bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental context predicts state fluctuations in negative symptoms in youth at clinical high risk for psychosis
Authors: Luther Lauren , Raugh Ian M. , Collins Delaney E. , Berglund Alysia , Knippenberg Anna R. , Mittal Vijay A. , Walker Elaine F. , Strauss Gregory P.
Published: May 2023

Background

Negative symptoms (avolition, anhedonia, asociality) are a prevalent symptom in those across the psychosis-spectrum and also occur at subclinical levels in the general population. Recent work has begun to examine how environmental contexts (e.g. locations) influence negative symptoms. However, limited work has evaluated how environments may contribute to negative symptoms among youth at clinical high risk for psychosis (CHR). The current study uses Ecological Momentary Assessment to assess how four environmental contexts (locations, activities, social interactions, social interaction method) impact state fluctuations in negative symptoms in CHR and healthy control (CN) participants.

Methods

CHR youth (n= 116) and CN (n= 61) completed 8 daily surveys for 6 days assessing negative symptoms and contexts.

Results

Mixed-effects modeling demonstrated that negative symptoms largely varied across contexts in both groups. CHR participants had higher negative symptoms than CN participants in most contexts, but groups had similar symptom reductions during recreational activities and phone call interactions. Among CHR participants, negative symptoms were elevated in several contexts, including studying/working, commuting, eating, running errands, and being at home.

Conclusions

Results demonstrate that negative symptoms dynamically change across some contexts in CHR participants. Negative symptoms were more intact in some contexts, while other contexts, notably some used to promote functional recovery, may exacerbate negative symptoms in CHR. Findings suggest that environmental factors should be considered when understanding state fluctuations in negative symptoms among those at CHR participants.
India's epidemics in theRiḥlaof Ibn Baṭṭūṭa: plague, cholera or lexical muddle?
Authors: Tresso Claudia Maria
Published: May 2023

The famous Moroccan traveller Muḥammad b. Baṭṭūṭa, who left Tangier in 1325, claims to have made a journey that took him across most of the then Islamicate world. The country in which he recounts having stayed the longest was India, where he says he remained from 1333 to 1341/1342, mostly in the Islamic Sultanate of Delhi. A long section of hisRiḥlais dedicated to the sub-continent and modern historians of this region ascribe to it an important documentary value, although it has been argued that Ibn Baṭṭūṭa may have borrowed – not to imply copied – information from other sources in other parts of the work. As concerns India, Ibn Baṭṭūṭa speaks of two epidemics and one deadly disease that occurred in 1334–5 and 1344. Some scholars have referred to them as cholera, while others have suggested it was the plague – thus supporting the hypothesis that the medieval plague pandemic had struck India before reaching the Middle East. How did this confusion arise? What exactly does Ibn Baṭṭūṭa'sRiḥlarelate? Do Indo-Persian sources confirm these epidemics? Do they and/or Ibn Baṭṭūṭa'sRiḥlaallow us to discount the presence of the Medieval Plague in India, or rather do they assert it?

In order to answer these questions, this paper analyses the information on the Indian epidemics in Ibn Baṭṭūṭa'sRiḥlaand compares the text with its translations in the principal European languages and with Indo-Persian chronicles. These analyses reveal something of a lexical muddle which, in my opinion, has contributed to some errors and misunderstandings regarding the diseases in question. But another question arises: is it possible to read the information provided by Ibn Baṭṭūṭa and the Indian chronicles in a consilient way, that is, taking into account not only the analysis of written documents, but also the recent and current findings in genetics of plague, and in particular on the Black Death? Finally, an attempt is made to answer a question that has to be asked, particularly in light of the criticism often levelled at Ibn Baṭṭūṭa. Considering that in one of these events he claims to have witnessed the epidemic, is there any reason to suppose that he did not? Regarding the other two events that he did not claim to witness firsthand, is there any cause to doubt his claims?
State inspection in contexts of cultural and sociopolitical conflict: The case of social services offered to Arab-Palestinian young women in Israel
Authors: Levin Lia , Karram-Elias Haneen , Pagorek Eshel Shira , Alnabilsy Raghda
Published: May 2023

Inspectors are the executing branch of state regulation. Existing literature focuses on their tasks and operations, mostly with regard to their commitments to the state and their complex relations with inspectees. The present study explores a heretofore-unexamined issue: the playing out of inspection in a sociopolitical context of national conflict and discriminatory majority-minority relations. Namely, it focuses on the work of inspectors of social services overseen by the Israeli welfare state but provided by local or contracted agencies, offered to one of the country’s most oppressed and marginalized populations: Arab-Palestinian young women. The research was based on interviews with 25 national and district inspectors in the field of services for young women in Israel, and reveals numerous barriers hindering effective inspection, resulting from having to inspect the implementation of universalist policy in a context of local needs; and the implementation of welfare policy in a context of national sociopolitical inequality. This is discussed in terms of the severe toll that color-blind and gender-blind policy can have on the feasibility of enforcing regulation, and on the potential to ensure that Arab-Palestinian young women receive adequate social services.
Incoherent and Indefensible? A Normative Analysis of Young People’s Position in England’s Welfare and Homelessness Systems
Authors: Colliver Kit
Published: May 2023

