bluuebunny/crossref_metadata_2025 huggingface dataset:
Nano-ecotoxicology in a changing ocean
Authors: Dedman Craig J.
Published: September 2022

The ocean faces an era of change, driven in large by the release of anthropogenic CO2, and the unprecedented entry of pollutants into the water column. Nanomaterials, those particles < 100 nm, represent an emerging contaminant of environmental concern. Research on the ecotoxicology and fate of nanomaterials in the natural environment has increased substantially in recent years. However, commonly such research does not consider the wider environmental changes that are occurring in the ocean,i.e., ocean warming and acidification, and occurrence of co-contaminants. In this review, the current literature available on the combined impacts of nanomaterial exposure and (i) ocean warming, (ii) ocean acidification, (iii) co-contaminant stress, upon marine biota is explored. Here, it is identified that largely co-stressors influence nanomaterial ecotoxicity by altering their fate and behaviour in the water column, thus altering their bioavailability to marine organisms. By acting in this way, such stressors, are able to mitigate or elevate toxic effects of nanomaterials in a material-specific manner. However, current evidence is limited to a relatively small set of test materials and model organisms. Indeed, data is biased towards effects upon marine bivalve species. In future, expanding studies to involve other ecologically significant taxonomic groups, primarily marine phytoplankton will be highly beneficial. Although limited in number, the available evidence highlights the importance of considering co-occurring environmental changes in ecotoxicological research, as it is likely in the natural environment, the material of interest will not be the sole stressor encountered by biota. As such, research examining ecotoxicology alongside co-occurring environmental stressors is essential to effectively evaluating risk and develop effective long-term management strategies.
In vitro toxicological assessment of PhSeZnCl in human liver cells
Authors: di Vito Raffaella , Levorato Sara , Fatigoni Cristina , Acito Mattia , Sancineto Luca , Traina Giovanna , Villarini Milena , Santi Claudio , Moretti Massimo
Published: September 2022

Phenylselenenylzinc chloride (PhSeZnCl) is an air-stable selenolate, easily synthesizable through oxidative insertion of elemental zinc into the Se-halogen bond of the commercially available phenylselenyl chloride. PhSeZnCl was shown to possess a marked GPx-like activity both in NMR and in vitro tests, and to effectively react with cellular thiols, and was supposed for a potential use in the chemotherapy of drug-resistant cancers. However, activity of PhSeZnCl in hepatic cells has never been tested before now. In this in vitro approach, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as the effects on cell cycle of PhSeZnCl in two preclinical hepatic models, namely HepG2 and HepaRG cells. Results showed that cell viability of HepG2 and HepaRG cells decreased in a dose-dependent manner, with a more marked effect in HepG2 tumour cells. Moreover, treatment with 50 µg/mL PhSeZnCl caused an increase of primary DNA damage (4 h) and a statistically significant increase of HepG2 cells arrested in G2/M phase. In addition, it altered mitochondrial membrane potential and induced chromosomal DNA fragmentation (24 h). In HepaRG cells, PhSeZnCl was able to determine a cell cycle-independent induction of apoptosis. Particularly, 50 µg/mL induced mitochondrial membrane depolarization after 24 h and apoptosis after 4 h treatment. Futhermore, all PhSeZnCl concentrations tested determined a significant increase of apoptotic cells after 24 h. Apoptosis was also highlighted by the detection of active Caspase-3 by Western Blot analysis after 24 h exposure. In conclusion, this first toxicological assessment provides new insights into the biological activity of PhSeZnCl in preclinical hepatic models that will be useful in future safety assessment investigation of this compound as a potential pharmaceutical.
Characterization and Treatment of Spinal Tumors
Authors: Amadasu Efosa , Panther Eric , Lucke-Wold Brandon
Published: September 2022

The prevalence of spinal tumors is rare in comparison to brain tumors which encompass most central nervous system tumors. Tumors of the spine can be divided into primary and metastatic tumors with the latter being the most common presentation. Primary tumors are subdivided based on their location on the spinal column and in the spinal cord into intramedullary, intradural extramedullary, and primary bone tumors. Back pain is a common presentation in spine cancer patients; however, other radicular pain may be present. Magnetic resonance imaging (MRI) is the imaging modality of choice for intradural extramedullary and intramedullary tumors. Plain radiographs are used in the initial diagnosis of primary bone tumors while Computed tomography (CT) and MRI may often be necessary for further characterization. Complete surgical resection is the treatment of choice for spinal tumors and may be curative for well circumscribed lesions. However, intralesional resection along with adjuvant radiation and chemotherapy can be indicated for patients that would experience increased morbidity from damage to nearby neurological structures caused by resection with wide margins. Even with the current treatment options, the prognosis for aggressive spinal cancer remains poor. Advances in novel treatments including molecular targeting, immunotherapy and stem cell therapy provide the potential for greater control of malignant and metastatic tumors of the spine.
Impunity and Capitalism
Authors: Jackson Trevor
Published: September 2022

