results: Prior suicide attempt associated with a medical visit increases risk for suicide death by 39.1 times, particularly for women ( OR = 79.2). However, only 11.3% of suicide deaths were associated with an attempt that required medical attention. The association was the strongest for children 10–14 years old ( OR = 98.0). Most suicide attempts were recorded during the 20-week period prior to death. Limitations: Our study is limited to suicide attempts for which individuals sought medical care. Conclusion: In the US, prior suicide attempt is associated with an increased risk of suicide death; the risk is high especially during the period immediately following a nonlethal attempt.
Suicidal as Normal – A Lesbian, Gay, and Bisexual Youth Script?
Authors: Canetto Silvia Sara , Antonelli Paolo , Ciccotti Anna , Dettore Davide , Lamis Dorian A.
Published: November 2020

Abstract. Background: Lesbian, gay, and bisexual (LGB) youth are more likely to report suicidal thoughts and/or behavior (STB) than heterosexual youth. The elevated suicidality of LGB youth is not fully accounted for by sexual-minority stress, according to a meta-analysis. A less-tested explanation is that suicidality has become an expected idiom of LGB youth distress. This explanation is consistent with suicide script theory and evidence that suicidal behavior is most likely when it is relatively acceptable. Aims: Building on suicide script theory and evidence, two studies were designed: one of LGB youth attitudes about suicidal behavior, and the other of LGB youth attitudes about suicidal individuals. Method: Surveys of LGB and heterosexual youth (total N = 300; M age = 20; 51% female) were conducted. Results: LGB youth were more accepting of and empathic toward suicidal behavior than heterosexual youth. They also viewed suicidal individuals as more emotionally adjusted. Limitations: Attitudes were not examined by sexual-minority subgroups. Conclusion: LGB youth's understanding attitudes may translate into less judgmental behavior toward suicidal peers, but also into normalizing suicidality as a way to express distress and cope with life problems. There may be utility in evaluating LGB youth suicide attitudes in suicide prevention initiatives.
Greening the Friendly Skies
Authors: Betancourt Mark
Published: November 2020

Decarbonizing the aviation industry won’t be easy. The coronavirus pandemic complicates the situation but also presents an opportunity.
Joint Inversions of Ground Deformation, Extrusion Flux, and Gas Emissions Using Physics‐Based Models for the Mount St. Helens 2004–2008 Eruption
Authors: Wong Ying‐Qi , Segall Paul
Published: November 2020

With the increasing quantity and quality of data collected at volcanoes, there is growing potential to incorporate all the data into analyses of magmatic systems. Physics‐based models provide a natural and meaningful way to bring together real‐time monitoring data and laboratory analyses of eruption products, with the goal of better understanding volcanic processes. We develop a framework for joint inversions of diverse time series data using the physics‐based model for dome‐forming eruptions from Wong and Segall (2019, https://doi.org/10.1029/2019JB017585). Applying this method to the 2004–2008 eruption at Mount St. Helens, we estimate essential system parameters, including chamber geometry, pressure, volatile content, and material properties, from extruded volume, ground deformation, and carbon dioxide emissions time series. The model parameter space is first sampled using the neighborhood search algorithm (Sambridge, 1999b, https://doi.org/10.1046/j.1365-246X.1999.00876.x). The resulting ensemble of models is resampled to generate posterior probability density functions on the parameters (Sambridge, 1999a, https://doi.org/10.1046/j.1365-246x.1999.00900.x). We find models that fit all three data sets well. Posterior probability density functions suggest an elongate chamber with aspect ratio less than 0.55, located at 9–17 km depth. Since the model calculates pressure change during the eruption, we can constrain chamber volume to 64–256 km3. Volume loss in the chamber during the eruption is 20–66 million m3. At the top of the chamber, total (dissolved and exsolved) water contents are 5.0–6.4 wt% and total carbon dioxide contents are 1,600–3,900 ppm, giving a porosity of 5%–16% depending on the conduit length. Compared to previous inversions using a steady‐state conduit model, we obtain a lower magma permeability scale, radius, and friction coefficient.
Tectonics, Dynamics, and Plio‐Pleistocene Magmatism in the Central Tyrrhenian Sea: Insights From the Submarine Transitional Basalts of the Ventotene Volcanic Ridge (Pontine Islands, Italy)
Authors: Conte A. M. , Perinelli C. , Bosman A. , Castorina F. , Conti A. , Cuffaro M. , Di Vincenzo G. , Martorelli E. , Bigi S.
Published: November 2020