Young people experience different treatment compared to older adults in the English welfare and homelessness systems, encountering varying levels of protection and disadvantage. This paper uses a value-pluralist perspective to explore the normative rationales for and the ethical defensibility of these policy differences. Evidence from 38 key informant interviews suggests that the English homelessness system is shifting towards a vulnerability-oriented response to young people. But an inconsistent value framework within the welfare system systematically disadvantages them without offering a corresponding degree of protection. As such, these closely-connected areas of social policy pull in opposing directions. Although individual positions targeting young people may (to greater and lesser extents) be justifiable, this disparity in values creates an incoherent and indefensible welfare policy landscape for this group.
How Incarcerating Children Affects their Labour Market Outcomes
Authors: Dorsett Richard , Thomson David
Published: May 2023

We investigate the labour market effects of incarcerating children. Using linked administrative data to track outcomes for English schoolchildren, we estimate an econometric model of transitions between education, custody, employment and NEET (not in employment, education or training), along with earnings for those starting work. We allow outcomes to vary according to the individual’s state in the preceding spell and, by controlling for personal characteristics and unobserved heterogeneity, interpret such variation as capturing causal impacts. For males, the main effect of incarceration is a reduction of more than 10% in the probability of employment. For females, there is no overall impact on employment but, for those entering work, wages are reduced by 25%. These negative impacts suggest roles for policy in deterring delinquency, finding alternatives to custody, rehabilitating those incarcerated and supporting resettlement on release. Appropriate labour market policy may differ by gender, with males needing help to overcome employer discrimination and females needing encouragement to achieve better-paid work.
Hip-hop sampling aesthetics and the legacy ofGrand Upright v. Warner
Authors: Mcleish Claire E.A.
Published: May 2023

In 1991, Gilbert O'Sullivan sued Biz Markie for sampling without permission: this lawsuit,Grand Upright v. Warner, became a landmark case for music copyright, and for some scholars, represented a symbolic end to hip hop's golden age. This paper uses the lawsuit as a point of entry into debates about hip hop during a time of aesthetic transformation. Specifically, I present a corpus study spanning 1988–1993, consisting of hip hop songs of various subgenres drawn from Billboard charts. Unlike previous studies on this period, I consider both canonical artists, whose mastery of sampling is widely admired (such as Public Enemy), and more commercially successful artists (like the Fresh Prince), who used fewer samples. My study reveals a decrease in the average number of samples per song, and a radical shift in how these remaining samples are used. I situate Grand Upright at the intersection of legal institutions and musical aesthetics
Compliant peg-in-hole assembly for nonconvex axisymmetric components based on attractive region in environment
Authors: Liu Yang , Chen Ziyu , Qiao Hong , Gan Shuai
Published: May 2023

With the development of intelligent manufacturing, more and more nonstandard parts are used in high-precision assembly. The robotic assembly method based on attractive region in environment (ARIE) has been proven to have good performance in the high-precision assembly under the limitation of robot system accuracy or sensing accuracy. However, for the assembly of nonstandard parts, especially nonconvex parts, the existing ARIE-based strategy lacks a targeted design. In the assembly process, the nonconvex structure may cause blocking problems, which will lead to assembly failure when using the strategy. In order to solve this problem, this paper proposes a new assembly method by using the geometric features of constraint region based on the concept of ARIE. Specifically, first, when using the ARIE-based classic strategy, the reasons for the possible blocking problem in the assembly of a class of nonconvex axisymmetric parts are analyzed in detail. Second, a multi-step sliding strategy is proposed based on the theory of ARIE to solve the possible blocking problem in the assembly process. Third, impedance control is used to enable the peg to achieve the desired compliant motion in the proposed strategy. The improvement in the success rate of the proposed method is verified by the comparison experiment of small clearance peg-in-hole assembly, where the structure of the peg is nonconvex and axisymmetric.
Investigating the vision-based intervertebral motion estimation of the Cadaver’s craniovertebral junction
Authors: Zubair Mohammad , Kansal Sachin , Mukherjee Sudipto
Published: May 2023

Craniovertebral junction (CVJ) is one of the more complex parts of the spinal column. It provides mobility to the cranium and houses the spinal cord. In a healthy subject, the CVJ contributes 25% of the flexion–extension motion and 50% of the axial rotation of the neck. This work reports instrumentation development and results for evaluating implant performance in the stabilized CVJ after surgical procedures. Typically, some bony parts of the vertebrae causing compression to the spinal cord are removed and subsequently stabilized by the instrumenting implant in the CVJ. Pose estimation of the Cadaveric CVJ region is estimated using a monocular vision-based setup. The cervical spine’s first three vertebrae surround the CVJ area, where most cervical spine mobility originates. We aim to evaluate the performance of vision-based intervertebral motion estimation of the Cadaver’s CVJ in the Indian population, particularly in older people. A series of tests were performed on the Cadaver’s CVJ to evaluate the vision system-based motion estimation performance.
Theoretical study on a modified rocker-bogie suspension for robotic rovers
Authors: Cosenza Chiara , Niola Vincenzo , Pagano Stefano , Savino Sergio
Published: May 2023

