bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing neophobia and exploration while accounting for social context: an example application in scimitar-horned oryx
Authors: Mertes Katherine , Ressijac Catherine A. , Moraes Rosana N. , Hughey Lacey F. , Alegre Luisa H. Porto , Horning Megan , Buk Tara , Harwood Arielle , Layman Lawrence , Mathews Christopher , Vance Morgan , Reed Dolores , Stabach Jared A. , Goldenberg Shifra Z.
Published: November 2022

Spatial neophobia and exploration are often assessed in nonhuman animals by measuring behavioral responses to novel environments. These traits may especially affect the performance of individuals translocated to novel environments for conservation purposes. Here, we present methods to administer and analyze a minimally invasive novel environment test that accounts for the social context of focal individuals. We used an aerial platform to capture video footage of a captive herd of scimitar-horned oryx (Oryx dammah) entering an unfamiliar enclosure. We analyzed footage for seven individually identifiable oryx, scoring their behavioral responses (i.e., latency to enter the enclosure, and movement and posture after entering the enclosure) and social context (i.e., relative position and number of nearby animals). We performed a principal components analysis (PCA) to explore individual traits and responses, and used generalized linear mixed models (GLMMs) to determine the effect of individual traits and social context on individual posture and movement behaviors. Both PCA and GLMMs supported our expectation that social context affects individual behavior: high neighbor density and relative position were negatively related to individual movement, and variation in social context was positively related with head-up postures and movement. Oryx were well differentiated along two principal components that reflected (1) vigilance or caution, and (2) changing social context and age. These methods provide a framework for assessing individual responses to a novel environment in a group setting, which can inform reintroduction and wildlife management efforts, while minimizing interference with animal behavior and management operations.
Mary Magdalene
Authors: Almond Philip C.
Published: November 2022

Mary Magdalene is a key figure in the history of Christianity. After Mary, the mother of Jesus, she remains the most important female saint in her guise both as primary witness to the resurrection and 'apostle of the apostles'. This volume, the first major work on the Magdalene in more than thirty years, focuses on her 'lives' as these have been imagined and reimagined within Christian tradition. Philip Almond expertly disentangles the numerous narratives that have shaped the story of Mary over the past two millennia. Exploring the 'idea' of the Magdalene – her cult, her relics, her legacy – the author deftly peels back complex layers of history and myth to reveal many different Maries, including penitent prostitute; demoniac; miracle worker; wife and lover of Jesus; symbol of the erotic; and New Age goddess. By challenging uniform or homogenised readings of the Magdalene, this absorbing new book brings fascinating insights to its subject.
Syed Ross Masood and a Japanese Model for Education, Nationalism, and Modernity in Hyderabad
Authors: Hanaoka Mimi
Published: November 2022

Syed Ross Masood (1889-1937), grandson of the Muslim modernist Syed Ahmad Khan and former principal of Osmania University, traveled in 1922 from India to Japan as Director of Public Instruction for Hyderabad to assess Japan's educational system. In Japan and Its Educational System, a report published in 1923, Masood concluded that education had been key to Japan's rapid modernization and recommended that Hyderabad follow the country's model of modernization and educational reform: transmit Western knowledge through widespread vernacular education, and focus on the imperial tradition, freedom from foreign control, and patriotic nationalism. Masood sought to use mass vernacular education to create in Hyderabad a nationalist subject, loyal to the ruling Muslim dynasty, who absorbed modern scientific knowledge with its Western epistemic foundations but who remained untainted by Western norms. This study contextualizes and historicizes Masood's attempt to create in Hyderabad a new nationalist subject, focusing on his 1923 report about Japan.
From the Periphery to Center Stage: The Mainstreaming of Italian in the Australian Education System (1960s to 1990s)
Authors: Hajek John , Aliani Renata , Slaughter Yvette
Published: November 2022

This article examines the complex drivers of change in language education that have resulted in Australia having the highest number of students learning Italian in the world. An analysis of academic and non-academic literature, policy documents, and quantitative data helps trace the trajectory of the Italian language in the Australian education system, from the 1960s to the 1990s, illustrating the interaction of different variables that facilitated the shift in Italian's status from a largely immigrant language to one of the most widely studied languages in Australia. This research documents the factors behind the successful mainstreaming of Italian into schools, which, in addition to the active support it received from the Italian community and the Italian government, also included, notably, the ability of different Australian governments to address societal transformation and to respond to the emerging practical challenges in scaling up new language education initiatives in a detailed and comprehensive manner.
Asymptotic behavior and quasi-limiting distributions on time-fractional birth and death processes
Authors: Littin Curinao Jorge
Published: November 2022

In this article we provide new results for the asymptotic behavior of a time-fractional birth and death process
$N_{\alpha}(t)$
, whose transition probabilities
$\mathbb{P}[N_{\alpha}(t)=\,j\mid N_{\alpha}(0)=i]$
are governed by a time-fractional system of differential equations, under the condition that it is not killed. More specifically, we prove that the concepts of quasi-limiting distribution and quasi-stationary distribution do not coincide, which is a consequence of the long-memory nature of the process. In addition, exact formulas for the quasi-limiting distribution and its rate convergence are presented. In the first sections, we revisit the two equivalent characterizations for this process: the first one is a time-changed classic birth and death process, whereas the second one is a Markov renewal process. Finally, we apply our main theorems to the linear model originally introduced by Orsingher and Polito [23].
RECENT SPATIAL DISTRIBUTION OF RADIOCARBON IN URBAN TREE LEAVES AT GYEONGJU, SOUTH KOREA
Authors: Lee Sang-Hun , Kong Min-Ji , Lee Seung-Gyu , Park Sae-Hoon , Kim Yu-Seok
Published: November 2022