In the Tyrrhenian back‐arc basin, the Ventotene Volcanic Ridge (VR) represents a NW‐SE‐oriented morphological high, located 25 km north of Ventotene Island in the Eastern Pontine Islands. It is considered part of an alignment of volcanic edifices developed in the central‐eastern Tyrrhenian Sea, from the western Pontine Islands (WPI) to the Campanian Volcanic Region. The samples dredged along the VR are basalts to trachybasalts belonging to the transitional (TR) rock‐series, with a 40Ar‐39Ar age of 2.760 ± 0.039 Ma. Petrological and geochronological data link the VR basalts to the TR peralkaline rhyolites cropping out at the WPI (∼1.6‐1.1 Ma); here, during a time span of ∼4.5‐1.0 Ma highly differentiated products of high‐potassium calc‐alkaline (HKCA, ∼4.5‐2.9 Ma) and K‐alkaline (KA, ∼1 Ma) series were also erupted. Notably, the parental melts of the three rock‐series were recognized in the continental slope close to the WPI (TR, HKCA) and eastward, namely in eastern Pontine Islands (KA), at the VR (TR), and in the Campanian Plain (HKCA). All the parental melts show typical orogenic geochemical signatures being originated from a similar heterogeneous suprasubduction mantle source, without the involvement of anorogenic sources. Tectonically, the faults bordering the VR, associated to the Pliocene E‐W directed rifting stage of the Tyrrhenian back‐arc basin were characterized by a more intense activity during the time span ∼5.0‐2.0 Ma (the emplacement time of HKCA and TR series), while KA products are related to a later stage of extension deformation (<∼2.0 Ma) when the extensional direction changed to NW‐SE and the VR fault activity decreased.
Aerosol Forcing Masks and Delays the Formation of the North Atlantic Warming Hole by Three Decades
Authors: Dagan Guy , Stier Philip , Watson‐Parris Duncan
Published: November 2020

The North Atlantic warming hole (NAWH) is referred to as a reduced warming, or even cooling, of the North Atlantic during an anthropogenic‐driven global warming. A NAWH is predicted by climate models during the 21st century, and its pattern is already emerging in observations. Despite the known key role of the North Atlantic surface temperatures in setting the Northern Hemisphere climate, the mechanisms behind the NAWH are still not fully understood. Using state‐of‐the‐art climate models, we show that anthropogenic aerosol forcing opposes the formation of the NAWH (by leading to a local warming) and delays its emergence by about 30 years. In agreement with previous studies, we also demonstrate that the relative warming of the North Atlantic under aerosol forcing is due to changes in ocean heat fluxes, rather than air‐sea fluxes. These results suggest that the predicted reduction in aerosol forcing during the 21st century may accelerate the formation of the NAWH.
On the Thermal Signature of the Residual Foam in Breaking Waves
Authors: Masnadi Naeem , Chickadel C. Chris , Jessup Andrew T.
Published: November 2020

Quantifying energy dissipation due to wave breaking remains an essential but elusive goal for studying and modeling air‐sea fluxes of heat, gas, and momentum. Previous observations have shown that lifetimes of bubble plumes and surface foam are directly related to the dissipated energy. Specifically, the foam decay time can be used to estimate the timescale of the subsurface bubble plume and the energy dissipated in the breaking process. A mitigating factor is that the foam decay time can be significantly affected by the surfactant concentration. Here we present an experimental investigation of a new technique that exploits the thermal signature of cooling foam to infer wave breaking dynamics. The experiments were conducted in a laboratory wave tank using artificial seawater with and without the addition of a surfactant. We show that the time from the start of the breaking process to the onset of cooling scales with the bubble plume decay time and the dissipated energy, and is not significantly affected by the presence of additional surfactants. We confirm observations from the field of the spatial variability of the temperature of foam generated by an individual breaking event, which has implications for inferring the spatial variability of bubble plume depth.
Including Regional Knowledge Improves Baseflow Signature Predictions in Large Sample Hydrology
Authors: Gnann Sebastian J. , McMillan Hilary K. , Woods Ross A. , Howden Nicholas J. K.
Published: November 2020

