bluuebunny/crossref_metadata_2025 huggingface dataset:
Social factors in accent recognition: a large-scale study in perceptual dialectology
Authors: Pinget Anne-France , Voeten Cesko C.
Published: July 2023

This perceptual-dialectology study investigates how listener-related social factors impact the geographical recognition of regional accents. In contrast to much prior research on English, our focus is on Dutch, which lends itself well to our study, allowing for notable regional accents within a well-defined standard language. Using a map-based recognition task in which 1,578 listeners placed forty representative speakers on a map based on fragments of their speech, we investigated the regional biases in accent recognition and the extent to which each listener’s awareness of these depends on their familiarity and proximity. Education, geographical knowledge, and distance to listeners’ own regions significantly predicted their accent-recognition accuracy. Moreover, we found a curvilinear age effect, which we interpret in terms of age-related changes in geographical and social mobility. We show how these effects in our design lead to meaningful accent-recognition patterns in groups of listeners.
Future projections for the Antarctic ice sheet until the year 2300 with a climate-index method
Authors: Greve Ralf , Chambers Christopher , Obase Takashi , Saito Fuyuki , Chan Wing-Le , Abe-Ouchi Ayako
Published: July 2023

As part of the Coupled Model Intercomparison Project Phase 6 (CMIP6), the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6) was devised to assess the likely sea-level-rise contribution from the Earth's ice sheets. Here, we construct an ensemble of climate forcings for Antarctica until the year 2300 based on original ISMIP6 forcings until 2100, combined with climate indices from simulations with the MIROC4m climate model until 2300. We then use these forcings to run simulations for the Antarctic ice sheet with the SICOPOLIS model. For the unabated warming pathway RCP8.5/SSP5-8.5, the ice sheet suffers a severe mass loss, amounting to ~ 1.5 m SLE (sea-level equivalent) for the fourteen-experiment mean, and ~ 3.3 m SLE for the most sensitive experiment. Most of this loss originates from West Antarctica. For the reduced emissions pathway RCP2.6/SSP1-2.6, the loss is limited to a three-experiment mean of ~ 0.16 m SLE. The means are approximately two times larger than what was found in a previous study (Chambers and others, 2022, doi:10.1017/jog.2021.124) that assumed a sustained late-21st-century climate beyond 2100, demonstrating the importance of post-2100 climate trends on Antarctic mass changes in the 22nd and 23rd centuries.
Looking into the border. Whiteness, (un)desirable encounters and research containment at the Spanish–Moroccan border
Authors: Gazzotti Lorena
Published: July 2023

How is the white researcher perceived by the border apparatus? What does this interaction say about the border itself? Ethnographic research has framed such questions as a debate on ‘insiders’ and ‘outsiders’ in fieldwork. This is problematic, as it assumes that a researcher can really be ‘external’ to the social worlds they investigate, as if the field site existed in isolation from transnational processes of racialised extraction. This paper challenges such an assumption by arguing that the white researcher cannot be an ‘outsider’ to the North African border: they approach it as the beneficiaries of a system of colonial and capital extractivism that feeds itself through migration control. I build on Ahmed's work on white phenomenology to analyse how various border workers perceived, made sense of and reacted to my presence as a white European woman at three different sites on the Spanish–Moroccan border. I argue that the white researcher is an expected presence at the border, as the accumulated history of (post)colonial encounters leads them where others have been before. Although whiteness opens doors, only a certain kind of performed whiteness remains welcome in the borderscape. The white researcher who appears not to be aligning with or supporting the premises of migration control is perceived by border workers as a potentially disruptive presence, and contained in different ways.
The role of speaker sex and sexuality in an ongoing sound change: Nasal vowels in Parisian French
Authors: Mooney Damien
Published: July 2023

This article examines the progression of the counter-clockwise nasal vowel chain shift in Parisian French, investigating in particular the influence of biological sex and of sexuality on the propagation of this change from below. The research presented forms part of a study on the participation of sexual minorities in ongoing sound change; this study aims to address the continued exclusion of sexual minorities from sociolinguistic studies, which not only invisibilizes queer people, but underlines their behaviour, linguistic or otherwise, as gender-deviant. Using a sociophonetic methodology, an analysis of nasal vowel quality provides evidence for sex- and sexuality-differential linguistic behaviour in the advancement of the nasal vowel chain shift. The results confirm the progressive but non-conformative linguistic behaviour of women, both straight and queer, as outlined by Labov (1990) and numerous other sociolinguistic studies, but also indicate that queer men are centre-stage in driving the change forward. This research is a first step in formalizing data-driven principles about the linguistic behaviour of sexual minorities and their role in language change, akin to the principles advanced to account for the behaviour of women.
Acheulean Handaxes in Medieval France: An Earlier ‘Modern’ Social History for Palaeolithic Bifaces
Authors: Key Alastair , Clark James , DeSilva Jeremy , Kangas Steven
Published: July 2023

