bluuebunny/crossref_metadata_2025 huggingface dataset:
Who Will Watch the Watchmen? The Ethico-political Arrangements of Algorithmic Proctoring for Academic Integrity
Authors: Henry Jade Vu , Oliver Martin
Published: November 2021

Critics of artificial intelligence have suggested that the principles of fairness, accountability and transparency (FATE) have been used for ‘ethics washing’, in order to appease industrial interests. In this article, we develop this relational and context-dependent analysis, arguing that ethics should not be understood as abstract values or design decisions, but as socio-technical achievements, enacted in the practices of students, teachers and corporations. We propose that the ethics of using AI in education are political, involving the distribution of power, privilege and resources. To illustrate this, we trace the controversies that followed from an incident in which a student was misclassified as a cheat by an online proctoring platform during the Covid-19 lockdown, analysing this incident to reveal the socio-technical arrangements of academic integrity. We then show how Joan Tronto’s work on the ethics of care can help think about the politics of these socio-technical arrangements — that is, about historically constituted power relations and the delegation of responsibilities within these institutions. The paper concludes by setting the immediate need for restorative justice against the slower temporality of systemic failure, and inviting speculation that could create new relationships between universities, students, businesses, algorithms and the idea of academic integrity.
We Need to Talk
Authors: Levendusky Matthew S. , Stecula Dominik A.
Published: November 2021

Americans today are affectively polarized: they dislike and distrust those from the opposing political party more than they did in the past, with damaging consequences for their democracy. This Element tests one strategy for ameliorating such animus: having ordinary Democrats and Republicans come together for cross-party political discussions. Building on intergroup contact theory, the authors argue that such discussions will mitigate partisan animosity. Using an original experiment, they find strong support for this hypothesis – affective polarization falls substantially among subjects who participate in heterogeneous discussion (relative to those who participate in either homogeneous political discussion or an apolitical control). This Element also provides evidence for several of the mechanisms underlying these effects, and shows that they persist for at least one week after the initial experiment. These findings have considerable importance for efforts to ameliorate animus in the mass public, and for understanding American politics more broadly.
Whose 'Eyes on the Street' Control Crime?
Authors: Linning Shannon J. , Eck John E.
Published: November 2021

Jane Jacobs coined the phrase 'eyes on the street' to depict those who maintain order in cities. Most criminologists assume these eyes belong to residents. In this Element we show that most of the eyes she described belonged to shopkeepers and property owners. They, along with governments, wield immense power through property ownership and regulation. From her work, we propose a Neo-Jacobian perspective to reframe how crime is connected to neighborhood function through deliberate decision-making at places. It advances three major turning points for criminology. This includes turns from: 1. residents to place managers as the primary source of informal social control; 2. ecological processes to outsiders' deliberate actions that create crime opportunities; and 3. a top-down macro- to bottom-up micro-spatial explanation of crime patterns. This perspective demonstrates the need for criminology to integrate further into economics, political science, urban planning, and history to improve crime control policies.
Mechanisms of cognitive-behavioral therapy effects on symptoms of body dysmorphic disorder: a network intervention analysis
Authors: Bernstein Emily E. , Phillips Katharine A. , Greenberg Jennifer L. , Curtiss Joshua , Hoeppner Susanne S. , Wilhelm Sabine
Published: November 2021

Background

Body dysmorphic disorder (BDD) is a severe and undertreated condition. Although cognitive-behavioral therapy (CBT) is the first-line psychosocial treatment for this common disorder, how the intervention works is insufficiently understood. Specific pathways have been hypothesized, but only one small study has examined the precise nature of treatment effects of CBT, and no prior study has examined the effects of supportive psychotherapy (SPT).

Methods

This study re-examined a large trial (n = 120) comparing CBT to SPT for BDD. Network intervention analyses were used to explore symptom-level data across time. We computed mixed graphical models at multiple time points to examine relative differences in direct and indirect effects of the two interventions.

Results

In the resulting networks, CBT and SPT appeared to differentially target certain symptoms. The largest differences included CBT increasing efforts to disengage from and restructure unhelpful thoughts and resist BDD rituals, while SPT was directly related to improvement in BDD-related insight. Additionally, the time course of differences aligned with the intended targets of CBT; cognitive effects emerged first and behavioral effects second, paralleling cognitive restructuring in earlier sessions and the emphasis on exposure and ritual prevention in later sessions. Differences in favor of CBT were most consistent for behavioral targets.