A catchment's hydrological response is controlled by climatic forcing and by the landscape through which water moves. Yet when we compare large samples of catchments, we often find climate to be the only good predictor of the hydrological response and a lot of variability is left unexplained. This contradicts extensive evidence from field and regional studies which shows the importance of catchment form (e.g., geology) on catchment hydrological processes, particularly on baseflow processes. We hypothesize that this is due to limitations in (a) the catchment attributes we use to inform our analyses and (b) the hydrological signatures we use to describe the hydrological response. To test these hypotheses, we use a large sample of catchment data across the contiguous United States. By reviewing literature from several U.S. regions, we show that region‐specific knowledge is underutilized in large sample studies. To organize the findings from these regions, we propose and apply a framework based on standardized perceptual models. Informed by these perceptual models, we use both available and newly calculated catchment attributes to show that baseflow signature predictions can be improved regionally. Multiple baseflow signatures are needed to better distinguish between different baseflow sources, such as the subsurface, surface water bodies, and snow. We conclude with pointing at potential future directions and argue that we should aim at a more systematic and hydrologically motivated selection of catchment attributes and hydrological signatures.
Crystalline iron oxides stimulate methanogenic benzoate degradation in marine sediment-derived enrichment cultures
Authors: Aromokeye David A , Oni Oluwatobi E , Tebben Jan , Yin Xiuran , Richter-Heitmann Tim , Wendt Jenny , Nimzyk Rolf , Littmann Sten , Tienken Daniela , Kulkarni Ajinkya C , Henkel Susann , Hinrichs Kai-Uwe , Elvert Marcus , Harder Tilmann , Kasten Sabine , Friedrich Michael W
Published: November 2020

Elevated dissolved iron concentrations in the methanic zone are typical geochemical signatures of rapidly accumulating marine sediments. These sediments are often characterized by co-burial of iron oxides with recalcitrant aromatic organic matter of terrigenous origin. Thus far, iron oxides are predicted to either impede organic matter degradation, aiding its preservation, or identified to enhance organic carbon oxidation via direct electron transfer. Here, we investigated the effect of various iron oxide phases with differing crystallinity (magnetite, hematite, and lepidocrocite) during microbial degradation of the aromatic model compound benzoate in methanic sediments. In slurry incubations with magnetite or hematite, concurrent iron reduction, and methanogenesis were stimulated during accelerated benzoate degradation with methanogenesis as the dominant electron sink. In contrast, with lepidocrocite, benzoate degradation, and methanogenesis were inhibited. These observations were reproducible in sediment-free enrichments, even after five successive transfers. Genes involved in the complete degradation of benzoate were identified in multiple metagenome assembled genomes. Four previously unknown benzoate degraders of the genera Thermincola (Peptococcaceae, Firmicutes), Dethiobacter (Syntrophomonadaceae, Firmicutes), Deltaproteobacteria bacteria SG8_13 (Desulfosarcinaceae, Deltaproteobacteria), and Melioribacter (Melioribacteraceae, Chlorobi) were identified from the marine sediment-derived enrichments. Scanning electron microscopy (SEM) and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) images showed the ability of microorganisms to colonize and concurrently reduce magnetite likely stimulated by the observed methanogenic benzoate degradation. These findings explain the possible contribution of organoclastic reduction of iron oxides to the elevated dissolved Fe2+ pool typically observed in methanic zones of rapidly accumulating coastal and continental margin sediments.
Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings
Authors: Ramoz Nicolas , Hoertel Nicolas , Nobile Bénédicte , Voegeli Géraldine , Nasr Ariane , Le Strat Yann , Courtet Philippe , Gorwood Philip
Published: November 2020

Polymorphisms of genes involved in the hypothalamic–pituitary–adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6–8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C–rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.
Molecular basis of CTCF binding polarity in genome folding
Authors: Nora Elphège P. , Caccianini Laura , Fudenberg Geoffrey , So Kevin , Kameswaran Vasumathi , Nagle Abigail , Uebersohn Alec , Hajj Bassam , Saux Agnès Le , Coulon Antoine , Mirny Leonid A. , Pollard Katherine S. , Dahan Maxime , Bruneau Benoit G.
Published: November 2020