Handaxes have a uniquely prominent role in the history of Palaeolithic archaeology, and their early study provides crucial information concerning the epistemology of the field. We have little conclusive evidence, however, of their investigation or societal value prior to the mid seventeenth century. Here we investigate the shape, colour and potential flake scarring on a handaxe-like stone object seen in the Melun Diptych, painted by the French fifteenth-century artist Jean Fouquet, and compare its features with artefacts from diverse (including French) Acheulean handaxe assemblages. Commissioned by a high-status individual, Étienne Chevalier, Fouquet's work (Étienne Chevalier with Saint Stephen) depicts an important religious context, while the handaxe-like object points to the stoning to death of an important Christian saint. Our results strongly support the interpretation that the painted stone object represents a flint Acheulean handaxe, likely sourced from northern France, where Fouquet lived. Identifying a fifteenth-century painting of a handaxe does not change what we know about Acheulean individuals, but it does push back the evidence for when handaxes became a prominent part of the ‘modern’ social and cultural world.
The Environmental Sustainability of the European Union Countries: Collective Identity as a Stratum for Decarbonization
Authors: Direkli Mehmet , Chiyoru Dike Glory
Published: July 2023

To stay within a ‘well below 2°C’ climate change track, the Paris Agreement and goal 13 of the Sustainable Development Goals (SDGs) call for climate action – a global decrease in Green House Gas (GHG) emissions. Arguments in this study are derived from the hypothesis that a collective identity among the EU states would foster collective actions toward reducing global warming. Thus, the objective of this study is to explore how different EU countries (Poland, Italy, and Germany) employ three decarbonization pillars: waste recycling, eco-innovation, and policy innovation (WEP) as a yardstick to mitigate global warming and attain the EU’s ‘net-zero’ emissions by 2050. The study also utilizes annual data collected from the Eurostat indicator from 2014 to 2020. The findings reveal that Germany has the most successful average recycling rate in Europe; 65.5% of the country’s domestic waste is either recycled or reused. On the other hand, Poland is a low performer in eco-innovation. Additionally, an analysis of policy regulations reveals that both Germany and Italy can comply with the policy and regulations of the EU on carbon neutrality. At the same time, Poland, on the other hand, lacks the commitment to carbon neutrality due to its reliance on carbon-intensive coal. Therefore, this study recommends translating EU climatic laws in their simplest forms into local laws. More so, citizens’ behaviour will be further influenced toward environmental sustainability by this collective mindset.
Remembrances of Rashīd: life-histories as lessons in the Dēōband movement
Authors: Jones Justin
Published: July 2023

The tazkira, a long-established genre of life-history writing in South Asian literature, was increasingly used over the course of the twentieth century to document the lives and achievements of ‘ulamā (‘learned men’, or scholars of religion). This article explores a foundational work within this genre: ‘Ashīq Ilahī Mīrutī's Tazkira't al-Rashīd (first published in 1908–1910), a life-history of the Dēōbandī scholar and Sūfī shāykh Rashīd Ahmad Gangōhī. It argues that such life-histories of ‘ulamā were written not merely as historical records but as ‘lessons’ to their readers. This article illustrates how the tazkira appropriated Gangōhī's life and teachings to provide an indispensable repository of Dēōbandī understanding on issues such as tarīqah (the Sūfī path), sharī‘ah (religious law), pīrī-murīdī (the master-disciple relationship), religious and social conduct, and relations with the state. The article thus makes a case for understanding the tazkira as an important vehicle for informing and shaping the religious behaviour of a Muslim public, which was employed ultimately by both the Dēōbandī and other Islamic revivalist movements.
Portfolio management for insurers and pension funds and COVID-19: targeting volatility for equity, balanced, and target-date funds with leverage constraints
Authors: Doan Bao , Reeves Jonathan J. , Sherris Michael
Published: July 2023

Insurers and pension funds face the challenges of historically low-interest rates and high volatility in equity markets, that have been accentuated due to the COVID-19 pandemic. Recent advances in equity portfolio management with a target volatility have been shown to deliver improved on average risk-adjusted return, after transaction costs. This paper studies these targeted volatility portfolios in applications to equity, balanced, and target-date funds with varying constraints on leverage. Conservative leverage constraints are particularly relevant to pension funds and insurance companies, with more aggressive leverage levels appropriate for alternative investments. We show substantial improvements in fund performance for differing leverage levels, and of most interest to insurers and pension funds, we show that the highest Sharpe ratios and smallest drawdowns are in targeted volatility-balanced portfolios with equity and bond allocations. Furthermore, we demonstrate the outperformance of targeted volatility portfolios during major stock market crashes, including the crash from the COVID-19 pandemic.
Substance use before or during pregnancy and the risk of child mortality, perinatal morbidities and congenital anomalies
Authors: Lee Charles Tzu-Chi , Chen Vincent Chin-Hung , Lee Johnny Kuang-Wu , Wu Shu-I , Cheng Gillian , Kao Tzu-Min , Wang Shih-Yuan , Gossop Michael
Published: July 2023

Aims

We aimed to investigate child mortality, perinatal morbidities and congenital anomalies born by women with substance misuse during or before pregnancy (DP or BP).

Methods

Taiwan Birth Registration from 2004 to 2014 linking Integrated Illicit Drug Databases used to include substance misuse participates. Children born by mothers convicted of substance misuse DP or BP were the substance-exposed cohort. Two substance-unexposed comparison cohorts were established: one comparison cohort selected newborns from the rest of the population on a ratio of 1:1 and exact matched by the child’s gender, child’s birth year, mother’s birth year and child’s first use of the health insurance card; another comparison cohort matched newborns from exposed and unexposed mothers by their propensity scores calculated from logistic regression.