Conclusions

CBT and SPT primarily affected different symptoms. To improve patient care, the field needs a better understanding of how and when BDD treatments and treatment components succeed. Considering patient experiences at the symptom level and over time can aid in refining or reorganizing treatments to better fit patient needs.
Novel metaphor translation is modulated by translation direction
Authors: Jankowiak Katarzyna , Lehka-Paul Olha
Published: November 2021

Previous translation process research has pointed to an increased cognitive load when translating metaphoric compared to literal language. Yet, studies conducted thus far have not examined the role of translation direction (i.e., L1–L2 vs. L2–L1) in novel metaphor translation and have not tested whether and how this process might be modulated by the linguistic form of a novel meaning. In the present study, Polish (L1) – English (L2) translation students translated novel nominal metaphors (A is B), novel similes (A is like B), and literal sentences, in either L1–L2 or L2–L1 translation directions, while their translation behavior was recorded using a keystroke logging method. The results revealed longer translation durations for both metaphors and similes relative to literal utterances. Furthermore, we found slower translation times for novel nominal metaphors compared to novel similes and literal sentences, yet only in the L2–L1 translation direction. Such results might indicate that novel meaning translation is more cognitively taxing in the case of novel nominal metaphors, which require a more robust activation of comparison mechanisms, relative to novel similes. Importantly, this effect might be stronger when translating in the direction in which access to semantic representations is potentially more automatic (i.e., L2–L1 translation).
‘Keeping up appearances’ – negotiating identities of being fit in older age: a multi-site ethnographic study of daily life in contemporary day centres
Authors: Øye Christine , Norvoll Reidun , Vabø Mia
Published: November 2021

As governments adapt to ‘active ageing’ policies, care services are increasingly oriented towards helping older adults to stay active in order to maintain their physiological and cognitive capacity. Day centres for the frail old adults are adding more planned activities to their conventional social programmes. Although evidence indicates that they may benefit from physical fitness sessions and brain training, little is known about the way in which the activation agenda influences social interaction among participants. The article aims to fill this knowledge gap by exploring how staff and participants manoeuvre between the new activation agenda and processes of coming to terms with the functional decline of ageing bodies. We draw on ethnographic data, collected in four day centres in Denmark and Norway, constituting participant observation of 18 days, 19 interviews with older participants and 18 interviews with staff members. With reference to the dramaturgical approach of Erving Goffman, we demonstrate how different fitness identities are negotiated on different social stages. Firstly, we identify a social stage at a crossroad between staff acting as motivators in training sessions and older participants as active contributors. We demonstrate how day-care staff assist participants in keeping up appearances as fit for one's age by recognising their performance and concealing flawed performances. Secondly, we identify a social stage where participants socialise with co-participants around the lunch table and other social events. Here the act of ‘keeping up appearances’ turns into a complex art whereby people strive to retain their fitness identity by comparing themselves with peers. Finally, based on observation ‘backstage’, we reveal how participants distance themselves from the functional decline of old age by claiming that they are fit enough. We conclude that day centres are contested sites for active-ageing policies.
Code-Switching patterns differentially shape cognitive control: Testing the predictions of the adaptive control hypothesis
Authors: Ng Gilaine , Yang Hwajin
Published: November 2021

Bilinguals engage in qualitatively different code-switching patterns (alternation, insertion, and congruent lexicalization) to different degrees, according to their engagement in different types of interactional contexts (single-language context, dual-language context, and dense code-switching context). Drawing on the adaptive control hypothesis, we examined whether bilinguals’ code-switching patterns would differentially shape multiple aspects of cognitive control (interference control, salient cue detection, and opportunistic planning). We found that a dense code-switching context, which predominantly involves insertion and congruent lexicalization, was positively associated with verbal opportunistic planning but negatively associated with interference control and salient cue detection. In contrast, a dual-language context, which predominantly involves alternation, was not associated with interference control or salient cue detection, but with significantly reduced response times for opportunistic planning. Our findings partially corroborate the theoretical predictions of the adaptive control hypothesis. Altogether, our study illustrates the importance of bilinguals’ disparate code-switching practices in shaping cognitive control outcomes.
A Modified Evaporation Model Indicates That the Effects of Air Warming on Global Drying Trends Have Been Overestimated
Authors: Liu Meixian , Xu Xianli , Scanlon Bridget R. , Sun Alexander Y. , Wang Kelin
Published: November 2021

Potential evapotranspiration (PET) is a key input to hydrologic models simulating the atmospheric water demand. Thus, uncertainties in PET would result in considerable uncertainty in model outputs. Among numerous PET algorithms, the Penman‐Monteith equation (PM equation) is most widely used because of its clear physical basis and acceptable estimation. However, PM equation has a physical limitation resulting from the linear approximation of the saturation water vapor pressure differences between the evaporation surface and the surrounding air, which can affect markedly the responses of PET to air warming. By considering a modified PM‐type evaporation model, we revisited the global drying trends based on the widely used Palmer Drought Severity Index (PDSI). We demonstrate that the studies, which based on the classic PM equation, often overestimate the effects of air warming on global drying trends. Particularly, the PET_PM (PET calculated using the classic PM equation) driven PDSI, overestimates global mean drought‐affected areas by 60%, drought intensity by 65%, and drought duration by 35% on average over the globe, and tends to overestimate drying trends in areas that are drying and underestimate wetting trends in areas that are becoming wetter.
Isotopic Evidence for the High Contribution of Wintertime Photochemistry to Particulate Nitrate Formation in Northern China
Authors: Zhang Zhongyi , Jiang Zhuang , Guan Hui , Liang Yue , Zheng Nengjian , Guo Wei
Published: November 2021

