bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutions in the politics of policy change: who can play, how they play in multiple streams
Authors: Bolukbasi H. Tolga , Yıldırım Deniz
Published: March 2022

This article explores the politics of policy change by focusing on agenda setting through the lens of the Multiple Streams Approach (MSA), which has been travelling to ever-larger geographies. We aim to produce signposts for future case studies of policy change by bringing together insights from MSA and New Institutionalism. We ask: Which institutions should we focus on when studying agenda-setting politics in different geographies? How do these institutions shape MSA’s structural elements – problem stream, policy stream, political stream, policy windows, and policy entrepreneur? In answering these questions, we hope to weave not only formal but also informal institutions into MSA’s backbone more tightly. We bring together diverse case studies that are sufficiently abstract and whose findings travel easily across other institutional contexts. We revisit the structural elements of MSA and illustrate how key formal and informal rules structure the politics in these structural elements.
Addressing Contingency in REEES Fields
Authors: Aizman Ania
Published: March 2022

Research on how faculty have attempted to subvert the casualization of academic labor, that is, the conversion of stable and well-paying jobs into temporary ones, has been going on for decades. The COVID-19 pandemic and the resulting economic crisis have cast academic contingency in new light. Given the prevalence of contingency in Slavic and REEES, and the threat of budget cuts in the humanities, REEES faculty have a particular stake in undertaking anti-contingency efforts to protect their colleagues, institutions, and scholarship. This article will assess the conclusions of some recent studies, opinion pieces, debates, and policy recommendations with a view to their potential to address contingency in REEES and Slavic Studies.
CME: Plantarfasziitis
Authors: Barth Sebastian , Zeller Andreas
Published: March 2022

Zusammenfassung. Die Plantarfasziitis ist eine häufige Pathologie in der Hausarztpraxis und nicht immer einfach zu behandeln. Es gibt in der Literatur unzählige beschriebene Behandlungsoptionen, jedoch wurde bisher noch kein anerkannter Behandlungsalgorithmus vorgestellt, der diese Problematik für die Praktikerin/den Praktiker einfacher zu handhaben vermag. In diesem Artikel wird in Anlehnung an die Arbeitsgruppe um Morrisey et al. versucht, einen Behandlungsalgorithmus vorzustellen, der die wirkungsvollsten Therapien in zeitlich sinnvoller Abfolge klar und einfach darstellt. Interessant dabei ist, dass die Patientin/der Patient selbst einen sehr grossen Einfluss auf die Heilung hat, wenn sie/er von Hausarzt oder Hausärztin gut aufgeklärt wurde, die Krankheit versteht und den aktiven Teil der Behandlungsstrategie konsequent durchführt. Meist ist die konservative Behandlung erfolgsversprechend und innerhalb weniger Monate eine Remission erreichbar.
A Thermo‐Compositional Model of the African Cratonic Lithosphere
Authors: Finger N.‐P. , Kaban M. K. , Tesauro M. , Mooney W. D. , Thomas M.
Published: March 2022

Recently, the continually increasing availability of seismic data has allowed high‐resolution imaging of lithospheric structure beneath the African cratons. In this study, S‐wave seismic tomography is combined with high resolution satellite gravity data in an integrated approach to investigate the structure of the cratonic lithosphere of Africa. A new model for the Moho depth and data on the crustal density structure is employed along with global dynamic models to calculate residual topography and mantle gravity residuals. Corrections for thermal effects of an initially juvenile mantle are estimated based on S‐wave tomography and mineral physics. Joint inversion of the residuals yields necessary compositional adjustments that allow to recalculate the thermal effects. After several iterations, we obtain a consistent model of upper mantle temperature, thermal and compositional density variations, and Mg# as a measure of depletion, as well as an improved crustal density model. Our results show that thick and cold depleted lithosphere underlies West African, northern to central eastern Congo, and Zimbabwe Cratons. However, for most of these regions, the areal extent of their depleted lithosphere differs from the respective exposed Archean shields. Meanwhile, the lithosphere of Uganda, Tanzania, most of eastern and southern Congo, and the Kaapvaal Craton is thinner, warmer, and shows little or no depletion. Furthermore, the results allow to infer that the lithosphere of the exposed Archean shields of Congo and West African cratons was depleted before the single blocks were merged into their respective cratons.
The Deep‐Penetrating South Equatorial Undercurrent in the Tropical South Indian Ocean
Authors: Chen Gengxin , Han Weiqing , Zu Tingting , Chu Xiaoqing , Chen Ju
Published: March 2022

A narrow eastward jet is detected beneath the westward‐flowing South Equatorial Current in the tropical South Indian Ocean (SIO) using in‐situ observation and reanalysis data. This jet is dubbed the South Equatorial Undercurrent (SEUC). The SEUC exists across the basin from about 60° to 105°E, with a core centered around 8°S in the west and shifted to approximately 10°S in the east and vertically extending from 200 m to more than 2,000 m. The SEUC is a seasonal feature that mainly occurs from January to June, and gradually weakens in July and August. The SEUC exhibits similar features as Tsuchiya jets in the Pacific and Atlantic Oceans, but also has its own uniqueness. This is the first time the SEUC is detected in the Indian Ocean, contributing to our understanding of the current system in the SIO, and basin‐scale and interbasin mass and property exchanges.
Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated Nr3c1 gene
Authors: Caradonna Salvatore G. , Einhorn Nathan R. , Saudagar Vikram , Khalil Huzefa , Petty Gordon H. , Lihagen Axel , LeFloch Claire , Lee Francis S. , Akil Huda , Guidotti Alessandro , McEwen Bruce S. , Gatta Eleonora , Marrocco Jordan
Published: March 2022

