bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in self-reported psychological distress among college and university students from 2010 to 2018
Authors: Knapstad Marit , Sivertsen Børge , Knudsen Ann Kristin , Smith Otto Robert Frans , Aarø Leif Edvard , Lønning Kari Jussie , Skogen Jens Christoffer
Published: November 2019

Background

An increase in reported psychological distress, particularly among adolescent girls, is observed across a range of countries. Whether a similar trend exists among students in higher education remains unknown. The aim of the current study was to describe trends in self-reported psychological distress among Norwegian college and university students from 2010 to 2018.

Methods

We employed data from the Students' Health and Wellbeing Study (SHoT), a nationwide survey for higher education in Norway including full-time students aged 18–34. Numbers of participants (participation rates) were n = 6065 (23%) in 2010, n = 13 663 (29%) in 2014 and n = 49 321 (31%) in 2018. Psychological distress was measured using the Hopkins Symptom Checklist-25 (HSCL-25).

Results

Overall, a statistically significant increase in self-reported psychological distress was observed over time across gender and age-groups. HSCL-25 scores were markedly higher for women than for men at all time-points. Effect-size of the mean change was also stronger for women (time-by-gender interaction: χ2 = 70.02, df = 2, p < 0.001): in women, mean HSCL-25 score increased from 1.62 in 2010 to 1.82 in 2018, yielding a mean change effect-size of 0.40. The corresponding change in men was from 1.42 in 2010 to 1.53 in 2018, giving an effect-size of 0.26.

Conclusions

Both the level and increase in self-reported psychological distress among Norwegian students in higher education are potentially worrying. Several mechanisms may contribute to the observed trend, including changes in response style and actual increase in distress. The relative low response rates in SHoT warrant caution when interpreting and generalising the findings.
Mateo and Juana: Racial Silencing, Epistemic Violence, and Counterarchives in Puerto Rican Labor History
Authors: Meléndez-Badillo Jorell A.
Published: November 2019

During the first three decades of the twentieth century, a cluster of self-educated workers that called themselvesobreros ilustrados(enlightened workers) sought to dominate the means of knowledge production, reproduction, and documentation. The discourses produced by this group of working-class intellectuals did not challenge but complemented the elite's contempt towards the laboring masses. In order to be legible in the “Archive of Puertorriqueñidad”—an archive crossed by centuries of colonialism, slavery, and imperial violence—these ragged intellectuals created various layers of exclusions that silenced those individuals that unapologetically upheld their Blackness. These silencing practices not only had power in the moment in which they took place but also influenced later historical production. To explore these dynamics, this paper uses the stories of Juana Colón and Mateo Pérez Sanjurjo. Both were highly-respected Black illiterate labor organizers that were absent in the historical narratives obreros ilustrados wrote about the labor movement. Ultimately, this article seeks to create counterarchives by unearthing, imagining, and retelling the lives of those that were not deemed worthy of being represented in the historical record.
Small Spatial‐Scale Field‐Aligned Currents in the Plasma Sheet Boundary Layer Surveyed by Magnetosphere Multiscale Spacecraft
Authors: Chen Yuanqiang , Zhang Tielong , Wu Mingyu , Wang Guoqiang , Schmid Daniel , Baumjohann Wolfgang , Nakamura Rumi , Russell Christopher T. , Giles Barbara J. , Burch James L.
Published: November 2019

Field‐aligned currents play a significant role in the magnetosphere‐ionosphere coupling. With the multipoint measurements and the advanced instruments of the four Magnetosphere Multiscale spacecraft, we estimate the fine structure of field‐aligned currents in the plasma sheet boundary layer (PSBL) by using the plasma moment data from the Fast Plasma Investigation. Those fine field‐aligned currents under higher temporal resolutions could be quite different from that under the lower temporal resolution: Bipolar current signals can be observed under higher resolutions, while no current signal appears under the lower resolution; higher current density magnitude and shorter time scale of the current layer under higher resolutions are observed than that under the lower resolution. The essential reason could be that the spatial scale of some field‐aligned current layers in the PSBL is too small to be found by low temporal measurements; thus, our results demonstrate the necessity of high data resolutions in resolving the subproton‐scale structure of the field‐aligned current and dynamics in the PSBL.
Orogenic Recycling of Detrital Zircons Characterizes Age Distributions of North American Cordilleran Strata
Authors: Schwartz T.M. , Schwartz R.K. , Weislogel A.L.
Published: November 2019