Stable isotopic constraint and observationally coupled atmospheric chemistry model are two robust means to identify the oxidation mechanisms for atmospheric particulate nitrate (NO3−) production. However, large discrepancies between the two approaches have been noted in the heavily polluted environments of North China Plain (NCP). Herein, daily PM2.5samples (n = 418) were collected at five urban cities across NCP during the winter of 2017–2018; the ionic species (e.g., NO3−and methanesulfonic acid: MSA) and the dual‐isotopic signatures of NO3−were quantified. In this study, we revisited the O isotopic signatures of atmospheric O‐bearing molecules, especially that of OH radical in accordance with the up‐to‐date field measurements conducted in NCP regions. In brief, the δ18O‐OH was determined by the competition between the OH loss reaction rate and its isotopic equilibration reaction with H2O. Our improved isotopic results suggested that the daytime OH oxidation pathway was as important as the nocturnal channels in wintertime nitrate production in NCP (46.4% vs. 53.6%), whereas the exceedingly high loadings of NO3−in haze days were attributed to the heterogeneous chemistry of N2O5hydrolysis. Chemical analysis also confirmed the importance of active photochemistry in secondary components production, as the MSA (a photooxidation product) linearly correlated with the NO3−(R2 = 0.86,p < 0.05). Our preliminary results compared well with the recent model simulations (e.g., sophisticated 3D model and observationally constraint model). To alleviate the winter haze in NCP, future emission regulations should aim to reduce the photochemical oxidants, particularly their precursors of NOxand VOCs simultaneously.
The Influence of Three‐Dimensional Topography on Turbulent Flow Structures Over Dunes in Unidirectional Flows
Authors: Hardy R. J. , Best J. L. , Marjoribanks T. I. , Parsons D. R. , Ashworth P. J.
Published: November 2021

Dunes are the most prevalent bedform present in sand‐bedded rivers and their morphology typically comprises multiple scales of three‐dimensional topography. However, our understanding of flow over dunes is predicated largely on two‐dimensional models, a condition which is rare in nature. Here, we present results of Large Eddy Simulations over a static, three‐dimensional dune field, using a two‐ and three‐ dimensional topographic realisation, to investigate the interaction between bed topography and turbulent flow structures. We show that flow over two‐dimensional bedforms increases the velocity over the stoss slope and reduces the size of the leeside separation zone as compared to 3D topography. Flow over three‐dimensional bedforms generates twice as many vortices as over two‐dimensional bedforms, and these vortices are longer, wider and taller than flow over their two‐dimensional counterparts. Turbulence is dominated by hairpin‐shaped vortices and Kelvin‐Helmholtz instabilities that interact with the bed in the brink point region of the dune crest and down the lee slope, and generate high shear stresses for long durations. These results are used to propose a new conceptual model showing the differences between flow over two‐ and three‐dimensional bedforms. The findings highlight how the size, morphology and stacking of coherent flow structures into larger flow superstructures may be critical in sediment entrainment, and may dictate the relationship between event duration and magnitude that drives sediment impulses at the bed. This will ultimately lead to an increased in the three‐dimensionality of bedform morphology.
Hydrogeomorphic Recovery and Temporal Changes in Rainfall Thresholds for Debris Flows Following Wildfire
Authors: Hoch Olivia J. , McGuire Luke A. , Youberg Ann M. , Rengers Francis K.
Published: November 2021

Wildfire‐induced changes to soil and vegetation promote runoff‐generated debris flows in steep watersheds. Postfire debris flows are most commonly observed in steep watersheds during the first wet season following a wildfire, but it is unclear how long the elevated threat of debris flow persists and why debris‐flow potential changes in recovering burned areas. This work quantifies how rainfall intensity‐duration (ID) thresholds for debris‐flow initiation change with time since burning and provides a mechanistic explanation for these changes. We constrained a hydrologic model using field and remotely sensed measurements of soil‐infiltration capacity, vegetation cover, runoff, and debris‐flow activity. We applied this model to estimate rainfall ID thresholds for debris‐flow initiation within three burned areas in the southwestern United States over a postfire recovery period of three to four years. Modeling suggests ID thresholds are lowest immediately following the fire (below a one‐year recurrence interval [RI] storm) and increase with time, such that a 10‐ to 25‐year RI storm would be required to generate a debris flow after three years of recovery. Modeled changes in rainfall ID thresholds result from increases in soil infiltration capacity, canopy interception, hydraulic roughness, and median grain size of sediment entrained in an incipient debris flow. The relative importance of each of these factors varied among our three sites. Results improve our ability to assess temporal changes in postfire debris‐flow potential, highlight how site‐specific factors may alter the persistence of postfire debris‐flow hazards, and provide additional constraints on the timescale of recovery following wildfire.
Cancer drivers and clonal dynamics in acute lymphoblastic leukaemia subtypes
Authors: Studd James B. , Cornish Alex J. , Hoang Phuc H. , Law Philip , Kinnersley Ben , Houlston Richard
Published: November 2021