Results

The exposure group included 1776 DP, 1776 BP and 3552 unexposed individuals in exact-matched cohorts. A fourfold increased risk of deaths in children born by mothers exposed to substance during pregnancy was found compared to unexposed group (hazard ratio [HR] = 4.54, 95% confidence interval (CI): 2.07–9.97]. Further multivariate Cox regression models with adjustments and propensity matching substantially attenuated HRs on mortality in the substance-exposed cohort (aHR = 1.62, 95% CI: 1.10–2.39). Raised risks of perinatal morbidities and congenital anomalies were also found.

Conclusions

Increased risks of child mortality, perinatal morbidities or congenital anomalies were found in women with substance use during pregnancy. From estimates before and after adjustments, our results showed that having outpatient visits or medical utilizations during pregnancy were associated with substantially attenuated HRs on mortality in the substance-exposed cohort. Therefore, the excess mortality risk might be partially explained by the lack of relevant antenatal clinical care. Our finding may suggest that the importance of early identification, specific abstinence program and access to appropriate antenatal care might be helpful in reducing newborn mortality. Adequate prevention policies may be formulated.
Non‐Orographic Gravity Waves and Turbulence Caused by Merging Jet Streams
Authors: Woiwode W. , Dörnbrack A. , Geldenhuys M. , Friedl‐Vallon F. , Giez A. , Gulde T. , Höpfner M. , Johansson S. , Kaifler B. , Kleinert A. , Krasauskas L. , Kretschmer E. , Maucher G. , Neubert T. , Nordmeyer H. , Piesch C. , Preusse P. , Rapp M. , Riese M. , Schumann U. , Ungermann J.
Published: July 2023

Jet streams are important sources of non‐orographic internal gravity waves and clear air turbulence (CAT). We analyze non‐orographic gravity waves and CAT during a merger of the polar front jet stream (PFJ) with the subtropical jet stream (STJ) above the southern Atlantic. Thereby, we use a novel combination of airborne observations covering the meso‐scale and turbulent scale in combination with high‐resolution deterministic short‐term forecasts. Coherent phase lines of temperature perturbations by gravity waves stretching along a highly sheared tropopause fold are simulated by the ECMWF IFS (integrated forecast system) forecasts. During the merging event, the PFJ reverses its direction from approximately antiparallel to parallel with respect to the STJ, going along with strong wind shear and horizontal deformation. Temperature perturbations in limb‐imaging and lidar observations onboard the research aircraft HALO during the SouthTRAC campaign show remarkable agreement with the IFS data. Ten hours earlier, the IFS data show an “X‐shaped” pattern in the temperature perturbations emanating from the sheared tropopause fold. Tendencies of the IFS wind components show that these gravity waves are excited by spontaneous emission adjusting the strongly divergent flow when the PFJ impinges the STJ. In situ observations of temperature and wind components at 100 Hz confirm upward propagation of the probed portion of the gravity waves. They furthermore reveal embedded episodes of light‐to‐moderate CAT, Kelvin Helmholtz waves, and indications for partial wave reflection. Patches of low Richardson numbers in the IFS data coincide with the CAT observations, suggesting that this event was accessible to turbulence forecasting.
Large Scale Crop Water Footprint Evaluation Based on Remote Sensing Methods: A Case Study of Maize
Authors: Li Zheng , Sun Shikun , Zhao Jinfeng , Li Chong , Gao Zihan , Yin Yali , Wang Yubao , Wu Pute
Published: July 2023

Agriculture is the world's largest consumer of water resources, and accurate measurement of crop water footprint (CWF) can provide a scientific basis for evaluating the water use characteristics of agricultural production and guiding water management. The measurement of regional CWF requires large amounts of ground data, and remote sensing provides an effective means to scientifically measure the CWF on a large scale. In this study, we developed an effective means to estimate regional maize CWF based on global evapotranspiration (MOD16 and Global Land Data Assimilation System (GLDAS)‐Noah) products in China. And we also calculated the CWF based on the FAO Penman‐Monteith equation (FAO‐PM) on the site scale in China. We assessed the accuracy of these methods by comparing them against eight eddy‐covariance based flux tower measurements. Links and differences behind the results of the three water footprint calculations were analyzed in terms of the basic principles and characteristics of the calculations. The results showed that the CWF had a similar distribution based on the MOD16 and GLDAS‐Noah, reflecting the influence of regional soil moisture on the CWF. Computational rationale analysis of the three quantitative methods showed that the ETc‐based method from the FAO‐PM model was similar to the MOD16‐ and GLDAS‐Noah‐based CWF in the wetter areas, two remote sensing‐based methods considered the water constraints during soil evaporation and water dissipation during dry and wet canopy conditions, and were closer to reality than the ETc‐based methods in measuring the CWF in arid and semi‐arid regions.
A nanonewton-scale biomimetic mechanosensor
Authors: Zhang Chi , Wu Mengxi , Li Ming , Che Lixuan , Tan Zhiguang , Guo Di , Kang Zhan , Cao Shuye , Zhang Siqi , Sui Yu , Sun Jining , Wang Liding , Liu Junshan
Published: July 2023