Detrital zircon (DZ) analysis has become the standard tool for source‐to‐sink sediment routing studies at many spatial and temporal scales. In North American source‐to‐sink studies, DZ distributions are commonly classified according to the presence/absence and proportions of DZ age groups associated with North American crustal provinces as well as peri‐Gondwanan and Cordilleran terranes. Although such a classification scheme is descriptive, these age groups typically do not uniquely identify most recent DZ source areas. Using a compilation of >19,000 individual DZ ages for Mesoproterozoic‐Paleogene strata of the northern Rocky Mountains, including 2,053 new analyses from the Paleogene Renova Formation and its equivalents in southwestern Montana, we demonstrate periodic derivation of first‐cycle DZ from crystalline sources and widespread recycling of poly‐cycle DZ from sedimentary sources over multimillion‐year timescales. Results show that (1) DZ age distributions become increasingly complex between Mesoproterozoic and Paleogene time with the introduction of new DZ sources to the study area, but (2) once an age group appears in the northern Rocky Mountains stratigraphy, grains of that age persist up‐section. These trends show that most DZ age groups are spatiotemporally ubiquitous and nonunique. We largely attribute this to periodic, tectonically induced recycling of DZ into progressively younger sedimentary systems, rather than prolonged derivation of DZ from crystalline basement sources, a trend that reflects the growth of increasingly complex topography associated with the North American Cordillera.
White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals
Authors: Koshiyama Daisuke , Fukunaga Masaki , Okada Naohiro , Morita Kentaro , Nemoto Kiyotaka , Usui Kaori , Yamamori Hidenaga , Yasuda Yuka , Fujimoto Michiko , Kudo Noriko , Azechi Hirotsugu , Watanabe Yoshiyuki , Hashimoto Naoki , Narita Hisashi , Kusumi Ichiro , Ohi Kazutaka , Shimada Takamitsu , Kataoka Yuzuru , Yamamoto Maeri , Ozaki Norio , Okada Go , Okamoto Yasumasa , Harada Kenichiro , Matsuo Koji , Yamasue Hidenori , Abe Osamu , Hashimoto Ryuichiro , Takahashi Tsutomu , Hori Tomoki , Nakataki Masahito , Onitsuka Toshiaki , Holleran Laurena , Jahanshad Neda , van Erp Theo G. M. , Turner Jessica , Donohoe Gary , Thompson Paul M. , Kasai Kiyoto , Hashimoto Ryota ,   COCORO
Published: November 2019

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.
The functional variant of NTN1 contributes to the risk of nonsyndromic cleft lip with or without cleft palate
Authors: Li Dandan , Zhu Guirong , Lou Shu , Ma Lan , Zhang Chi , Pan Yongchu , Wang Lin
Published: November 2019

Previous genome-wide association study of nonsyndromic cleft lip with or without cleft palate (NSCL/P) identified a susceptible variant (rs4791774). We hypothesized that the functional single nucleotide polymorphism (SNP) may be in linkage disequilibrium with this lead SNP. The potential functional SNP (rs4791331) was identified by bioinformatic analysis. A case–control study with 891 orofacial cleft cases and 830 controls was designed to investigate its association with orofacial cleft. The allele-specific DNA-protein binding preference was predicted by JASPAR database. Cell proliferation, cycle and apoptosis, luciferase activity and netrin-1 (NTN1) expression were examined after transfection with the rs4791331 C/T vector in HEK-293 and HEPM cell lines. Forty-six lip tissues of NSCL/P patients were collected to detect NTN1 expression. ntn1a knockout zebrafish models were generated by CRISPR/Cas9 and observed with micro-CT. In the case–control study, the rs4791331-T allele was associated with an increased risk of nonsyndromic orofacial cleft (OR = 1.41, 95% CI = 1.19–1.68), as well as the subgroups cleft lip only (OR = 1.46, 95% CI = 1.14–1.87) and cleft lip and palate (OR = 1.58, 95% CI = 1.27–1.96). The T allele of rs4791331 exhibited anti-apoptotic effects and promoted cell cycle progression at the G1/S transition. Decreased enhancer activity and reduced NTN1 expression following transfection of the T allele were observed. Carriers of the CT/TT genotypes showed significantly lower expression of NTN1 than CC carriers. The ntn1a−/− zebrafish showed relatively wider intermaxillary fissures. These results indicate that rs4791331 (C > T) disrupted motif binding and led to abnormal expression of NTN1, which may be involved in the development of NSCL/P.
Long-range versus short-range effects in cold molecular ion-neutral collisions
Authors: Dörfler Alexander D. , Eberle Pascal , Koner Debasish , Tomza Michał , Meuwly Markus , Willitsch Stefan
Published: November 2019

The investigation of cold interactions between ions and neutrals has recently emerged as a new scientific frontier at the interface of physics and chemistry. Here, we report a study of charge-transfer (CT) collisions of Rb atoms with N$${}_{2}^{+}$$2+ and O$${}_{2}^{+}$$2+ ions in the mK regime using a dynamic ion-neutral hybrid trapping experiment. We observe markedly different CT kinetics and dynamics for the different systems and reaction channels studied. While the kinetics in some channels are consistent with classical capture theory, others show distinct non-universal dynamics. The experimental results are interpreted with the help of classical-capture, quasiclassical-trajectory and quantum-scattering calculations using ab-initio potentials for the highly excited molecular states involved. The theoretical analysis reveals an intricate interplay between short- and long-range effects in the different reaction channels which ultimately determines the CT dynamics and rates. Our results illustrate salient mechanisms that determine the efficiency of cold molecular CT reactions.
Southern Africa crustal anisotropy reveals coupled crust-mantle evolution for over 2 billion years
Authors: Thybo H. , Youssof M. , Artemieva I. M.
Published: November 2019