To obtain a comprehensive picture of composite genetic driver events and clonal dynamics in subtypes of paediatric acute lymphoblastic leukaemia (ALL) we analysed tumour-normal whole genome sequencing and expression data from 361 newly diagnosed patients. We report the identification of both structural drivers, as well as recurrent non-coding variation in promoters. Additionally we found the transcriptional profile of histone gene cluster 1 and CTCF altered tumours shared hallmarks of hyperdiploid ALL suggesting a ‘hyperdiploid like’ subtype. ALL subtypes are driven by distinct mutational processes with AID mutagenesis being confined to ETV6-RUNX1 tumours. Subclonality is a ubiquitous feature of ALL, consistent with Darwinian evolution driving selection and expansion of tumours. Driver mutations in B-cell developmental genes (IKZF1, PAX5, ZEB2) tend to be clonal and RAS/RTK mutations subclonal. In addition to identifying new avenues for therapeutic exploitation, this analysis highlights that targeted therapies should take into account composite mutational profile and clonality.
Circ_0058106 promotes proliferation, metastasis and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway through miR-185-3p in hypopharyngeal squamous cell carcinoma
Authors: Li Ce , Li Wenming , Cao Shengda , Xu Jianing , Qian Ye , Pan Xinliang , Lei Dapeng , Wei Dongmin
Published: November 2021

Hypopharyngeal squamous cell carcinoma (HSCC) accounts 95% of hypopharyngeal cancer, which is characterized by high early metastasis rate and poor prognosis. It is reported that circular RNA is involved in the occurrence and development of cancer; however, the role of circRNA in hypopharyngeal cancer has little been investigated. We performed hypopharyngeal carcinoma circRNA microarray and qRT-PCR verification. The results showed circ_0058106 expression level was significantly upregulated in tumor tissues than in corresponding normal tissues. We found that circ_0058106 upregulation promoted proliferation, migration and invasion of HSCC cells, while knockdown of circ_0058106 inhibited proliferation, migration and invasion of HSCC cells both in vitro and in vivo. Bioinformatics predicted circ_0058106 may interact with miR-185-3p. We verified circ_0058106 directly bound miR-185-3p and downregulated miR-185-3p expression by using dual-luciferase reporter assay and qRT-PCR. Moreover, we proved circ_0058106 promoted HSCC cells tumorigenesis and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway via miR-185-3p. In conclusion, our findings firstly confirmed the carcinogenic effect of circ_0058106 in promoting HSCC cells tumorigenesis, metastasis, invasion and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway through sponging miR-185-3p, indicating that circ_0058106 may be a new therapeutic target and prognostic marker for HSCC.
Mid-lateral cerebellar complex spikes encode multiple independent reward-related signals during reinforcement learning
Authors: Sendhilnathan Naveen , Ipata Anna , Goldberg Michael E.
Published: November 2021

Although the cerebellum has been implicated in simple reward-based learning recently, the role of complex spikes (CS) and simple spikes (SS), their interaction and their relationship to complex reinforcement learning and decision making is still unclear. Here we show that in a context where a non-human primate learned to make novel visuomotor associations, classifying CS responses based on their SS properties revealed distinct cell-type specific encoding of the probability of failure after the stimulus onset and the non-human primate’s decision. In a different context, CS from the same cerebellar area also responded in a cell-type and learning independent manner to the stimulus that signaled the beginning of the trial. Both types of CS signals were independent of changes in any motor kinematics and were unlikely to instruct the concurrent SS activity through an error based mechanism, suggesting the presence of context dependent, flexible, multiple independent channels of neural encoding by CS and SS. This diversity in neural information encoding in the mid-lateral cerebellum, depending on the context and learning state, is well suited to promote exploration and acquisition of wide range of cognitive behaviors that entail flexible stimulus-action-reward relationships but not necessarily motor learning.
Lysine acetylation regulates the interaction between proteins and membranes
Authors: Okada Alan K. , Teranishi Kazuki , Ambroso Mark R. , Isas Jose Mario , Vazquez-Sarandeses Elena , Lee Joo-Yeun , Melo Arthur Alves , Pandey Priyatama , Merken Daniel , Berndt Leona , Lammers Michael , Daumke Oliver , Chang Karen , Haworth Ian S. , Langen Ralf
Published: November 2021