Biomimetic mechanosensors have profound implications for various areas, including health care, prosthetics, human‒machine interfaces, and robotics. As one of the most important parameters, the sensitivity of mechanosensors is intrinsically determined by the detection resolution to mechanical force. In this manuscript, we expand the force detection resolution of current biomimetic mechanosensors from the micronewton to nanonewton scale. We develop a nanocrack-based electronic whisker-type mechanosensor that has a detection resolution of 72.2 nN. We achieve the perception of subtle mechanical stimuli, such as tiny objects and airflow, and the recognition of surface morphology down to a 30 nm height, which is the finest resolution ever reported in biomimetic mechanosensors. More importantly, we explore the use of this mechanosensor in wearable devices for sensing gravity field orientation with respect to the body, which has not been previously achieved by these types of sensors. We develop a wearable smart system for sensing the body’s posture and movements, which can be used for remote monitoring of falls in elderly people. In summary, the proposed device offers great advantages for not only improving sensing ability but also expanding functions and thus can be used in many fields not currently served by mechanosensors.
Human preterm colostrum stimulates outgrowth in neurogenic tissue
Authors: Kaps Julian , Georgieva Veronica S. , Oberholz Laura , Kribs Angela , Brachvogel Bent , Keller Titus
Published: July 2023

Background

The olfactory bulb has a key role for nasal delivery of drugs to the brain by its access from the nasal mucosa and its connection to the subventricular zone. The aim of this study was to investigate the neuromodulatory capacity of human milk of premature infants on the olfactory bulb.

Methods

Olfactory bulbs from P1 mice were embedded in a collagen I gel and incubated with DMEM supplemented with the aqueous phase of human colostrum (Col) of five mothers after very preterm birth, mature milk (Mat) of the same mothers or without supplement (Ctrl). After 7 days, the neurite outgrowth was quantified. Proteome analysis of the milk samples was performed using unlabeled mass spectrometry.

Results

Outgrowth increased significantly in bulbs exposed to Col but not when exposed to Mat. Mass spectrometry revealed profound differences in the proteome of Col versus Mat. Among 21 upregulated proteins in Col were proteins involved in neurite outgrowth, axon guidance, neuromodulation and longevity.

Conclusions

A high bioactivity of human preterm colostrum on murine neonatal neurogenic tissue is demonstrated to be associated with a proteome profoundly differing from mature milk.

Impact

The hypothesis has been raised that neonatal brain damage in a preterm infant could potentially be ameliorated by intranasal application of maternal breast milk.

In an in-vitro model using neonatal murine olfactory bulb explants a significant stimulatory effect by human preterm colostrum is observed.

Proteomics reveals upregulated neuroactive proteins in human colostrum compared to mature milk.

A confirmation of this exploratory study would indicate that preterm colostrum stimulates neurogenic tissue.

Early intranasal colostrum application might attenuate perinatal loss of neurogenic tissue thereby contributing to reducing complications such as cerebral palsy.
Functional changes in neural mechanisms underlying post-traumatic stress disorder in World Trade Center responders
Authors: Invernizzi Azzurra , Rechtman Elza , Curtin Paul , Papazaharias Demetrios M. , Jalees Maryam , Pellecchia Alison C. , Santiago-Michels Stephanie , Bromet Evelyn J. , Lucchini Roberto G. , Luft Benjamin J. , Clouston Sean A. , Tang Cheuk Y. , Horton Megan K.
Published: July 2023

World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have a high prevalence of chronic WTC-related post-traumatic stress disorder (WTC-PTSD). We investigated neural mechanisms underlying WTC-PTSD by applying eigenvector centrality (EC) metrics and data-driven methods on resting state functional magnetic resonance (fMRI). We identified how EC differences relate to WTC-exposure and behavioral symptoms. We found that connectivity differentiated significantly between WTC-PTSD and non-PTSD responders in nine brain regions, as these differences allowed an effective discrimination of PTSD and non-PTSD responders based solely on analysis of resting state data. Further, we found that WTC exposure duration (months on site) moderates the association between PTSD and EC values in two of the nine brain regions; the right anterior parahippocampal gyrus and the left amygdala (p = 0.010;p = 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, a dimensional measure of symptom severity was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Functional neuroimaging can provide effective tools to identify neural correlates of diagnostic and dimensional indicators of PTSD.
Glc7/PP1 dephosphorylates histone H3T11 to regulate autophagy and telomere silencing in response to nutrient availability
Authors: Zhang Xinyu , Yu Qi , Wu Yinsheng , Zhang Yuan , He Yi , Wang Rongsha , Yu Xilan , Li Shanshan
Published: July 2023