Whose fault are financial crises, and who is responsible for stopping them, or repairing the damage? Impunity and Capitalism develops a new approach to the history of capitalism and inequality by using the concept of impunity to show how financial crises stopped being crimes and became natural disasters. Trevor Jackson examines the legal regulation of capital markets in a period of unprecedented expansion in the complexity of finance ranging from the bankruptcy of Europe's richest man in 1709, to the world's first stock market crash in 1720, to the first Latin American debt crisis in 1825. He shows how, after each crisis, popular anger and improvised policy responses resulted in efforts to create a more just financial capitalism but succeeded only in changing who could act with impunity, and how. Henceforth financial crises came to seem normal and legitimate, caused by impersonal international markets, with the costs borne by domestic populations and nobody in particular at fault.
Mathematical Logic and Computation
Authors: Avigad Jeremy
Published: September 2022

This new book on mathematical logic by Jeremy Avigad gives a thorough introduction to the fundamental results and methods of the subject from the syntactic point of view, emphasizing logic as the study of formal languages and systems and their proper use. Topics include proof theory, model theory, the theory of computability, and axiomatic foundations, with special emphasis given to aspects of mathematical logic that are fundamental to computer science, including deductive systems, constructive logic, the simply typed lambda calculus, and type-theoretic foundations. Clear and engaging, with plentiful examples and exercises, it is an excellent introduction to the subject for graduate students and advanced undergraduates who are interested in logic in mathematics, computer science, and philosophy, and an invaluable reference for any practicing logician's bookshelf.
Feeling, Thinking, and Talking
Authors: Ritchie L. David
Published: September 2022

The way the brain, body, and mind interact with social structure to shape communication has so far not received the attention it deserves. This book addresses this gap by providing a novel account of communication as a social, biological and neurological force. Combining theories from communication studies and psycholinguistics, and drawing on biological and evolutionary perspectives, it shows how communication is inherently both biological and social, and that language and the neural systems that support it have evolved in response to a complex social environment. It introduces a clear set of terms based on current research, and illustrates key concepts using real-life examples from everyday conversation - speaking to a number of current debates around the evolutionary and biological basis of language, and the relationship between language, cognition, and environment. Thought provoking and engaging, it will change the way we think about the relationship between communication and cognition.
Optimal multiple stopping problem under nonlinear expectation
Authors: Li Hanwu
Published: September 2022

In this paper, we study the optimal multiple stopping problem under the filtration-consistent nonlinear expectations. The reward is given by a set of random variables satisfying some appropriate assumptions, rather than a process that is right-continuous with left limits. We first construct the optimal stopping time for the single stopping problem, which is no longer given by the first hitting time of processes. We then prove by induction that the value function of the multiple stopping problem can be interpreted as the one for the single stopping problem associated with a new reward family, which allows us to construct the optimal multiple stopping times. If the reward family satisfies some strong regularity conditions, we show that the reward family and the value functions can be aggregated by some progressive processes. Hence, the optimal stopping times can be represented as hitting times.
Prison, Islamic Radicalization and the COVID-19 Pandemic in Italy
Authors: Ravagnani Luisa , Romano Carlo Alberto
Published: September 2022

Radicalization in prison is a well-developed field of research that, particularly in the aftermath of 11 September 2001, has involved academics and practitioners in the attempt to highlight possible push and pull factors and dynamics, as well as useful strategies for preventing and countering extremism inside the facilities. Like every subject of great interest, it has given rise to numerous theories about the possible approaches to radical violence, some even at odds with each other. However, there is almost unanimous agreement that isolation from external society and the inadequate management of the right to profess one’s religious faith within prisons may be elements that increase the risk of intramural radicalization. In Italy, the COVID-19 pandemic interfered heavily not only in the lives of people belonging to free society but also – and perhaps even more – in the lives of prisoners, resulting in the total isolation of prison facilities from the outside community. The dramatic efforts to protect public health have effectively eclipsed every other right, including – for prisoners – practising one’s faith with the guidance of authorized religious leaders. The present article explores how and why these anti-virus changes in the management of the Italian penitentiary could have influenced the risk of intramural radicalization.
Invisible Rulers: The ‘Latent Power Structure’ in Two Spanish Governments (2004 and 2012)
Authors: Villena-Oliver Andrés , Aldeguer Bernabé , Lucena-Piquero Delio
Published: September 2022

Beyond the observation of official positions and incorporating the ‘Latent Power Structure’ (LPS), this article offers a broadened view of the organization of democratic governments. We define the LPS as a set of former officials, parliamentary and party members, and business directors who are closely related to government members, since they have recruited one or more of them for certain positions in the past. Applied to a Social Network Analysis of two Spanish governments, the LPS reveals a more concentrated structure of power with a far greater range of resources. The LPS analysis shows that governments rely on certain influential organizations in the social structure, to a greater extent than might initially be believed. This finding indicates the existence of government structures that represent a greater risk to democratic representation, and provides evidence for understanding how the state and other critical institutions are related in the social structure.
CORRIGENDUM TO “CLUSTER CATEGORIES FROM GRASSMANNIANS AND ROOT COMBINATORICS”
Authors: BAUR KARIN , BOGDANIC DUSKO , GARCIA ELSENER ANA
Published: September 2022