Radiocarbon (14C) in natural samples undergoes changes due to variations in atmospheric CO2 resulting from anthropogenic activities. To analyze the variation of the 14C ratio in atmospheric CO2, deciduous tree leaves were collected in Gyeongju, a popular tourist city in South Korea. Leaf samples were collected from Prunus subg. Cerasus trees at five different sampling points throughout the city over 3 years (2018, 2020, and 2021). The 14C data of the samples were categorized into three groups (downtown, rural, and tourist sites) and analyzed for variations among the different years. The 14C ratio at downtown sites was stable after 2018, the rural site ratio increased between 2018 and 2020 and then decreased between 2020 and 2021, and the tourist site ratio increased after 2018. We theorize that the increased 14C ratio at the tourist site was caused by a decrease in tourism after 2018.
OHNO–ZAGIER TYPE RELATIONS FOR MULTIPLE t-VALUES
Authors: LI ZHONGHUA , SONG YUTONG
Published: November 2022

We study Ohno–Zagier type relations for multiple t-values and multiple t-star values. We represent the generating function of sums of multiple t-(star) values with fixed weight, depth and height in terms of the generalised hypergeometric function
$\,_3F_2$
. As applications, we get a formula for the generating function of sums of multiple t-(star) values of maximal height and a weighted sum formula for sums of multiple t-(star) values with fixed weight and depth.
Monolingual comparative normativity in bilingualism research is out of “control”: Arguments and alternatives
Authors: Rothman Jason , Bayram Fatih , DeLuca Vincent , Di Pisa Grazia , Duñabeitia Jon Andoni , Gharibi Khadij , Hao Jiuzhou , Kolb Nadine , Kubota Maki , Kupisch Tanja , Laméris Tim , Luque Alicia , van Osch Brechje , Pereira Soares Sergio Miguel , Prystauka Yanina , Tat Deniz , Tomić Aleksandra , Voits Toms , Wulff Stefanie
Published: November 2022

Herein, we contextualize, problematize, and offer some insights for moving beyond the problem of monolingual comparative normativity in (psycho) linguistic research on bilingualism. We argue that, in the vast majority of cases, juxtaposing (functional) monolinguals to bilinguals fails to offer what the comparison is supposedly intended to do: meet the standards of empirical control in line with the scientific method. Instead, the default nature of monolingual comparative normativity has historically contributed to inequalities in many facets of bilingualism research and continues to impede progress on multiple levels. Beyond framing our views on the matter, we offer some epistemological considerations and methodological alternatives to this standard practice that improve empirical rigor while fostering increased diversity, inclusivity, and equity in our field.
The Value of the Patient Voice: A Review of Salt in My Soul by Mallory Smith
Authors: LaBonte Michelle
Published: November 2022

Mallory Smith’s posthumously published book, Salt in My Soul: An Unfinished Life, is an insightful and moving account of one young woman’s experience living with a chronic, often invisible, illness.1 Mallory was diagnosed with cystic fibrosis (CF) at age three and began writing in a journal when she was 15. According to those close to her, Mallory wrote consistently over the span of 10 years, until shortly before she died at age 25 from complications related to a double lung transplant. Much of what Mallory included in her journal was too difficult for her to share with family and friends while she was alive, yet she hoped that her writing would one day “offer insight for people living with, or loving someone with, chronic illness.” (page x) As Mallory explained, “I want to create a piece so moving that people are in disbelief. And I want it to be like handing people a pair of glasses, giving them a way of seeing something they didn’t even realize they weren’t seeing.” (page 291) Shortly before Mallory died, she shared the password to her 2,500-page journal with her mother, along with instructions for how to select excerpts for what would become Salt in My Soul.
Herbicides in unexpected places: non-target impacts from tree root exudation of aminopyralid and triclopyr following basal bark treatments of invasive chokecherry (Prunus padus) in Alaska
Authors: Graziano Gino , Tomco Patrick , Seefeldt Steven , Mulder Christa P. H. , Redman Zachary
Published: November 2022