The long-term stability of Precambrian continental lithosphere depends on the rheology of the lithospheric mantle as well as the coupling between crust and mantle lithosphere, which may be inferred by seismic anisotropy. Anisotropy has never been detected in cratonic crust. Anisotropy in southern Africa, detected by the seismological SKS-splitting method, usually is attributed to the mantle due to asthenospheric flow or frozen-in features of the lithosphere. However, SKS-splitting cannot distinguish between anisotropy in the crust and the mantle. We observe strong seismic anisotropy in the crust of southern African cratons by Receiver Function analysis. Fast axes are uniform within tectonic units and parallel to SKS axes, orogenic strike in the Limpopo and Cape fold belts, and the strike of major dyke swarms. Parallel fast axes in the crust and mantle indicate coupled crust-mantle evolution for more than 2 billion years with implications for strong rheology of the lithosphere.
Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma
Authors: Enfield Katey S. S. , Marshall Erin A. , Anderson Christine , Ng Kevin W. , Rahmati Sara , Xu Zhaolin , Fuller Megan , Milne Katy , Lu Daniel , Shi Rocky , Rowbotham David A. , Becker-Santos Daiana D. , Johnson Fraser D. , English John C. , MacAulay Calum E. , Lam Stephen , Lockwood William W. , Chari Raj , Karsan Aly , Jurisica Igor , Lam Wan L.
Published: November 2019

Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity. We discover a region of focal amplification at chromosome 1q32.1 encompassing the ELF3 locus in LUAD which is absent in the squamous subtype. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. ELF3 expression was required for tumor growth and a pan-cancer expression network analysis supports its subtype and tissue specificity. We further show that ELF3 displays strong prognostic value in LUAD but not LUSC. We conclude that, contrary to many other tumors of epithelial origin, ELF3 is an oncogene and putative therapeutic target in LUAD.
A general orientation distribution function for clay-rich media
Authors: Dabat Thomas , Hubert Fabien , Paineau Erwan , Launois Pascale , Laforest Claude , Grégoire Brian , Dazas Baptiste , Tertre Emmanuel , Delville Alfred , Ferrage Eric
Published: November 2019

The role of the preferential orientation of clay platelets on the properties of a wide range of natural and engineered clay-rich media is well established. However, a reference function for describing the orientation of clay platelets in these different materials is still lacking. Here, we conducted a systematic study on a large panel of laboratory-made samples, including different clay types or preparation methods. By analyzing the orientation distribution functions obtained by X-ray scattering, we identified a unique signature for the preferred orientation of clay platelets and determined an associated reference orientation function using the maximum-entropy method. This new orientation distribution function is validated for a large set of engineered clay materials and for representative natural clay-rich rocks. This reference function has many potential applications where consideration of preferred orientation is required, including better long-term prediction of water and solute transfer or improved designs for new generations of innovative materials.
Primary decidual zone formation requires Scribble for pregnancy success in mice
Authors: Yuan Jia , Aikawa Shizu , Deng Wenbo , Bartos Amanda , Walz Gerd , Grahammer Florian , Huber Tobias B. , Sun Xiaofei , Dey Sudhansu K.
Published: November 2019

Scribble (Scrib) is a scaffold protein with multifunctional roles in PCP, tight junction and Hippo signaling. This study shows that Scrib is expressed in stromal cells around the implantation chamber following implantation. Stromal cells transform into epithelial-like cells to form the avascular primary decidual zone (PDZ) around the implantation chamber (crypt). The PDZ creates a permeability barrier around the crypt restricting immune cells and harmful agents from maternal circulation to protect embryonic health. The mechanism underlying PDZ formation is not yet known. We found that uterine deletion of Scrib by a Pgr-Cre driver leads to defective PDZ formation and implantation chamber (crypt) formation, compromising pregnancy success. Interestingly, epithelial-specific Scrib deletion by a lactoferrin-Cre (Ltf-Cre) driver does not adversely affect PDZ formation and pregnancy success. These findings provide evidence for a previously unknown function of stromal Scrib in PDZ formation, potentially involving ZO-1 and Hippo signaling.
Electrochemical oxidation induced intermolecular aromatic C-H imidation
Authors: Hu Xia , Zhang Guoting , Nie Lei , Kong Taige , Lei Aiwen
Published: November 2019