Lysine acetylation regulates the function of soluble proteins in vivo, yet it remains largely unexplored whether lysine acetylation regulates membrane protein function. Here, we use bioinformatics, biophysical analysis of recombinant proteins, live-cell fluorescent imaging and genetic manipulation of Drosophila to explore lysine acetylation in peripheral membrane proteins. Analysis of 50 peripheral membrane proteins harboring BAR, PX, C2, or EHD membrane-binding domains reveals that lysine acetylation predominates in membrane-interaction regions. Acetylation and acetylation-mimicking mutations in three test proteins, amphiphysin, EHD2, and synaptotagmin1, strongly reduce membrane binding affinity, attenuate membrane remodeling in vitro and alter subcellular localization. This effect is likely due to the loss of positive charge, which weakens interactions with negatively charged membranes. In Drosophila, acetylation-mimicking mutations of amphiphysin cause severe disruption of T-tubule organization and yield a flightless phenotype. Our data provide mechanistic insights into how lysine acetylation regulates membrane protein function, potentially impacting a plethora of membrane-related processes.
Network analysis reveals rare disease signatures across multiple levels of biological organization
Authors: Buphamalai Pisanu , Kokotovic Tomislav , Nagy Vanja , Menche Jörg
Published: November 2021

Rare genetic diseases are typically caused by a single gene defect. Despite this clear causal relationship between genotype and phenotype, identifying the pathobiological mechanisms at various levels of biological organization remains a practical and conceptual challenge. Here, we introduce a network approach for evaluating the impact of rare gene defects across biological scales. We construct a multiplex network consisting of over 20 million gene relationships that are organized into 46 network layers spanning six major biological scales between genotype and phenotype. A comprehensive analysis of 3,771 rare diseases reveals distinct phenotypic modules within individual layers. These modules can be exploited to mechanistically dissect the impact of gene defects and accurately predict rare disease gene candidates. Our results show that the disease module formalism can be applied to rare diseases and generalized beyond physical interaction networks. These findings open up new venues to apply network-based tools for cross-scale data integration.
Four-band non-Abelian topological insulator and its experimental realization
Authors: Jiang Tianshu , Guo Qinghua , Zhang Ruo-Yang , Zhang Zhao-Qing , Yang Biao , Chan C. T.
Published: November 2021

Very recently, increasing attention has been focused on non-Abelian topological charges, e.g., the quaternion group Q8. Different from Abelian topological band insulators, these systems involve multiple entangled bulk bandgaps and support nontrivial edge states that manifest the non-Abelian topological features. Furthermore, a system with an even or odd number of bands will exhibit a significant difference in non-Abelian topological classification. To date, there has been scant research investigating even-band non-Abelian topological insulators. Here, we both theoretically explore and experimentally realize a four-band PT (inversion and time-reversal) symmetric system, where two new classes of topological charges as well as edge states are comprehensively studied. We illustrate their difference in the four-dimensional (4D) rotation sense on the stereographically projected Clifford tori. We show the evolution of the bulk topology by extending the 1D Hamiltonian onto a 2D plane and provide the accompanying edge state distributions following an analytical method. Our work presents an exhaustive study of four-band non-Abelian topological insulators and paves the way towards other even-band systems.
Monovalent lanthanide(I) in borozene complexes
Authors: Li Wan-Lu , Chen Teng-Teng , Chen Wei-Jia , Li Jun , Wang Lai-Sheng
Published: November 2021

Lanthanide (Ln) elements are generally found in the oxidation state +II or +III, and a few examples of +IV and +V compounds have also been reported. In contrast, monovalent Ln(+I) complexes remain scarce. Here we combine photoelectron spectroscopy and theoretical calculations to study Ln-doped octa-boron clusters (LnB8−, Ln = La, Pr, Tb, Tm, Yb) with the rare +I oxidation state. The global minimum of the LnB8−species changes fromCstoC7vsymmetry accompanied by an oxidation-state change from +III to +I from the early to late lanthanides. All theC7v-LnB8−clusters can be viewed as a monovalent Ln(I) coordinated by a η8-B82−doubly aromatic ligand. The B73−, B82−, and B9−series of aromatic boron clusters are analogous to the classical aromatic hydrocarbon molecules, C5H5−, C6H6, and C7H7+, respectively, with similar trends of size and charge state and they are named collectively as “borozenes”. Lanthanides with variable oxidation states and magnetic properties may be formed with different borozenes.
Co-evolution based machine-learning for predicting functional interactions between human genes
Authors: Stupp Doron , Sharon Elad , Bloch Idit , Zitnik Marinka , Zuk Or , Tabach Yuval
Published: November 2021