Robotic rovers equipped with articulated rocker-bogie suspension have aroused great interest after the explorations on Mars; this interest has also shifted to different types of terrestrial applications such as in the agriculture, military, and rescue fields. The suspension can be designed so that, when the rover is on flat and horizontal ground, the weight is evenly distributed among the wheels; in this way, all wheels have the same traction capability and offer the same rolling resistance. As the operating conditions vary due to sloping ground, uneven ground surface, or different payload position, the weight distribution can undergo considerable variations. This type of suspension is statically determined with respect to weight, but it is indeterminate with respect to traction forces; the traction control system aims to avoid the wheels slippage. In this paper, the traction contribution that each wheel can provide, to overcome a step obstacle, is shown. Furthermore, the possibility of regulating the distribution of vertical loads among the wheels adopting a torsion spring, with adjustable preload, arranged between rocker and bogie, is evaluated. A suitable spring preload facilitates the initial phase of the obstacle overcoming if the rover advances with the bogie forward. Numerical simulations show that to increase the possibility of overcoming an obstacle it is sufficient for the spring preload to reduce the vertical load on the front wheel; in any case, a higher load variation would not be advisable as it could involves an excessive load difference among the wheels.
Estimating reliability for response-time difference measures: Toward a standardized, model-based approach
Authors: Hui Bronson , Wu Zhiyi
Published: May 2023

A slowdown or a speedup in response times across experimental conditions can be taken as evidence of online deployment of knowledge. However, response-time difference measures are rarely evaluated on their reliability, and there is no standard practice to estimate it. In this article, we used three open data sets to explore an approach to reliability that is based on mixed-effects modeling and to examine model criticism as an outlier treatment strategy. The results suggest that the model-based approach can be superior but show no clear advantage of model criticism. We followed up these results with a simulation study to identify the specific conditions in which the model-based approach has the most benefits. Researchers who cannot include a large number of items and have a moderate level of noise in their data may find this approach particularly useful. We concluded by calling for more awareness and research on the psychometric properties of measures in the field.
Making Wonder in Miniature: A New Approach to Theorizing the Affective Properties and Social Consequences of Small-Scale Artworks from Hellenistic Babylonia
Authors: Langin-Hooper Stephanie M.
Published: May 2023

This article proposes an interpretive framework of paradox and wonder as a new approach to understanding the affective properties and social consequences of miniature objects in the archaeological record. Building upon current scholarly theories of miniatures as inherently intimate, this approach accounts for how small-scale artworks were also designed and deliberately manufactured to elude user attempts at full sensory access and immersive escapism. This desire-provoking tension between intimacy and distance—which lures viewers into small-scale encounters only to insist upon the object's life-size existence—is wonder, and it is what gives miniature objects their social relevance and ability not only to reflect, but also to influence, the real world. The benefits and applicability of this approach to miniaturization are illustrated through analysis of case studies of miniature objects (figurines, coins, seals and seal impressions, and jewellery) from Hellenistic Babylonia (Seleucid and Parthian periods in southern Mesopotamia, modern Iraq, 323 bce–ce 224).
Social Exclusion in Ancient Egypt: A Sociological Approach
Authors: Jiménez Meroño Beatriz
Published: May 2023

Social exclusion has been faced in modern societies as a phenomenon to be prevented in terms of equality. However, it can also be explored in past societies, where some individuals could confront situations of marginalization and exclusion. Previous scholars have accepted or rejected the existence of social exclusion in Ancient Egypt, although none of them has employed a theoretical framework to study it. This paper shows social exclusion as a phenomenon present in Ancient Egypt, analyses the available Egyptian evidence from a theoretical basis inherent to the social sciences, especially Sociology, and applies it to two case studies.
Fragments of a Revolution
Authors: Khajehi Yassaman , Zamani Mohammad Amin , Schechner Richard
Published: May 2023

With the Iranian protest movement “Woman, Life, Freedom,” public spaces have become scenes of collective performance. As women openly defy the authoritarian and religious powers, theatre artists are faced with a question: What role can we imagine for theatre when citizens themselves perform their struggle to reclaim the public space and sphere of power?
Manipulating device-to-body forces in passive exosuit: An experimental investigation on the effect of moment arm orientation using passive back-assist exosuit emulator
Authors: Bhardwaj Siddharth , Shinde Akshayraj B. , Singh Randheer , Vashista Vineet
Published: May 2023