In this note, we correct an oversight regarding the modules from Definition 4.2 and proof of Lemma 5.12 in Baur et al. (Nayoga Math. J., 2020, 240, 322–354). In particular, we give a correct construction of an indecomposable rank
$2$
module
$\operatorname {\mathbb {L}}\nolimits (I,J)$
, with the rank 1 layers I and J tightly
$3$
-interlacing, and we give a correct proof of Lemma 5.12.
Simon the Composite Sorcerer
Authors: Eastman David L.
Published: September 2022

Simon Magus is a key figure in the earliest apocryphal Acts of Peter. He is a sorcerer and confidant of the emperor who clashes with Peter and, in later apocryphal texts, with both Peter and Paul. However, this is not simply the villain of the Acts of the Apostles. In this article I will argue that the apocryphal Simon is a composite figure drawn substantially, but not necessarily wholly, from the Simon of Acts 8 and the Elymas/Bar-Jesus figure who opposes Paul in Acts 13.
Psalm 143.2 and the Argument of Galatians 3.10
Authors: Moore Peter C.
Published: September 2022

In the ongoing discussions of Gal 3.10–14, interpreters have underappreciated the connection between Paul's argument in 3.10 and his use of Ps 143.2 in 2.16. This article argues that Paul bases his denial of justification by works in 2.16 on the confession of humanity's universal sinfulness in Ps 143.2. Given the rhetorical function of 2.15–21 as well as the close verbal and logical ties between 2.16 and 3.10, it contends the same thought underlies Paul's charge in 3.10 that those of works are under a curse. On this basis, the article assesses various interpretations of Gal 3.10.
Postseismic Process Inversion Using Full Time Series of Surface Deformation: Full Time‐Series Inversion (FTI) Theory and Its Application to the 2017 Sarpol‐e Zahab Earthquake
Authors: Yue Han , Wang Kang , Xue Lian , Shen Zhengkang , Sun Jianbao
Published: September 2022

Postseismic processes provide important opportunities to probe into and investigate the frictional, viscous, and porous properties of the seismogenic fault and the surrounding Earth media. To accommodate the temporal and spatial resolutions and long‐term baseline stability of different deformation data, we develop a full time‐series inversion (FTI) technique, which jointly inverts for afterslip patterns using full time series of Global Navigation Satellite System, SAR, and strainmeter data. The FTI linearizes the inversion problem with a prescribed source evolution function to achieve efficient inversion. We conduct synthetic tests to validate the spatial and temporal resolution of the FTI algorithm. FTI outperforms static inversion techniques in terms of inversion stability under high noise level. We apply different parameterization strategies to evaluate its resolution for slip evolution parameters. The tests show that FTI can discriminate spatially separated afterslip with distinct evolution functions. Finally, we apply FTI to investigate the afterslip process following the 2017 Mw 7.3 Sarpol‐e Zahab earthquake that occurred along the Iran‐Iraq border in northwestern Zagros using Synthetic Aperture Radar Interferometry time series derived from the Sentinel‐1 observations 1 year after the mainshock. Similar to the synthetic tests, the algorithm is capable to discriminate afterslip with different evolution functions in the up‐ and downdip portions of the coseismic rupture zone. By comparing with the stress‐driven afterslip model simulated using rate‐strengthening frictional law, we demonstrate the stability of FTI in resolving the afterslip process. We emphasize the importance of incorporating early postseismic observations for deciphering afterslip evolution and frictional parameters.
Investigation of Tropical Cyclone Wind Models With Application to Storm Tide Simulations
Authors: Wang Shuai , Lin Ning , Gori Avantika
Published: September 2022

The hazards induced by tropical cyclones (TCs), for example, high winds, extreme precipitation, and storm tides, are closely related to the TC surface wind field. Parametric models for TC surface wind distribution have been widely used for hazards and risk analysis due to their simplicity and efficiency in application. Here we revisit the parametric modeling of TC wind fields, including the symmetrical and asymmetrical components, and its applications in storm tide modeling in the North Atlantic. The asymmetrical wind field has been related to TC motion and vertical wind shear; however, we find that a simple and empirical background‐wind model, based solely on a rotation and scaling of the TC motion vector, can largely capture the observed surface wind asymmetry. The implicit inclusion of the wind shear effect can be understood with the climatological relationship between the general TC motion and wind shear directions during hurricane seasons. For the symmetric wind field, the widely used Holland wind profile is chosen as a benchmark model, and we find that a physics‐based complete wind profile model connecting the inner core and outer region performs superiorly compared to a wind analysis data set. When used as wind forcing for storm tide simulations, the physics‐based complete wind profile integrated with the background‐wind asymmetry model can reproduce the observed storm tides with lower errors than the often‐used Holland model coupled with a translation‐speed‐based method.
Measuring “Weather Whiplash” Events in North America: A New Large‐Scale Regime Approach
Authors: Francis Jennifer A. , Skific Natasa , Vavrus Steven J. , Cohen Judah
Published: September 2022