The genomic effects of circulating glucocorticoids are particularly relevant in cortico-limbic structures, which express a high concentration of steroid hormone receptors. To date, no studies have investigated genomic differences in hippocampal subregions, namely the dorsal (dHPC) and ventral (vHPC) hippocampus, in preclinical models treated with exogenous glucocorticoids. Chronic oral corticosterone (CORT) in mouse is a pharmacological approach that disrupts the activity of the hypothalamic-pituitary-adrenal axis, increases affective behavior, and induces genomic changes after stress in the HPC of wildtype (WT) mice and mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met (hMet), a variant associated with genetic susceptibility to stress. Using RNA-sequencing, we investigated the genomic signatures of oral CORT in the dHPC and vHPC of WT and hMet male and female mice, and examined sex and genotype differences in response to oral CORT. Males under CORT showed lower glycemia and increased anxiety- and depression-like behavior compared to females that showed instead opposite affective behavior in response to CORT. Rank–rank-hypergeometric overlap (RRHO) was used to identify genes from a continuous gradient of significancy that were concordant across groups. RRHO showed that CORT-induced differentially expressed genes (DEGs) in WT mice and hMet mice converged in the dHPC of males and females, while in the vHPC, DEGs converged in males and diverged in females. The vHPC showed a higher number of DEGs compared to the dHPC and exhibited sex differences related to glucocorticoid receptor (GR)-binding genes and epigenetic modifiers. Methyl-DNA-immunoprecipitation in the vHPC revealed differential methylation of the exons 1C and 1F of the GR gene (Nr3c1) in hMet females. Together, we report behavioral and endocrinological sex differences in response to CORT, as well as epigenetic signatures that i) differ in the dHPC and vHPC,ii) are distinct in males and females, and iii) implicate differential methylation of Nr3c1 selectively in hMet females.
TrkA-cholinergic signaling modulates fear encoding and extinction learning in PTSD-like behavior
Authors: Yanpallewar Sudhirkumar , Tomassoni-Ardori Francesco , Palko Mary Ellen , Hong Zhenyi , Kiris Erkan , Becker Jodi , Fulgenzi Gianluca , Tessarollo Lino
Published: March 2022

Recent studies have suggested that the use of cognitive enhancers as adjuncts to exposure-based therapy in individuals suffering from post-traumatic stress disorder (PTSD) may be beneficial. Brain cholinergic signaling through basal forebrain projections to the hippocampus is an established pathway mediating fear response and cognitive flexibility. Here we employed a genetic strategy to enhance cholinergic activity through increased signaling of the NGF receptor TrkA. This strategy leads to increased levels of the marker of cholinergic activation, acetylcholine synthesizing enzyme choline acetyltransferase, in forebrain cholinergic regions and their projection areas such as the hippocampus. Mice with increased cholinergic activity do not display any neurobehavioral abnormalities except a selective attenuation of fear response and lower fear expression in extinction trials. Reduction in fear response is rescued by the GABA antagonist picrotoxin in mutant mice, and, in wild-type mice, is mimicked by the GABA agonist midazolam suggesting that GABA can modulate cholinergic functions on fear circuitries. Importantly, mutant mice also show a reduction in fear processing under stress conditions in a single prolonged stress (SPS) model of PTSD-like behavior, and augmentation of cholinergic signaling by the drug donepezil in wild-type mice promotes extinction learning in a similar SPS model of PTSD-like behavior. Donepezil is already in clinical use for the treatment of dementia suggesting a new translational application of this drug for improving exposure-based psychotherapy in PTSD patients.
Cytogenetic abnormalities in essential thrombocythemia: Clinical and molecular correlates and prognostic relevance in 809 informative cases
Authors: Gangat Naseema , Jadoon Yamna , Szuber Natasha , Hanson Curtis A. , Wolanskyj-Spinner Alexandra P. , Ketterling Rhett P. , Pardanani Animesh , Tefferi Ayalew
Published: March 2022

Cytogenetic studies among 809 consecutive patients with essential thrombocythemia (ET; median age 59 years; 65% females) revealed normal karyotype in 754 (93%), loss of chromosome Y only (-Y) in 16 (2%), and abnormalities other than -Y in 39 (4.8%), the most frequent being sole 20q- (n = 8). At presentation, abnormal karyotype, excluding -Y, was associated with older age (p = 0.04), higher leukocyte count (p = 0.03) and arterial thrombosis history (p = 0.02); no associations were apparent for JAK2/CALR/MPL mutations whereas ASXL1 mutations clustered with normal karyotype/-Y and TP53 with abnormal karyotype. Survival was significantly shorter in patients with abnormal karyotype or -Y, compared to those with normal karyotype (median 12, 10, and 21 years, respectively; p < 0.0001). During multivariable analysis that included IPSET (international prognostic score for ET) variables, abnormal karyotype (p < 0.01, HR 2.0), age >60 years (p < 0.01, HR 4.5), leukocytosis >11 × 109/L (p < 0.01, HR 1.5), and male gender (p < 0.01, HR 1.4) were independently associated with inferior survival; abnormal karyotype and age >60 years remained significant, along with SF3B1/SRSF2/U2AF1/TP53 mutations (p = 0.04; HR 2.9), when the latter was included in the multivariable model. The current study suggests prognostic relevance for karyotype in ET.
GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms
Authors: Jin Lu , Zhang Wei , Yao Ming-Yu , Tian Ye , Xue Bo-xin , Tao Wei
Published: March 2022