Basal bark treatment of invasive trees is an approach designed to limit damage to non-target vegetation in the vicinity, but non-target injury is still documented. No study of basal bark treatments has examined the release of herbicide residues from roots of treated plants and resulting non-target impacts. Studies were conducted in Alaska interior and coastal boreal forests on basal bark treatments with aminopyralid and triclopyr on active-growth and dormant invasive chokecherry (Prunus padus L.). The study assessed non-target damage and soil herbicide residue using a combination of visual evaluations, bioassays, and soil residue analyses. Non-target damage from herbicide residues were identified in 40% of treatments containing aminopyralid with triclopyr, 60% of treatments containing aminopyralid alone, and 5% of treatments containing only triclopyr. Laboratory studies of aminopyralid treatments to saplings isolated the effects of herbicide exudation from roots, which was found to be significant, and the magnitude was dependent on dose. Herbicide soil residues in field and laboratory experiments were quantified with analytical detection and plant bioassays. Aminopyralid soil residues were identified in 57% of field treatments receiving 8 to 60 ml of herbicide solution (2% ai) and 70% of laboratory treatments receiving 10 µl of herbicide solution (2% to 16% ai). Triclopyr residues were found from one field treatment following dosage with 28 ml of herbicide solution (18.5% ai). Anatomically, plants grown in soils associated with herbicide-treated trees, both in the field and lab, grew less dry mass than non–herbicide treated controls. This study provides the first evidence that root exudation of herbicide following basal bark treatments contributes to non-target damage of adjacent vegetation and to accumulation of soil herbicide residues. This is an important new factor for integrated pest management within basal bark treatment systems and has implications for other herbicide application types such as injections and frill, as well as determining whether root exudation is species or herbicide specific.
Measurement Invariance of the Satisfaction With Life Scale in South	Korea
Authors: Joshanloo Mohsen
Published: November 2022

Abstract: This study examined the cross-group and temporal measurement invariance of the Satisfaction With Life Scale in Korea. A nationally representative sample ( N = 13,824) and a convenience sample collected at four-time points over approximately 14 months ( N = 338) were used. Full measurement invariance (i.e., equal factor loadings and intercepts) was supported across groups based on gender, age, education, data collection method (face-to-face versus non-face-to-face), and two alternative translations of the scale. Temporal measurement invariance was also supported. Accordingly, the same underlying construct is measured, and the items of the scale are understood and answered similarly across groups and across time in Korea. Supplemental analysis revealed that Item 5 was not invariant between Korea and Japan, with Korean respondents tending to rate this item higher than Japanese respondents.
Homework Approach Scale for Middle School Students
Authors: Yang Fuyi , Xu Jianzhong , Gallo Kasia , Núñez José Carlos
Published: November 2022

Abstract: This investigation assessed the psychometric properties of the Homework Approach Scale (HAS) using 1,072 students in Grades 7 and 8. Having randomly divided the sample ( n = 1,072) into two subsamples, we conducted exploratory factor analysis (EFA) on subsample 1 and confirmatory factor analysis (CFA) on subsample 2. Factorial results indicated that the HAS contained two factors: Deep Approach and Surface Approach. Provided with sufficient measurement invariance, the factor means were tested across gender and grade levels. Males scored significantly lower in Deep Approach yet higher in the Surface Approach. There were nonsignificant differences in Deep Approach and Surface Approach across the grade level. Congruent with theoretical predictions, homework completion and mathematics achievement were related positively to Deep Approach and negatively to Surface Approach. This investigation offers robust evidence that the HAS is a valid measure for assessing students’ approaches to homework.
An Initial Comparison of the Psychometric Properties of the Dark Triad Dirty Dozen in Spanish and Portuguese
Authors: Jonason Peter K. , Tosi Michele , Silva Sofia , Antunes Rui , Brito-Costa Sónia
Published: November 2022

Abstract. We tested the psychometric properties of the Dark Triad Dirty Dozen measure of psychopathy, narcissism, and Machiavellianism in Portugal ( n = 1,034) and Spain ( n = 386). Adult ( M = 43.40, SD = 14.81, range = 18–88) participants (1,113 women) completed the Dirty Dozen measure of each trait along with ultrabrief measures of extraversion, openness, neuroticism, agreeableness, conscientiousness, and religiousness and a lengthier measure of individual differences in depression, anxiety, and stress. Using confirmatory factor analysis and multigroup confirmatory factor analysis, we found evidence for measurement invariance for a 3-factor model of the Dirty Dozen in the sexes and countries. The Dark Triad traits and disagreeableness were present across the traits and countries. Across depression, anxiety, and stress, correlations with the Dark Triad traits were stronger in men than women. Our results suggest that the scale translations – in each country – are trustworthy paving the way for inter-Iberian and international collaborations.
Moored Observations of the Timor Passage Currents in the Indonesian Seas
Authors: Wang Jing , Zhang Zhengbei , Li Xiang , Wang Zheng , Li Yao , Hao Jiajia , Zhao Xia , Corvianawatie Corry , Surinati Dewi , Yuan Dongliang , Xu Tengfei
Published: November 2022

The structure and variability of the currents in the Timor Passage are studied based on the measurements from a subsurface mooring deployed in the center of the passage from September 2017 to December 2019. The annual mean currents are found to flow westward into the Indian Ocean in the upper 1,400 m, with a maximum velocity core at ∼50 m. The mean volume transport through the Timor Passage into the Indian Ocean is estimated to be −9.9 ± 1.0 Sv (1 Sv = 106 m3 s−1) in the upper 1,400 m with much of this transport concentrated in the upper 480 m (−8.9 Sv). This value contrasts with the estimate of −7.5 Sv above 1,890 m based on INSTANT measurements. The transport during the 2019 positive Indian Ocean Dipole event was only slightly larger than that during the 2018 normal year in the upper 480 m. The variability in the along‐strait velocity in the Timor Passage is dominated by an annual cycle in the upper 150 m and a semiannual cycle in the lower layer. The annual cycle in the upper layer is mainly driven by local monsoonal forcing. Downward energy propagation is observed below 200 m, which is shown to be mainly driven by remote Kelvin waves from the Indian Ocean. The transport variability through the Timor Passage is dominated by a semiannual cycle, associated with the semiannual circulation over the equatorial Indian Ocean, with the transport in the upper and lower layers largely canceling each other in the annual cycle.
Incidence of anxiety and depression in children and young people with life-limiting conditions
Authors: Barker Mary M. , Beresford Bryony , Fraser Lorna K.
Published: November 2022

Background

The aim of this study was to investigate the incidence of anxiety and depression in children and young people with life-limiting conditions.