Over the next decade, more than a million eukaryotic species are expected to be fully sequenced. This has the potential to improve our understanding of genotype and phenotype crosstalk, gene function and interactions, and answer evolutionary questions. Here, we develop a machine-learning approach for utilizing phylogenetic profiles across 1154 eukaryotic species. This method integrates co-evolution across eukaryotic clades to predict functional interactions between human genes and the context for these interactions. We benchmark our approach showing a 14% performance increase (auROC) compared to previous methods. Using this approach, we predict functional annotations for less studied genes. We focus on DNA repair and verify that 9 of the top 50 predicted genes have been identified elsewhere, with others previously prioritized by high-throughput screens. Overall, our approach enables better annotation of function and functional interactions and facilitates the understanding of evolutionary processes underlying co-evolution. The manuscript is accompanied by a webserver available at: https://mlpp.cs.huji.ac.il.
Type VI secretion system mutations reduced competitive fitness of classical Vibrio cholerae biotype
Authors: Kostiuk Benjamin , Santoriello Francis J. , Diaz-Satizabal Laura , Bisaro Fabiana , Lee Kyung-Jo , Dhody Anna N. , Provenzano Daniele , Unterweger Daniel , Pukatzki Stefan
Published: November 2021

The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We investigated the ability of classical V. cholerae of the 2nd and 6th pandemics to engage their type six secretion system (T6SS) in microbial competition against non-pandemic and 7th pandemic strains. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains to microbial attack by non-pandemic strains and subsequently caused 6th pandemic strains to become vulnerable to El Tor biotype V. cholerae intraspecific competition. The chronology of these T6SS-debilitating mutations agrees with the decline of 6th pandemic classical strains and the emergence of 7th pandemic El Tor V. cholerae.
Screening of cashmere fineness-related genes and their ceRNA network construction in cashmere goats
Authors: Hui Taiyu , Zheng Yuanyuan , Yue Chang , Wang Yanru , Bai Zhixian , Sun Jiaming , Cai Weidong , Zhang Xinjiang , Bai Wenlin , Wang Zeying
Published: November 2021

Competitive endogenous RNA (ceRNA) is a transcript that can be mutually regulated at the post-transcriptional level by competing shared miRNAs. The ceRNA network connects the function of protein-encoded mRNA with the function of non-coding RNA, such as microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). However, compared with the ceRNA, the identification and combined analysis of lncRNAs, mRNAs, miRNAs, and circRNAs in the cashmere fineness have not been completed. Using RNA-seq technology, we first identified the miRNAs presented in Liaoning Cashmere Goat (LCG) skin, and then analyzed the mRNAs, lncRNAs, circRNAs expressed in LCG and Inner Mongolia cashmere goat (MCG) skin. As a result, 464 known and 45 new miRNAs were identified in LCG skin. In LCG and MCG skin, 1222 differentially expressed mRNAs were identified, 170 differentially expressed lncRNAs and 32 differentially expressed circRNAs were obtained. Then, qRT-PCR was used to confirm further the representative lncRNAs, mRNAs, circRNAs and miRNAs. In addition, miRanda predicted the relationships of ceRNA regulatory network among lncRNAs, circRNAs, miRNAs and mRNAs, the potential regulatory effects were investigated by Go and KEGG analysis. Through the screening and analysis of the results, the ceRNA network regulating cashmere fineness was constructed. LncRNA MSTRG14109.1 and circRNA452 were competed with miRNA-2330 to regulated the expression of TCHH, KRT35 and JUNB, which may provide a potential basis for further research on the process of regulating the cashmere fineness.
Evaluation of antimicrobial activities of plant aqueous extracts against Salmonella Typhimurium and their application to improve safety of pork meat
Authors: Gavriil Alkmini , Zilelidou Evangelia , Papadopoulos Angelis-Evangelos , Siderakou Danae , Kasiotis Konstantinos M. , Haroutounian Serkos A. , Gardeli Chrysavgi , Giannenas Ilias , Skandamis Panagiotis N.
Published: November 2021

Nine odorless laboratory-collected hydro-distilled aqueous extracts (basil, calendula, centrifuged oregano, corn silk, laurel, oregano, rosemary, spearmint, thyme) and one industrial steam-distilled oregano hydrolate acquired as by-products of essential oils purification were screened for their in vitro antimicrobial activity against three Salmonella Typhimurium strains (4/74, FS8, FS115) at 4 and 37 °C. Susceptibility to the extracts was mainly plant- and temperature-dependent, though strain dependent effects were also observed. Industrial oregano hydrolate eliminated strains immediately after inoculation, exhibiting the highest antimicrobial potential. Hydro-distilled extracts eliminated/reduced Salmonella levels during incubation at 4 °C. At 37 °C, oregano, centrifuged oregano, thyme, calendula and basil were bactericidal while spearmint, rosemary and corn silk bacteriostatic. A strain-dependent effect was observed for laurel. The individual or combined effect of marinades and edible coatings prepared of industrial hydrolate and hydro-distilled oregano extracts with or without oregano essential oil (OEO) was tested in pork meat at 4 °C inoculated with FS8 strain. Lower in situ activity was observed compared to in vitro assays. Marinades and edible coatings prepared of industrial oregano hydrolate + OEO were the most efficient in inhibiting pathogen. Marination in oregano extract and subsequent coating with either 50% oregano extract + OEO or water + OEO enhanced the performance of oregano extract. In conclusion, by-products of oregano essential oil purification may be promising alternative antimicrobials to pork meat stored under refrigeration when applied in the context of multiple hurdle approach.
Breath and plasma metabolomics to assess inflammation in acute stroke
Authors: Ahmed Waqar , White Iain R. , Wilkinson Maxim , Johnson Craig F. , Rattray Nicholas , Kishore Amit K. , Goodacre Royston , Smith Craig J. , Fowler Stephen J.
Published: November 2021