The term “weather whiplash” was recently coined to describe abrupt swings in weather conditions from one extreme to another, such as from a prolonged, frigid cold spell to anomalous warmth or from drought to heavy precipitation. These events are often highly disruptive to agriculture, ecosystems, and daily activities. In this study, we propose and demonstrate a novel metric to identify weather whiplash events (WWEs) and track their frequency over time. We define a WWE as a transition from one persistent continental‐scale circulation regime to another distinctly different pattern, as determined using an objective pattern clustering analysis called self‐organizing maps. We focus on the domain spanning North America and the eastern N. Pacific Ocean. A matrix of representative atmospheric patterns in 500‐hPa geopotential height anomalies is created from 72 years of daily fields. We analyze the occurrence of WWEs originating with long‐duration events (LDEs) (defined as lasting four or more days) in each pattern, as well as the associated extremes in temperature and precipitation. A WWE is detected when the pattern 2 days following a LDE is substantially different, measured using internal matrix distances and thresholds. Changes in WWE frequency are assessed objectively based on reanalysis and historical climate model simulations, and for the future using climate model projections. Temporal changes in the future under representative concentration pathway 8.5 forcing are more robust than those in recent decades. We find consistent increases in WWEs originating in patterns with an anomalously warm Arctic and decreases in cold‐Arctic patterns.
Characterizing Continental US Hurricane Risk: Which Intensity Metric Is Best?
Authors: Klotzbach Philip J. , Chavas Daniel R. , Bell Michael M. , Bowen Steven G. , Gibney Ethan J. , Schreck Carl J.
Published: September 2022

The damage potential of a hurricane is widely considered to depend more strongly on an integrated measure of the hurricane wind field, such as integrated kinetic energy (IKE), than a point‐based wind measure, such as maximum sustained wind speed (Vmax). Recent work has demonstrated that minimum sea level pressure (MSLP) is also an integrated measure of the wind field. This study investigates how well historical continental US hurricane damage is predicted by MSLP compared to both Vmax and IKE for continental United States hurricane landfalls for the period 1988–2021. We first show for the entire North Atlantic basin that MSLP is much better correlated with IKE (rrank = 0.50) than Vmax (rrank = 0.26). We then show that continental US hurricane normalized damage is better predicted by MSLP (rrank = 0.83) than either Vmax (rrank = 0.67) or IKE (rrank = 0.65). For Georgia to Maine hurricane landfalls specifically, MSLP and IKE show similar levels of skill at predicting damage, whereas Vmax provides effectively no predictive power. Conclusions for IKE extend to power dissipation as well, as the two quantities are highly correlated because wind radii closely follow a Modified Rankine vortex. The physical relationship of MSLP to IKE and power dissipation is discussed. In addition to better representing damage, MSLP is also much easier to measure via aircraft or surface observations than either Vmax or IKE, and it is already routinely estimated operationally. We conclude that MSLP is an ideal metric for characterizing hurricane damage risk.
Assessment of Using Field‐Aligned Currents to Drive the Global Ionosphere Thermosphere Model: A Case Study for the 2013 St Patrick’s Day Geomagnetic Storm
Authors: Zhu Qingyu , Lu Gang , Maute Astrid , Deng Yue , Anderson Brian
Published: September 2022

In this study, field‐aligned currents (FACs) obtained from the Active Magnetosphere and Planetary Electrodynamics Response Experiment data set have been used to specify the high‐latitude electric potential in the Global Ionosphere Thermosphere Model (GITM). The advantages and challenges of the FAC‐driven simulation are investigated based on a series of numerical experiments and data‐model comparisons for the 2013 St Patrick's Day geomagnetic storm. It is found that the cross‐track ion drift measured by the Defense Meteorological Satellite Program satellites can be well reproduced in the FAC‐driven simulation when the electron precipitation pattern obtained from Assimilative Mapping of Ionospheric Electrodynamics (AMIE) technique is used in GITM. It is also found that including the neutral wind dynamo properly is very important when using FACs to derive the high‐latitude electric field. Without the neutral wind dynamo, the cross‐polar‐cap potential and hemispheric integrated Joule heating could be underestimated by more than 20%. Moreover, the FAC‐driven simulation is able to well reproduce the ionospheric response to the geomagnetic storm in the American sector. However, the FAC‐driven simulation yields relatively larger data‐model discrepancies compared to the AMIE‐driven GITM simulation. This may result from inaccurate Joule heating estimations in the FAC‐driven simulation caused by the inconsistency between the FAC and electron precipitation patterns. This study indicates that the FAC‐driven technique could be a useful tool for studying the coupled ionosphere and thermosphere system provided that the FACs and electron precipitation patterns can be accurately specified.
Space Weather Bibliometrics for 2022: Going Beyond Impact Factor
Authors: Lugaz Noé
Published: September 2022

I discuss the impact factor of Space Weather for 2021, its small decrease with respect to the number in 2020, and potential causes for this decrease. The limitations of the impact factor are emphasized as reported in past studies, in particular due to the large weight of highly cited papers. For Space Weather, over several years, the median number of citations received by a paper per year is close to the impact factor at the time of publication, with very few papers receiving no citations. I expect that, as the solar cycle ramps up, the impact factor will start to grow again.
Mathematical operations and equation solving with reconfigurable metadevices
Authors: Tzarouchis Dimitrios C. , Mencagli Mario Junior , Edwards Brian , Engheta Nader
Published: September 2022