GNE-493 is a novel PI3K/mTOR dual inhibitor with improved metabolic stability, oral bioavailability, and excellent pharmacokinetic parameters. Here GNE-493 potently inhibited viability, proliferation, and migration in different primary and established (LNCaP and PC-3 lines) prostate cancer cells, and provoking apoptosis. GNE-493 blocked Akt-mTOR activation in primary human prostate cancer cells. A constitutively-active mutant Akt1 restored Akt-mTOR activation but only partially ameliorated GNE-493-induced prostate cancer cell death. Moreover, GNE-493 was still cytotoxic in Akt1/2-silenced primary prostate cancer cells. Significant oxidative stress and programmed necrosis cascade activation were detected in GNE-493-treated prostate cancer cells. Moreover, GNE-493 downregulated Sphingosine Kinase 1 (SphK1), causing ceramide accumulation in primary prostate cancer cells. Daily single dose GNE-493 oral administration robustly inhibited the growth of the prostate cancer xenograft in the nude mice. Akt-mTOR inactivation, SphK1 downregulation, ceramide level increase, and oxidative injury were detected in GNE-493-treated prostate cancer xenograft tissues. Together, GNE-493 inhibited prostate cancer cell growth possibly through the Akt-mTOR-dependent and -independent mechanisms.
Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity
Authors: Katz-Summercorn A. C. , Jammula S. , Frangou A. , Peneva I. , O’Donovan M. , Tripathi M. , Malhotra S. , di Pietro M. , Abbas S. , Devonshire G. , Januszewicz W. , Blasko A. , Nowicki-Osuch K. , MacRae S. , Northrop A. , Redmond A. M. , Wedge D. C. , Fitzgerald R. C.
Published: March 2022

Barrett’s esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett’s natural history and may inform the potential for cancer beyond the clinically discernible phenotype.
Human rhinovirus promotes STING trafficking to replication organelles to promote viral replication
Authors: Triantafilou Martha , Ramanjulu Joshi , Booty Lee M. , Jimenez-Duran Gisela , Keles Hakan , Saunders Ken , Nevins Neysa , Koppe Emma , Modis Louise K. , Pesiridis G. Scott , Bertin John , Triantafilou Kathy
Published: March 2022

Human rhinovirus (HRV), like coronavirus (HCoV), are positive-strand RNA viruses that cause both upper and lower respiratory tract illness, with their replication facilitated by concentrating RNA-synthesizing machinery in intracellular compartments made of modified host membranes, referred to as replication organelles (ROs). Here we report a non-canonical, essential function for stimulator of interferon genes (STING) during HRV infections. While the canonical function of STING is to detect cytosolic DNA and activate inflammatory responses, HRV infection triggers the release of STIM1-bound STING in the ER by lowering Ca2+, thereby allowing STING to interact with phosphatidylinositol 4-phosphate (PI4P) and traffic to ROs to facilitates viral replication and transmission via autophagy. Our results thus hint a critical function of STING in HRV viral replication and transmission, with possible implications for other RO-mediated RNA viruses.
Real-space nanoimaging of THz polaritons in the topological insulator Bi2Se3
Authors: Chen Shu , Bylinkin Andrei , Wang Zhengtianye , Schnell Martin , Chandan Greeshma , Li Peining , Nikitin Alexey Y. , Law Stephanie , Hillenbrand Rainer
Published: March 2022

Plasmon polaritons in topological insulators attract attention from a fundamental perspective and for potential THz photonic applications. Although polaritons have been observed by THz far-field spectroscopy on topological insulator microstructures, real-space imaging of propagating THz polaritons has been elusive so far. Here, we show spectroscopic THz near-field images of thin Bi2Se3 layers (prototypical topological insulators) revealing polaritons with up to 12 times increased momenta as compared to photons of the same energy and decay times of about 0.48 ps, yet short propagation lengths. From the images we determine and analyze the polariton dispersion, showing that the polaritons can be explained by the coupling of THz radiation to various combinations of Dirac and massive carriers at the Bi2Se3 surfaces, massive bulk carriers and optical phonons. Our work provides critical insights into the nature of THz polaritons in topological insulators and establishes instrumentation and methodology for imaging of THz polaritons.
Medial prefrontal cortex and anteromedial thalamus interaction regulates goal-directed behavior and dopaminergic neuron activity
Authors: Yang Chen , Hu Yuzheng , Talishinsky Aleksandr D. , Potter Christian T. , Calva Coleman B. , Ramsey Leslie A. , Kesner Andrew J. , Don Reuben F. , Junn Sue , Tan Aaron , Pierce Anne F. , Nicolas Céline , Arima Yosuke , Lee Seung-Chan , Su Conghui , Coudriet Jensine M. , Mejia-Aponte Carlos A. , Wang Dong V. , Lu Hanbing , Yang Yihong , Ikemoto Satoshi
Published: March 2022

The prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.
Chemistry-mediated Ostwald ripening in carbon-rich C/O systems at extreme conditions
Authors: Lindsey Rebecca K. , Goldman Nir , Fried Laurence E. , Bastea Sorin
Published: March 2022

There is significant interest in establishing a capability for tailored synthesis of next-generation carbon-based nanomaterials due to their broad range of applications and high degree of tunability. High pressure (e.g., shockwave-driven) synthesis holds promise as an effective discovery method, but experimental challenges preclude elucidating the processes governing nanocarbon production from carbon-rich precursors that could otherwise guide efforts through the prohibitively expansive design space. Here we report findings from large scale atomistically-resolved simulations of carbon condensation from C/O mixtures subjected to extreme pressures and temperatures, made possible by machine-learned reactive interatomic potentials. We find that liquid nanocarbon formation follows classical growth kinetics driven by Ostwald ripening (i.e., growth of large clusters at the expense of shrinking small ones) and obeys dynamical scaling in a process mediated by carbon chemistry in the surrounding reactive fluid. The results provide direct insight into carbon condensation in a representative system and pave the way for its exploration in higher complexity organic materials. They also suggest that simulations using machine-learned interatomic potentials could eventually be employed as in-silico design tools for new nanomaterials.
Structural basis for activation and gating of IP3 receptors
Authors: Schmitz Emily A. , Takahashi Hirohide , Karakas Erkan
Published: March 2022

A pivotal component of the calcium (Ca2+) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP3) receptor (IP3R), which mediates Ca2+ release from the endoplasmic reticulum (ER), controlling cytoplasmic and organellar Ca2+ concentrations. IP3Rs are co-activated by IP3 and Ca2+, inhibited by Ca2+ at high concentrations, and potentiated by ATP. However, the underlying molecular mechanisms are unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human type-3 IP3R obtained from a single dataset in multiple gating conformations: IP3-ATP bound pre-active states with closed channels, IP3-ATP-Ca2+ bound active state with an open channel, and IP3-ATP-Ca2+ bound inactive state with a closed channel. The structures demonstrate how IP3-induced conformational changes prime the receptor for activation by Ca2+, how Ca2+ binding leads to channel opening, and how ATP modulates the activity, providing insights into the long-sought questions regarding the molecular mechanism underpinning receptor activation and gating.
Decoding lip language using triboelectric sensors with deep learning
Authors: Lu Yijia , Tian Han , Cheng Jia , Zhu Fei , Liu Bin , Wei Shanshan , Ji Linhong , Wang Zhong Lin
Published: March 2022

Lip language is an effective method of voice-off communication in daily life for people with vocal cord lesions and laryngeal and lingual injuries without occupying the hands. Collection and interpretation of lip language is challenging. Here, we propose the concept of a novel lip-language decoding system with self-powered, low-cost, contact and flexible triboelectric sensors and a well-trained dilated recurrent neural network model based on prototype learning. The structural principle and electrical properties of the flexible sensors are measured and analysed. Lip motions for selected vowels, words, phrases, silent speech and voice speech are collected and compared. The prototype learning model reaches a test accuracy of 94.5% in training 20 classes with 100 samples each. The applications, such as identity recognition to unlock a gate, directional control of a toy car and lip-motion to speech conversion, work well and demonstrate great feasibility and potential. Our work presents a promising way to help people lacking a voice live a convenient life with barrier-free communication and boost their happiness, enriches the diversity of lip-language translation systems and will have potential value in many applications.
Growing single crystals of two-dimensional covalent organic frameworks enabled by intermediate tracing study
Authors: Kang Chengjun , Yang Kuiwei , Zhang Zhaoqiang , Usadi Adam K. , Calabro David C. , Baugh Lisa Saunders , Wang Yuxiang , Jiang Jianwen , Zou Xiaodong , Huang Zhehao , Zhao Dan
Published: March 2022

Resolving single-crystal structures of two-dimensional covalent organic frameworks (2D COFs) is a great challenge, hindered in part by limited strategies for growing high-quality crystals. A better understanding of the growth mechanism facilitates development of methods to grow high-quality 2D COF single crystals. Here, we take a different perspective to explore the 2D COF growth process by tracing growth intermediates. We discover two different growth mechanisms, nucleation and self-healing, in which self-assembly and pre-arrangement of monomers and oligomers are important factors for obtaining highly crystalline 2D COFs. These findings enable us to grow micron-sized 2D single crystalline COF Py-1P. The crystal structure of Py-1P is successfully characterized by three-dimensional electron diffraction (3DED), which confirms that Py-1P does, in part, adopt the widely predicted AA stacking structure. In addition, we find the majority of Py-1P crystals (>90%) have a previously unknown structure, containing 6 stacking layers within one unit cell.
Strain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome
Authors: Forster Samuel C. , Liu Junyan , Kumar Nitin , Gulliver Emily L. , Gould Jodee A. , Escobar-Zepeda Alejandra , Mkandawire Tapoka , Pike Lindsay J. , Shao Yan , Stares Mark D. , Browne Hilary P. , Neville B. Anne , Lawley Trevor D.
Published: March 2022

Mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) disseminate ARGs when they mobilise into new bacterial hosts. The nature of such horizontal gene transfer (HGT) events between human gut commensals and pathogens remain poorly characterised. Here, we compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species) and find 64,188 MGE-mediated ARG transfer events between the two groups using established methods. Among the 5931 MGEs, we find 15 broad host range elements predicted to have crossed different bacterial phyla while also occurring in animal and environmental microbiomes. We experimentally demonstrate that predicted broad host range MGEs can mobilise from commensals Dorea longicatena and Hungatella hathewayi to pathogen Klebsiella oxytoca, crossing phyla simultaneously. Our work establishes the MGE-mediated ARG dissemination network between human gut commensals and pathogens and highlights broad host range MGEs as targets for future ARG dissemination management.
Extracting quantitative dielectric properties from pump-probe spectroscopy
Authors: Ashoka Arjun , Tamming Ronnie R. , Girija Aswathy V. , Bretscher Hope , Verma Sachin Dev , Yang Shang-Da , Lu Chih-Hsuan , Hodgkiss Justin M. , Ritchie David , Chen Chong , Smith Charles G. , Schnedermann Christoph , Price Michael B. , Chen Kai , Rao Akshay
Published: March 2022

Optical pump-probe spectroscopy is a powerful tool for the study of non-equilibrium electronic dynamics and finds wide applications across a range of fields, from physics and chemistry to material science and biology. However, a shortcoming of conventional pump-probe spectroscopy is that photoinduced changes in transmission, reflection and scattering can simultaneously contribute to the measured differential spectra, leading to ambiguities in assigning the origin of spectral signatures and ruling out quantitative interpretation of the spectra. Ideally, these methods would measure the underlying dielectric function (or the complex refractive index) which would then directly provide quantitative information on the transient excited state dynamics free of these ambiguities. Here we present and test a model independent route to transform differential transmission or reflection spectra, measured via conventional optical pump-probe spectroscopy, to changes in the quantitative transient dielectric function. We benchmark this method against changes in the real refractive index measured using time-resolved Frequency Domain Interferometry in prototypical inorganic and organic semiconductor films. Our methodology can be applied to existing and future pump-probe data sets, allowing for an unambiguous and quantitative characterisation of the transient photoexcited spectra of materials. This in turn will accelerate the adoption of pump-probe spectroscopy as a facile and robust materials characterisation and screening tool.
Identification of plasmon-driven nanoparticle-coalescence-dominated growth of gold nanoplates through nanopore sensing
Authors: Huang Bintong , Miao Longfei , Li Jing , Xie Zhipeng , Wang Yong , Chai Jia , Zhai Yueming
Published: March 2022

The fascinating phenomenon that plasmon excitation can convert isotropic silver nanospheres to anisotropic nanoprisms has already been developed into a general synthetic technique since the discovery in 2001. However, the mechanism governing the morphology conversion is described with different reaction processes. So far, the mechanism based on redox reactions dominated anisotropic growth by plasmon-produced hot carriers is widely accepted and developed. Here, we successfully achieved plasmon-driven high yield conversion of gold nanospheres into nanoplates with iodine as the inducer. To investigate the mechanism, nanopore sensing technology is established to statistically study the intermediate species at the single-nanoparticle level. Surprisingly, the morphology conversion is proved as a hot hole-controlled coalescence-dominated growth process. This work conclusively elucidates that a controllable plasmon-driven nanoparticle-coalescence mechanism could enable the production of well-defined anisotropic metal nanostructures and suggests that the nanopore sensing could be of general use for studying the growth process of nanomaterials.
RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
Authors: Liu Geng , Du Wenya , Sang Xiongbo , Tong Qiyu , Wang Ye , Chen Guoqing , Yuan Yi , Jiang Lili , Cheng Wei , Liu Dan , Tian Yan , Fu Xianghui
Published: March 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have devastating consequences worldwide. Recently, great efforts have been made to identify SARS-CoV-2 host factors, but the regulatory mechanisms of these host molecules, as well as the virus per se, remain elusive. Here we report a role of RNA G-quadruplex (RG4) in SARS-CoV-2 infection. Combining bioinformatics, biochemical and biophysical assays, we demonstrate the presence of RG4s in both SARS-CoV-2 genome and host factors. The biological and pathological importance of these RG4s is then exemplified by a canonical 3-quartet RG4 within Tmprss2, which can inhibit Tmprss2 translation and prevent SARS-CoV-2 entry. Intriguingly, G-quadruplex (G4)-specific stabilizers attenuate SARS-CoV-2 infection in pseudovirus cell systems and mouse models. Consistently, the protein level of TMPRSS2 is increased in lungs of COVID-19 patients. Our findings reveal a previously unknown mechanism underlying SARS-CoV-2 infection and suggest RG4 as a potential target for COVID-19 prevention and treatment.
Trends in oxygenate/hydrocarbon selectivity for electrochemical CO(2) reduction to C2 products
Authors: Peng Hong-Jie , Tang Michael T. , Halldin Stenlid Joakim , Liu Xinyan , Abild-Pedersen Frank
Published: March 2022