Inflammation is strongly implicated in both injury and repair processes occurring after stroke. In this exploratory study we assessed the feasibility of repeated sampling of exhaled volatile organic compounds and performed an untargeted metabolomic analysis of plasma collected at multiple time periods after stroke. Metabolic profiles were compared with the time course of the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Serial breath sampling was well-tolerated by all patients and the measurement appears feasible in this group. We found that exhaled decanal tracks CRP and IL-6 levels post-stroke and correlates with several metabolic pathways associated with a post-stroke inflammatory response. This suggests that measurement of breath and blood metabolites could facilitate development of novel therapeutic and diagnostic strategies. Results are discussed in relation to the utility of breath analysis in stroke care, such as in monitoring recovery and complications including stroke associated infection.
Multifaceted phytogenic silver nanoparticles by an insectivorous plant Drosera spatulata Labill var. bakoensis and its potential therapeutic applications
Authors: Gaddam Susmila Aparna , Kotakadi Venkata Subbaiah , Subramanyam Gunasekhar Kalavakunta , Penchalaneni Josthna , Challagundla Varadarajulu Naidu , DVR Sai Gopal , Pasupuleti Visweswara Rao
Published: November 2021

The current investigation highlights the green synthesis of silver nanoparticles (AgNPs) by the insectivorous plant Drosera spatulata Labill var. bakoensis, which is the first of its kind. The biosynthesized nanoparticles revealed a UV visible surface plasmon resonance (SPR) band at 427 nm. The natural phytoconstituents which reduce the monovalent silver were identified by FTIR. The particle size of the Ds-AgNPs was detected by the Nanoparticle size analyzer confirms that the average size of nanoparticles was around 23 ± 2 nm. Ds-AgNPs exhibit high stability because of its high negative zeta potential (− 34.1 mV). AFM studies also revealed that the Ds-AgNPs were spherical in shape and average size ranges from 10 to 20 ± 5 nm. TEM analysis also revealed that the average size of Ds-AgNPs was also around 21 ± 4 nm and the shape is roughly spherical and well dispersed. The crystal nature of Ds-AgNPs was detected as a face-centered cube by the XRD analysis. Furthermore, studies on antibacterial and antifungal activities manifested outstanding antimicrobial activities of Ds-AgNPs compared with standard antibiotic Amoxyclav. In addition, demonstration of superior free radical scavenging efficacy coupled with potential in vitro cytotoxic significance on Human colon cancer cell lines (HT-29) suggests that the Ds-AgNPs attain excellent multifunctional therapeutic applications.
Adaptation strategies and collective dynamics of extraction in networked commons of bistable resources
Authors: Schauf Andrew , Oh Poong
Published: November 2021

When populations share common-pool resources (CPRs), individuals decide how much effort to invest towards resource extraction and how to allocate this effort among available resources. We investigate these dual aspects of individual choice in networked games where resources undergo regime shifts between discrete quality states (viable or depleted) depending on collective extraction levels. We study the patterns of extraction that emerge on various network types when agents are free to vary extraction from each CPR separately to maximize their short-term payoffs. Using these results as a basis for comparison, we then investigate how results are altered if agents fix one aspect of adaptation (magnitude or allocation) while letting the other vary. We consider two constrained adaptation strategies: uniform adaptation, whereby agents adjust their extraction levels from all CPRs by the same amount, and reallocation, whereby agents selectively shift effort from lower- to higher-quality resources. A preference for uniform adaptation increases collective wealth on degree-heterogeneous agent-resource networks. Further, low-degree agents retain preferences for these constrained strategies under reinforcement learning. Empirical studies have indicated that some CPR appropriators ignore—while others emphasize—allocation aspects of adaptation; our results demonstrate that structural patterns of resource access can determine which behavior is more advantageous.
Dirac semimetal phase and switching of band inversion in XMg2Bi2 (X = Ba and Sr)
Authors: Takane Daichi , Kubota Yuya , Nakayama Kosuke , Kawakami Tappei , Yamauchi Kunihiko , Souma Seigo , Kato Takemi , Sugawara Katsuaki , Ideta Shin-ichiro , Tanaka Kiyohisa , Kitamura Miho , Horiba Koji , Kumigashira Hiroshi , Oguchi Tamio , Takahashi Takashi , Segawa Kouji , Sato Takafumi
Published: November 2021