Performing analog computations with metastructures is an emerging wave-based paradigm for solving mathematical problems. For such devices, one major challenge is their reconfigurability, especially without the need for a priori mathematical computations or computationally-intensive optimization. Their equation-solving capabilities are applied only to matrices with special spectral (eigenvalue) distribution. Here we report the theory and design of wave-based metastructures using tunable elements capable of solving integral/differential equations in a fully-reconfigurable fashion. We consider two architectures: the Miller architecture, which requires the singular-value decomposition, and an alternative intuitive direct-complex-matrix (DCM) architecture introduced here, which does not require a priori mathematical decomposition. As examples, we demonstrate, using system-level simulation tools, the solutions of integral and differential equations. We then expand the matrix inverting capabilities of both architectures toward evaluating the generalized Moore–Penrose matrix inversion. Therefore, we provide evidence that metadevices can implement generalized matrix inversions and act as the basis for the gradient descent method for solutions to a wide variety of problems. Finally, a general upper bound of the solution convergence time reveals the rich potential that such metadevices can offer for stationary iterative schemes.
GANscan: continuous scanning microscopy using deep learning deblurring
Authors: Fanous Michael John , Popescu Gabriel
Published: September 2022

Most whole slide imaging (WSI) systems today rely on the “stop-and-stare” approach, where, at each field of view, the scanning stage is brought to a complete stop before the camera snaps a picture. This procedure ensures that each image is free of motion blur, which comes at the expense of long acquisition times. In order to speed up the acquisition process, especially for large scanning areas, such as pathology slides, we developed an acquisition method in which the data is acquired continuously while the stage is moving at high speeds. Using generative adversarial networks (GANs), we demonstrate this ultra-fast imaging approach, referred to as GANscan, which restores sharp images from motion blurred videos. GANscan allows us to complete image acquisitions at 30x the throughput of stop-and-stare systems. This method is implemented on a Zeiss Axio Observer Z1 microscope, requires no specialized hardware, and accomplishes successful reconstructions at stage speeds of up to 5000 μm/s. We validate the proposed method by imaging H&E stained tissue sections. Our method not only retrieves crisp images from fast, continuous scans, but also adjusts for defocusing that occurs during scanning within +/− 5 μm. Using a consumer GPU, the inference runs at <20 ms/ image.
Early impairment of cortical circuit plasticity and connectivity in the 5XFAD Alzheimer’s disease mouse model
Authors: Chen Chang , Ma Xiaokuang , Wei Jing , Shakir Neha , Zhang Jessica K. , Zhang Le , Nehme Antoine , Cui Yuehua , Ferguson Deveroux , Bai Feng , Qiu Shenfeng
Published: September 2022

Genetic risk factors for neurodegenerative disorders, such as Alzheimer’s disease (AD), are expressed throughout the life span. How these risk factors affect early brain development and function remain largely unclear. Analysis of animal models with high constructive validity for AD, such as the 5xFAD mouse model, may provide insights on potential early neurodevelopmental effects that impinge on adult brain function and age-dependent degeneration. The 5XFAD mouse model over-expresses human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations. It is unclear how the expression of these mutant proteins affects early developing brain circuits. We found that the prefrontal cortex (PFC) layer 5 (L5) neurons in 5XFAD mice exhibit transgenic APP overloading at an early post-weaning age. Impaired synaptic plasticity (long-term potentiation, LTP) was seen at 6–8 weeks age in L5 PFC circuit, which was correlated with increased intracellular APP. APP overloading was also seen in L5 pyramidal neurons in the primary visual cortex (V1) during the critical period of plasticity (4–5 weeks age). Whole-cell patch clamp recording in V1 brain slices revealed reduced intrinsic excitability of L5 neurons in 5XFAD mice, along with decreased spontaneous miniature excitatory and inhibitory inputs. Functional circuit mapping using laser scanning photostimulation (LSPS) combined with glutamate uncaging uncovered reduced excitatory synaptic connectivity onto L5 neurons in V1, and a more pronounced reduction in inhibitory connectivity, indicative of altered excitation and inhibition during VC critical period. Lastly, in vivo single-unit recording in V1 confirmed that monocular visual deprivation-induced ocular dominance plasticity during critical period was impaired in 5XFAD mice. Our study reveals plasticity deficits across multiple cortical regions and indicates altered early cortical circuit developmental trajectory as a result of mutant APP/PS1 over-expression.
Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake
Authors: Reiner Benjamin C. , Zhang Yafang , Stein Lauren M. , Perea Emilie Dávila , Arauco-Shapiro Gabriella , Ben Nathan Jennifer , Ragnini Kael , Hayes Matthew R. , Ferraro Thomas N. , Berrettini Wade H. , Schmidt Heath D. , Crist Richard C.
Published: September 2022

