bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxane‐based induction chemotherapy and concurrent chemo‐radiotherapy in the modern era
Authors: Ghosh‐Laskar Sarbani , Pilar Avinash , Johnny Carlton , Prabhash Kumar , Joshi Amit , Agarwal Jai Prakash , Gupta Tejpal , Budrukkar Ashwini , Murthy Vedang , Swain Monali , Noronha Vanita , Patil Vijay Maruthi , Pai Prathamesh , Nair Deepa , Chaukar Devendra Arvind , Thiagarajan Shivakumar , Pantvaidya Gouri , Deshmukh Anuja , Chaturvedi Pankaj , Nair Sudhir , D'Cruz Anil
Published: April 2020

Objective

To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension (ICE) treated with induction chemotherapy (ICT) followed by chemo‐intensity‐modulated radiotherapy (CTRT) at a tertiary cancer center.

Methods

We retrospectively analyzed 45 patients with histologically proven, non‐metastatic NPC with ICE treated at our institute between October 2008 and October 2016. Patients were classified as minor ICE or major ICE, based on the extent of ICE. All the patients received 2–3 cycles of a taxane‐based ICT regimen followed by CTRT. Radiotherapy was delivered with “risk‐adapted” intensity‐modulated radiotherapy (IMRT) technique in all patients.

Results

After a median follow up of 45 months (range: 8–113 months), the estimated 5‐year DFS, LRFS, DMFS, and OS of the entire cohort was 58%, 82%, 67% and 74% respectively. On multivariate analysis, histological subtype was an independent predictor of LRFS, and age was an independent predictor of DFS. The extent of ICE showed only a trend towards worse DFS (P = 0.06). None of the factors significantly predicted for DMFS or OS. Gender, N‐stage, and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 22% of patients and grade 2 or worse xerostomia was seen in 24% of patients at last follow up. Thirty‐three percent of the patients developed clinical hypothyroidism at last follow up. None of the patients experienced any neurological or vascular complications.

Conclusions

Taxane‐based induction chemotherapy followed by chemo‐intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension. Distant metastasis continues to be the predominant problem in these patients.
A REDCap-based model for electronic consent (eConsent): Moving toward a more personalized consent
Authors: Lawrence Colleen E. , Dunkel Leah , McEver Mark , Israel Tiffany , Taylor Robert , Chiriboga Germán , Goins Karin Valentine , Rahn Elizabeth J. , Mudano Amy S. , Roberson Erik D. , Chambless Carol , Wadley Virginia G. , Danila Maria I. , Fischer Melissa A. , Joosten Yvonne , Saag Kenneth G. , Allison Jeroan J. , Lemon Stephenie C. , Harris Paul A.
Published: April 2020

Introduction:

The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).

Methods:

We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.

Results:

The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.

Conclusions:

Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.
Case Report on Early Diagnosis of COVID-19
Authors: Zhou Yang , Yang Le , Han Ming , Huang Minqiang , Sun Xuedong , Zheng Weidong , Han Wei , Wang Jinhong
Published: April 2020

The coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, spread rapidly throughout China and gradually to some countries abroad. How is the development of an epidemic controlled? Early diagnosis is one of the important contents in prevention and control. COVID-19 patients with early mild pneumonia often lack typical evidence to make a definitive diagnosis. Based on the analysis of the cases of 4 patients, this article finds that early diagnosis requires a combination of epidemiology, clinical manifestations, imaging, and etiology, with particular emphasis on epidemiology history and chest computed tomography (CT) manifestations.
The Macedonian “Name” Dispute: The Macedonian Question—Resolved?
Authors: Nimetz Matthew
Published: April 2020

The dispute between Greece and the newly formed state referred to as the “Former Yugoslav Republic of Macedonia” that emerged out of the collapse of Yugoslavia in 1991 was a major source of instability in the Western Balkans for more than 25 years. It was resolved through negotiations between Athens and Skopje, mediated by the United Nations, resulting in the Prespa (or Prespes) Agreement, which was signed on June 17, 2018, and ratified by both parliaments amid controversy in their countries. The underlying issues involved deeply held and differing views relating to national identity, history, and the future of the region, which were resolved through a change in the name of the new state and various agreements as to identity issues. The author, the United Nations mediator in the dispute for 20 years and previously the United States presidential envoy with reference to the dispute, describes the basis of the dispute, the positions of the parties, and the factors that led to a successful resolution.
Eating game: proteins, international conservation and the rebranding of African wildlife, 1955–1965
Authors: DE BONT RAF
Published: April 2020