The dehydrogenative aryl C-H/N-H cross-coupling is a powerful synthetic methodology to install nitrogen functionalities into aromatic compounds. Herein, we report an electrochemical oxidation induced intermolecular cross-coupling between aromatics and sulfonimides with high regioselectivity through N-radical addition pathway under external-oxidant-free and catalyst-free conditions. A wide variety of arenes, heteroarenes, alkenes and sulfonimides are applicable scaffolds in this transformation. In addition, aryl sulfonamides or amines (aniline derivatives) can be obtained through different deprotection process. The cyclic voltammetry mechanistic study indicates that the N-centered imidyl radicals are generated via proton-coupled electron transfer event jointly mediated by tetrabutylammonium acetate and anode oxidation process.
Effect of Parkinson’s disease and related medications on the composition of the fecal bacterial microbiota
Authors: Weis Severin , Schwiertz Andreas , Unger Marcus M. , Becker Anouck , Faßbender Klaus , Ratering Stefan , Kohl Matthias , Schnell Sylvia , Schäfer Karl-Herbert , Egert Markus
Published: November 2019

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. PD patients suffer from gastrointestinal dysfunctions and alterations of the autonomous nervous system, especially its part in the gut wall, i.e., the enteric nervous system (ENS). Such alterations and functional gastrointestinal deficits often occur years before the classical clinical symptoms of PD appear. Until now, only little is known about PD-associated changes in gut microbiota composition and their potential implication in PD development. In order to increase knowledge in this field, fecal samples of 34 PD patients and 25 healthy, age-matched control persons were investigated. Here, the V4 and V5 hypervariable region of bacterial 16S rRNA genes was PCR-amplified and sequenced using an Ion Torrent PGM platform. Within the PD group, we observed a relative decrease in bacterial taxa which are linked to health-promoting, anti-inflammatory, neuroprotective or other beneficial effects on the epithelial barrier, such as Faecalibacterium and Fusicatenibacter. Both taxa were lowered in PD patients with elevated levels of the fecal inflammation marker calprotectin. In addition, we observed an increase in shares of the Clostridiales family XI and their affiliated members in these samples. Finally, we found that the relative abundances of the bacterial genera Peptoniphilus, Finegoldia, Faecalibacterium Fusicatenibacter, Anaerococcus, Bifidobacterium, Enterococcus, and Ruminococcus were significantly influenced by medication with L-dopa and entacapone, respectively. Our data confirm previously reported effects of COMT inhibitors on the fecal microbiota of PD patients and suggest a possible effect of L-dopa medication on the relative abundance of several bacterial genera.
Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer
Authors: Verma Sumit S. , Rai Vipin , Awasthee Nikee , Dhasmana Anupam , Rajalaksmi Dhanya S , Nair Mangalam S. , Gupta Subash C.
Published: November 2019

The sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering suggested the apoptosis inducing potential of IDET. The treatment with IDET also induced an accumulation of cells in the sub-G1 and G2/M phases. The exposure of breast cancer cells to the lactone was associated with a depolarization in mitochondrial membrane potential, and cleavage of caspase and PARP. The lactone induced reactive oxygen species (ROS) generation in breast cancer cells. Further, the use of N-acetyl cysteine (NAC) suppressed IDET induced ROS generation and apoptosis. The NF-κB-p65 nuclear translocation induced by okadaic acid (OA) was suppressed by the sesquiterpene. IDET also suppressed the expression of NF-κB regulated tumorigenic proteins, and induced the expression of proapoptotic gene (Bax) in cancer cells. While the expression of oncogenic lncRNAs was suppressed, the tumor suppressor lncRNAs were induced by the sesquiterpene. Collectively, the modulation of multiple cell signaling molecules by IDET may contribute to its activities in breast cancer cells.
Brazilian montane rainforest expansion induced by Heinrich Stadial 1 event
Authors: Pinaya Jorge L. D. , Cruz Francisco W. , Ceccantini Gregório C. T. , Corrêa Pedro L. P. , Pitman Nigel , Vemado Felipe , Lopez Maria del Carmen S. , Pereira Filho Augusto J. , Grohmann Carlos H. , Chiessi Cristiano M. , Stríkis Nicolás M. , Horák-Terra Ingrid , Pinaya Walter H. L. , de Medeiros Vanda B. , Santos Rudney de A. , Akabane Thomas K. , Silva Maicon A. , Cheddadi Rachid , Bush Mark , Henrot Alexandra-Jane , François Louis , Hambuckers Alain , Boyer Frédéric , Carré Matthieu , Coissac Eric , Ficetola Francesco , Huang Kangyou , Lézine Anne-Marie , Nourelbait Majda , Rhoujjati Ali , Taberlet Pierre , Sarmiento Fausto , Abel-Schaad Daniel , Alba-Sánchez Francisca , Zheng Zhuo , De Oliveira Paulo E.
Published: November 2019