How cells adapt their gene expression to nutritional changes remains poorly understood. Histone H3T11 is phosphorylated by pyruvate kinase to repress gene transcription. Here, we identify the protein phosphatase 1 (PP1), Glc7 as the enzyme that specifically dephosphorylates H3T11. We also characterize two novel Glc7-containing complexes and reveal their roles in regulating gene expression upon glucose starvation. Specifically, the Glc7–Sen1 complex dephosphorylates H3T11 to activate the transcription of autophagy-related genes. The Glc7–Rif1–Rap1 complex dephosphorylates H3T11 to derepress the transcription of telomere-proximal genes. Upon glucose starvation, Glc7 expression is up-regulated and more Glc7 translocates into the nucleus to dephosphorylate H3T11, leading to induction of autophagy and derepressed transcription of telomere-proximal genes. Furthermore, the functions of PP1/Glc7 and the two Glc7-containing complexes are conserved in mammals to regulate autophagy and telomere structure. Collectively, our results reveal a novel mechanism that regulate gene expression and chromatin structure in response to glucose availability.
Hydrodynamic spin-orbit coupling in asynchronous optically driven micro-rotors
Authors: Modin Alvin , Ben Zion Matan Yah , Chaikin Paul M.
Published: July 2023

Vortical flows of rotating particles describe interactions ranging from molecular machines to atmospheric dynamics. Yet to date, direct observation of the hydrodynamic coupling between artificial micro-rotors has been restricted by the details of the chosen drive, either through synchronization (using external magnetic fields) or confinement (using optical tweezers). Here we present a new active system that illuminates the interplay of rotation and translation in free rotors. We develop a non-tweezing circularly polarized beam that simultaneously rotates hundreds of silica-coated birefringent colloids. The particles rotate asynchronously in the optical torque field while freely diffusing in the plane. We observe that neighboring particles orbit each other with an angular velocity that depends on their spins. We derive an analytical model in the Stokes limit for pairs of spheres that quantitatively explains the observed dynamics. We then find that the geometrical nature of the low Reynolds fluid flow results in a universal hydrodynamic spin-orbit coupling. Our findings are of significance for the understanding and development of far-from-equilibrium materials.
Imbalanced unfolded protein response signaling contributes to 1-deoxysphingolipid retinal toxicity
Authors: Rosarda Jessica D. , Giles Sarah , Harkins-Perry Sarah , Mills Elizabeth A. , Friedlander Martin , Wiseman R. Luke , Eade Kevin T.
Published: July 2023

The accumulation of atypical, cytotoxic 1-deoxysphingolipids (1-dSLs) has been linked to retinal diseases such as diabetic retinopathy and Macular Telangiectasia Type 2. However, the molecular mechanisms by which 1-dSLs induce toxicity in retinal cells remain poorly understood. Here, we integrate bulk and single-nucleus RNA-sequencing to define biological pathways that modulate 1-dSL toxicity in human retinal organoids. Our results demonstrate that 1-dSLs differentially activate signaling arms of the unfolded protein response (UPR) in photoreceptor cells and Müller glia. Using a combination of pharmacologic activators and inhibitors, we show that sustained PERK signaling through the integrated stress response (ISR) and deficiencies in signaling through the protective ATF6 arm of the UPR are implicated in 1-dSL-induced photoreceptor toxicity. Further, we demonstrate that pharmacologic activation of ATF6 mitigates 1-dSL toxicity without impacting PERK/ISR signaling. Collectively, our results identify new opportunities to intervene in 1-dSL linked diseases through targeting different arms of the UPR.
Hypoxia-reprogramed megamitochondrion contacts and engulfs lysosome to mediate mitochondrial self-digestion
Authors: Hao Tianshu , Yu Jianglong , Wu Zhida , Jiang Jie , Gong Longlong , Wang Bingjun , Guo Hanze , Zhao Huabin , Lu Bin , Engelender Simone , He He , Song Zhiyin
Published: July 2023

Mitochondria are the key organelles for sensing oxygen, which is consumed by oxidative phosphorylation to generate ATP. Lysosomes contain hydrolytic enzymes that degrade misfolded proteins and damaged organelles to maintain cellular homeostasis. Mitochondria physically and functionally interact with lysosomes to regulate cellular metabolism. However, the mode and biological functions of mitochondria-lysosome communication remain largely unknown. Here, we show that hypoxia remodels normal tubular mitochondria into megamitochondria by inducing broad inter-mitochondria contacts and subsequent fusion. Importantly, under hypoxia, mitochondria-lysosome contacts are promoted, and certain lysosomes are engulfed by megamitochondria, in a process we term megamitochondria engulfing lysosome (MMEL). Both megamitochondria and mature lysosomes are required for MMEL. Moreover, the STX17-SNAP29-VAMP7 complex contributes to mitochondria-lysosome contacts and MMEL under hypoxia. Intriguingly, MMEL mediates a mode of mitochondrial degradation, which we termed mitochondrial self-digestion (MSD). Moreover, MSD increases mitochondrial ROS production. Our results reveal a mode of crosstalk between mitochondria and lysosomes and uncover an additional pathway for mitochondrial degradation.
Trackable and scalable LC-MS metabolomics data processing using asari
Authors: Li Shuzhao , Siddiqa Amnah , Thapa Maheshwor , Chi Yuanye , Zheng Shujian
Published: July 2023