Around 1960, leading figures in the international conservation circuit – such as Julian Huxley, Frank Fraser Darling and E. Barton Worthington – successfully propagated new visions about the value of undomesticated African mammals. Against traditional ideas, they presented these mammals as a highly efficient source of protein for growing African populations. In line with this vision, they challenged non-interventionist ideals of nature preservation, and launched proposals for active management through game ‘ranching’ and ‘cropping’. As such, they created a new socio-technical imaginary for Africa's future, in which the consumption of wildlife meat took up a central position. This article explores the motivations of Western conservationists for this drastic rebranding. It argues that the rationale of considering African wildlife in terms of protein played an important symbolical role at various levels. It was crucial in the reorganization of the transnational networks of conservation, but also in the boosting of their scientific reputation, in the restructuring of their institutional ties, and in their attempts to maintain an authoritative position for Western ecologists in a rapidly decolonizing world.
Physiological changes in the size of the septal swell body correlate with changes in inferior turbinate size
Authors: Wong E H , Noussair M , Hasan Z , Duvnjak M , Singh N
Published: April 2020

Objective

The nasal septal swell body is a normal anatomical structure located in the superior nasal septum anterior to the middle turbinate. However, the impact of the septal swell body in nasal breathing during normal function and disease remains unclear. This study aimed to establish that the septal swell body varies in size over time and correlates this with the natural variation of the inferior turbinates.

Method

Consecutive patients who underwent at least two computed tomography scans were identified. The width and height of the septal swell body and the inferior turbinates was recorded. A correlation between the difference in septal swell body and turbinates between the two scans was performed using a Pearson's coefficient.

Results

A total of 34 patients (53 per cent female with a mean age of 58.3 ± 20.2 years) were included. The mean and mean difference in septal swell body width between scans for the same patient was 1.57 ± 1.00 mm. The mean difference in turbinate width between scans was 2.23 ± 2.52 mm. A statistically significant correlation was identified between the difference in septal swell body and total turbinate width (r = 0.35, p = 0.04).

Conclusion

The septal swell body is a dynamic structure that varies in width over time in close correlation to the inferior turbinates. Further research is required to quantify its relevance as a surgical area of interest.
Fault, knowledge and risk within the framework of positive obligations under the European Convention on Human Rights
Authors: Stoyanova Vladislava
Published: April 2020

The European Court of Human Rights has consistently reiterated that positive obligations under the European Convention on Human Rights arise when state authorities knoworought to have known about the risk of harm. This article attempts to describe and assess the role of state knowledge in the framework of positive obligations, and to situate the Court’s approach to knowledge about risk within an intelligible framework of analysis. The main argument is that the assessment of state knowledge is imbued with normative considerations. The assessment of whether the state ‘ought to have known’ is intertwined with, first, concerns that positive obligations should not impose unreasonable burden on the state and, second, the establishment of causal links between state omissions and harm.
Investigating translated Chinese and its variants using machine learning
Authors: Hu Hai , Kübler Sandra
Published: April 2020

Translations are generally assumed to share universal features that distinguish them from texts that are originally written in the same language. Thus, we can argue that these translations constitute their own variety of a language, often called translationese. However, translations are also influenced by their source languages and thus show different characteristics depending on the source language. Consequently, we argue that these variants constitute different “dialects” of translations into the same target language. Studies using machine learning techniques on Indo-European languages have investigated the universal characteristics of translationese and how translations from various source languages differ. However, for typologically very different languages such as Chinese, there are only few corpus studies that tap into the intricate relation between translations and the originals, as well as into the relations among translations themselves. In this contribution, we investigate the following questions: (1) What are the characteristics of Chinese translationese, both in general and with respect to different source languages? (2) Can we find differences not only at the lexical but also on the syntactic level? and (3) Based on the characteristics found in the previous questions, which of the proposed laws and universals can we corroborate based on our evidence from Chinese? We use machine learning to operationalize determining the importance of different characteristics and comparing their importance for our Chinese dataset with characteristics previously reported in studies on English. In addition, our methodology allows us to add syntactic features, which have rarely been used to study translations into Chinese. Our results show that Chinese translations as a whole can be reliably distinguished from non-translations, even based on only five features. More interestingly, typological traces from the source languages can often be found in their translations, therefore creating what we call dialects of translationese. For instance, translations from two Altaic languages exhibit more noun repetition and less frequent use of pronouns. Additionally, some characteristics that are not discriminative for English work well for Chinese, possibly because the distance between Chinese and the source languages is greater than that in English studies.
Combined Anastrozole and Antiplatelet Therapy Treatment Differentially Promotes Breast Cancer Cell Survival
Authors: Xulu Kutlwano , Duarte Raquel , Augustine Tanya
Published: April 2020

Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment strategy against cancer-associated thromboembolic disorders; however, the efficacy of such dual treatment has not been established. This study reports novel findings on the response of hormone-dependent breast cancer cell lines (MCF7/T47D) following 24 h treatment with Anastrozole, combined with Aspirin and Clopidogrel cocktail; and Atopaxar. Neutral red and lactate dehydrogenase assays were conducted to assess viability and cytotoxicity respectively. Flow cytometric Annexin-V/PI assay was used to assess the mode of cell death. Morphological alterations were studied using scanning electron microscopy. Statistical analysis was conducted using Statistica V13. Definitive outcomes were established with flow cytometric detection of phosphatidylserine exposure and propidium iodide staining, complemented with ultrastructural analysis. Results showed that a few cells were undergoing death mainly through secondary necrosis. Morphological features suggesting induced cell motility (pseudopodia/ruffled membranes) were observed in both cell lines; notably, T47D cells presented pronounced features than MCF7 cells. Overall, these findings suggest that such combined treatment may differentially promote cell survival, inducing a more aggressive breast cancer phenotype.
Direct Observation of the Surface Topography at High Temperature with SEM
Authors: Podor Renaud , Le Goff Xavier , Lautru Joseph , Brau Henri-Pierre , Barreau Mathias , Carrier Xavier , Mendonça Jerôme , Nogues Dorian , Candeias Antoine
Published: April 2020

High-temperature scanning electron microscopy allows the direct study of the temperature behavior of materials. Using a newly developed heating stage, tilted images series were recorded at high temperature and 3D images of the sample surface were reconstructed. By combining 3D images recorded at different temperatures, the variations of material roughness can be accurately described and associated with local changes in the topography of the sample surface.
Association between mercury in cord serum and sex-specific DNA methylation in cord tissues
Authors: Nishizawa-Jotaki Shino , Sakurai Kenichi , Eguchi Akifumi , Tanabe Hiromi , Watanabe Masahiro , Mori Chisato
Published: April 2020

Prenatal exposure to mercuryin uterocauses abnormal foetal growth and adverse outcomes. DNA methylation is currently considered a possible mechanism through which this occurs. However, few studies have investigated the association between prenatal exposure to mercury and DNA methylation in detail. This study aimed to clarify the relationship between prenatal exposure to total mercury (Hg) and DNA methylation and its associations with sex-specific characteristics in male and female offspring. In a birth cohort study known as the Chiba study of Mother and Child Health, the DNA methylation status in cord tissue and Hg concentrations in cord serum were examined. A total of 67 participants (27 males and 40 females) were analysed based on Spearmanʼs correlations, adjusted by a false discovery rate of the sex of each offspring. Only one methylated locus was positively correlated with Hg concentrations in cord serum in male offspring, but not in female offspring, and was annotated to the haloacid dehalogenase-like hydrolase domain-containing protein 1 (HDHD1) gene on chromosome X. This locus was located in the intron of theHDHD1gene body and is a binding site for the zinc finger protein CCCTC-binding factor. One of the other loci, located inHDHD1, was highly methylated in the group with higher mercury concentrations, and this locus was in the gene body ofHDHD1. Our results suggest that prenatal exposure to Hg might affect the epigenetic status of male foetuses.
Unterrichtsstörungen präventiv begegnen
Authors: Jung Marvin
Published: April 2020

Zusammenfassung. Der Umgang mit Unterrichtsstörungen stellt für viele Lehrende eine Herausforderung im Schulalltag dar. Besonders „angehende Lehrerinnen und Lehrer erleben in ihrem ersten Schulpraktikum, im Referendariat oder in ihren ersten eigenen Stunden […] einen Praxisschock“ (Kostorz & Schlosser, 2014, S. 9).
Lernbegleitung auf einer Interprofessionellen Ausbildungsstation
Authors: Straub Christine , Dürkop Alexandra , Bode Sebastian
Published: April 2020

Zusammenfassung. Auf der ersten Interprofessionellen Ausbildungsstation in der Pädiatrie in Deutschland (IPAPÄD) versorgen Auszubildende der Gesundheits- und Kinderkrankenpflege (AGKKP) ab dem zweiten Ausbildungsjahr gemeinsam mit Medizinstudierenden im Praktischen Jahr (PJ) Patient_innen weitgehend selbständig. Eine pflegerische Praxisanleitung begleitet sie als interprofessionelle Lernbegleitung (IPPLB).
Leung Receives 2019 Bert Bolin Global Environmental Change Award
Authors:   AGU
Published: April 2020

L. Ruby Leung has been selected as the 2019 Bert Bolin awardee and lecturer of the AGU Global Environmental Change section. She received the award and presented this lecture at AGU’s Fall Meeting 2019, held 9–13 December in San Francisco, Calif. The award recognizes an Earth scientist for “groundbreaking research and/or leadership in global environmental change through cross-disciplinary, interdisciplinary, and transdisciplinary research in the past 10 years.”
New Classification System for Lakes Forecasts a Warming Trend
Authors: Hornyak Tim
Published: April 2020

Researchers devised a system of nine thermal categories for lakes and estimate that 79% of northern frigid lakes could become warmer types.
Treatment and unmet needs in steroid-refractory acute graft-versus-host disease
Authors: Malard Florent , Huang Xiao-Jun , Sim Joycelyn P. Y.
Published: April 2020

Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the number of patients undergoing alloHCT increases, developing safe and effective treatments for aGVHD will become increasingly important, especially for those whose disease becomes refractory to systemic steroid therapy. This paper reviews current treatment options for patients with steroid-refractory aGVHD and discusses data from recently published clinical studies to outline emerging therapeutic strategies.
In TFIIH the Arch domain of XPD is mechanistically essential for transcription and DNA repair
Authors: Peissert Stefan , Sauer Florian , Grabarczyk Daniel B. , Braun Cathy , Sander Gudrun , Poterszman Arnaud , Egly Jean-Marc , Kuper Jochen , Kisker Caroline
Published: April 2020

The XPD helicase is a central component of the general transcription factor TFIIH which plays major roles in transcription and nucleotide excision repair (NER). Here we present the high-resolution crystal structure of the Arch domain of XPD with its interaction partner MAT1, a central component of the CDK activating kinase complex. The analysis of the interface led to the identification of amino acid residues that are crucial for the MAT1-XPD interaction. More importantly, mutagenesis of the Arch domain revealed that these residues are essential for the regulation of (i) NER activity by either impairing XPD helicase activity or the interaction of XPD with XPG; (ii) the phosphorylation of the RNA polymerase II and RNA synthesis. Our results reveal how MAT1 shields these functionally important residues thereby providing insights into how XPD is regulated by MAT1 and defining the Arch domain as a major mechanistic player within the XPD scaffold.
Optogenetic restoration of retinal ganglion cell activity in the living primate
Authors: McGregor Juliette E. , Godat Tyler , Dhakal Kamal R. , Parkins Keith , Strazzeri Jennifer M. , Bateman Brittany A. , Fischer William S. , Williams David R. , Merigan William H.
Published: April 2020

Optogenetic therapies for vision restoration aim to confer intrinsic light sensitivity to retinal ganglion cells when photoreceptors have degenerated and light sensitivity has been irreversibly lost. We combine adaptive optics ophthalmoscopy with calcium imaging to optically record optogenetically restored retinal ganglion cell activity in the fovea of the living primate. Recording from the intact eye of a living animal, we compare the patterns of activity evoked by the optogenetic actuator ChrimsonR with natural photoreceptor mediated stimulation in the same retinal ganglion cells. Optogenetic responses are recorded more than one year following administration of the therapy and two weeks after acute loss of photoreceptor input in the living animal. This in vivo imaging approach could be paired with any therapy to minimize the number of primates required to evaluate restored activity on the retinal level, while maximizing translational benefit by using an appropriate pre-clinical model of the human visual system.
RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression
Authors: Casanova-Acebes María , Menéndez-Gutiérrez María Piedad , Porcuna Jesús , Álvarez-Errico Damiana , Lavin Yonit , García Ana , Kobayashi Soma , Le Berichel Jessica , Núñez Vanessa , Were Felipe , Jiménez-Carretero Daniel , Sánchez-Cabo Fátima , Merad Miriam , Ricote Mercedes
Published: April 2020

Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found that serous-cavity TRMs (LPMs) are highly enriched in RXR transcripts and RXR-response elements. Here, we show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. RXR deficiency impairs neonatal expansion of the LPM pool and reduces the survival of adult LPMs through excess lipid accumulation. We also find that peritoneal LPMs infiltrate early ovarian tumours and that RXR deletion diminishes LPM accumulation in tumours and strongly reduces ovarian tumour progression in mice. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes.
Large non-thermal contribution to picosecond strain pulse generation using the photo-induced phase transition in VO2
Authors: Mogunov Iaroslav A. , Lysenko Sergiy , Fedianin Anatolii E. , Fernández Félix E. , Rúa Armando , Kent Anthony J. , Akimov Andrey V. , Kalashnikova Alexandra M.
Published: April 2020

Picosecond strain pulses are a versatile tool for investigation of mechanical properties of meso- and nano-scale objects with high temporal and spatial resolutions. Generation of such pulses is traditionally realized via ultrafast laser excitation of a light-to-strain transducer involving thermoelastic, deformation potential, or inverse piezoelectric effects. These approaches unavoidably lead to heat dissipation and a temperature rise, which can modify delicate specimens, like biological tissues, and ultimately destroy the transducer itself limiting the amplitude of generated picosecond strain. Here we propose a non-thermal mechanism for generating picosecond strain pulses via ultrafast photo-induced first-order phase transitions (PIPTs). We perform experiments on vanadium dioxide VO2 films, which exhibit a first-order PIPT accompanied by a lattice change. We demonstrate that during femtosecond optical excitation of VO2 the PIPT alone contributes to ultrafast expansion of this material as large as 0.45%, which is not accompanied by heat dissipation, and, for excitation density of 8 mJ cm−2, exceeds the contribution from thermoelastic effect by a factor of five.
Origins of fast diffusion of water dimers on surfaces
Authors: Fang Wei , Chen Ji , Pedevilla Philipp , Li Xin-Zheng , Richardson Jeremy O. , Michaelides Angelos
Published: April 2020