Current models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially stabilize loops, the molecular basis of this polarity remains unclear. By combining ChIP-seq and single molecule live imaging we report that CTCF positions cohesin, but does not control its overall binding dynamics on chromatin. Using an inducible complementation system, we find that CTCF mutants lacking the N-terminus cannot insulate TADs properly. Cohesin remains at CTCF sites in this mutant, albeit with reduced enrichment. Given the orientation of CTCF motifs presents the N-terminus towards cohesin as it translocates from the interior of TADs, these observations explain how the orientation of CTCF binding sites translates into genome folding patterns.
Regionalized tissue fluidization is required for epithelial gap closure during insect gastrulation
Authors: Jain Akanksha , Ulman Vladimir , Mukherjee Arghyadip , Prakash Mangal , Cuenca Marina B. , Pimpale Lokesh G. , Münster Stefan , Haase Robert , Panfilio Kristen A. , Jug Florian , Grill Stephan W. , Tomancak Pavel , Pavlopoulos Anastasios
Published: November 2020

Many animal embryos pull and close an epithelial sheet around the ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the spreading epithelium is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the insect Tribolium castaneum, the non-proliferative serosa becomes regionalized into a solid-like dorsal region with larger non-rearranging cells, and a more fluid-like ventral region surrounding the leading edge with smaller cells undergoing intercalations. Our results suggest that a heterogeneous actomyosin cable contributes to the fluidization of the leading edge by driving sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.
Structural insights into the mechanism of rhodopsin phosphodiesterase
Authors: Ikuta Tatsuya , Shihoya Wataru , Sugiura Masahiro , Yoshida Kazuho , Watari Masahito , Tokano Takaya , Yamashita Keitaro , Katayama Kota , Tsunoda Satoshi P. , Uchihashi Takayuki , Kandori Hideki , Nureki Osamu
Published: November 2020

Rhodopsin phosphodiesterase (Rh-PDE) is an enzyme rhodopsin belonging to a recently discovered class of microbial rhodopsins with light-dependent enzymatic activity. Rh-PDE consists of the N-terminal rhodopsin domain and C-terminal phosphodiesterase (PDE) domain, connected by 76-residue linker, and hydrolyzes both cAMP and cGMP in a light-dependent manner. Thus, Rh-PDE has potential for the optogenetic manipulation of cyclic nucleotide concentrations, as a complementary tool to rhodopsin guanylyl cyclase and photosensitive adenylyl cyclase. Here we present structural and functional analyses of the Rh-PDE derived from Salpingoeca rosetta. The crystal structure of the rhodopsin domain at 2.6 Å resolution revealed a new topology of rhodopsins, with 8 TMs including the N-terminal extra TM, TM0. Mutational analyses demonstrated that TM0 plays a crucial role in the enzymatic photoactivity. We further solved the crystal structures of the rhodopsin domain (3.5 Å) and PDE domain (2.1 Å) with their connecting linkers, which showed a rough sketch of the full-length Rh-PDE. Integrating these structures, we proposed a model of full-length Rh-PDE, based on the HS-AFM observations and computational modeling of the linker region. These findings provide insight into the photoactivation mechanisms of other 8-TM enzyme rhodopsins and expand the definition of rhodopsins.
Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin
Authors: Dyring-Andersen Beatrice , Løvendorf Marianne Bengtson , Coscia Fabian , Santos Alberto , Møller Line Bruun Pilgaard , Colaço Ana R. , Niu Lili , Bzorek Michael , Doll Sophia , Andersen Jørgen Lock , Clark Rachael A. , Skov Lone , Teunissen Marcel B. M. , Mann Matthias
Published: November 2020

Human skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combine advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantify 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and previously undescribed proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research (https://skin.science/).
Bryophytes are predicted to lag behind future climate change despite their high dispersal capacities
Authors: Zanatta F. , Engler R. , Collart F. , Broennimann O. , Mateo R. G. , Papp B. , Muñoz J. , Baurain D. , Guisan A. , Vanderpoorten A.
Published: November 2020

The extent to which species can balance out the loss of suitable habitats due to climate warming by shifting their ranges is an area of controversy. Here, we assess whether highly efficient wind-dispersed organisms like bryophytes can keep-up with projected shifts in their areas of suitable climate. Using a hybrid statistical-mechanistic approach accounting for spatial and temporal variations in both climatic and wind conditions, we simulate future migrations across Europe for 40 bryophyte species until 2050. The median ratios between predicted range loss vs expansion by 2050 across species and climate change scenarios range from 1.6 to 3.3 when only shifts in climatic suitability were considered, but increase to 34.7–96.8 when species dispersal abilities are added to our models. This highlights the importance of accounting for dispersal restrictions when projecting future distribution ranges and suggests that even highly dispersive organisms like bryophytes are not equipped to fully track the rates of ongoing climate change in the course of the next decades.
Cerebral dopamine neurotrophic factor (CDNF) protects against quinolinic acid-induced toxicity in in vitro and in vivo models of Huntington’s disease
Authors: Stepanova P. , Srinivasan V. , Lindholm D. , Voutilainen M. H.
Published: November 2020