The electrochemical conversion of carbon di-/monoxide into commodity chemicals paves a way towards a sustainable society but it also presents one of the great challenges in catalysis. Herein, we present the trends in selectivity towards specific dicarbon oxygenate/hydrocarbon products from carbon monoxide reduction on transition metal catalysts, with special focus on copper. We unveil the distinctive role of electrolyte pH in tuning the dicarbon oxygenate/hydrocarbon selectivity. The understanding is based on density functional theory calculated energetics and microkinetic modeling. We identify the critical reaction steps determining selectivity and relate their transition state energies to two simple descriptors, the carbon and hydroxide binding strengths. The atomistic insight gained enables us to rationalize a number of experimental observations and provides avenues towards the design of selective electrocatalysts for liquid fuel production from carbon di-/monoxide.
Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia
Authors: Binder Moritz , Carr Ryan M. , Lasho Terra L. , Finke Christy M. , Mangaonkar Abhishek A. , Pin Christopher L. , Berger Kurt R. , Mazzone Amelia , Potluri Sandeep , Ordog Tamas , Robertson Keith D. , Marks David L. , Fernandez-Zapico Martin E. , Gaspar-Maia Alexandre , Patnaik Mrinal M.
Published: March 2022

Myeloid neoplasms are clonal hematopoietic stem cell disorders driven by the sequential acquisition of recurrent genetic lesions. Truncating mutations in the chromatin remodeler ASXL1 (ASXL1MT) are associated with a high-risk disease phenotype with increased proliferation, epigenetic therapeutic resistance, and poor survival outcomes. We performed a multi-omics interrogation to define gene expression and chromatin remodeling associated with ASXL1MTin chronic myelomonocytic leukemia (CMML). ASXL1MTare associated with a loss of repressive histone methylation and increase in permissive histone methylation and acetylation in promoter regions. ASXL1MTare further associated with de novo accessibility of distal enhancers binding ETS transcription factors, targeting important leukemogenic driver genes. Chromatin remodeling of promoters and enhancers is strongly associated with gene expression and heterogenous among overexpressed genes. These results provide a comprehensive map of the transcriptome and chromatin landscape of ASXL1MTCMML, forming an important framework for the development of novel therapeutic strategies targeting oncogenic cis interactions.
Targeted introduction of heritable point mutations into the plant mitochondrial genome
Authors: Forner Joachim , Kleinschmidt Dennis , Meyer Etienne H. , Fischer Axel , Morbitzer Robert , Lahaye Thomas , Schöttler Mark A. , Bock Ralph
Published: March 2022

The development of technologies for the genetic manipulation of mitochondrial genomes remains a major challenge. Here we report a method for the targeted introduction of mutations into plant mitochondrial DNA (mtDNA) that we refer to as transcription activator-like effector nuclease (TALEN) gene-drive mutagenesis (GDM), or TALEN-GDM. The method combines TALEN-induced site-specific cleavage of the mtDNA with selection for mutations that confer resistance to the TALEN cut. Applying TALEN-GDM to the tobacco mitochondrial nad9 gene, we isolated a large set of mutants carrying single amino acid substitutions in the Nad9 protein. The mutants could be purified to homochondriomy and stably inherited their edited mtDNA in the expected maternal fashion. TALEN-GDM induces both transitions and transversions, and can access most nucleotide positions within the TALEN binding site. Our work provides an efficient method for targeted mitochondrial genome editing that produces genetically stable, homochondriomic and fertile plants with specific point mutations in their mtDNA.
Fully integrated parity–time-symmetric electronics
Authors: Cao Weidong , Wang Changqing , Chen Weijian , Hu Song , Wang Hua , Yang Lan , Zhang Xuan
Published: March 2022

Harnessing parity–time symmetry with balanced gain and loss profiles has created a variety of opportunities in electronics from wireless energy transfer to telemetry sensing and topological defect engineering. However, existing implementations often employ ad hoc approaches at low operating frequencies and are unable to accommodate large-scale integration. Here we report a fully integrated realization of parity–time symmetry in a standard complementary metal–oxide–semiconductor process technology. Our work demonstrates salient parity–time symmetry features such as phase transition as well as the ability to manipulate broadband microwave generation and propagation beyond the limitations encountered by existing schemes. The system shows 2.1 times the bandwidth and 30% noise reduction compared to conventional microwave generation in the oscillatory mode, and displays large non-reciprocal microwave transport from 2.75 to 3.10 GHz in the non-oscillatory mode due to enhanced nonlinearities. This approach could enrich integrated circuit design methodology beyond well-established performance limits and enable the use of scalable integrated circuit technology to study topological effects in high-dimensional non-Hermitian systems.
Water cycles in a Hadean CO2 atmosphere drive the evolution of long DNA
Authors: Ianeselli Alan , Atienza Miguel , Kudella Patrick W. , Gerland Ulrich , Mast Christof B. , Braun Dieter
Published: March 2022