The origin of modern disjunct plant distributions in the Brazilian Highlands with strong floristic affinities to distant montane rainforests of isolated mountaintops in the northeast and northern Amazonia and the Guyana Shield remains unknown. We tested the hypothesis that these unexplained biogeographical patterns reflect former ecosystem rearrangements sustained by widespread plant migrations possibly due to climatic patterns that are very dissimilar from present-day conditions. To address this issue, we mapped the presence of the montane arboreal taxa Araucaria, Podocarpus, Drimys, Hedyosmum, Ilex, Myrsine, Symplocos, and Weinmannia, and cool-adapted plants in the families Myrtaceae, Ericaceae, and Arecaceae (palms) in 29 palynological records during Heinrich Stadial 1 Event, encompassing a latitudinal range of 30°S to 0°S. In addition, Principal Component Analysis and Species Distribution Modelling were used to represent past and modern habitat suitability for Podocarpus and Araucaria. The data reveals two long-distance patterns of plant migration connecting south/southeast to northeastern Brazil and Amazonia with a third short route extending from one of them. Their paleofloristic compositions suggest a climatic scenario of abundant rainfall and relative lower continental surface temperatures, possibly intensified by the effects of polar air incursions forming cold fronts into the Brazilian Highlands. Although these taxa are sensitive to changes in temperature, the combined pollen and speleothems proxy data indicate that this montane rainforest expansion during Heinrich Stadial 1 Event was triggered mainly by a less seasonal rainfall regime from the subtropics to the equatorial region.
Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release – a cohort study design combined with an experimental study
Authors: Eliasson Pernilla , Dietrich-Zagonel Franciele , Lundin Anna-Carin , Aspenberg Per , Wolk Alicja , Michaëlsson Karl
Published: November 2019

Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21–1.85) and 1.21 (1.02–1.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24–1.65) and women (aHR 1.41; 0.97–2.05). Former users did not confer a higher risk of tendinopathies. In vitro experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries.
Germline de novo variants in CSNK2B in Chinese patients with epilepsy
Authors: Li Jinliang , Gao Kai , Cai Shuying , Liu Yin , Wang Yuzhen , Huang Shaoping , Zha Jian , Hu Wenjing , Yu Shujie , Yang Zhixian , Xie Han , Yan Huifang , Wang Jingmin , Wu Ye , Jiang Yuwu
Published: November 2019

CSNK2B, which encodes the beta subunit of casein kinase II (CK2), plays an important role in neuron morphology and synaptic transmission. Variants in CSNK2B associated with epilepsy and/or intellectual disability (ID)/developmental delay (DD) have been reported in five cases only. Among the 816 probands suspected hereditary epilepsy whose initial report of trio-based whole exome sequencing (WES) were negative, 10 de novo pathogenic or likely pathogenic variants of CSNK2B in nine probands were identified after reanalysis of their raw Trio-WES data. Six of the nine epileptic patients had ID/DD. The age of seizure onset of these nine patients with CSNK2B variants ranged from 2–12 months. Eight patients had age of seizure onset of less than 6 months. The epilepsy of most probands (8/9) was generalized tonic-clonic seizure and clustered (6/9). Most patients had normal electroencephalogram (5/9) and brain magnetic resonance image (7/9) results. Most patients (7/9) had easy-to-control seizures. Levetiracetam was the most commonly used drug in seizure-free patients (5/7). The variants detected in five patients (5/9, 55.6%) were located in the zinc-binding domain. In summary, our research provided evidence that variants in CSNK2B are associated with epilepsy with or without ID/DD. CSNK2B-related epilepsy is relatively easy to be controlled. The zinc-binding domain appears to be the hotspot region for mutation.
Marine fish traits follow fast-slow continuum across oceans
Authors: Beukhof Esther , Frelat Romain , Pecuchet Laurene , Maureaud Aurore , Dencker Tim Spaanheden , Sólmundsson Jón , Punzón Antonio , Primicerio Raul , Hidalgo Manuel , Möllmann Christian , Lindegren Martin
Published: November 2019

A fundamental challenge in ecology is to understand why species are found where they are and predict where they are likely to occur in the future. Trait-based approaches may provide such understanding, because it is the traits and adaptations of species that determine which environments they can inhabit. It is therefore important to identify key traits that determine species distributions and investigate how these traits relate to the environment. Based on scientific bottom-trawl surveys of marine fish abundances and traits of >1,200 species, we investigate trait-environment relationships and project the trait composition of marine fish communities across the continental shelf seas of the Northern hemisphere. We show that traits related to growth, maturation and lifespan respond most strongly to the environment. This is reflected by a pronounced “fast-slow continuum” of fish life-histories, revealing that traits vary with temperature at large spatial scales, but also with depth and seasonality at more local scales. Our findings provide insight into the structure of marine fish communities and suggest that global warming will favour an expansion of fast-living species. Knowledge of the global and local drivers of trait distributions can thus be used to predict future responses of fish communities to environmental change.
A SUMO-dependent pathway controls elongating RNA Polymerase II upon UV-induced damage
Authors: Heckmann Irina , Kern Maximilian J. , Pfander Boris , Jentsch Stefan
Published: November 2019