Huntington’s disease (HD) is a neurodegenerative disorder with a progressive loss of medium spiny neurons in the striatum and aggregation of mutant huntingtin in the striatal and cortical neurons. Currently, there are no rational therapies for the treatment of the disease. Cerebral dopamine neurotrophic factor (CDNF) is an endoplasmic reticulum (ER) located protein with neurotrophic factor (NTF) properties, protecting and restoring the function of dopaminergic neurons in animal models of PD more effectively than other NTFs. CDNF is currently in phase I–II clinical trials on PD patients. Here we have studied whether CDNF has beneficial effects on striatal neurons in in vitro and in vivo models of HD. CDNF was able to protect striatal neurons from quinolinic acid (QA)-induced cell death in vitro via increasing the IRE1α/XBP1 signalling pathway in the ER. A single intrastriatal CDNF injection protected against the deleterious effects of QA in a rat model of HD. CDNF improved motor coordination and decreased ataxia in QA-toxin treated rats, and stimulated the neurogenesis by increasing doublecortin (DCX)-positive and NeuN-positive cells in the striatum. These results show that CDNF positively affects striatal neuron viability reduced by QA and signifies CDNF as a promising drug candidate for the treatment of HD.
Simple method for large-scale production of macrophage activating factor GcMAF
Authors: Nabeshima Yoko , Abe Chiaki , Kawauchi Takeshi , Hiroi Tomoko , Uto Yoshihiro , Nabeshima Yo-ichi
Published: November 2020

Human group-specific component protein (Gc protein) is a multifunctional serum protein which has three common allelic variants, Gc1F, Gc1S and Gc2 in humans. Gc1 contains an O-linked trisaccharide [sialic acid-galactose-N-acetylgalactosamine (GalNAc)] on the threonine420(Thr420) residue and can be converted to a potent macrophage activating factor (GcMAF) by selective removal of sialic acid and galactose, leaving GalNAc at Thr420. In contrast, Gc2 is not glycosylated. GcMAF is considered a promising candidate for immunotherapy and antiangiogenic therapy of cancers and has attracted great interest, but it remains difficult to compare findings among research groups because different procedures have been used to prepare GcMAF. Here, we present a simple, practical method to prepare high-quality GcMAF by overexpressing Gc-protein in a serum-free suspension culture of ExpiCHO-S cells, without the need for a de-glycosylation step. We believe this protocol is suitable for large-scale production of GcMAF for functional analysis and clinical testing.
Evening home lighting adversely impacts the circadian system and sleep
Authors: Cain Sean W. , McGlashan Elise M. , Vidafar Parisa , Mustafovska Jona , Curran Simon P. N. , Wang Xirun , Mohamed Anas , Kalavally Vineetha , Phillips Andrew J. K.
Published: November 2020

The regular rise and fall of the sun resulted in the development of 24-h rhythms in virtually all organisms. In an evolutionary heartbeat, humans have taken control of their light environment with electric light. Humans are highly sensitive to light, yet most people now use light until bedtime. We evaluated the impact of modern home lighting environments in relation to sleep and individual-level light sensitivity using a new wearable spectrophotometer. We found that nearly half of homes had bright enough light to suppress melatonin by 50%, but with a wide range of individual responses (0–87% suppression for the average home). Greater evening light relative to an individual’s average was associated with increased wakefulness after bedtime. Homes with energy-efficient lights had nearly double the melanopic illuminance of homes with incandescent lighting. These findings demonstrate that home lighting significantly affects sleep and the circadian system, but the impact of lighting for a specific individual in their home is highly unpredictable.
Dual antiplatelet therapy reduced stroke risk in transient ischemic attack with positive diffusion weighted imaging
Authors: Pei Lu-lu , Chen Pei , Fang Hui , Cao Yuan , Guo Yi-nan , Zhang Rui , Zhao Lu , Gao Yuan , Wu Jun , Sun Shi-lei , Wang Xiao-ying , Lo Eng H. , Buonanno Ferdinando S. , Ning Ming-ming , Xu Yu-ming , Song Bo
Published: November 2020