Methods

A comparative cohort study was conducted, using primary and secondary care data from the Clinical Practice Research Datalink (CPRD) in England. Anxiety and depression codes were identified using diagnostic, symptom and prescription codes. Incidence rates of anxiety and depression were compared across condition groups using Poisson regression, adjusting for sex, age, ethnicity, and deprivation status.

Results

A total of 25,313 children and young people were included in the study: 5527 with life-limiting conditions, 6729 with chronic conditions, and 13,057 with no long-term conditions. The incidence of anxiety (IRRadj: 1.39, 95% CI: 1.09–1.77) and depression (IRRadj: 1.41, 95% CI: 1.08–1.83) was significantly higher in children and young people with life-limiting conditions, compared to children and young people with no long-term conditions.

Conclusions

The higher incidence of anxiety and depression observed among children and young people with life-limiting conditions highlights the need for psychological support in this population, including further efforts to prevent, identify, and treat anxiety and depression.

Impact

The analysis of primary and secondary healthcare data from England revealed that the incidence of anxiety and depression was higher among children and young people with life-limiting conditions, compared to those with no long-term conditions.

This is the first study to investigate the incidence of anxiety and depression in children and young people with a wide range of life-limiting conditions.

The higher incidence of anxiety and depression observed in children and young people with life-limiting conditions highlights the need for psychological support aiming to prevent, identify, and treat anxiety and depression in this population group.
Developmental disruption and restoration of brain synaptome architecture in the murine Pax6 neurodevelopmental disease model
Authors: Tomas-Roca Laura , Qiu Zhen , Fransén Erik , Gokhale Ragini , Bulovaite Edita , Price David J. , Komiyama Noboru H. , Grant Seth G. N.
Published: November 2022

Neurodevelopmental disorders of genetic origin delay the acquisition of normal abilities and cause disabling phenotypes. Nevertheless, spontaneous attenuation and even complete amelioration of symptoms in early childhood and adolescence can occur in many disorders, suggesting that brain circuits possess an intrinsic capacity to overcome the deficits arising from some germline mutations. We examined the molecular composition of almost a trillion excitatory synapses on a brain-wide scale between birth and adulthood in mice carrying a mutation in the homeobox transcription factor Pax6, a neurodevelopmental disorder model. Pax6 haploinsufficiency had no impact on total synapse number at any age. By contrast, the molecular composition of excitatory synapses, the postnatal expansion of synapse diversity and the acquisition of normal synaptome architecture were delayed in all brain regions, interfering with networks and electrophysiological simulations of cognitive functions. Specific excitatory synapse types and subtypes were affected in two key developmental age-windows. These phenotypes were reversed within 2-3 weeks of onset, restoring synapse diversity and synaptome architecture to the normal developmental trajectory. Synapse subtypes with rapid protein turnover mediated the synaptome remodeling. This brain-wide capacity for remodeling of synapse molecular composition to recover and maintain the developmental trajectory of synaptome architecture may help confer resilience to neurodevelopmental genetic disorders.
Glycolytic flux control by drugging phosphoglycolate phosphatase
Authors: Jeanclos Elisabeth , Schlötzer Jan , Hadamek Kerstin , Yuan-Chen Natalia , Alwahsh Mohammad , Hollmann Robert , Fratz Stefanie , Yesilyurt-Gerhards Dilan , Frankenbach Tina , Engelmann Daria , Keller Angelika , Kaestner Alexandra , Schmitz Werner , Neuenschwander Martin , Hergenröder Roland , Sotriffer Christoph , von Kries Jens Peter , Schindelin Hermann , Gohla Antje
Published: November 2022

Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, we discover and analyze a compound (CP1) that inhibits PGP with high selectivity and submicromolar potency. CP1 locks the phosphatase in a catalytically inactive conformation, dampens glycolytic flux, and phenocopies effects of cellular PGP-deficiency. This study provides key insights into effective and precise PGP targeting, at the same time validating an allosteric approach to control glycolysis that could advance discoveries of innovative therapeutic candidates.
Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England
Authors: Whitaker Matthew , Elliott Joshua , Bodinier Barbara , Barclay Wendy , Ward Helen , Cooke Graham , Donnelly Christl A. , Chadeau-Hyam Marc , Elliott Paul
Published: November 2022

Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission −1 (REACT-1) study monitored the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell or taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and effects on daily activities will become increasingly important.
Dominant ARF3 variants disrupt Golgi integrity and cause a neurodevelopmental disorder recapitulated in zebrafish
Authors: Fasano Giulia , Muto Valentina , Radio Francesca Clementina , Venditti Martina , Mosaddeghzadeh Niloufar , Coppola Simona , Paradisi Graziamaria , Zara Erika , Bazgir Farhad , Ziegler Alban , Chillemi Giovanni , Bertuccini Lucia , Tinari Antonella , Vetro Annalisa , Pantaleoni Francesca , Pizzi Simone , Conti Libenzio Adrian , Petrini Stefania , Bruselles Alessandro , Prandi Ingrid Guarnetti , Mancini Cecilia , Chandramouli Balasubramanian , Barth Magalie , Bris Céline , Milani Donatella , Selicorni Angelo , Macchiaiolo Marina , Gonfiantini Michaela V. , Bartuli Andrea , Mariani Riccardo , Curry Cynthia J. , Guerrini Renzo , Slavotinek Anne , Iascone Maria , Dallapiccola Bruno , Ahmadian Mohammad Reza , Lauri Antonella , Tartaglia Marco
Published: November 2022

Vesicle biogenesis, trafficking and signaling via Endoplasmic reticulum-Golgi network support essential developmental processes and their disruption lead to neurodevelopmental disorders and neurodegeneration. We report that de novo missense variants in ARF3, encoding a small GTPase regulating Golgi dynamics, cause a developmental disease in humans impairing nervous system and skeletal formation. Microcephaly-associated ARF3 variants affect residues within the guanine nucleotide binding pocket and variably perturb protein stability and GTP/GDP binding. Functional analysis demonstrates variably disruptive consequences of ARF3 variants on Golgi morphology, vesicles assembly and trafficking. Disease modeling in zebrafish validates further the dominant behavior of the mutants and their differential impact on brain and body plan formation, recapitulating the variable disease expression. In-depth in vivo analyses traces back impaired neural precursors’ proliferation and planar cell polarity-dependent cell movements as the earliest detectable effects. Our findings document a key role of ARF3 in Golgi function and demonstrate its pleiotropic impact on development.
Remote near-field spectroscopy of vibrational strong coupling between organic molecules and phononic nanoresonators
Authors: Dolado Irene , Maciel-Escudero Carlos , Nikulina Elizaveta , Modin Evgenii , Calavalle Francesco , Chen Shu , Bylinkin Andrei , Alfaro-Mozaz Francisco Javier , Li Jiahan , Edgar James H. , Casanova Fèlix , Vélez Saül , Hueso Luis E. , Esteban Ruben , Aizpurua Javier , Hillenbrand Rainer
Published: November 2022

Phonon polariton (PhP) nanoresonators can dramatically enhance the coupling of molecular vibrations and infrared light, enabling ultrasensitive spectroscopies and strong coupling with minute amounts of matter. So far, this coupling and the resulting localized hybrid polariton modes have been studied only by far-field spectroscopy, preventing access to modal near-field patterns and dark modes, which could further our fundamental understanding of nanoscale vibrational strong coupling (VSC). Here we use infrared near-field spectroscopy to study the coupling between the localized modes of PhP nanoresonators made of h-BN and molecular vibrations. For a most direct probing of the resonator-molecule coupling, we avoid the direct near-field interaction between tip and molecules by probing the molecule-free part of partially molecule-covered nanoresonators, which we refer to as remote near-field probing. We obtain spatially and spectrally resolved maps of the hybrid polariton modes, as well as the corresponding coupling strengths, demonstrating VSC on a single PhP nanoresonator level. Our work paves the way for near-field spectroscopy of VSC phenomena not accessible by conventional techniques.
Creep fronts and complexity in laboratory earthquake sequences illuminate delayed earthquake triggering
Authors: Cebry Sara Beth L. , Ke Chun-Yu , Shreedharan Srisharan , Marone Chris , Kammer David S. , McLaskey Gregory C.
Published: November 2022

Earthquakes occur in clusters or sequences that arise from complex triggering mechanisms, but direct measurement of the slow subsurface slip responsible for delayed triggering is rarely possible. We investigate the origins of complexity and its relationship to heterogeneity using an experimental fault with two dominant seismic asperities. The fault is composed of quartz powder, a material common to natural faults, sandwiched between 760 mm long polymer blocks that deform the way 10 meters of rock would behave. We observe periodic repeating earthquakes that transition into aperiodic and complex sequences of fast and slow events. Neighboring earthquakes communicate via migrating slow slip, which resembles creep fronts observed in numerical simulations and on tectonic faults. Utilizing both local stress measurements and numerical simulations, we observe that the speed and strength of creep fronts are highly sensitive to fault stress levels left behind by previous earthquakes, and may serve as on-fault stress meters.
Peak refreezing in the Greenland firn layer under future warming scenarios
Authors: Noël Brice , Lenaerts Jan T. M. , Lipscomb William H. , Thayer-Calder Katherine , van den Broeke Michiel R.
Published: November 2022

Firn (compressed snow) covers approximately 90$$\%$$%of the Greenland ice sheet (GrIS) and currently retains about half of rain and meltwater through refreezing, reducing runoff and subsequent mass loss. The loss of firn could mark a tipping point for sustained GrIS mass loss, since decades to centuries of cold summers would be required to rebuild the firn buffer. Here we estimate the warming required for GrIS firn to reach peak refreezing, using 51 climate simulations statistically downscaled to 1 km resolution, that project the long-term firn layer evolution under multiple emission scenarios (1850–2300). We predict that refreezing stabilises under low warming scenarios, whereas under extreme warming, refreezing could peak and permanently decline starting in southwest Greenland by 2100, and further expanding GrIS-wide in the early 22$${}^{{nd}}$$ndcentury. After passing this peak, the GrIS contribution to global sea level rise would increase over twenty-fold compared to the last three decades.
SuperFi-Cas9 exhibits remarkable fidelity but severely reduced activity yet works effectively with ABE8e
Authors: Kulcsár Péter István , Tálas András , Ligeti Zoltán , Krausz Sarah Laura , Welker Ervin
Published: November 2022