Opioid exposure is known to cause transcriptomic changes in the nucleus accumbens (NAc). However, no studies to date have investigated cell type-specific transcriptomic changes associated with volitional opioid taking. Here, we use single nucleus RNA sequencing (snRNAseq) to comprehensively characterize cell type-specific alterations of the NAc transcriptome in rats self-administering morphine. One cohort of male Brown Norway rats was injected with acute morphine (10 mg/kg, i.p.) or saline. A second cohort of rats was allowed to self-administer intravenous morphine (1.0 mg/kg/infusion) for 10 consecutive days. Each morphine-experienced rat was paired with a yoked saline control rat. snRNAseq libraries were generated from NAc punches and used to identify cell type-specific gene expression changes associated with volitional morphine taking. We identified 1106 differentially expressed genes (DEGs) in the acute morphine group, compared to 2453 DEGs in the morphine self-administration group, across 27 distinct cell clusters. Importantly, we identified 1329 DEGs that were specific to morphine self-administration. DEGs were identified in novel clusters of astrocytes, oligodendrocytes, and D1R- and D2R-expressing medium spiny neurons in the NAc. Cell type-specific DEGs includedRgs9,Celf5,Oprm1, andPde10a. Upregulation ofRgs9andCelf5in D2R-expressing neurons was validated by RNAscope. Approximately 85% of all oligodendrocyte DEGs, nearly all of which were associated with morphine taking, were identified in two subtypes. Bioinformatic analyses identified cell type-specific upstream regulatory mechanisms of the observed transcriptome alterations and downstream signaling pathways, including both novel and previously identified molecular pathways. These findings show that volitional morphine taking is associated with distinct cell type-specific transcriptomic changes in the rat NAc and highlight specific striatal cell populations and novel molecular substrates that could be targeted to reduce compulsive opioid taking.
A novel cyclic γ-AApeptide-based long-acting pan-coronavirus fusion inhibitor with potential oral bioavailability by targeting two sites in spike protein
Authors: Xue Songyi , Wang Xinling , Wang Lei , Xu Wei , Xia Shuai , Sun Lujia , Wang Shaohui , Shen Ning , Yang Ziqi , Huang Bo , Li Sihao , Cao Chuanhai , Calcul Laurent , Sun Xingmin , Lu Lu , Cai Jianfeng , Jiang Shibo
Published: September 2022

The receptor-binding domain (RBD) in S1 subunit and heptad repeat 1 (HR1) domain in S2 subunit of SARS-CoV-2 spike (S) protein are the targets of neutralizing antibodies (nAbs) and pan-coronavirus (CoV) fusion inhibitory peptides, respectively. However, neither nAb- nor peptide-based drugs can be used orally. In this study, we screened a one-bead-two-compound (OBTC) cyclic γ-AApeptide library against SARS-CoV-2 S protein and identified a hit: S-20 with potent membrane fusion inhibitory activity, but moderate selectivity index (SI). After modification, one derivative, S-20-1, exhibited improved fusion inhibitory activity and SI (>1000). S-20-1 could effectively inhibit infection by pseudotyped and authentic SARS-CoV-2 and pseudotyped variants of concern (VOCs), including B.1.617.2 (Delta) and B.1.1.529 (Omicron), as well as MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. It could also inhibit infection of a pseudotyped SARS-related coronavirus WIV1 (SARSr-CoV-WIV1) from bats. Intranasal application of S-20-1 to mice before or after challenge with HCoV-OC43 or SARS-CoV-2 provided significant protection from infection. Importantly, S-20-1 was highly resistant to proteolytic degradation, had long half-life, and possessed favorable oral bioavailability. Mechanistic studies suggest that S-20-1 binds with high affinity to RBD in S1 and HR1 domain in S2 of SARS-CoV-2 S protein. Thus, with its pan-CoV fusion and entry inhibitory activity by targeting two sites in S protein, desirable half-life, and promising oral bioavailability, S-20-1 is a potential candidate for further development as a novel therapeutic and prophylactic drug against infection by SARS-CoV-2 and its variants, as well as future emerging and reemerging CoVs.
A genomic deletion encompassing CRYBB2-CRYBB2P1 is responsible for autosomal recessive congenital cataracts
Authors: Irum Bushra , Kabir Firoz , Shoshany Nadav , Khan Shahid Y. , Rauf Bushra , Naeem Muhammad Asif , Qaiser Tanveer A. , Riazuddin Sheikh , Hejtmancik J. Fielding , Riazuddin S. Amer
Published: September 2022

Here we report a consanguineous Pakistani family with multiple affected individuals with autosomal recessive congenital cataract (arCC). Exclusion analysis established linkage to chromosome 22q, and Sanger sequencing coupled with PCR-based chromosome walking identified a large homozygous genomic deletion. Our data suggest that this deletion leads to CRYBB2-CRYBB2P1 fusion, consisting of exons 1–5 of CRYBB2 and exon 6 of CRYBB2P1, the latter of which harbors the c.463 C > T (p.Gln155*) mutation, and is responsible for arCC.
Drivers and distribution of global ocean heat uptake over the last half century
Authors: Huguenin Maurice F. , Holmes Ryan M. , England Matthew H.
Published: September 2022