Dual antiplatelet therapy (DAPT) reduced stroke risk in high-risk transient ischemic attack (TIA) patients assessed by ABCD2 score. Patients with positive diffusion-weighted imaging (DWI) were identified as imaging-based high-risk. The present study aims to investigate whether DAPT could reduce stroke risk in TIA with DWI positive. The study enrolled TIA patients within 72 h of onset from the prospective TIA database of the First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischemic stroke at 90-day. The relationship between DAPT and stroke was analyzed in a cox proportional hazards model. The Kaplan–Meier curves of TIA patients with DAPT and monotherapy were plotted. Total of 661 TIA patients were enrolled, 279 of whom were DWI positive and 281 used DAPT. The 90-day stroke risk was higher in patients used monotherapy than those used DAPT in TIA with positive DWI (23.7% vs. 13.4%, p = 0.029). DAPT was associated with reduced stroke risk in TIA patients with positive DWI (hazard ratio [HR] = 0.54; 95% confidence interval [CI], 0.30–0.97; p = 0.037). However, the benefit didn’t exist in TIA patients with negative DWI (HR = 0.43; 95% CI, 0.14–1.33; p = 0.142). Early use of DAPT reduced stroke risk in TIA patients with positive DWI.
Novel genetic risk factors influence progression of islet autoimmunity to type 1 diabetes
Authors: Onengut-Gumuscu Suna , Paila Umadevi , Chen Wei-Min , Ratan Aakrosh , Zhu Zhennan , Steck Andrea K. , Frohnert Brigitte I. , Waugh Kathleen C. , Webb-Robertson Bobbie-Jo M. , Norris Jill M. , Lange Leslie A. , Rewers Marian J. , Rich Stephen S.
Published: November 2020

Type 1 diabetes arises from the autoimmune destruction of insulin-producing beta-cells of the pancreas, resulting in dependence on exogenously administered insulin to maintain glucose homeostasis. In this study, our aim was to identify genetic risk factors that contribute to progression from islet autoimmunity to clinical type 1 diabetes. We analyzed 6.8 million variants derived from whole genome sequencing of 160 islet autoantibody positive subjects, including 87 who had progressed to type 1 diabetes. The Cox proportional-hazard model for survival analysis was used to identify genetic variants associated with progression. We identified one novel region, 20p12.1 (TASP1; genome-wide P < 5 × 10–8) and three regions, 1q21.3 (MRPS21–PRPF3), 2p25.2 (NRIR), 3q22.1 (COL6A6), with suggestive evidence of association (P < 8.5 × 10–8) with progression from islet autoimmunity to type 1 diabetes. Once islet autoimmunity is initiated, functional mapping identified two critical pathways, response to viral infections and interferon signaling, as contributing to disease progression. These results provide evidence that genetic pathways involved in progression from islet autoimmunity differ from those pathways identified once disease has been established. These results support the need for further investigation of genetic risk factors that modulate initiation and progression of subclinical disease to inform efforts in development of novel strategies for prediction and intervention of type 1 diabetes.
Efficacy based ginger fingerprinting reveals potential antiproliferative analytes for triple negative breast cancer
Authors: Zhao Lihan , Rupji Manali , Choudhary Ishita , Osan Remus , Kapoor Shobhna , Zhang Hong-Jie , Yang Chunhua , Aneja Ritu
Published: November 2020

Ginger (Zingiber officinale) is one of the most widely consumed dietary supplements worldwide. Its anticancer potential has been demonstrated in various studies. However, ginger roots obtained from different geographical locations showed extensive variability in their activities, mainly due to differences in the levels of bioactive compounds. Here we evaluated the effect of these differences on the anticancer activity of ginger by performing efficacy-based fingerprinting. We characterized the fingerprint profiles of 22 ginger samples using liquid chromatography-mass spectroscopy, followed by a principal component analysis (PCA) and pearson correlation analysis. We also evaluated the anti-proliferative effects (IC50) of these samples on triple-negative breast cancer cells using the MTT assays. The supervised PCA identified a subset of analytes whose abundance strongly associated with the IC50 values of the ginger extracts, providing a link between ginger extract composition and in vitro anticancer efficacy. This study demonstrated that variation in the ginger fingerprint profiles resulting from differences in their chemical composition could have a significant impact on efficacy and bioactivity of ginger extracts. Also, this first-of-a-kind efficacy-based fingerprinting approach proposed here can identify potent anticancer candidates from the ginger fingerprint without the need for isolating individual components from the extracts.
Unsupervised and supervised learning with neural network for human transcriptome analysis and cancer diagnosis
Authors: Yuan Bo , Yang Dong , Rothberg Bonnie E. G. , Chang Hao , Xu Tian
Published: November 2020