RNA polymerase II (RNAPII) is the workhorse of eukaryotic transcription and produces messenger RNAs and small nuclear RNAs. Stalling of RNAPII caused by transcription obstacles such as DNA damage threatens functional gene expression and is linked to transcription-coupled DNA repair. To restore transcription, persistently stalled RNAPII can be disassembled and removed from chromatin. This process involves several ubiquitin ligases that have been implicated in RNAPII ubiquitylation and proteasomal degradation. Transcription by RNAPII is heavily controlled by phosphorylation of the C-terminal domain of its largest subunit Rpb1. Here, we show that the elongating form of Rpb1, marked by S2 phosphorylation, is specifically controlled upon UV-induced DNA damage. Regulation of S2-phosphorylated Rpb1 is mediated by SUMOylation, the SUMO-targeted ubiquitin ligase Slx5-Slx8, the Cdc48 segregase as well as the proteasome. Our data suggest an RNAPII control pathway with striking parallels to known disassembly mechanisms acting on defective RNA polymerase III.
Exacerbation of ozone-induced pulmonary and systemic effects by β2-adrenergic and/or glucocorticoid receptor agonist/s
Authors: Henriquez Andres R. , Snow Samantha J. , Schladweiler Mette C. , Miller Colette N. , Dye Janice A. , Ledbetter Allen D. , Hargrove Marie M. , Richards Judy E. , Kodavanti Urmila P.
Published: November 2019

Agonists of β2adrenergic receptors (β2AR) and glucocorticoid receptors (GR) are prescribed to treat pulmonary diseases. Since ozone effects are mediated through the activation of AR and GR, we hypothesized that the treatment of rats with relevant therapeutic doses of long acting β2AR agonist (LABA; clenbuterol; CLEN) and/or GR agonist (dexamethasone; DEX) would exacerbate ozone-induced pulmonary and systemic changes. In the first study, male 12-week-old Wistar-Kyoto rats were injected intraperitoneally with vehicle (saline), CLEN (0.004 or 0.02 mg/kg), or DEX (0.02 or 0.1 mg/kg). Since dual therapy is commonly used, in the second study, rats received either saline or combined CLEN + DEX (each at 0.005 or 0.02 mg/kg) one day prior to and on both days of exposure (air or 0.8ppm ozone, 4 hr/day x 2-days). In air-exposed rats CLEN, DEX or CLEN + DEX did not induce lung injury or inflammation, however DEX and CLEN + DEX decreased circulating lymphocytes, spleen and thymus weights, increased free fatty acids (FFA) and produced hyperglycemia and glucose intolerance. Ozone exposure of vehicle-treated rats increased bronchoalveolar lavage fluid protein, albumin, neutrophils, IL-6 and TNF-α. Ozone decreased circulating lymphocytes, increased FFA, and induced hypeerglycemia  and glucose intolerance. Drug treatment did not reverse ozone-induced ventillatory changes, however, lung effects (protein and albumin leakage, inflammation, and IL-6 increase) were exacerbated by CLEN and CLEN + DEX pre-treatment in a dose-dependent manner (CLEN > CLEN + DEX). Systemic effects induced by DEX and CLEN + DEX but not CLEN in air-exposed rats were analogous to and more pronounced than those induced by ozone. These data suggest that adverse air pollution effects might be exacerbated in people receiving LABA or LABA plus glucocorticoids.
Information Content of Prefrontal Cortex Activity Quantifies the Difficulty of Narrated Stories
Authors: Keshmiri Soheil , Sumioka Hidenobu , Yamazaki Ryuji , Shiomi Masahiro , Ishiguro Hiroshi
Published: November 2019

The ability to realize the individuals’ impressions during the verbal communication allows social robots to significantly facilitate their social interactions in such areas as child education and elderly care. However, such impressions are highly subjective and internalized and therefore cannot be easily comprehended through behavioural observations. Although brain-machine interface suggests the utility of the brain information in human-robot interaction, previous studies did not consider its potential for estimating the internal impressions during verbal communication. In this article, we introduce a novel approach to estimation of the individuals’ perceived difficulty of stories using the quantified information content of their prefrontal cortex activity. We demonstrate the robustness of our approach by showing its comparable performance in face-to-face, humanoid, speaker, and video-chat settings. Our results contribute to the field of socially assistive robotics by taking a step toward enabling robots determine their human companions’ perceived difficulty of conversations, thereby enabling these media to sustain their communication with humans by adapting to individuals’ pace and interest in response to conversational nuances and complexity.
Overweight and obesity are associated with cardiac adverse structure remodeling in Chinese elderly with hypertension
Authors: Liu Cheng , Li Gang , Laukkanen Jari A. , Hao Lan , Zhao Qianping , Zhang Jing , Zhang Xu
Published: November 2019