The diffusion of water molecules and clusters across the surfaces of materials is important to a wide range of processes. Interestingly, experiments have shown that on certain substrates, water dimers can diffuse more rapidly than water monomers. Whilst explanations for anomalously fast diffusion have been presented for specific systems, the general underlying physical principles are not yet established. We investigate this through a systematic ab initio study of water monomer and dimer diffusion on a range of surfaces. Calculations reveal different mechanisms for fast water dimer diffusion, which is found to be more widespread than previously anticipated. The key factors affecting diffusion are the balance of water-water versus water-surface bonding and the ease with which hydrogen-bond exchange can occur (either through a classical over-the-barrier process or through quantum-mechanical tunnelling). We anticipate that the insights gained will be useful for understanding future experiments on the diffusion and clustering of hydrogen-bonded adsorbates.
The critical role of humidity in modeling summer electricity demand across the United States
Authors: Maia-Silva Debora , Kumar Rohini , Nateghi Roshanak
Published: April 2020

Cooling demand is projected to increase under climate change. However, most of the existing projections are based on rising air temperatures alone, ignoring that rising temperatures are associated with increased humidity; a lethal combination that could significantly increase morbidity and mortality rates during extreme heat events. We bridge this gap by identifying the key measures of heat stress, considering both air temperature and near-surface humidity, in characterizing the climate sensitivity of electricity demand at a national scale. Here we show that in many of the high energy consuming states, such as California and Texas, projections based on air temperature alone underestimates cooling demand by as much as 10–15% under both present and future climate scenarios. Our results establish that air temperature is a necessary but not sufficient variable for adequately characterizing the climate sensitivity of cooling load, and that near-surface humidity plays an equally important role.
An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis
Authors: Zhu Song , Wang Ji-Zhong , Chen De , He Yu-Tian , Meng Nan , Chen Min , Lu Rui-Xun , Chen Xin-Hui , Zhang Xiao-Lan , Yan Guang-Rong
Published: April 2020

N6-methyladenosine (m6A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m6A relies on m6A readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of m6A readers are involved in the m6A recognition on RNAs. Here we discover that the long noncoding RNA (lncRNA) LINC00266-1 encodes a 71-amino acid peptide. The peptide mainly interacts with the RNA-binding proteins, including the m6A reader IGF2BP1, and is thus named “RNA-binding regulatory peptide” (RBRP). RBRP binds to IGF2BP1 and strengthens m6A recognition by IGF2BP1 on RNAs, such as c-Myc mRNA, to increase the mRNA stability and expression of c-Myc, thereby promoting tumorigenesis. Cancer patients with RBRPhigh have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of m6A readers and strengthens m6A recognition on the target RNAs by the m6A reader to exert its oncogenic functions.
Angiotensin II induces coordinated calcium bursts in aldosterone-producing adrenal rosettes
Authors: Guagliardo Nick A. , Klein Peter M. , Gancayco Christina A. , Lu Adam , Leng Sining , Makarem Rany R. , Cho Chelsea , Rusin Craig G. , Breault David T. , Barrett Paula Q. , Beenhakker Mark P.
Published: April 2020

Aldosterone-producing zona glomerulosa (zG) cells of the adrenal gland arrange in distinct multi-cellular rosettes that provide a structural framework for adrenal cortex morphogenesis and plasticity. Whether this cyto-architecture also plays functional roles in signaling remains unexplored. To determine if structure informs function, we generated mice with zG-specific expression of GCaMP3 and imaged zG cells within their native rosette structure. Here we demonstrate that within the rosette, angiotensin II evokes periodic Cav3-dependent calcium events that form bursts that are stereotypic in form. Our data reveal a critical role for angiotensin II in regulating burst occurrence, and a multifunctional role for the rosette structure in activity-prolongation and coordination. Combined our data define the calcium burst as the fundamental unit of zG layer activity evoked by angiotensin II and highlight a novel role for the rosette as a facilitator of cell communication.
Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development
Authors: Popovitchenko Tatiana , Park Yongkyu , Page Nicholas F. , Luo Xiaobing , Krsnik Zeljka , Liu Yuan , Salamon Iva , Stephenson Jessica D. , Kraushar Matthew L. , Volk Nicole L. , Patel Sejal M. , Wijeratne H. R. Sagara , Li Diana , Suthar Kandarp S. , Wach Aaron , Sun Miao , Arnold Sebastian J. , Akamatsu Wado , Okano Hideyuki , Paillard Luc , Zhang Huaye , Buyske Steven , Kostovic Ivica , De Rubeis Silvia , Hart Ronald P. , Rasin Mladen-Roko
Published: April 2020

Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational regulation of specific isoforms during neurodevelopment and the mechanisms behind it remain unknown. Using RNA-seq analysis of mouse neocortical polysomes, here we report translationally repressed and derepressed mRNA isoforms during neocortical neurogenesis whose orthologs include risk genes for neurodevelopmental disorders. We demonstrate that the translation of distinct mRNA isoforms of the RNA binding protein (RBP), Elavl4, in radial glia progenitors and early neurons depends on its alternative 5′ UTRs. Furthermore, 5′ UTR-driven Elavl4 isoform-specific translation depends on upstream control by another RBP, Celf1. Celf1 regulation of Elavl4 translation dictates development of glutamatergic neurons. Our findings reveal a dynamic interplay between distinct RBPs and alternative 5′ UTRs in neuronal development and underscore the risk of post-transcriptional dysregulation in co-occurring neurodevelopmental disorders.
Kinase inhibition profiles as a tool to identify kinases for specific phosphorylation sites
Authors: Watson Nikolaus A. , Cartwright Tyrell N. , Lawless Conor , Cámara-Donoso Marcos , Sen Onur , Sako Kosuke , Hirota Toru , Kimura Hiroshi , Higgins Jonathan M. G.
Published: April 2020

There are thousands of known cellular phosphorylation sites, but the paucity of ways to identify kinases for particular phosphorylation events remains a major roadblock for understanding kinase signaling. To address this, we here develop a generally applicable method that exploits the large number of kinase inhibitors that have been profiled on near-kinome-wide panels of protein kinases. The inhibition profile for each kinase provides a fingerprint that allows identification of unknown kinases acting on target phosphosites in cell extracts. We validate the method on diverse known kinase-phosphosite pairs, including histone kinases, EGFR autophosphorylation, and Integrin β1 phosphorylation by Src-family kinases. We also use our approach to identify the previously unknown kinases responsible for phosphorylation of INCENP at a site within a commonly phosphorylated motif in mitosis (a non-canonical target of Cyclin B-Cdk1), and of BCL9L at S915 (PKA). We show that the method has clear advantages over in silico and genetic screening.
Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease
Authors: Janelidze Shorena , Stomrud Erik , Smith Ruben , Palmqvist Sebastian , Mattsson Niklas , Airey David C. , Proctor Nicholas K. , Chai Xiyun , Shcherbinin Sergey , Sims John R. , Triana-Baltzer Gallen , Theunis Clara , Slemmon Randy , Mercken Marc , Kolb Hartmuth , Dage Jeffrey L. , Hansson Oskar
Published: April 2020

Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.
Infrared dielectric metamaterials from high refractive index chalcogenides
Authors: Krishnamoorthy H. N. S. , Adamo G. , Yin J. , Savinov V. , Zheludev N. I. , Soci C.
Published: April 2020

High-index dielectric materials are in great demand for nanophotonic devices and applications, from ultrathin optical elements to metal-free sub-diffraction light confinement and waveguiding. Here we show that chalcogenide topological insulators are particularly apt candidates for dielectric nanophotonics architectures in the infrared spectral range, by reporting metamaterial resonances in chalcogenide crystals sustained well inside the mid-infrared, choosing Bi2Te3 as case study within this family of materials. Strong resonant modulation of the incident electromagnetic field is achieved thanks to the exceptionally high refractive index ranging between 7 and 8 throughout the 2–10 μm region. Analysis of the complex mode structure in the metamaterial allude to the excitation of circular surface currents which could open pathways for enhanced light-matter interaction and low-loss plasmonic configurations by coupling to the spin-polarized topological surface carriers, thereby providing new opportunities to combine dielectric, plasmonic and magnetic metamaterials in a single platform.
Reduced-dimensional perovskite photovoltaics with homogeneous energy landscape
Authors: He Tingwei , Li Saisai , Jiang Yuanzhi , Qin Chaochao , Cui Minghuan , Qiao Lu , Xu Hongyu , Yang Jien , Long Run , Wang Huanhua , Yuan Mingjian
Published: April 2020

Reduced-dimensional (quasi-2D) perovskite materials are widely applied for perovskite photovoltaics due to their remarkable environmental stability. However, their device performance still lags far behind traditional three dimensional perovskites, particularly high open circuit voltage (Voc) loss. Here, inhomogeneous energy landscape is pointed out to be the sole reason, which introduces extra energy loss, creates band tail states and inhibits minority carrier transport. We thus propose to form homogeneous energy landscape to overcome the problem. A synergistic approach is conceived, by taking advantage of material structure and crystallization kinetic engineering. Accordingly, with the help of density functional theory guided material design, (aminomethyl) piperidinium quasi-2D perovskites are selected. The lowest energy distribution and homogeneous energy landscape are achieved through carefully regulating their crystallization kinetics. We conclude that homogeneous energy landscape significantly reduces the Shockley-Read-Hall recombination and suppresses the quasi-Fermi level splitting, which is crucial to achieve high Voc.
Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension
Authors: Reyes-Palomares Armando , Gu Mingxia , Grubert Fabian , Berest Ivan , Sa Silin , Kasowski Maya , Arnold Christian , Shuai Mao , Srivas Rohith , Miao Simon , Li Dan , Snyder Michael P. , Rabinovitch Marlene , Zaugg Judith B.
Published: April 2020