Since the 1970s, the ocean has absorbed almost all of the additional energy in the Earth system due to greenhouse warming. However, sparse observations limit our knowledge of where ocean heat uptake (OHU) has occurred and where this heat is stored today. Here, we equilibrate a reanalysis-forced ocean-sea ice model, using a spin-up that improves on earlier approaches, to investigate recent OHU trends basin-by-basin and associated separately with surface wind trends, thermodynamic properties (temperature, humidity and radiation) or both. Wind and thermodynamic changes each explain ~ 50% of global OHU, while Southern Ocean forcing trends can account for almost all of the global OHU. This OHU is enabled by cool sea surface temperatures and sensible heat gain when atmospheric thermodynamic properties are held fixed, while downward longwave radiation dominates when winds are fixed. These results address long-standing limitations in multidecadal ocean-sea ice model simulations to reconcile estimates of OHU, transport and storage.
Ultra-depleted hydrogen isotopes in hydrated glass record Late Cretaceous glaciation in Antarctica
Authors: Nelson Demian A. , Cottle John M. , Bindeman Ilya N. , Camacho Alfredo
Published: September 2022

The Early Jurassic Butcher Ridge Igneous Complex (BRIC) in the Transantarctic Mountains contains abundant and variably hydrated silicic glass which has the potential to preserve a rich paleoclimate record. Here we present Fourier Transform Infrared Spectroscopic data that indicates BRIC glasses contain up to ~8 wt.% molecular water (H2Om), and low (<0.8 wt.%) hydroxyl (OH) component, interpreted as evidence for secondary hydration by meteoric water. BRIC glasses contain the most depleted hydrogen isotopes yet measured in terrestrial rocks, down to δD = −325 ‰. In situ 40Ar/39Ar geochronology of hydrated glasses with ultra-depleted δD values yield ages from 105 Ma to 72 Ma with a peak at c. 91.4 Ma. Combined, these data suggest hydration of BRIC glasses by polar glacial ice and melt water during the Late Cretaceous, contradicting paleoclimate reconstructions of this period that suggest Antarctica was ice-free and part of a global hot greenhouse.
Parallel triplet formation pathways in a singlet fission material
Authors: Maity Nilabja , Kim Woojae , Panjwani Naitik A. , Kundu Arup , Majumder Kanad , Kasetty Pranav , Mishra Divji , Bittl Robert , Nagesh Jayashree , Dasgupta Jyotishman , Musser Andrew J. , Patil Satish
Published: September 2022

Harvesting long-lived free triplets in high yields by utilizing organic singlet fission materials can be the cornerstone for increasing photovoltaic efficiencies potentially. However, except for polyacenes, which are the most studied systems in the singlet fission field, spin-entangled correlated triplet pairs and free triplets born through singlet fission are relatively poorly characterized. By utilizing transient absorption and photoluminescence spectroscopy in supramolecular aggregate thin films consisting of Hamilton-receptor-substituted diketopyrrolopyrrole derivatives, we show that photoexcitation gives rise to the formation of spin-0 correlated triplet pair 1(TT) from the lower Frenkel exciton state. The existence of 1(TT) is proved through faint Herzberg-Teller emission that is enabled by vibronic coupling and correlated with an artifact-free triplet-state photoinduced absorption in the near-infrared. Surprisingly, transient electron paramagnetic resonance reveals that long-lived triplets are produced through classical intersystem crossing instead of 1(TT) dissociation, with the two pathways in competition. Moreover, comparison of the triplet-formation dynamics in J-like and H-like thin films with the same energetics reveals that spin-orbit coupling mediated intersystem crossing persists in both. However, 1(TT) only forms in the J-like film, pinpointing the huge impact of intermolecular coupling geometry on singlet fission dynamics.
Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
Authors: Francis Caitlin R. , Kincross Hayle , Kushner Erich J.
Published: September 2022

In early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood vessel development is unknown. Rab35 has been shown to play an enigmatic role in cellular behaviors which differs greatly between tissue-type and organism. Importantly, Rab35 has never been characterized for its potential contribution in sprouting angiogenesis; thus, our goal was to map Rab35’s primary function in angiogenesis. Our results demonstrate that Rab35 is critical for sprout formation; in its absence, apicobasal polarity is entirely lost in vitro and in vivo. To determine mechanism, we systematically explored established Rab35 effectors and show that none are operative in endothelial cells. However, we find that Rab35 partners with DENNd1c, an evolutionarily divergent guanine exchange factor, to localize to actin. Here, Rab35 regulates actin polymerization through limiting Rac1 and RhoA activity, which is required to set up proper apicobasal polarity during sprout formation. Our findings establish that Rab35 is a potent brake of actin remodeling during blood vessel development.
MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner
Authors: Paniagua Inés , Tayeh Zainab , Falcone Mattia , Hernández Pérez Santiago , Cerutti Aurora , Jacobs Jacqueline J. L.
Published: September 2022