Significant challenges remain in the computational processing of data from liquid chomratography-mass spectrometry (LC-MS)-based metabolomic experiments into metabolite features. In this study, we examine the issues of provenance and reproducibility using the current software tools. Inconsistency among the tools examined is attributed to the deficiencies of mass alignment and controls of feature quality. To address these issues, we develop the open-source software tool asari for LC-MS metabolomics data processing. Asari is designed with a set of specific algorithmic framework and data structures, and all steps are explicitly trackable. Asari compares favorably to other tools in feature detection and quantification. It offers substantial improvement in computational performance over current tools, and it is highly scalable.
Spatial cellular architecture predicts prognosis in glioblastoma
Authors: Zheng Yuanning , Carrillo-Perez Francisco , Pizurica Marija , Heiland Dieter Henrik , Gevaert Olivier
Published: July 2023

Intra-tumoral heterogeneity and cell-state plasticity are key drivers for the therapeutic resistance of glioblastoma. Here, we investigate the association between spatial cellular organization and glioblastoma prognosis. Leveraging single-cell RNA-seq and spatial transcriptomics data, we develop a deep learning model to predict transcriptional subtypes of glioblastoma cells from histology images. Employing this model, we phenotypically analyze 40 million tissue spots from 410 patients and identify consistent associations between tumor architecture and prognosis across two independent cohorts. Patients with poor prognosis exhibit higher proportions of tumor cells expressing a hypoxia-induced transcriptional program. Furthermore, a clustering pattern of astrocyte-like tumor cells is associated with worse prognosis, while dispersion and connection of the astrocytes with other transcriptional subtypes correlate with decreased risk. To validate these results, we develop a separate deep learning model that utilizes histology images to predict prognosis. Applying this model to spatial transcriptomics data reveal survival-associated regional gene expression programs. Overall, our study presents a scalable approach to unravel the transcriptional heterogeneity of glioblastoma and establishes a critical connection between spatial cellular architecture and clinical outcomes.
Hedonic and autonomic responses in promoting affective touch
Authors: Mazza Alessandro , Cariola Monia , Capiotto Francesca , Diano Matteo , Schintu Selene , Pia Lorenzo , Dal Monte Olga
Published: July 2023

Interpersonal touch is intrinsically reciprocal since it entails a person promoting and another receiving the touch. While several studies have investigated the beneficial effects of receiving affective touch, the affective experience of caressing another individual remains largely unknown. Here, we investigated the hedonic and autonomic responses (skin conductance and heart rate) in the person promoting affective touch. We also examined whether interpersonal relationship, gender, and eye contact modulate these responses. As expected, caressing the partner was perceived as more pleasant than caressing a stranger, especially if the affective touch occurred together with mutual eye contact. Promoting affective touch to the partner also resulted in a decrease of both autonomic responses and anxiety levels, suggesting the occurrence of a calming effect. Additionally, these effects were more pronounced in females compared to males, indicating that hedonic and autonomic aspects of affective touch are modulated by both social relationship and gender. These findings show for the first time that caressing a beloved one is not only pleasant but also reduces autonomic responses and anxiety in the person promoting the touch. This might suggest that affective touch has an instrumental role for romantic partners in promoting and reinforcing their affective bonding.
Acoustic and phonemic processing are impaired in individuals with aphasia
Authors: Kries Jill , De Clercq Pieter , Lemmens Robin , Francart Tom , Vandermosten Maaike
Published: July 2023

Acoustic and phonemic processing are understudied in aphasia, a language disorder that can affect different levels and modalities of language processing. For successful speech comprehension, processing of the speech envelope is necessary, which relates to amplitude changes over time (e.g., the rise times). Moreover, to identify speech sounds (i.e., phonemes), efficient processing of spectro-temporal changes as reflected in formant transitions is essential. Given the underrepresentation of aphasia studies on these aspects, we tested rise time processing and phoneme identification in 29 individuals with post-stroke aphasia and 23 healthy age-matched controls. We found significantly lower performance in the aphasia group than in the control group on both tasks, even when controlling for individual differences in hearing levels and cognitive functioning. Further, by conducting an individual deviance analysis, we found a low-level acoustic or phonemic processing impairment in 76% of individuals with aphasia. Additionally, we investigated whether this impairment would propagate to higher-level language processing and found that rise time processing predicts phonological processing performance in individuals with aphasia. These findings show that it is important to develop diagnostic and treatment tools that target low-level language processing mechanisms.
Genetic diversity and conservation of Siberian apricot (Prunus sibirica L.) based on microsatellite markers
Authors: Wang Xinxin , Wang Li , Sun Yongqiang , Chen Jianhua , Liu Quangang , Dong Shengjun
Published: July 2023