There is limited information on the association of overweight and obesity with cardiac remodeling in elderly population. Therefore, we investigated whether overweight and obesity are associated with cardiac geometric structures and function in Chinese elderly. A total of 1183 hospitalized patients (aged 65–99 years) with primary hypertension were collected retrospectively in a cross-sectional study, and divided into underweight, normal weight, overweight and obesity patient groups according to their body mass index (BMI). Cardiac echocardiographic parameters were compared between the groups. BMI was 17.2 ± 1.2, 21.4 ± 1.2, 25.1 ± 1.2, 30.2 ± 2.6 kg/m2 in underweight, normal weight, overweight and obesity groups respectively. Aortic and left atrial diameter, interventricular septal and left ventricular (LV) posterior wall thickness, LV end-diastolic and end-systolic diameter, and indexed LV mass, and prevalence of E/A reversal were higher, while LV ejection fraction and fractional shortening were lower in elderly with overweight or obesity, as compared with whose with underweight or normal weight separately (All P < 0.05). However, multivariable regression analysis showed that overweight and obesity are independently related to increased LV wall thickness, end-diastolic diameter and mass (All P < 0.05). In conclusions, this study demonstrates that overweight and obesity are associated with increased LV wall thickness, end-diastolic diameter and mass in Asian elderly.
Cortisol metabolism in pregnancies with small for gestational age neonates
Authors: Siemiątkowska Anna , Kosicka Katarzyna , Szpera-Goździewicz Agata , Krzyścin Mariola , Bręborowicz Grzegorz H. , Główka Franciszek K.
Published: November 2019

Small for gestational age (SGA) newborns are often born from hypertensive pregnancies. This study aimed to compare the systemic metabolism of cortisol (F) in pregnancies with SGA and appropriate for gestational age (AGA) infants, considering both the normotensive (NT) and hypertensive patients. We hypothesized that the disturbances in systemic metabolism of F in pre-eclampsia (PE) might be attributed not to hypertension only, but to SGA. The study included 117 pregnants in the third trimester, divided into groups: NT pregnancy and SGA neonate (SGA-NT); NT pregnancy and AGA neonate (AGA-NT; controls), and respective groups with PE: SGA-PE and AGA-PE. We assessed the glucocorticoid balance with the function of enzymes involved in systemic metabolism of F: 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 11β-HSD2), 5α- and 5β-reductase. The enzymes’ functions were estimated with the levels of F, cortisone (E), and their metabolites in plasma or urine, which we measured with HPLC-FLD and HPLC-MS/MS. The plasma F/E and urinary free F/E (UFF/UFE) ratios correlated significantly only in patients with the normal function of 5α- and 5β-reductase. The increased function of 11β-HSD2 was noted in all pre-eclamptic pregnancies. Increased function of 5α- and 5β-reductase was specific only for SGA-PE pregnancies, and the function of 5α-reductase was dependent on fetal sex. The SGA-NT pregnancies with male fetuses trended towards the higher function of renal 11β-HSD2 and 5β-reductase; SGA-NT pregnancies with female fetuses lacked any systemic glucocorticoid imbalance. In conclusion, systemic metabolism of F is the most intensive in pre-eclamptic pregnancies complicated by SGA with female fetuses. Our study supports the hypothesis about the different origins of PE and idiopathic intrauterine growth restriction and suggests the sex-specific mechanisms responsible for fetal growth restriction.
miR302a and 122 are deregulated in small extracellular vesicles from ARPE-19 cells cultured with H2O2
Authors: Oltra Maria , Vidal-Gil Lorena , Maisto Rosa , Oltra Sara S. , Romero Francisco Javier , Sancho-Pelluz Javier , Barcia Jorge Miguel
Published: November 2019

Age related macular degeneration (AMD) is a common retina-related disease leading to blindness. Little is known on the origin of the disease, but it is well documented that oxidative stress generated in the retinal pigment epithelium and choroid neovascularization are closely involved. The study of circulating miRNAs is opening new possibilities in terms of diagnosis and therapeutics. miRNAs can travel associated to lipoproteins or inside small Extracellular Vesicles (sEVs). A number of reports indicate a significant deregulation of circulating miRNAs in AMD and experimental approaches, but it is unclear whether sEVs present a significant miRNA cargo. The present work studies miRNA expression changes in sEVs released from ARPE-19 cells under oxidative conditions (i.e. hydrogen peroxide, H2O2). H2O2 increased sEVs release from ARPE-19 cells. Moreover, 218 miRNAs could be detected in control and H2O2 induced-sEVs. Interestingly, only two of them (hsa-miR-302a and hsa-miR-122) were significantly under-expressed in H2O2-induced sEVs. Results herein suggest that the down regulation of miRNAs 302a and 122 might be related with previous studies showing sEVs-induced neovascularization after oxidative challenge in ARPE-19 cells.
High crop load and low temperature delay the onset of bud initiation in apple
Authors: Kofler Julian , Milyaev Anton , Capezzone Filippo , Stojnić Slobodan , Mićić Nikola , Flachowsky Henryk , Hanke Magda-Viola , Wünsche Jens-Norbert
Published: November 2019