Several advancements have been made to SpCas9, the most widely used CRISPR/Cas genome editing tool, to reduce its unwanted off-target effects. The most promising approach is the development of increased-fidelity nuclease (IFN) variants of SpCas9, however, their fidelity has increased at the cost of reduced activity. SuperFi-Cas9 has been developed recently, and it has been described as a next-generation high-fidelity SpCas9 variant, free from the drawbacks of first-generation IFNs. In this study, we characterize the on-target activity and the off-target propensity of SuperFi-Cas9 in mammalian cells, comparing it to first-generation IFNs. SuperFi-Cas9 demonstrates strongly reduced activity but high fidelity features that are in many aspects similar to those of some first-generation variants, such as evo- and HeFSpCas9. SuperFi-cytosine (CBE3) and -adenine (ABE7.10) base editors, as well as SuperFi-prime editor show no meaningful activity. When combined with ABE8e, SuperFi-Cas9, similarly to HeFSpCas9, executes DNA editing with high activity as well as high specificity reducing both bystander and SpCas9-dependent off-target base editing.
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation
Authors: Boix Olga , Martinez Marion , Vidal Santiago , Giménez-Alejandre Marta , Palenzuela Lluís , Lorenzo-Sanz Laura , Quevedo Laura , Moscoso Olivier , Ruiz-Orera Jorge , Ximénez-Embún Pilar , Ciriaco Nikaoly , Nuciforo Paolo , Stephan-Otto Attolini Camille , Albà M. Mar , Muñoz Javier , Tian Tian V. , Varela Ignacio , Vivancos Ana , Ramón y Cajal Santiago , Muñoz Purificación , Rivas Carmen , Abad María
Published: November 2022

The human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation and under cellular stress. By gain- and loss-of-function studies, we demonstrate that pTINCR is a key inducer of epithelial differentiation in vitro and in vivo. Interestingly, low expression of TINCR associates with worse prognosis in several epithelial cancers, and pTINCR overexpression reduces malignancy in patient-derived xenografts. At the molecular level, pTINCR binds to SUMO through its SUMO interacting motif (SIM) and to CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and epithelial differentiation. Moreover, pTINCR increases CDC42 SUMOylation and promotes its activation, triggering a pro-differentiation cascade. Our findings suggest that the microproteome is a source of new regulators of cell identity relevant for cancer.
Single atom catalysts in Van der Waals gaps
Authors: Jiang Huaning , Yang Weiwei , Xu Mingquan , Wang Erqing , Wei Yi , Liu Wei , Gu Xiaokang , Liu Lixuan , Chen Qian , Zhai Pengbo , Zou Xiaolong , Ajayan Pulickel M. , Zhou Wu , Gong Yongji
Published: November 2022

Single-atom catalysts provide efficiently utilized active sites to improve catalytic activities while improving the stability and enhancing the activities to the level of their bulk metallic counterparts are grand challenges. Herein, we demonstrate a family of single-atom catalysts with different interaction types by confining metal single atoms into the van der Waals gap of two-dimensional SnS2. The relatively weak bonding between the noble metal single atoms and the host endows the single atoms with more intrinsic catalytic activity compared to the ones with strong chemical bonding, while the protection offered by the layered material leads to ultrahigh stability compared to the physically adsorbed single-atom catalysts on the surface. Specifically, the trace Pt-intercalated SnS2 catalyst has superior long-term durability and comparable performance to that of commercial 10 wt% Pt/C catalyst in hydrogen evolution reaction. This work opens an avenue to explore high-performance intercalated single-atom electrocatalysts within various two-dimensional materials.
Influenza A virus reassortment in mammals gives rise to genetically distinct within-host subpopulations
Authors: Ganti Ketaki , Bagga Anish , Carnaccini Silvia , Ferreri Lucas M. , Geiger Ginger , Joaquin Caceres C. , Seibert Brittany , Li Yonghai , Wang Liping , Kwon Taeyong , Li Yuhao , Morozov Igor , Ma Wenjun , Richt Juergen A. , Perez Daniel R. , Koelle Katia , Lowen Anice C.
Published: November 2022