Deep learning analysis of images and text unfolds new horizons in medicine. However, analysis of transcriptomic data, the cause of biological and pathological changes, is hampered by structural complexity distinctive from images and text. Here we conduct unsupervised training on more than 20,000 human normal and tumor transcriptomic data and show that the resulting Deep-Autoencoder, DeepT2Vec, has successfully extracted informative features and embedded transcriptomes into 30-dimensional Transcriptomic Feature Vectors (TFVs). We demonstrate that the TFVs could recapitulate expression patterns and be used to track tissue origins. Trained on these extracted features only, a supervised classifier, DeepC, can effectively distinguish tumors from normal samples with an accuracy of 90% for Pan-Cancer and reach an average 94% for specific cancers. Training on a connected network, the accuracy is further increased to 96% for Pan-Cancer. Together, our study shows that deep learning with autoencoder is suitable for transcriptomic analysis, and DeepT2Vec could be successfully applied to distinguish cancers, normal tissues, and other potential traits with limited samples.
Chromosome-scale genome assembly for the duckweed Spirodela intermedia, integrating cytogenetic maps, PacBio and Oxford Nanopore libraries
Authors: Hoang Phuong T. N. , Fiebig Anne , Novák Petr , Macas Jiří , Cao Hieu X. , Stepanenko Anton , Chen Guimin , Borisjuk Nikolai , Scholz Uwe , Schubert Ingo
Published: November 2020

Duckweeds are small, free-floating, morphologically highly reduced organisms belonging to the monocot order Alismatales. They display the most rapid growth among flowering plants, vary ~ 14-fold in genome size and comprise five genera. Spirodela is the phylogenetically oldest genus with only two mainly asexually propagating species: S. polyrhiza (2n = 40; 160 Mbp/1C) and S. intermedia (2n = 36; 160 Mbp/1C). This study combined comparative cytogenetics and de novo genome assembly based on PacBio, Illumina and Oxford Nanopore (ON) reads to obtain the first genome reference for S. intermedia and to compare its genomic features with those of the sister species S. polyrhiza. Both species’ genomes revealed little more than 20,000 putative protein-coding genes, very low rDNA copy numbers and a low amount of repetitive sequences, mainly Ty3/gypsy retroelements. The detection of a few new small chromosome rearrangements between both Spirodela species refined the karyotype and the chromosomal sequence assignment for S. intermedia.
Searching for target-specific and multi-targeting organics for Covid-19 in the Drugbank database with a double scoring approach
Authors: Murugan Natarajan Arul , Kumar Sanjiv , Jeyakanthan Jeyaraman , Srivastava Vaibhav
Published: November 2020