Siberian apricot (Prunus sibirica L.) is a woody tree species of ecological, economic, and social importance. To evaluate the genetic diversity, differentiation, and structure of P. sibirica, we analyzed 176 individuals from 10 natural populations using 14 microsatellite markers. These markers generated 194 alleles in total. The mean number of alleles (13.8571) was higher than the mean number of effective alleles (6.4822). The average expected heterozygosity (0.8292) was higher than the average observed heterozygosity (0.3178). Shannon information index and polymorphism information content were separately 2.0610 and 0.8093, demonstrating the rich genetic diversity of P. sibirica. Analysis of molecular variance revealed that 85% of the genetic variation occurred within populations, with only 15% among them. The genetic differentiation coefficient and gene flow were separately 0.151 and 1.401, indicating a high degree of genetic differentiation. Clustering results showed that a genetic distance coefficient of 0.6 divided the 10 natural populations into two subgroups (subgroups A and B). STRUCTURE and principal coordinate analysis divided the 176 individuals into two subgroups (clusters 1 and 2). Mantel tests revealed that genetic distance was correlated with geographical distance and elevation differences. These findings can contribute to the effective conservation and management of P. sibirica resources.
Clinical and pathological features of second primary neoplasms arising in head and neck reconstructive skin flaps
Authors: Eguchi Kohtaro , Kobayashi Kenya , Honma Yoshitaka , Ryo Eijitsu , Sakyo Airi , Yokoyama Kazuki , Watanabe Takane , Aihara Yusuke , Sakai Azusa , Matsumoto Yoshifumi , Sakai Toshihiko , Omura Go , Yatabe Yasushi , Yoshimoto Seiichi , Mori Taisuke
Published: July 2023

The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center’s experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL, respectively. All lesions were grossly exophytic and accompanied by inflamed stroma. In FC and PL, the incidences of altered p53 types were 43% and 29%, respectively, and those of positive p16 stains were 57% and 64%, respectively. Mutation of TP53 in FC and PL were 17% and 29%, respectively. All except one patient with FC under long-term immunosuppressive therapy survived in this study. SNAFs are grossly exophytic tumors with an inflammatory background and show a relatively low altered p53 and TP53 rate and a high p16 positivity rate. They are slow-growing neoplasms with good prognoses. Diagnosis is often difficult; therefore, repeated or excisional biopsy of the lesion may be desirable.
Changes in atmospheric circulation and evapotranspiration are reducing rainfall in the Brazilian Cerrado
Authors: Hofmann G. S. , Silva R. C. , Weber E. J. , Barbosa A. A. , Oliveira L. F. B. , Alves R. J. V. , Hasenack H. , Schossler V. , Aquino F. E. , Cardoso M. F.
Published: July 2023

Here we analyze the trends of rainfall and the frequency of rainy days over the Brazilian Cerrado between 1960 and 2021 in four distinct periods according to the seasonal patterns over the region. We also evaluated trends in evapotranspiration, atmospheric pressure, winds, and atmospheric humidity over the Cerrado to elucidate the possible reasons for the detected trends. We recorded a significant reduction in rainfall and frequency of rainy days in the northern and central Cerrado regions for all periods except at the beginning of the dry season. The most pronounced negative trends were recorded during the dry season and the beginning of the wet season, where we recorded reductions of up to 50% in total rainfall and the number of rainy days. These findings are associated with the intensification of the South Atlantic Subtropical Anticyclone, which has been shifting atmospheric circulation and raising regional subsidence. Moreover, during the dry season and the beginning of the wet season, there was a reduction in regional evapotranspiration, which also potentially contributed to the rainfall reduction. Our results suggest an expansion and intensification of the dry season in the region, potentially bringing broad environmental and social impacts that transcend the Cerrado boundaries.
Reduced slow-wave activity and autonomic dysfunction during sleep precede cognitive deficits in Alzheimer’s disease transgenic mice
Authors: Chen Chieh-Wen , Kwok Yam-Ting , Cheng Yu-Ting , Huang Yu-Shan , Kuo Terry B. J. , Wu Cheng-Han , Du Pei-Jing , Yang Albert C. , Yang Cheryl C. H.
Published: July 2023

Occurrence of amyloid-β (Aβ) aggregation in brain begins before the clinical onset of Alzheimer’s disease (AD), as preclinical AD. Studies have reported that sleep problems and autonomic dysfunction associate closely with AD. However, whether they, especially the interaction between sleep and autonomic function, play critical roles in preclinical AD are unclear. Therefore, we investigated how sleep patterns and autonomic regulation at different sleep–wake stages changed and whether they were related to cognitive performance in pathogenesis of AD mice. Polysomnographic recordings in freely-moving APP/PS1 and wild-type (WT) littermates were collected to study sleep patterns and autonomic function at 4 (early disease stage) and 8 months of age (advanced disease stage), cognitive tasks including novel object recognition and Morris water maze were performed, and Aβ levels in brain were measured. APP/PS1 mice at early stage of AD pathology with Aβ aggregation but without significant differences in cognitive performance had frequent sleep–wake transitions, lower sleep-related delta power percentage, lower overall autonomic activity, and lower parasympathetic activity mainly during sleep compared with WT mice. The same phenomenon was observed in advanced-stage APP/PS1 mice with significant cognitive deficits. In mice at both disease stages, sleep-related delta power percentage correlated positively with memory performance. At early stage, memory performance correlated positively with sympathetic activity during wakefulness; at advanced stage, memory performance correlated positively with parasympathetic activity during both wakefulness and sleep. In conclusion, sleep quality and distinction between wake- and sleep-related autonomic function may be biomarkers for early AD detection.
An investigation of genetic diversity in three Dezhou donkey original breeding farms
Authors: Wang Tianqi , Liu Ziwen , Shi Xiaoyuan , Zhang Zhenwei , Li Yuhua , Huang Bingjian , Ren Wei , Wang Xinrui , Wang Changfa , Chai Wenqiong
Published: July 2023