Passive exosuits have been vastly researched in the past decade for lifting tasks to alleviate the mechanical loading on the spine and reduce the lower back muscle activities in lifting tasks. Despite promising advantages of exosuits, factors such as comfort directly influence the user’s acceptability of such body-worn devices. Exosuits’ routing/anchoring points, which transmit device-to-body forces, remain the leading cause of discomfort among users. In the present study, we sought to investigate the effect of the routing element, that is, the “moment arm,” in altering the device-to-body forces and perceived discomfort. We first presented a simplified human–exosuit model to establish insight into the effect of the moment arm on the device-to-body forces acting at the shoulder (FS) and waist (FW). Further, an experimental investigation was conducted on 10 participants with six different exosuit moment arm configurations (C1, C2, C3, C4, C5, and C6) to investigate their effect on the device-to-body forces, perceived discomfort, and muscle activity using a passive back-assist exosuit emulator in a lifting/lowering task. Configuration C4 was found to be most beneficial in reducing device-to-body forces at the shoulder and waist by up to 44.6 and 22.2%, respectively, during lifting. Subjective scores also comprehended with the device-to-body forces, indicating that C4 produces significantly less discomfort for participants. The outcome of the study illustrates the importance of selecting an appropriate moment arm configuration for passive back support exosuits in alleviating the device-to-body forces and perceived discomfort.
Investigating Spectral Estimates of Stress Drop for Small to Moderate Earthquakes With Heterogeneous Slip Distribution: Examples From the 2016–2017 Amatrice Earthquake Sequence
Authors: Calderoni Giovanna , Abercrombie Rachel E.
Published: May 2023

Estimates of spectral stress drop are fundamental to understanding the factors controlling earthquake rupture and high frequency ground motion, but are known to include large, poorly‐constrained uncertainties. We use earthquakes from the 2016–2017 sequence in the Italian Appenines (largest event at Norcia, Mw 6.3) to investigate these uncertainties and their causes. The similarly‐sized events near Amatrice (Mw 6.0) and Visso (Mw 5.9) enable better constrained relative analysis. We calculate S wave source spectra, corner frequencies, and spectral stress drop for 30 of the larger events. We compare both empirical and modeling approaches to isolate the source spectra and calculate source parameters; we also compare our results with those from published studies. Both random and systematic inter‐study variations are larger than the standard errors reported by any individual study. The reported magnitude dependence of stress drop varies between studies, being largest for generalized inversions and smallest for more individual event based approaches. The relative spectral estimates of inter‐event stress drop are more consistent; all approaches estimated higher stress drop in the Amatrice earthquake than the similar‐sized Visso earthquake. In contrast, finite fault inversions of these two earthquakes found that the Visso earthquake had the larger region of concentrated, higher slip, whereas the Amatrice earthquake had multiple, lower slip, subevents. The Amatrice spectra contain more high frequency energy than those of the Visso earthquake. This comparison suggests that consistent measurement of a higher spectral stress drop indicates greater high‐frequency ground motion but may correspond to greater rupture complexity rather than higher stress drop.
Downwind Ozone Changes of the 2019 Williams Flats Wildfire: Insights From WRF‐Chem/DART Assimilation of OMI NO2, HCHO, and MODIS AOD Retrievals
Authors: Pouyaei Arman , Mizzi Arthur P. , Choi Yunsoo , Mousavinezhad Seyedali , Khorshidian Nima
Published: May 2023

This study investigates the impacts of the Williams Flats wildfire (August 3‐9, 2019) on ozone conccentrations and chemistry in the downwind region using an assimilation framework with satellite retrievals and meterological measurements. By assimilating satellite‐retrieved nitrogen dioxide (NO2) and formaldehyde (HCHO) columns, we improve surface ozone simulations (index of agreement of 0.94 compared to station measurements) and utilize aerosol optical depth (AOD) retrievals to simulate spatial dynamics of wildfire plumes better. Comparing simulated ozone with the Fire Influence on Regional to Global Environments and Air Quality aircraft measurements reveals a fair simulation of ozone in smoke and non‐smoke plumes within the lower troposphere (7.00 ppbv mean absolute error). Comparing near‐distance and far‐distance locations, the study observed higher‐than‐average concentrations of nitrogen oxides, peroxyacetyl nitrate, nitric acid, and oxygenated volatile organic compounds due to wildfire emissions, which increased ozone concentrations by 3–5 ppbv during the wildfire in near‐distance locations and 2–3 ppbv in far‐distance locations. During more intense wildfire days, above 120 ppbv carbon monoxide plumes transported over the Rocky Mountains to the east. Ozone regime indicators showed a clear transition area downwind of the wildfire region that exacerbated the formation of ozone downwind. Our findings suggest that a joint assimilation of NO2 column, HCHO column, and AOD can enhance our understanding of wildfire‐associated ozone chemistry and dynamics.
WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer
Authors: Taouis Karim , Vacher Sophie , Guirouilh-Barbat Josée , Camonis Jacques , Formstecher Etienne , Popova Tatiana , Hamy Anne-Sophie , Petitalot Ambre , Lidereau Rosette , Caputo Sandrine M. , Zinn-Justin Sophie , Bièche Ivan , Driouch Keltouma , Lallemand François
Published: May 2023