Topological Dirac semimetals (TDSs) offer an excellent opportunity to realize outstanding physical properties distinct from those of topological insulators. Since TDSs verified so far have their own problems such as high reactivity in the atmosphere and difficulty in controlling topological phases via chemical substitution, it is highly desirable to find a new material platform of TDSs. By angle-resolved photoemission spectroscopy combined with first-principles band-structure calculations, we show that ternary compound BaMg2Bi2 is a TDS with a simple Dirac-band crossing around the Brillouin-zone center protected by the C3 symmetry of crystal. We also found that isostructural SrMg2Bi2 is an ordinary insulator characterized by the absence of band inversion due to the reduction of spin–orbit coupling. Thus, XMg2Bi2 (X = Sr, Ba, etc.) serves as a useful platform to study the interplay among crystal symmetry, spin–orbit coupling, and topological phase transition around the TDS phase.
Tunable control of CAR T cell activity through tetracycline mediated disruption of protein–protein interaction
Authors: Hotblack Alastair , Kokalaki Evangelia K. , Palton Morgan J. , Cheung Gordon Weng-Kit , Williams Iwan P. , Manzoor Somayya , Grothier Thomas I. , Piapi Alice , Fiaccadori Valeria , Wawrzyniecka Patrycja , Roddy Harriet A. , Agliardi Giulia , Roddie Claire , Onuoha Shimobi , Thomas Simon , Cordoba Shaun , Pule Martin
Published: November 2021

Chimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an “off-switch” by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule.
Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials
Authors: Kiss Szabolcs , Gede Noémi , Hegyi Péter , Nagy Bettina , Deák Rita , Dembrovszky Fanni , Bunduc Stefania , Erőss Bálint , Leiner Tamás , Szakács Zsolt , Alizadeh Hussain
Published: November 2021

Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33–5.61)] and sCR [OR = 2.29 (CI 1.49–3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39–0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76–10.66)] and sCR [OR = 3.08 (CI 2.00–4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37–0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.
Local, multimodal intralesional therapy renders distant brain metastases susceptible to PD-L1 blockade in a preclinical model of triple-negative breast cancer
Authors: Yokoi Toshihiro , Oba Takaaki , Kajihara Ryutaro , Abrams Scott I. , Ito Fumito
Published: November 2021

Despite recent progress in therapeutic strategies, prognosis of metastatic triple-negative breast cancer (TNBC) remains dismal. Evidence suggests that the induction and activation of tumor-residing conventional type-1 dendritic cells (cDC1s) is critical for the generation of CD8+ T cells that mediate the regression of mammary tumors and potentiate anti-PD-1/PD-L1 therapeutic efficacy. However, it remains unknown whether this strategy is effective against metastatic TNBC, which is poorly responsive to immunotherapy. Here, using a mouse model of TNBC, we established orthotopic mammary tumors and brain metastases, and treated mammary tumors with in situ immunomodulation (ISIM) consisting of intratumoral injections of Flt3L to mobilize cDC1s, local irradiation to induce immunogenic tumor cell death, and TLR3/CD40 stimulation to activate cDC1s. ISIM treatment of the mammary tumor increased circulating T cells with effector phenotypes, and infiltration of CD8+ T cells into the metastatic brain lesions, resulting in delayed progression of brain metastases and improved survival. Furthermore, although anti-PD-L1 therapy alone was ineffective against brain metastases, ISIM overcame resistance to anti-PD-L1 therapy, which rendered these tumor-bearing mice responsive to anti-PD-L1 therapy and further improved survival. Collectively, these results illustrate the therapeutic potential of multimodal intralesional therapy for patients with unresectable and metastatic TNBC.
Expression analyses in Ginkgo biloba provide new insights into the evolution and development of the seed
Authors: Zumajo-Cardona Cecilia , Little Damon P. , Stevenson Dennis , Ambrose Barbara A.
Published: November 2021

Although the seed is a key morphological innovation, its origin remains unknown and molecular data outside angiosperms is still limited. Ginkgo biloba, with a unique place in plant evolution, being one of the first extant gymnosperms where seeds evolved, can testify to the evolution and development of the seed. Initially, to better understand the development of the ovules in Ginkgo biloba ovules, we performed spatio-temporal expression analyses in seeds at early developing stages, of six candidate gene homologues known in angiosperms: WUSCHEL, AINTEGUMENTA, BELL1, KANADI, UNICORN, and C3HDZip. Surprisingly, the expression patterns of most these ovule homologues indicate that they are not wholly conserved between angiosperms and Ginkgo biloba. Consistent with previous studies on early diverging seedless plant lineages, ferns, lycophytes, and bryophytes, many of these candidate genes are mainly expressed in mega- and micro-sporangia. Through in-depth comparative transcriptome analyses of Ginkgo biloba developing ovules, pollen cones, and megagametophytes we have been able to identify novel genes, likely involved in ovule development. Finally, our expression analyses support the synangial or neo-synangial hypotheses for the origin of the seed, where the sporangium developmental network was likely co-opted and restricted during integument evolution.