The reproductive cycle of apple (Malus × domestica Borkh.) starts with the induction of floral development, however, first morphological changes within the bud appear during the following period of bud initiation. This study identifies the onset and duration of bud initiation in the apple cultivars ‘Fuji’ and ‘Gala’, characterized by biennial and non-biennial bearing behaviour, respectively, and describes the effect of crop load and heat accumulation on the temporal pattern of floral development. The onset of flower bud initiation in heavy cropping ‘Gala’ trees was delayed for 20 days compared to trees with no crop load, but the rate of initiation was not affected by crop load. Bud initiation on heavy cropping ‘Fuji’ trees was minor, whereas trees with no crop load started initiating buds 19 days earlier than those of ‘Gala’ despite the same cropping status and growing degree hours in a given year. The onset of bud initiation in ‘Fuji’ ‘off’ trees was 5 and 20 days after summer solstice, respectively, in two consecutive growing seasons, suggesting that this process is driven by heat accumulation rather than by daylength. The results indicate, that the genetic make-up of the cultivar determines the onset of bud initiation. This can be delayed by increasing crop loads and low temperatures at the beginning of the flower formation process.
Laryngeal vibration as a non-invasive neuromodulation therapy for spasmodic dysphonia
Authors: Khosravani Sanaz , Mahnan Arash , Yeh I-Ling , Aman Joshua E. , Watson Peter J. , Zhang Yang , Goding George , Konczak Jürgen
Published: November 2019

Spasmodic dysphonia (SD) is an incurable focal dystonia of the larynx that impairs speech and communication. Vibro-tactile stimulation (VTS) alters afferent proprioceptive input to sensorimotor cortex that controls speech. This proof-of-concept study examined the effect of laryngeal VTS on speech quality and cortical activity in 13 SD participants who vocalized the vowel /a/ while receiving VTS for 29 minutes. In response to VTS, 9 participants (69%) exhibited a reduction of voice breaks and/or a meaningful increase insmoothed cepstral peak prominence, an acoustic measure of voice/speech quality. Symptom improvements persisted for 20 minutes past VTS. Application of VTS induced a significant suppression of theta band power over the left somatosensory-motor cortex and a significant rise of gamma rhythm over right somatosensory-motor cortex. Such suppression of theta oscillations is observed in patients with cervical dystonia who apply effective sensory tricks, suggesting that VTS in SD may activate a similar neurophysiological mechanism. Results of this feasibility study indicate that laryngeal VTS modulates neuronal synchronization over sensorimotor cortex, which can induce short-term improvements in voice quality. The effects of long-term VTS and its optimal dosage for treating voice symptoms in SD are still unknown and require further systematic study.
Open-Source Remote Gait Analysis: A Post-Surgery Patient Monitoring Application
Authors: Gurchiek Reed D. , Choquette Rebecca H. , Beynnon Bruce D. , Slauterbeck James R. , Tourville Timothy W. , Toth Michael J. , McGinnis Ryan S.
Published: November 2019

Critical to digital medicine is the promise of improved patient monitoring to allow assessment and personalized intervention to occur in real-time. Wearable sensor-enabled observation of physiological data in free-living conditions is integral to this vision. However, few open-source algorithms have been developed for analyzing and interpreting these data which slows development and the realization of digital medicine. There is clear need for open-source tools that analyze free-living wearable sensor data and particularly for gait analysis, which provides important biomarkers in multiple clinical populations. We present an open-source analytical platform for automated free-living gait analysis and use it to investigate a novel, multi-domain (accelerometer and electromyography) asymmetry measure for quantifying rehabilitation progress in patients recovering from surgical reconstruction of the anterior cruciate ligament (ACL). Asymmetry indices extracted from 41,893 strides were more strongly correlated (r = −0.87, p < 0.01) with recovery time than standard step counts (r = 0.25, p = 0.52) and significantly differed between patients 2- and 17-weeks post-op (p < 0.01, effect size: 2.20–2.96), and controls (p < 0.01, effect size: 1.74–4.20). Results point toward future use of this open-source platform for capturing rehabilitation progress and, more broadly, for free-living gait analysis.
Amplified Spontaneous Emission Threshold Reduction and Operational Stability Improvement in CsPbBr3 Nanocrystals Films by Hydrophobic Functionalization of the Substrate
Authors: De Giorgi Maria Luisa , Krieg Franziska , Kovalenko Maksym V. , Anni Marco
Published: November 2019

The use of lead halide perovskites in optoelectronic and photonic devices is mainly limited by insufficient long-term stability of these materials. This issue is receiving growing attention, mainly owing to the operational stability improvement of lead halide perosvkites solar cells. On the contrary, fewer efforts are devoted to the stability improvement of light amplification and lasing. In this report we demonstrate that a simple hydrophobic functionalization of the substrates with hexamethyldisilazane (HMDS) allows to strongly improve the Amplified Spontaneous Emission (ASE) properties of drop cast CsPbBr3 nanocrystal (NC) thin films. In particular we observe an ASE threshold decrease down to 45% of the value without treatment, an optical gain increase of up to 1.5 times and an ASE operational stability increase of up to 14 times. These results are ascribed to a closer NC packing in the films on HMDS treated substrate, allowing an improved energy transfer towards the larger NCs within the NC ensemble, and to the reduction of the film interaction with moisture. Our results propose hydrophobic functionalization of the substrates as an easy approach to lower the ASE and lasing thresholds, while simultaneously increasing the active material stability.