The current outbreak of Covid-19 infection due to SARS-CoV-2, a virus from the coronavirus family, has become a major threat to human healthcare. The virus has already infected more than 44 M people and the number of deaths reported has reached more than 1.1 M which may be attributed to lack of medicine. The traditional drug discovery approach involves many years of rigorous research and development and demands for a huge investment which cannot be adopted for the ongoing pandemic infection. Rather we need a swift and cost-effective approach to inhibit and control the viral infection. With the help of computational screening approaches and by choosing appropriate chemical space, it is possible to identify lead drug-like compounds for Covid-19. In this study, we have used the Drugbank database to screen compounds against the most important viral targets namely 3C-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp) and the spike (S) protein. These targets play a major role in the replication/transcription and host cell recognition, therefore, are vital for the viral reproduction and spread of infection. As the structure based computational screening approaches are more reliable, we used the crystal structures for 3C-like main protease and spike protein. For the remaining targets, we used the structures based on homology modeling. Further, we employed two scoring methods based on binding free energies implemented in AutoDock Vina and molecular mechanics—generalized Born surface area approach. Based on these results, we propose drug cocktails active against the three viral targets namely 3CLpro, PLpro and RdRp. Interestingly, one of the identified compounds in this study i.e. Baloxavir marboxil has been under clinical trial for the treatment of Covid-19 infection. In addition, we have identified a few compounds such as Phthalocyanine, Tadalafil, Lonafarnib, Nilotinib, Dihydroergotamine, R-428 which can bind to all three targets simultaneously and can serve as multi-targeting drugs. Our study also included calculation of binding energies for various compounds currently under drug trials. Among these compounds, it is found that Remdesivir binds to targets, 3CLpro and RdRp with high binding affinity. Moreover, Baricitinib and Umifenovir were found to have superior target-specific binding while Darunavir is found to be a potential multi-targeting drug. As far as we know this is the first study where the compounds from the Drugbank database are screened against four vital targets of SARS-CoV-2 and illustrates that the computational screening using a double scoring approach can yield potential drug-like compounds against Covid-19 infection.
An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms
Authors: Wildisen Lea , Del Giovane Cinzia , Moutzouri Elisavet , Beglinger Shanthi , Syrogiannouli Lamprini , Collet Tinh-Hai , Cappola Anne R. , Åsvold Bjørn O. , Bakker Stephan J. L. , Yeap Bu B. , Almeida Osvaldo P. , Ceresini Graziano , Dullaart Robin P. F. , Ferrucci Luigi , Grabe Hans , Jukema J. Wouter , Nauck Matthias , Trompet Stella , Völzke Henry , Westendorp Rudi , Gussekloo Jacobijn , Klöppel Stefan , Aujesky Drahomir , Bauer Douglas , Peeters Robin , Feller Martin , Rodondi Nicolas
Published: November 2020

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck’s Depression Inventory (BDI) scale (range 0–63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval =  − 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (− 0.10, 95% confidence interval =  − 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.
Association between clustering of unhealthy lifestyle factors and risk of new-onset atrial fibrillation: a nationwide population-based study
Authors: Lee So-Ryoung , Choi Eue-Keun , Ahn Hyo-Jeong , Han Kyung-Do , Oh Seil , Lip Gregory Y. H.
Published: November 2020

We aimed to investigate the association between the combination of unhealthy lifestyle and risk of AF. Subjects aged 66 years who underwent health examination from 2009 to 2015 were included. The cohort was divided into 8 groups by the combination of unhealthy lifestyle including current smoking, heavy drinking (> 30 g/day), and lack of regular exercise, and followed up for new-onset AF till December 31, 2017. Among 1,719,401 subjects, 47,334 had incident AF (5.5 per 1000 person-years) during a 5-year mean follow-up period. Lack of regular exercise was the most powerful factor to be associated with a higher risk of AF as a single factor (adjusted hazard ratio 1.11, 95% confidence interval 1.08–1.13). Amongst combinations of two unhealthy lifestyle factors, current smoking with heavy drinking, lack of regular exercise with heavy drinking, and lack of regular exercise with current smoking were associated with a 6%, 15%, and 20% higher risks of AF, respectively. A cluster of three unhealthy lifestyle components was associated with a 22% higher risk of AF. Increased numbers of unhealthy lifestyle factors were associated with a higher risk of incident AF. These findings support the promotion of a healthy lifestyle to lower the risk of new-onset AF.
Hypoxia-inducible factor-2α is crucial for proper brain development
Authors: Kleszka Kira , Leu Tristan , Quinting Theresa , Jastrow Holger , Pechlivanis Sonali , Fandrey Joachim , Schreiber Timm
Published: November 2020

Sufficient tissue oxygenation is required for regular brain function; thus oxygen supply must be tightly regulated to avoid hypoxia and irreversible cell damage. If hypoxia occurs the transcription factor complex hypoxia-inducible factor (HIF) will accumulate and coordinate adaptation of cells to hypoxia. However, even under atmospheric O2 conditions stabilized HIF-2α protein was found in brains of adult mice. Mice with a neuro-specific knockout of Hif-2α showed a reduction of pyramidal neurons in the retrosplenial cortex (RSC), a brain region responsible for a range of cognitive functions, including memory and navigation. Accordingly, behavioral studies showed disturbed cognitive abilities in these mice. In search of the underlying mechanisms for the specific loss of pyramidal cells in the RSC, we found deficits in migration in neural stem cells from Hif-2α knockout mice due to altered expression patterns of genes highly associated with neuronal migration and positioning.