Protection of stalled replication forks is essential to prevent genome instability, a major driving force of tumorigenesis. Several key regulators of DNA double-stranded break (DSB) repair, including 53BP1 and RIF1, have been implicated in fork protection. MAD2L2, also known as REV7, plays an important role downstream of 53BP1/RIF1 by counteracting resection at DSBs in the recently discovered shieldin complex. The ability to bind and counteract resection at exposed DNA ends at DSBs makes MAD2L2/shieldin a prime candidate for also suppressing nucleolytic processing at stalled replication forks. However, the function of MAD2L2/shieldin outside of DNA repair is unknown. Here we address this by using genetic and single-molecule analyses and find that MAD2L2 is required for protecting and restarting stalled replication forks. MAD2L2 loss leads to uncontrolled MRE11-dependent resection of stalled forks and single-stranded DNA accumulation, which causes irreparable genomic damage. Unexpectedly, MAD2L2 limits resection at stalled forks independently of shieldin, since fork protection remained unaffected by shieldin loss. Instead, MAD2L2 cooperates with the DNA polymerases REV3L and REV1 to promote fork stability. Thus, MAD2L2 suppresses aberrant nucleolytic processing both at DSBs and stalled replication forks by differentially engaging shieldin and REV1/REV3L, respectively.
Structural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro
Authors: Hameedi Mikhail A. , T. Prates Erica , Garvin Michael R. , Mathews Irimpan I. , Amos B. Kirtley , Demerdash Omar , Bechthold Mark , Iyer Mamta , Rahighi Simin , Kneller Daniel W. , Kovalevsky Andrey , Irle Stephan , Vuong Van-Quan , Mitchell Julie C. , Labbe Audrey , Galanie Stephanie , Wakatsuki Soichi , Jacobson Daniel
Published: September 2022

In addition to its essential role in viral polyprotein processing, the SARS-CoV-2 3C-like protease (3CLpro) can cleave human immune signaling proteins, like NF-κB Essential Modulator (NEMO) and deregulate the host immune response. Here, in vitro assays show that SARS-CoV-2 3CLpro cleaves NEMO with fine-tuned efficiency. Analysis of the 2.50 Å resolution crystal structure of 3CLpro C145S bound to NEMO226–234reveals subsites that tolerate a range of viral and host substrates through main chain hydrogen bonds while also enforcing specificity using side chain hydrogen bonds and hydrophobic contacts. Machine learning- and physics-based computational methods predict that variation in key binding residues of 3CLpro-NEMO helps explain the high fitness of SARS-CoV-2 in humans. We posit that cleavage of NEMO is an important piece of information to be accounted for, in the pathology of COVID-19.
Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity
Authors: Huyghe A. , Furlan G. , Schroeder J. , Cascales E. , Trajkova A. , Ruel M. , Stüder F. , Larcombe M. , Yang Sun Y. Bo , Mugnier F. , De Matteo L. , Baygin A. , Wang J. , Yu Y. , Rama N. , Gibert B. , Kielbassa J. , Tonon L. , Wajda P. , Gadot N. , Brevet M. , Siouda M. , Mulligan P. , Dante R. , Liu P. , Gronemeyer H. , Mendoza-Parra M. , Polo J. M. , Lavial F.
Published: September 2022

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.
Gene expression profiles of specific chicken skeletal muscles
Authors: Kui Hua , Ran Bo , Yang Maosen , Shi Xin , Luo Yingyu , Wang Yujie , Wang Tao , Li Diyan , Shuai Surong , Li Mingzhou
Published: September 2022

The chicken provides large amounts of protein for the human diet and is also used as a model organism for biomedical research. Increasing meat production is an important goal in the poultry industry and skeletal muscles have highly diverse origins, shapes, metabolic features, and physical functions. Previous gene expression atlases have largely ignored the differences among diverse types of skeletal muscles; therefore, comprehensive transcriptional maps of all skeletal muscles are needed to improve meat production traits. In this study, we sequenced 58 samples from 10 different skeletal muscles of 42-day-old White Plymouth Rock chickens. We also measured myofiber diameter and generated myofiber-type datasets of these 10 tissues. We generated 418.4 Gb high-quality bulk RNA-Seq data from four or six biological replicates of each skeletal muscle (four replicates from extraocular samples) (approximately 7.4 Gb per sample). This dataset provides valuable information for understanding the muscle fiber characteristics of White Plymouth Rock chickens. Furthermore, our data can be used as a model for heterogeneity analysis between tissues with similar properties.
Spatiotemporal heterogeneity of land subsidence in Beijing
Authors: Duan Guangyao , Gong Huili , Chen Beibei , Li Xiaojuan , Pan Xingyao , Shi Min , Zhang Hang
Published: September 2022

Land subsidence induced by groundwater level decline has spatiotemporal variations. Taking the Interferometric Synthetic Aperture Radar (InSAR) results and the groundwater subsidence data acquired by the monitoring stations as the source material, this paper aims to reveal the spatiotemporal heterogeneity of groundwater-land subsidence in Beijing plain by using the Wind Rose Map (WRM) method and the Change Point Analysis (CPA) method. The WRM results show that the amount and variation in subsidence differs in different directions. This method detected the formation of new subsidence centers and the slowdown of land subsidence in 2008. The CPA results show that obvious changes are detected in subsidence development at the Wangsiying (WSY), Tianzhu (TZ) and Wangjing (WJ) stations. However, there is a relatively stable trend of groundwater decline and land subsidence at the Tianzhu (TZ) station. The stages of land subsidence development show a significant response to groundwater. Moreover, changes in land subsidence also show delayed response behind the changes in groundwater level. The time-lag could be affected by the variation in amplitude of the groundwater level.