Environmental and epigenetic factors often play an important role in polygenic disorders. However, how such factors affect disease-specific tissues at the molecular level remains to be understood. Here, we address this in pulmonary arterial hypertension (PAH). We obtain pulmonary arterial endothelial cells (PAECs) from lungs of patients and controls (n = 19), and perform chromatin, transcriptomic and interaction profiling. Overall, we observe extensive remodeling at active enhancers in PAH PAECs and identify hundreds of differentially active TFs, yet find very little transcriptomic changes in steady-state. We devise a disease-specific enhancer-gene regulatory network and predict that primed enhancers in PAH PAECs are activated by the differentially active TFs, resulting in an aberrant response to endothelial signals, which could lead to disturbed angiogenesis and endothelial-to-mesenchymal-transition. We validate these predictions for a selection of target genes in PAECs stimulated with TGF-β, VEGF or serotonin. Our study highlights the role of chromatin state and enhancers in disease-relevant cell types of PAH.
Direct evidence of spatial stability of Bose-Einstein condensate of magnons
Authors: Borisenko I. V. , Divinskiy B. , Demidov V. E. , Li G. , Nattermann T. , Pokrovsky V. L. , Demokritov S. O.
Published: April 2020

Bose-Einstein condensation of magnons is one of few macroscopic quantum phenomena observed at room temperature. Since its discovery, it became an object of intense research, which led to the observation of many exciting phenomena such as quantized vortices, second sound, and Bogolyubov waves. However, it remained unclear what physical mechanisms can be responsible for the spatial stability of the magnon condensate. Indeed, since magnons are believed to exhibit attractive interaction, it is generally expected that the condensate is unstable with respect to the real-space collapse, contrarily to experimental findings. Here, we provide direct experimental evidence that magnons in a condensate exhibit repulsive interaction resulting in the condensate stabilization and propose a mechanism, which is responsible for this interaction. Our experimental conclusions are additionally supported by the theoretical model based on the Gross-Pitaevskii equation. Our findings solve a long-standing problem, providing a new insight into the physics of magnon Bose-Einstein condensates.
Giant orbital magnetoelectric effect and current-induced magnetization switching in twisted bilayer graphene
Authors: He Wen-Yu , Goldhaber-Gordon David , Law K. T.
Published: April 2020

Recently, quantum anomalous Hall effect with spontaneous ferromagnetism was observed in twisted bilayer graphenes (TBG) near 3/4 filling. Importantly, it was observed that an extremely small current can switch the direction of the magnetization. This offers the prospect of realizing low energy dissipation magnetic memories. However, the mechanism of the current-driven magnetization switching is poorly understood as the charge currents in graphenes are generally believed to be non-magnetic. In this work, we demonstrate that in TBG, the twisting and substrate induced symmetry breaking allow an out of plane orbital magnetization to be generated by a charge current. Moreover, the large Berry curvatures of the flat bands give the Bloch electrons large orbital magnetic moments so that a small current can generate a large orbital magnetization. We further demonstrate how the charge current can switch the magnetization of the ferromagnetic TBG near 3/4 filling as observed in the experiments.
From quantum to continuum mechanics in the delamination of atomically-thin layers from substrates
Authors: Hauseux Paul , Nguyen Thanh-Tung , Ambrosetti Alberto , Ruiz Katerine Saleme , Bordas Stéphane P. A. , Tkatchenko Alexandre
Published: April 2020

Anomalous proximity effects have been observed in adhesive systems ranging from proteins, bacteria, and gecko feet suspended over semiconductor surfaces to interfaces between graphene and different substrate materials. In the latter case, long-range forces are evidenced by measurements of non-vanishing stress that extends up to micrometer separations between graphene and the substrate. State-of-the-art models to describe adhesive properties are unable to explain these experimental observations, instead underestimating the measured stress distance range by 2–3 orders of magnitude. Here, we develop an analytical and numerical variational approach that combines continuum mechanics and elasticity with quantum many-body treatment of van der Waals dispersion interactions. A full relaxation of the coupled adsorbate/substrate geometry leads us to conclude that wavelike atomic deformation is largely responsible for the observed long-range proximity effect. The correct description of this seemingly general phenomenon for thin deformable membranes requires a direct coupling between quantum and continuum mechanics.
Diagnosis and prognosis of myocardial infarction on a plasmonic chip
Authors: Xu Wei , Wang Lin , Zhang Ru , Sun Xuming , Huang Lin , Su Haiyang , Wei Xunbin , Chen Chia-Chun , Lou Jiatao , Dai Hongjie , Qian Kun
Published: April 2020