Dezhou donkey is one of the excellent large donkey breeds in China. In our study, eight microsatellite markers were used to genotype from each of three populations of Chinese Dezhou donkeys: 67 individuals in Liaocheng (pop1), 103 individuals in Binzhou 1 (pop2), and 102 individuals in Binzhou 2 (pop3), in order to study the genetic diversity of these populations. A total of 213 alleles were detected, and the PIC results showed that eight loci were all highly polymorphic. The means of Ho and He of pop2 were the highest, which were 0.646 and 0.717, respectively. The PCoA analysis demonstrated that the samples from three conservation farms were mixed together. The phylogenetic tree showed that pop 2 and pop 3 were closely related. The phylogenetic tree results clustered that 272 donkeys were divided into six groups. AMOVA analysis showed that the genetic variation was mainly concentrated within the population and the genetic differentiation among the populations was low. Fst values between populations also indicated that genetic differentiation between populations was too small to be considered. This indicated a low probability of inbreeding within the population. And this also showed that the conservation and breeding of Dezhou donkeys in recent years have achieved excellent results. The investigation of genetic diversity in three Dezhou donkey original breeding farms can provide reference data for the selection and breeding of excellent breeds of Dezhou donkey.
Risk of epilepsy in gonadal teratoma: a nationwide population-based study
Authors: Kim Seonghoon , Kim Hasung , Lee Jungkuk , Lee Si Baek , Hong Yun Jeong , Oh Yoon-Sang , Park Jeong Wook
Published: July 2023

Epilepsy is a common neurological disease. Systemic tumors are associated with an increased risk of epileptic events. Paraneoplastic encephalitis related to gonadal teratoma is frequently accompanied by seizures and life-threatening status epilepticus (SE). However, the risk of epilepsy in gonadal teratoma has not been studied. This study aims to investigate the relationship between epileptic events and gonadal teratoma. This retrospective cohort study used the Korean National Health Insurance (KNHI) database. The study population was divided into two study arms (ovarian teratoma vs. control and testicular teratoma vs. control) with 1:2 age and gender-matched control groups without a history of gonadal teratoma or other malignancy. Participants with other malignancies, neurologic disorders, and metastatic brain lesions were excluded. We observed the occurrence of epileptic events during the observation period (2013–2018) and investigated the risk of epileptic events in each gonadal teratoma group compared to controls. In addition, the influence of malignancy and tumor removal was investigated. The final analysis included 94,203 women with ovarian teratoma, 2314 men with testicular teratoma, and controls. Ovarian teratoma is associated with a higher risk of epilepsy without SE (HR, 1.244; 95% CI 1.112–1.391) and epilepsy with SE (HR, 2.012; 95% CI 1.220–3.318) compared to the control group. The risk of epilepsy without SE was higher in malignant ovarian teratoma (HR, 1.661; 95% CI 1.358–2.033) than in benign (HR, 1.172; 95% CI 1.037–1.324). Testicular teratoma did not show significant relations with epileptic events. The risk of epileptic events showed a tendency to decrease after removing the ovarian teratoma. This study found that ovarian teratoma is associated with a higher risk of epileptic events, especially in malignant tumors, whereas testicular teratoma did not show significant differences in epileptic events compared to the control group. This study adds to the current understanding of the association between gonadal teratoma and epileptic events.
Soft molecularly imprinted nanoparticles with simultaneous lossy mode and surface plasmon multi-resonances for femtomolar sensing of serum transferrin protein
Authors: Arcadio Francesco , Noël Laurent , Del Prete Domenico , Maniglio Devid , Seggio Mimimorena , Soppera Olivier , Cennamo Nunzio , Bossi Alessandra Maria , Zeni Luigi
Published: July 2023

The simultaneous interrogation of both lossy mode (LMR) and surface plasmon (SPR) resonances was herein exploited for the first time to devise a sensor in combination with soft molecularly imprinting of nanoparticles (nanoMIPs), specifically entailed of the selectivity towards the protein biomarker human serum transferrin (HTR). Two distinct metal-oxide bilayers, i.e. TiO2–ZrO2 and ZrO2–TiO2, were used in the SPR–LMR sensing platforms. The responses to binding of the target protein HTR of both sensing configurations (TiO2–ZrO2–Au-nanoMIPs, ZrO2–TiO2–Au-nanoMIPs) showed femtomolar HTR detection, LODs of tens of fM and KDapp ~ 30 fM. Selectivity for HTR was demonstrated. The SPR interrogation was more efficient for the ZrO2–TiO2–Au-nanoMIPs configuration (sensitivity at low concentrations, S = 0.108 nm/fM) than for the TiO2–ZrO2–Au-nanoMIPs one (S = 0.061 nm/fM); while LMR was more efficient for TiO2–ZrO2–Au-nanoMIPs (S = 0.396 nm/fM) than for ZrO2–TiO2–Au-nanoMIPs (S = 0.177 nm/fM). The simultaneous resonance monitoring is advantageous for point of care determinations, both in terms of measurement’s redundancy, that enables the cross-control of the measure and the optimization of the detection, by exploiting the individual characteristics of each resonance.