bluuebunny/crossref_metadata_2025 huggingface dataset:
A flexible high-precision photoacoustic retinal prosthesis
Authors: Leong Audrey , Li Yueming , Ruikes Thijs R. , Voillot Julien , Yuan Yuhao , Chen Guo , Facon Arnaud , Chhuon Chakrya-Anna , Joffrois Corentin , Tessier Gilles , Cornebois Marion , Dégardin Julie , Louise Jean-Damien , Cheng Ji-Xin , Yang Chen , Moulet Hélène , Picaud Serge
Published: September 2024

Retinal degenerative diseases of photoreceptors are a leading cause of blindness with no effective treatment. Retinal prostheses aim to restore sight by stimulating remaining retinal cells. Here, we present a photoacoustic retinal stimulation technology. We designed a polydimethylsiloxane and carbon-based flexible film that converts near-infrared laser pulses into a localized acoustic field with 56-µm lateral resolution, aiming at high-precision acoustic stimulation of mechanosensitive retinal cells. This photoacoustic stimulation resulted in robust and localized modulation of retinal ganglion cell activity in both wild-type and degeneratedex vivoretinae. When a millimeter-sized photoacoustic film was implanted in the rat subretinal space, pulsed laser stimulation generated neural modulationin vivoalong the visual pathway to the superior colliculus, as measured by functional ultrasound imaging. The biosafety of the film was confirmed by the absence of short-term adverse effects under optical coherence tomography retinal imaging, while local thermal increases were measured below 1 °C. These findings demonstrate the potential of photoacoustic stimulation for high-acuity visual restoration over a large field of view in blind patients.
Feasibility of mixed-reality telecollaboration to enhance pre-medical student shadowing education
Authors: Nasir Aleeza , Nasir Rida , Puca Daisy , Charles Kevin , LoGalbo Sandhya , Schwartz Jayme , Kaur Ishveer , Tsige Temesgen , Huynh Tran Tu , Iyeke Lisa , Jordan Lindsay , Richman Mark
Published: September 2024

Introduction

Medical school admissions are highly competitive, leading to high attrition rates, particularly among underserved minority (URM) students. Mentorship and clinical exposure are critical for the success of URM students, but limited access to these experiences can be due to factors such as time constraints and transportation barriers. Augmented reality (AR) has the potential to revolutionize medical education for pre-medical students by providing engaging and accessible clinical shadowing opportunities. This study aims to investigate the feasibility and impact of integrating OpticSurg’s Vision Beyond® AR platform into the educational experience of students shadowing the Emergency Department (ED). The study will focus on students’ experience using the Vision Beyond® platform and the potential strengths and weaknesses associated with the overall use of the device.

Methods

The study included Hofstra pre-medical undergraduate and post-baccalaureate students of good academic standing and character all cleared to shadow in the Long Island Jewish Medical Center Emergency Department (ED), aged 18 or older. This pilot study explored the use of Vision Beyond® AR glasses, for remote pre-medical education. Students who were not present in the ED accessed medical teaching materials using de-identified resources available on the internet, such as CT scans, EKGs, lab results, physical examination findings, ultrasounds, and X-rays. No patients were involved in the study. The educator used the Vision Beyond® goggles to start a session and invited the students to participate through the Vision Beyond® website. Students utilized the interactive feature to indicate areas where they desired greater detail or explanation. After each session, students completed a survey to assess their experience, including demographics, system usability, ease of use for specific topics, overall impression, and the strengths and weaknesses of the platform.

Result

Fifteen pre-medical and post-baccalaureate students participated in the study. Students rated the device on a 1-to-5 scale (1 = Strongly disagree, 5 = Strongly agree) for ease of use and learnability. On average, the ratings for these categories were 4 or above. The incidence of motion sickness and nausea received an average rating of 1.8 out of 5.