The tumor suppressor gene WWOX is localized in an unstable chromosomal region and its expression is decreased or absent in several types of cancer. A low expression of WWOX is associated with a poor prognosis in breast cancer (BC). It has recently been shown that WWOX contributes to genome stability through its role in the DNA damage response (DDR). In breast cancer cells, WWOX inhibits homologous recombination (HR), and thus promotes the repair of DNA double-stranded breaks (DSBs) by non-homologous end joining (NHEJ). The fine-tuning modulation of HR activity is crucial. Its under or overstimulation inducing genome alterations that can induce cancer. MERIT40 is a positive regulator of the DDR. This protein is indispensable for the function of the multi-protein complex BRCA1-A, which suppresses excessive HR activity. MERIT40 also recruits Tankyrase, a positive regulator of HR, to the DSBs to stimulate DNA repair. Here, we identified MERIT40 as a new molecular partner of WWOX. We demonstrated that WWOX inhibited excessive HR activity induced by overexpression of MERIT40. We showed that WWOX impaired the MERIT40-Tankyrase interaction preventing the role of the complex on DSBs. Furthermore, we found that MERIT40 is overexpressed in BC and that this overexpression is associated to a poor prognosis. These results strongly suggest that WWOX, through its interaction with MERIT40, prevents the deleterious impact of excessive HR on BC development by inhibiting MERIT40-Tankyrase association. This inhibitory effect of WWOX would oppose MERIT40-dependent BC development.
Electroacupuncture prevents astrocyte atrophy to alleviate depression
Authors: Lin Si-Si , Zhou Bin , Chen Bin-Jie , Jiang Ruo-Tian , Li Baoman , Illes Peter , Semyanov Alexey , Tang Yong , Verkhratsky Alexei
Published: May 2023

Astrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and in animal models of depression. Here we show that electroacupuncture prevents astrocyte atrophy in the prefrontal cortex and alleviates depressive-like behaviour in mice subjected to chronic unpredictable mild stress (CUMS). Treatment of mice with CUMS induced depressive-like phenotypes as confirmed by sucrose preference test, tail suspension test, and forced swimming test. These behavioural changes were paralleled with morphological atrophy of astrocytes in the prefrontal cortex, revealed by analysis of 3D reconstructions of confocal Z-stack images of mCherry expressing astrocytes. This morphological atrophy was accompanied by a decrease in the expression of cytoskeletal linker Ezrin, associated with formation of astrocytic leaflets, which form astroglial synaptic cradle. Electroacupuncture at the acupoint ST36, as well as treatment with anti-depressant fluoxetine, prevented depressive-like behaviours, astrocytic atrophy, and down-regulation of astrocytic ezrin. In conclusion, our data further strengthen the notion of a primary role of astrocytic atrophy in depression and reveal astrocytes as cellular target for electroacupuncture in treatment of depressive disorders.
Tests for associations between sexual dimorphism and patterns of quantitative genetic variation in the water strider, Aquarius remigis
Authors: Fairbairn Daphne J. , Roff Derek A. , Wolak Matthew E.
Published: May 2023

The evolution of sexual dimorphisms requires divergence between sexes in the evolutionary trajectories of the traits involved. Discerning how genetic architecture could facilitate such divergence has proven challenging because of the difficulty in estimating non-additive and sex-linked genetic variances using traditional quantitative genetic designs. Here we use a three-generation, double-first-cousin pedigree design to estimate additive, sex-linked and dominance (co)variances for 12 traits in the water strider, Aquarius remigis. Comparisons among these traits, which have size ratios ranging from 1 to 5 (larger/smaller), allow us to ask if sexual dimorphisms are associated with characteristic patterns of quantitative genetic variation. We frame our analysis around three main questions, derived from existing theory and empirical evidence: Are sexual dimorphisms associated with (1) lower additive inter-sex genetic correlations, (2) higher proportions of sex-linked variance, or (3) differences between sexes in autosomal additive and dominance genetic variances? For questions (1) and (2), we find weak and non-significant trends in the expected directions, which preclude definitive conclusions. However, in answer to question (3), we find strong evidence for a positive relationship between sexual dimorphism and differences between sexes in proportions of autosomal dominance variance. We also find strong interactions among the three genetic components indicating that their relative influence differs among traits and between sexes. These results highlight the need to include all three components of genetic (co)variance in both theoretical evolutionary models and empirical estimations of the genetic architecture of dimorphic traits.
Structures of Tetrahymena thermophila respiratory megacomplexes on the tubular mitochondrial cristae
Authors: Han Fangzhu , Hu Yiqi , Wu Mengchen , He Zhaoxiang , Tian Hongtao , Zhou Long
Published: May 2023