Influenza A virus (IAV) genetic exchange through reassortment has the potential to accelerate viral evolution and has played a critical role in the generation of multiple pandemic strains. For reassortment to occur, distinct viruses must co-infect the same cell. The spatio-temporal dynamics of viral dissemination within an infected host therefore define opportunity for reassortment. Here, we used wild type and synonymously barcoded variant viruses of a pandemic H1N1 strain to examine the within-host viral dynamics that govern reassortment in guinea pigs, ferrets and swine. The first two species are well-established models of human influenza, while swine are a natural host and a frequent conduit for cross-species transmission and reassortment. Our results show reassortment to be pervasive in all three hosts but less frequent in swine than in ferrets and guinea pigs. In ferrets, tissue-specific differences in the opportunity for reassortment are also evident, with more reassortants detected in the nasal tract than the lower respiratory tract. While temporal trends in viral diversity are limited, spatial patterns are clear, with heterogeneity in the viral genotypes detected at distinct anatomical sites revealing extensive compartmentalization of reassortment and replication. Our data indicate that the dynamics of viral replication in mammals allow diversification through reassortment but that the spatial compartmentalization of variants likely shapes their evolution and onward transmission.
Optical cavity-mediated exciton dynamics in photosynthetic light harvesting 2 complexes
Authors: Wu Fan , Finkelstein-Shapiro Daniel , Wang Mao , Rosenkampff Ilmari , Yartsev Arkady , Pascher Torbjörn , Nguyen- Phan Tu C. , Cogdell Richard , Börjesson Karl , Pullerits Tönu
Published: November 2022

Strong light-matter interaction leads to the formation of hybrid polariton states and alters the photophysical dynamics of organic materials and biological systems without modifying their chemical structure. Here, we experimentally investigated a well-known photosynthetic protein, light harvesting 2 complexes (LH2) from purple bacteria under strong coupling with the light mode of a Fabry-Perot optical microcavity. Using femtosecond pump probe spectroscopy, we analyzed the polariton dynamics of the strongly coupled system and observed a significant prolongation of the excited state lifetime compared with the bare exciton, which can be explained in terms of the exciton reservoir model. Our findings indicate the potential of tuning the dynamic of the whole photosynthetic unit, which contains several light harvesting complexes and reaction centers, with the help of strong exciton-photon coupling, and opening the discussion about possible design strategies of artificial photosynthetic devices.
A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain
Authors: Wang Ji , Deng Caiguangxi , Liu Ming , Liu Yihao , Li Liubing , Huang Zhangping , Shang Liru , Jiang Juan , Li Yongyong , Mo Ruohui , Zhang Hui , Liu Min , Peng Sui , Xiao Haipeng
Published: November 2022

The effectiveness of a 3rddose of SARS-CoV-2 vaccines waned quickly in the Omicron-predominant period. In response to fast-waning immunity and the threat of Omicron variant of concern (VOC) to healthcare workers (HCWs), we conduct a non-randomized trial (ChiCTR2200055564) in which 38 HCWs volunteer to receive a homologous booster of inactivated vaccines (BBIBP-CorV) 6 months after the 3rddose. The primary and secondary outcomes are neutralizing antibodies (NAbs) and the receptor-binding domain (RBD)-directed antibodies, respectively. The 4thdose recalls waned immunity while having distinct effects on humoral responses to different antigens. The peak antibody response to the RBD induced by the 4thdose is inferior to that after the 3rddose, whereas responses to the N-terminal domain (NTD) of spike protein are further strengthened significantly. Accordingly, the 4thdose further elevates the peak level of NAbs against ancestral SARS-CoV-2 and Omicron BA.2, but not BA.1 which has more NTD mutations. No severe adverse events related to vaccination are recorded during the trial. Here, we show that redistribution of immune focus after repeated vaccinations may modulate cross-protective immune responses against different VOCs.
Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity
Authors: Jia Deyong , Zhou Zhicheng , Kwon Oh-Joon , Zhang Li , Wei Xing , Zhang Yiqun , Yi Mingyang , Roudier Martine P. , Regier Mary C. , Dumpit Ruth , Nelson Peter S. , Headley Mark , True Lawrence , Lin Daniel W. , Morrissey Colm , Creighton Chad J. , Xin Li
Published: November 2022

Cancer-associated fibroblasts (CAFs) mediate an immunosuppressive effect, but the underlying mechanism remains incompletely defined. Here we show that increasing prostatic stromal Foxf2 suppresses the growth and progression of both syngeneic and autochthonous mouse prostate cancer models in an immunocompetent context. Mechanistically, Foxf2 moderately attenuates the CAF phenotype and transcriptionally downregulates Cxcl5, which diminish the immunosuppressive myeloid cells and enhance T cell cytotoxicity. Increasing prostatic stromal Foxf2 sensitizes prostate cancer to the immune checkpoint blockade therapies. Augmenting lung stromal Foxf2 also mediates an immunosuppressive milieu and inhibits lung colonization of prostate cancer. FOXF2 is expressed higher in the stroma of human transition zone (TZ) than peripheral zone (PZ) prostate. The stromal FOXF2 expression level in primary prostate cancers inversely correlates with the Gleason grade. Our study establishes Foxf2 as a stromal transcription factor modulating the tumor immune microenvironment and potentially explains why cancers are relatively rare and indolent in the TZ prostate.
Disulfiram ameliorates nonalcoholic steatohepatitis by modulating the gut microbiota and bile acid metabolism
Authors: Lei Yuanyuan , Tang Li , Chen Qiao , Wu Lingyi , He Wei , Tu Dianji , Wang Sumin , Chen Yuyang , Liu Shuang , Xie Zhuo , Wei Hong , Yang Shiming , Tang Bo
Published: November 2022