Dew is a common form of water that deposits from saturated air on colder surfaces. Although presumably common on primordial Earth, its potential involvement in the origin of life in early replication has not been investigated in detail. Here we report that it can drive the first stages of Darwinian evolution for DNA and RNA, first by periodically denaturing their structures at low temperatures and second by promoting the replication of long strands over short, faster replicating ones. Our experiments mimicked a partially water-filled primordial rock pore in the probable CO2 atmosphere of Hadean Earth. Under heat flow, water continuously evaporated and recondensed as acidic dew droplets that created the humidity, salt and pH cycles that match many prebiotic replication chemistries. In low-salt and low-pH regimes, the strands melted at 30 K below the bulk melting temperature, whereas longer sequences preferentially accumulated at the droplet interface. Under an enzymatic replication to mimic a sped-up RNA world, long sequences of more than 1,000 nucleotides emerged. The replication was biased by the melting conditions of the dew and the initial short ATGC strands evolved into long AT-rich sequences with repetitive and structured nucleotide composition.
The cancellation heuristic in intertemporal choice shifts people’s time preferences
Authors: Sengupta Arjun , Savani Krishna
Published: March 2022

Building on past research in risky decision making, the present research investigated whether the cancellation heuristic is evident in intertemporal choice. Specifically, the cancellation heuristic posits that whenever choice options are partitioned into multiple components, people ignore seemingly identical components and compare the non-identical components. We nudged people to employ the cancellation heuristic by partitioning both the smaller earlier reward and the larger later reward into a seemingly identical component and a non-identical component. Given diminishing marginal utility, we hypothesized that people would perceive an identical difference between the smaller earlier reward and the larger later reward as being subjectively greater when both amounts are smaller in magnitude, thereby increasing the relative attractiveness of the larger later reward in the partition condition. We conducted four studies, including two incentive-compatible lab experiments, one incentive-compatible lab-in-the-field experiment, and one survey study using choices among both gains and losses. We consistently found that this choice architecture intervention significantly increased people’s likelihood of choosing the larger later reward. Furthermore, we provide evidence of the underlying mechanism-people’s intertemporal decisions shifted to a greater extent in the cancellation condition, particularly if their marginal utility diminished faster. The findings indicate that two features of human psychology-diminishing marginal utility and the cancellation heuristic-can be simultaneously utilized to nudge people to make decisions that would be better for them in the long run.
Virtual reality reduces COVID-19 vaccine hesitancy in the wild: a randomized trial
Authors: Vandeweerdt Clara , Luong Tiffany , Atchapero Michael , Mottelson Aske , Holz Christian , Makransky Guido , Böhm Robert
Published: March 2022

Vaccine hesitancy poses one of the largest threats to global health. Informing people about the collective benefit of vaccination has great potential in increasing vaccination intentions. This research investigates the potential for engaging experiences in immersive virtual reality (VR) to strengthen participants’ understanding of community immunity, and therefore, their intention to get vaccinated. In a pre-registered lab-in-the-field intervention study, participants were recruited in a public park (tested: $$n = 232$$

n
=
232

, analyzed: $$n = 222$$

n
=
222

). They were randomly assigned to experience the collective benefit of community immunity in a gamified immersive virtual reality environment ($$\frac{2}{3}$$

2
3

of sample), or to receive the same information via text and images ($$\frac{1}{3}$$

1
3

of sample). Before and after the intervention, participants indicated their intention to take up a hypothetical vaccine for a new COVID-19 strain (0–100 scale) and belief in vaccination as a collective responsibility (1–7 scale). The study employs a crossover design (participants later received a second treatment), but the primary outcome is the effect of the first treatment on vaccination intention. After the VR treatment, for participants with less-than-maximal vaccination intention, intention increases by 9.3 points (95% CI: 7.0 to $$11.5,\, p < 0.001$$

11.5
,

p
<
0.001

). The text-and-image treatment raises vaccination intention by 3.3 points (difference in effects: 5.8, 95% CI: 2.0 to $$9.5,\, p = 0.003$$

9.5
,

p
=
0.003

). The VR treatment also increases collective responsibility by 0.82 points (95% CI: 0.37 to $$1.27,\, p < 0.001$$

1.27
,

p
<
0.001

). The results suggest that VR interventions are an effective tool for boosting vaccination intention, and that they can be applied “in the wild”—providing a complementary method for vaccine advocacy.
The effect of spermidine on autoimmunity and beta cell function in NOD mice
Authors: Karacay Ceren , Prietl Barbara , Harer Clemens , Ehall Barbara , Haudum Christoph W. , Bounab Kaddour , Franz Joakim , Eisenberg Tobias , Madeo Frank , Kolb Dagmar , Hingerl Kerstin , Hausl Markus , Magnes Christoph , Mautner Selma I. , Kotzbeck Petra , Pieber Thomas R.
Published: March 2022