Cardiovascular diseases lead to 31.5% of deaths globally, and particularly myocardial infarction (MI) results in 7.4 million deaths per year. Diagnosis of MI and monitoring for prognostic use are critical for clinical management and biomedical research, which require advanced tools with accuracy and speed. Herein, we developed a plasmonic gold nano-island (pGold) chip assay for diagnosis and monitoring of MI. On-chip microarray analysis of serum biomarkers (e.g., cardiac troponin I) afforded up to 130-fold enhancement of near-infrared fluorescence for ultra-sensitive and quantitative detection within controlled periods, using 10 μL of serum only. The pGold chip assay achieved MI diagnostic sensitivity of 100% and specificity of 95.54%, superior to the standard chemiluminescence immunoassay in cardiovascular clinics. Further, we monitored biomarker concentrations regarding percutaneous coronary intervention for prognostic purpose. Our work demonstrated a designed approach using plasmonic materials for enhanced diagnosis and monitoring for prognostic use towards point-of-care testing.
High-performance particulate matter including nanoscale particle removal by a self-powered air filter
Authors: Zhang Guo-Hao , Zhu Qiu-Hong , Zhang Lei , Yong Fang , Zhang Zhang , Wang Shuang-Long , Wang You , He Ling , Tao Guo-Hong
Published: April 2020

Particulate matter (PM) pollutants, including nanoscale particles (NPs), have been considered serious threats to public health. In this work, a self-powered air filter that can be used in high-efficiency removal of PM, including NPs, is presented. An ionic liquid–polymer (ILP) composite is irregularly distributed onto a sponge network to form an ILP@MF filter. Enabled by its unique electrochemical properties, the ILP@MF filter can remove PM2.5 and PM10 with high efficiencies of 99.59% and 99.75%, respectively, after applying a low voltage. More importantly, the charged ILP@MF filter realizes a superior removal for NPs with an efficiency of 93.77%. A micro-button lithium cell or silicon-based solar panel is employed as a power supply platform to fabricate a portable and self-powered face mask, which exhibits excellent efficacy in particulate removal compared to commercial masks. This work shows a great promise for high-performance purification devices and facile mask production to remove particulate pollutants.
Mechanism of ribosome shutdown by RsfS in Staphylococcus aureus revealed by integrative structural biology approach
Authors: Khusainov Iskander , Fatkhullin Bulat , Pellegrino Simone , Bikmullin Aydar , Liu Wen-ti , Gabdulkhakov Azat , Shebel Amr Al , Golubev Alexander , Zeyer Denis , Trachtmann Natalie , Sprenger Georg A. , Validov Shamil , Usachev Konstantin , Yusupova Gulnara , Yusupov Marat
Published: April 2020

For the sake of energy preservation, bacteria, upon transition to stationary phase, tone down their protein synthesis. This process is favored by the reversible binding of small stress-induced proteins to the ribosome to prevent unnecessary translation. One example is the conserved bacterial ribosome silencing factor (RsfS) that binds to uL14 protein onto the large ribosomal subunit and prevents its association with the small subunit. Here we describe the binding mode of Staphylococcus aureus RsfS to the large ribosomal subunit and present a 3.2 Å resolution cryo-EM reconstruction of the 50S-RsfS complex together with the crystal structure of uL14-RsfS complex solved at 2.3 Å resolution. The understanding of the detailed landscape of RsfS-uL14 interactions within the ribosome shed light on the mechanism of ribosome shutdown in the human pathogen S. aureus and might deliver a novel target for pharmacological drug development and treatment of bacterial infections.
Regulatory T cells confer a circadian signature on inflammatory arthritis
Authors: Hand L. E. , Gray K. J. , Dickson S. H. , Simpkins D. A. , Ray D. W. , Konkel J. E. , Hepworth M. R. , Gibbs J. E.
Published: April 2020

The circadian clock is an intrinsic oscillator that imparts 24 h rhythms on immunity. This clock drives rhythmic repression of inflammatory arthritis during the night in mice, but mechanisms underlying this effect are not clear. Here we show that the amplitude of intrinsic oscillators within macrophages and neutrophils is limited by the chronic inflammatory environment, suggesting that rhythms in inflammatory mediators might not be a direct consequence of intrinsic clocks. Anti-inflammatory regulatory T (Treg) cells within the joints show diurnal variation, with numbers peaking during the nadir of inflammation. Furthermore, the anti-inflammatory action of Treg cells on innate immune cells contributes to the night-time repression of inflammation. Treg cells do not seem to have intrinsic circadian oscillators, suggesting that rhythmic function might be a consequence of external signals. These data support a model in which non-rhythmic Treg cells are driven to rhythmic activity by systemic signals to confer a circadian signature to chronic arthritis.