Tetrahymena thermophila, a classic ciliate model organism, has been shown to possess tubular mitochondrial cristae and highly divergent electron transport chain involving four transmembrane protein complexes (I–IV). Here we report cryo-EM structures of its ~8 MDa megacomplex IV2 + (I + III2 + II)2, as well as a ~ 10.6 MDa megacomplex (IV2 + I + III2 + II)2 at lower resolution. In megacomplex IV2 + (I + III2 + II)2, each CIV2 protomer associates one copy of supercomplex I + III2 and one copy of CII, forming a half ring-shaped architecture that adapts to the membrane curvature of mitochondrial cristae. Megacomplex (IV2 + I + III2 + II)2 defines the relative position between neighbouring half rings and maintains the proximity between CIV2 and CIII2 cytochrome c binding sites. Our findings expand the current understanding of divergence in eukaryotic electron transport chain organization and how it is related to mitochondrial morphology.
Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice
Authors: Ramos-Pittol Jose M. , Fernandes-Freitas Isabel , Milona Alexandra , Manchishi Stephen M. , Rainbow Kara , Lam Brian Y. H. , Tadross John A. , Beucher Anthony , Colledge William H. , Cebola Inês , Murphy Kevin G. , Miguel-Aliaga Irene , Yeo Giles S. H. , Dhillo Waljit S. , Owen Bryn M.
Published: May 2023

Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It requires estrogen to restrain kisspeptin (KISS1)-neuron pulsatility in the arcuate hypothalamic nucleus, while also exerting a surge-like effect on KISS1-neuron activity in the AVPV hypothalamic nucleus. However, a mechanistic basis for this region-specific effect has remained elusive. Our genomic analysis in female mice demonstrate that some processes, such as restraint of KISS1-neuron activity in the arcuate nucleus, may be explained by region-specific estrogen receptor alpha (ERα) DNA binding at gene regulatory regions. Furthermore, we find that theKiss1-locus is uniquely regulated in these hypothalamic nuclei, and that the nuclear receptor co-repressor NR0B1 (DAX1) restrains its transcription specifically in the arcuate nucleus. These studies provide mechanistic insight into how ERα may control the KISS1-neuron, andKiss1gene expression, to couple gonadotropin release to the developmental stage of the oocyte.
LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models
Authors: Szabó Áron , Vincze Virág , Chhatre Aishwarya Sanjay , Jipa András , Bognár Sarolta , Varga Katalin Eszter , Banik Poulami , Harmatos-Ürmösi Adél , Neukomm Lukas J. , Juhász Gábor
Published: May 2023

Glial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms governing the efficiency of debris degradation in glia have remained largely unexplored. Here we show that LC3-associated phagocytosis (LAP), an engulfment pathway assisted by certain autophagy factors, promotes glial phagosome maturation in theDrosophilawing nerve. A LAP-specific subset of autophagy-related genes is required in glia for axon debris clearance, encoding members of the Atg8a (LC3) conjugation system and the Vps34 lipid kinase complex including UVRAG and Rubicon. Phagosomal Rubicon and Atg16 WD40 domain-dependent conjugation of Atg8a mediate proper breakdown of internalized axon fragments, and Rubicon overexpression in glia accelerates debris elimination. Finally, LAP promotes survival following traumatic brain injury. Our results reveal a role of glial LAP in the clearance of neuronal debris in vivo, with potential implications for the recovery of the injured nervous system.
Direct haplotype-resolved 5-base HiFi sequencing for genome-wide profiling of hypermethylation outliers in a rare disease cohort
Authors: Cheung Warren A. , Johnson Adam F. , Rowell William J. , Farrow Emily , Hall Richard , Cohen Ana S. A. , Means John C. , Zion Tricia N. , Portik Daniel M. , Saunders Christopher T. , Koseva Boryana , Bi Chengpeng , Truong Tina K. , Schwendinger-Schreck Carl , Yoo Byunggil , Johnston Jeffrey J. , Gibson Margaret , Evrony Gilad , Rizzo William B. , Thiffault Isabelle , Younger Scott T. , Curran Tom , Wenger Aaron M. , Grundberg Elin , Pastinen Tomi
Published: May 2023

Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and large hypermethylation events (>1 kb), respectively. We identify repeat expansions in proximal promoters predicting allelic gene silencing via hypermethylation and demonstrate allelic transcriptional events downstream. On average 30–40 rare hypermethylation tiles overlap rare disease genes per patient, providing indications for variation prioritization including a previously undiagnosed pathogenic allele in DIP2B causing global developmental delay. We propose that use of HiFi genome sequencing in unsolved rare disease cases will allow detection of unconventional diseases alleles due to loss of regulatory element activity.
An E2-E3 pair contributes to seed size control in grain crops
Authors: Tang Sha , Zhao Zhiying , Liu Xiaotong , Sui Yi , Zhang Dandan , Zhi Hui , Gao Yuanzhu , Zhang Hui , Zhang Linlin , Wang Yannan , Zhao Meicheng , Li Dongdong , Wang Ke , He Qiang , Zhang Renliang , Zhang Wei , Jia Guanqing , Tang Wenqiang , Ye Xingguo , Wu Chuanyin , Diao Xianmin
Published: May 2023