Spermidine is a natural polyamine which was shown to prolong lifespan of organisms and to improve cardiac and cognitive function. Spermidine was also reported to reduce inflammation and modulate T-cells. Autophagy is one of the mechanisms that spermidine exerts its effect. Autophagy is vital for β-cell homeostasis and autophagy deficiency was reported to lead to exacerbated diabetes in mice. The effect of spermidine in type 1 diabetes pathogenesis remains to be elucidated. Therefore, we examined the effect of spermidine treatment in non-obese diabetic (NOD) mice, a mouse model for type 1 diabetes. NOD mice were given untreated or spermidine-treated water ad libitum from 4 weeks of age until diabetes onset or 35 weeks of age. We found that treatment with 10 mM spermidine led to higher diabetes incidence in NOD mice despite unchanged pancreatic insulitis. Spermidine modulated tissue polyamine levels and elevated signs of autophagy in pancreas. Spermidine led to increased proportion of pro-inflammatory T-cells in pancreatic lymph nodes (pLN) in diabetic mice. Spermidine elevated the proportion of regulatory T-cells in early onset mice, whereas it reduced the proportion of regulatory T-cells in late onset mice. In summary spermidine treatment led to higher diabetes incidence and elevated proportion of T-cells in pLN.
Prediction of topological Dirac semimetal in Ca-based Zintl layered compounds CaM2X2 (M = Zn or Cd; X = N, P, As, Sb, or Bi)
Authors: Feng Liang-Ying , Villaos Rovi Angelo B. , Maghirang Aniceto B. , Huang Zhi-Quan , Hsu Chia-Hsiu , Lin Hsin , Chuang Feng-Chuan
Published: March 2022

Topological Dirac materials are attracting a lot of attention because they offer exotic physical phenomena. An exhaustive search coupled with first-principles calculations was implemented to investigate 10 Zintl compounds with a chemical formula of CaM2X2 (M = Zn or Cd, X = N, P, As, Sb, or Bi) under three crystal structures: CaAl2Si2-, ThCr2Si2-, and BaCu2S2-type crystal phases. All of the materials were found to energetically prefer the CaAl2Si2-type structure based on total ground state energy calculations. Symmetry-based indicators are used to evaluate their topological properties. Interestingly, we found that CaM2Bi2 (M = Zn or Cd) are topological crystalline insulators. Further calculations under the hybrid functional approach and analysis using k · p model reveal that they exhibit topological Dirac semimetal (TDSM) states, where the four-fold degenerate Dirac points are located along the high symmetry line in-between Г to A points. These findings are verified through Green's function surface state calculations under HSE06. Finally, phonon spectra calculations revealed that CaCd2Bi2 is thermodynamically stable. The Zintl phase of AM2X2 compounds have not been identified in any topological material databases, thus can be a new playground in the search for new topological materials.
Effect of noise sensitivity on psychophysiological response through monoscopic 360 video and stereoscopic sound environment experience: a randomized control trial
Authors: Jo Hyun In , Lee Kounseok , Jeon Jin Yong
Published: March 2022

Noise sensitivity is a crucial factor affecting subjective psychophysiological responses to the acoustic environment of various indoor and outdoor spaces. This study examines how noise sensitivity or hyperacusis affects the recovery of emotional and autonomic nervous system (ANS) responses when experiencing various monoscopic 360 video and stereoscopic sound environments (urban and natural) that represent the actual environment. A total of 60 general participants with mild depression, stress, and anxiety were examined using a survey to investigate individual characteristics, including noise sensitivity, and K-means clustering was used to classify them into sensitivity groups. Emotional and physiological responses were measured using the Korean edition of Profile of Mood States and by assessing heart rate variability, respectively. Overall, the emotional recovery effect was greater in the natural than the urban environment, and the homeostatic mechanism of the ANS was better maintained, thereby increasing stress resistance. Noise sensitivity did not have considerable effect on psychophysiological recovery in the natural environment, but had a significant effect on emotional response in the urban environment. This can be used as basic data in seeking customized emotional recovery for individuals using monoscopic 360 video and stereoscopic sound technology in the future.
Effect of serum sample storage temperature on metabolomic and proteomic biomarkers
Authors: Valo Erkka , Colombo Marco , Sandholm Niina , McGurnaghan Stuart J. , Blackbourn Luke A. K. , Dunger David B. , McKeigue Paul M. , Forsblom Carol , Groop Per-Henrik , Colhoun Helen M. , Turner Charles , Dalton R. Neil
Published: March 2022

Prospective biomarker studies can be used to identify biomarkers predictive of disease onset. However, if serum biomarkers are measured years after their collection, the storage conditions might affect analyte concentrations. Few data exists concerning which metabolites and proteins are affected by storage at − 20 °C vs − 80 °C. Our objectives were to document analytes affected by storage of serum samples at − 20 °C vs − 80 °C, and to identify those indicative of the storage temperature. We utilized liquid chromatography tandem mass spectrometry and Luminex to quantify 300 analytes from serum samples of 16 Finnish individuals with type 1 diabetes, with split-aliquot samples stored at − 80 °C and − 20 °C for a median of 4.2 years. Results were validated in 315 Finnish and 916 Scottish individuals with type 1 diabetes, stored at − 20 °C and at − 80 °C, respectively. After quality control, we analysed 193 metabolites and proteins of which 120 were apparently unaffected and 15 clearly susceptible to storage at − 20 °C vs − 80 °C. Further, we identified serum glutamate/glutamine ratio greater than 0.20 as a biomarker of storage at − 20 °C vs − 80 °C. The results provide a catalogue of analytes unaffected and affected by storage at − 20 °C vs − 80 °C and biomarkers indicative of sub-optimal storage.