Nonalcoholic steatohepatitis (NASH) has been linked with the gut-liver axis. Here, we investigate the potential for repurposing disulfiram (DSF), a drug commonly used to treat chronic alcoholism, for NASH. Using a mouse model, we show that DSF ameliorates NASH in a gut microbiota-dependent manner. DSF modulates the gut microbiota and directly inhibits the growth of Clostridium. Administration of Clostridium abolishes the ameliorating effects of DSF on NASH. Mechanistically, DSF reduces Clostridium-mediated 7α-dehydroxylation activity to suppress secondary bile acid biosynthesis, which in turn activates hepatic farnesoid X receptor signaling to ameliorate NASH. To assess the effect of DSF on human gut microbiota, we performed a self-controlled clinical trial (ChiCTR2100048035), including 23 healthy volunteers who received 250 mg-qd DSF for 7 days. The primary objective outcomes were to assess the effects of the intervention on the diversity, composition and functional profile of gut microbiota. The pilot study shows that DSF also reduces Clostridium-mediated 7α-dehydroxylation activity. All volunteers tolerated DSF well and there were no serious adverse events in the 7-day follow-up period. Transferring fecal microbiota obtained from DSF-treated humans into germ-free mice ameliorates NASH. Collectively, the observations of similar ameliorating effects of DSF on mice and humans suggest that DSF ameliorates NASH by modulating the gut microbiota and bile acid metabolism.
A flexible cross-platform single-cell data processing pipeline
Authors: Battenberg Kai , Kelly S. Thomas , Ras Radu Abu , Hetherington Nicola A. , Hayashi Makoto , Minoda Aki
Published: November 2022

Single-cell RNA-sequencing analysis to quantify the RNA molecules in individual cells has become popular, as it can obtain a large amount of information from each experiment. We introduce UniverSC (https://github.com/minoda-lab/universc), a universal single-cell RNA-seq data processing tool that supports any unique molecular identifier-based platform. Our command-line tool, docker image, and containerised graphical application enables consistent and comprehensive integration, comparison, and evaluation across data generated from a wide range of platforms. We also provide a cross-platform application to run UniverSC via a graphical user interface, available for macOS, Windows, and Linux Ubuntu, negating one of the bottlenecks with single-cell RNA-seq analysis that is data processing for researchers who are not bioinformatically proficient.
An electrochemical biosensor for the rapid genetic identification of Musang King durian
Authors: Azizi Mohammad Malek Faizal , Romeli Sohana , Razali Hazana , Ariffin Eda Yuhana , Tajol Ariffin Muhammad Afiq , Heng Lee Yook , Abu-Bakar Norliza , Lau Han Yih
Published: November 2022

More than 200 different cultivars of durian exist worldwide but Durio zibethinus or Musang King (MK) is the most premium and prized durian fruit among the recommended varieties. Early identification of this premium variety is critical to protect from non-authentic MK durian cultivars. However, the MK variety's morphological traits are nearly identical to other varieties. Currently, the identification of durian varieties is mostly performed via evaluation of leaf shape, fruit shape, aroma, taste and seed shape and this requires trained personnel for the morphology observation. To enable the rapid identification of the MK variety, PCR amplification of ten durian varieties using six gene candidates from the chloroplast genome was first performed to obtain DNA probes that were specific to the MK durian variety. PCR amplification of ten durian varieties using primers designed confirmed that the nadhA gene sequence showed an obvious difference in the MK variety from other durian varieties. The unique sequence of MK was used as a DNA probe to develop an electrochemical biosensor for the direct identification of the MK durian variety. The electrochemical biosensor was based on the hybridization response of the immobilized DNA probe with the target DNA from the MK variety and was monitored via differential pulse voltammetry technique. Under optimal conditions, the DNA electrochemical biosensor showed a low detection limit at 10% of MK genomic DNA concentration with a wide linear calibration range of 0.05–1.5 µM (R2 = 0.9891) and RSD value of 3.77% (n = 3). The results of the developed DNA biosensor provide high promise for the development of portable sensors employed in the determination of MK variety in the field.
Oxidative stress mediates end-organ damage in a novel model of acetaminophen-toxicity in Drosophila
Authors: Saeedi Bejan J. , Hunter-Chang Sarah , Luo Liping , Li Kaiyan , Liu Ken H. , Robinson Brian S.
Published: November 2022

Acetaminophen is the most common cause of acute drug-induced liver injury in the United States. However, research into the mechanisms of acetaminophen toxicity and the development of novel therapeutics is hampered by the lack of robust, reproducible, and cost-effective model systems. Herein, we characterize a novel Drosophila-based model of acetaminophen toxicity. We demonstrate that acetaminophen treatment of Drosophila results in similar pathophysiologic alterations as those observed in mammalian systems, including a robust production of reactive oxygen species, depletion of glutathione, and dose-dependent mortality. Moreover, these effects are concentrated in the Drosophila fat body, an organ analogous to the mammalian liver. Utilizing this system, we interrogated the influence of environmental factors on acetaminophen toxicity which has proven difficult in vertebrate models due to cost and inter-individual variability. We find that both increasing age and microbial depletion sensitize Drosophila to acetaminophen toxicity. These environmental influences both alter oxidative stress response pathways in metazoans. Indeed, genetic and pharmacologic manipulations of the antioxidant response modify acetaminophen toxicity in our model. Taken together, these data demonstrate the feasibility of Drosophila for the study of acetaminophen toxicity, bringing with it an ease of genetic and microbiome manipulation, high-throughput screening, and availability of transgenic animals.