Understanding the molecular mechanisms that regulate grain yield is important for improving agricultural productivity. Protein ubiquitination controls various aspects of plant growth but lacks understanding on how E2-E3 enzyme pairs impact grain yield in major crops. Here, we identified a RING-type E3 ligase SGD1 and its E2 partner SiUBC32 responsible for grain yield control in Setaria italica. The conserved role of SGD1 was observed in wheat, maize, and rice. Furthermore, SGD1 ubiquitinates the brassinosteroid receptor BRI1, stabilizing it and promoting plant growth. Overexpression of an elite SGD1 haplotype improved grain yield by about 12.8% per plant, and promote complex biological processes such as protein processing in endoplasmic reticulum, stress responses, photosystem stabilization, and nitrogen metabolism. Our research not only identifies the SiUBC32-SGD1-BRI1 genetic module that contributes to grain yield improvement but also provides a strategy for exploring key genes controlling important traits in Poaceae crops using the Setaria model system.
Photonic crystals with rainbow colors by centrifugation-assisted assembly of colloidal lignin nanoparticles
Authors: Liu Jinrong , Nero Mathias , Jansson Kjell , Willhammar Tom , Sipponen Mika H.
Published: May 2023

Photonic crystals are optical materials that are often fabricated by assembly of particles into periodically arranged structures. However, assembly of lignin nanoparticles has been limited due to lacking methods and incomplete understanding of the interparticle forces and packing mechanisms. Here we show a centrifugation-assisted fabrication of photonic crystals with rainbow structural colors emitted from the structure covering the entire visible spectrum. Our results show that centrifugation is crucial for the formation of lignin photonic crystals, because assembly of lignin nanoparticles without centrifugation assistance leads to the formation of stripe patterns rather than photonic crystals. We further prove that the functions of centrifugation are to classify lignin nanoparticles according to their particle size and produce monodispersed particle layers that display gradient colors from red to violet. The different layers of lignin nanoparticles were assembled in a way that created semi-closed packing structures, which gave rise to coherent scattering. The diameter of the lignin nanoparticles in each color layer is smaller than that predicted by a modified Bragg’s equation. In situ optical microscope images provided additional evidence on the importance of dynamic rearrangement of lignin nanoparticles during their assembly into semi-closed packing structures. The preparation of lignin nanoparticles combined with the methodology for their classification and assembly pave the way for sustainable photonic crystals.
Magnetic control of self-assembly and disassembly in organic materials
Authors: Jung You-jin , Kim Hyoseok , Cheong Hae-Kap , Lim Yong-beom
Published: May 2023

Because organic molecules and materials are generally insensitive or weakly sensitive to magnetic fields, a certain means to enhance their magnetic responsiveness needs to be exploited. Here we show a strategy to amplify the magnetic responsiveness of self-assembled peptide nanostructures by synergistically combining the concepts of perfect α-helix and rod-coil supramolecular building blocks. Firstly, we develop a monomeric, nonpolar, and perfect α-helix (MNP-helix). Then, we employ the MNP-helix as the rod block of rod-coil amphiphiles (rod-coils) because rod-coils are well-suited for fabricating responsive assemblies. We show that the self-assembly processes of the designed rod-coils and disassembly of rod-coil/DNA complexes can be controlled in a magnetically responsive manner using the relatively weak magnetic field provided by the ordinary neodymium magnet [0.07 ~ 0.25 Tesla (T)]. These results demonstrate that magnetically responsive organic assemblies usable under practical conditions can be realized by using rod-coil supramolecular building blocks containing constructively organized diamagnetic moieties.
Retention time prediction for chromatographic enantioseparation by quantile geometry-enhanced graph neural network
Authors: Xu Hao , Lin Jinglong , Zhang Dongxiao , Mo Fanyang
Published: May 2023

The enantioseparation of chiral molecules is a crucial and challenging task in the field of experimental chemistry, often requiring extensive trial and error with different experimental settings. To overcome this challenge, here we show a research framework that employs machine learning techniques to predict retention times of enantiomers and facilitate chromatographic enantioseparation. A documentary dataset of chiral molecular retention times in high-performance liquid chromatography (CMRT dataset) is established to handle the challenge of data acquisition. A quantile geometry-enhanced graph neural network is proposed to learn the molecular structure-retention time relationship, which shows a satisfactory predictive ability for enantiomers. The domain knowledge of chromatography is incorporated into the machine learning model to achieve multi-column prediction, which paves the way for chromatographic enantioseparation prediction by calculating the separation probability. The proposed research framework works well in retention time prediction and chromatographic enantioseparation facilitation, which sheds light on the application of machine learning techniques to the experimental scene and improves the efficiency of experimenters to speed up scientific discovery.
Highly lethal genotype I and II recombinant African swine fever viruses detected in pigs
Authors: Zhao Dongming , Sun Encheng , Huang Lianyu , Ding Leilei , Zhu Yuanmao , Zhang Jiwen , Shen Dongdong , Zhang Xianfeng , Zhang Zhenjiang , Ren Tao , Wang Wan , Li Fang , He Xijun , Bu Zhigao
Published: May 2023

African swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF_505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry.
Mechanism of action for small-molecule inhibitors of triacylglycerol synthesis
Authors: Sui Xuewu , Wang Kun , Song Kangkang , Xu Chen , Song Jiunn , Lee Chia-Wei , Liao Maofu , Farese Robert V. , Walther Tobias C.
Published: May 2023

Inhibitors of triacylglycerol (TG) synthesis have been developed to treat metabolism-related diseases, but we know little about their mechanisms of action. Here, we report cryo-EM structures of the TG-synthesis enzyme acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a membrane bound O-acyltransferase (MBOAT), in complex with two different inhibitors, T863 and DGAT1IN1. Each inhibitor binds DGAT1’s fatty acyl-CoA substrate binding tunnel that opens to the cytoplasmic side of the ER. T863 blocks access to the tunnel entrance, whereas DGAT1IN1 extends further into the enzyme, with an amide group interacting with more deeply buried catalytic residues. A survey of DGAT1 inhibitors revealed that this amide group may serve as a common pharmacophore for inhibition of MBOATs. The inhibitors were minimally active against the related MBOAT acyl-CoA:cholesterol acyltransferase 1 (ACAT1), yet a single-residue mutation sensitized ACAT1 for inhibition. Collectively, our studies provide a structural foundation for developing DGAT1 and other MBOAT inhibitors.
Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines
Authors: Yadav Shambhu , Waldeck-Weiermair Markus , Spyropoulos Fotios , Bronson Roderick , Pandey Arvind K. , Das Apabrita Ayan , Sisti Alexander C. , Covington Taylor A. , Thulabandu Venkata , Caplan Shari , Chutkow William , Steinhorn Benjamin , Michel Thomas
Published: May 2023

Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here we report studies of neurovascular oxidative stress in chemogenetic transgenic mouse lines expressing yeast D-amino acid oxidase (DAAO) in neurons and vascular endothelium. When these transgenic mice are fed D-amino acids, DAAO generates hydrogen peroxide in target tissues. DAAO-TGCdh5 transgenic mice express DAAO under control of the putatively endothelial-specific Cdh5 promoter. When we provide these mice with D-alanine, they rapidly develop sensory ataxia caused by oxidative stress and mitochondrial dysfunction in neurons within dorsal root ganglia and nodose ganglia innervating the heart. DAAO-TGCdh5 mice also develop cardiac hypertrophy after chronic chemogenetic oxidative stress. This combination of ataxia, mitochondrial dysfunction, and cardiac hypertrophy is similar to findings in patients with Friedreich’s ataxia. Our observations indicate that neurovascular oxidative stress is sufficient to cause sensory ataxia and cardiac hypertrophy. Studies of DAAO-TGCdh5 mice could provide mechanistic insights into Friedreich’s ataxia.
Computational discovery of ultra-strong, stable, and lightweight refractory multi-principal element alloys. Part I: design principles and rapid down-selection
Authors: Elder Kate L. M. , Berry Joel , Bocklund Brandon , McCall Scott K. , Perron Aurélien , McKeown Joseph T.
Published: May 2023

Refractory metal-based multi-principal element alloys (MPEAs) are compelling materials for high-temperature (1000–2000 K) structural applications. However, only a minuscule fraction of their vast and heterogeneous compositional design space has been explored, leaving many potentially interesting alloys undiscovered. In this two-part work, a large region of the 11-element Al-Cr-Fe-Hf-Mo-Nb-Ta-Ti-V-W-Zr design space is computationally explored to identify refractory MPEAs with simultaneously high yield strength or specific yield strength and body-centered cubic (BCC) solid solution stability. In Part I, two case studies illuminate key factors and considerations in the yield strength versus phase stability tradeoff, provide guidelines for narrowing the expansive design space, and identify many candidates predicted to be stronger than refractory MPEAs reported to date, with BCC phase stability. Our findings indicate that medium entropy ternary alloys can outperform alloys with more elements and highlight the importance of exploring regions away from the equiatomic center of composition space.
Linear Jacobi-Legendre expansion of the charge density for machine learning-accelerated electronic structure calculations
Authors: Focassio Bruno , Domina Michelangelo , Patil Urvesh , Fazzio Adalberto , Sanvito Stefano
Published: May 2023

Kohn–Sham density functional theory (KS-DFT) is a powerful method to obtain key materials’ properties, but the iterative solution of the KS equations is a numerically intensive task, which limits its application to complex systems. To address this issue, machine learning (ML) models can be used as surrogates to find the ground-state charge density and reduce the computational overheads. We develop a grid-centred structural representation, based on Jacobi and Legendre polynomials combined with a linear regression, to accurately learn the converged DFT charge density. This integrates into a ML pipeline that can return any density-dependent observable, including energy and forces, at the quality of a converged DFT calculation, but at a fraction of the computational cost. Fast scanning of energy landscapes and producing starting densities for the DFT self-consistent cycle are among the applications of our scheme.