Conclusion

The pilot program using OpticSurg’s Vision Beyond® platform showed promise, with students reporting a positive experience and finding the device easy to use. However, challenges such as internet connectivity issues and limitations of the AR goggles were noted. Future research should explore how this technology can enhance diversity in the medical field.
Neutralization and Stability of JN.1-derived LB.1, KP.2.3, KP.3 and KP.3.1.1 Subvariants
Authors: Li Pei , Faraone Julia N. , Hsu Cheng Chih , Chamblee Michelle , Liu Yajie , Zheng Yi-Min , Xu Yan , Carlin Claire , Horowitz Jeffrey C. , Mallampalli Rama K. , Saif Linda J. , Oltz Eugene M. , Jones Daniel , Li Jianrong , Gumina Richard J. , Bednash Joseph S. , Xu Kai , Liu Shan-Lu
Published: September 2024

During the summer of 2024, COVID-19 cases surged globally, driven by variants derived from JN.1 subvariants of SARS-CoV-2 that feature new mutations, particularly in the N-terminal domain (NTD) of the spike protein. In this study, we report on the neutralizing antibody (nAb) escape, infectivity, fusion, and stability of these subvariants—LB.1, KP.2.3, KP.3, and KP.3.1.1. Our findings demonstrate that all of these subvariants are highly evasive of nAbs elicited by the bivalent mRNA vaccine, the XBB.1.5 monovalent mumps virus-based vaccine, or from infections during the BA.2.86/JN.1 wave. This reduction in nAb titers is primarily driven by a single serine deletion (DelS31) in the NTD of the spike, leading to a distinct antigenic profile compared to the parental JN.1 and other variants. We also found that the DelS31 mutation decreases pseudovirus infectivity in CaLu-3 cells, which correlates with impaired cell-cell fusion. Additionally, the spike protein of DelS31 variants appears more conformationally stable, as indicated by reduced S1 shedding both with and without stimulation by soluble ACE2, and increased resistance to elevated temperatures. Molecular modeling suggests that the DelS31 mutation induces a conformational change that stabilizes the NTD and strengthens the NTD-Receptor-Binding Domain (RBD) interaction, thus favoring the down conformation of RBD and reducing accessibility to both the ACE2 receptor and certain nAbs. Additionally, the DelS31 mutation introduces an N-linked glycan modification at N30, which shields the underlying NTD region from antibody recognition. Our data highlight the critical role of NTD mutations in the spike protein for nAb evasion, stability, and viral infectivity, and suggest consideration of updating COVID-19 vaccines with antigens containing DelS31.
A DNA barcode library forCulexmosquitoes (Diptera: Culicidae) of South America with the description of two cryptic species of subgenusMelanoconion
Authors: Talaga Stanislas , Guidez Amandine , Thoisy Benoît de , Lavergne Anne , Carinci Romuald , Gaborit Pascal , Issaly Jean , Dusfour Isabelle , Duchemin Jean-Bernard
Published: September 2024

The genusCulexis one of the most diverse in the world and includes numerous known vector species of parasites and viruses to humans. Morphological identification ofCulexspecies is notoriously difficult and rely mostly on the examination of properly dissected male genitalia which largely prevents female and immature identification during entomological, ecological or arboviral surveys. The aims of this study were (i) to establish a DNA barcode library forCulexmosquitoes of French Guiana based on the mitochondrial gene cytochrome c oxidase I (COI) marker, (ii) to compare three approaches of molecular delimitation of species to morphological identification, and (iii) to test the effectiveness of the COI marker at a broader geographical scale across South America. Mosquitoes used in this study were sampled in French Guiana between 2013 and 2023. We provide 246 COI sequences for 90 morphologically identified species ofCulex, including five new country records and two newly described species. Overall, congruence between morphological identification and molecular delimitations using the COI barcode were high. The Barcode of Life Data clustering approach into Barcode Index Numbers gives the best result in terms of species delimitation, followed by the muti-rate Poisson Tree Processes and the Assemble Species by Automatic Partitioning methods. Inconsistencies between morphological identification and molecular delimitation can be explained by introgression, incomplete lineage sorting, imperfect taxonomy or the effect of the geographical scale of sampling. This increases by almost two-fold the number of mosquito species for which a DNA barcode is available in French Guiana, including 75% of the species ofCulexcurrently known in the territory. Finally, this study confirms the usefulness of the COI barcode in identifyingCulexmosquitoes of South America, but also points the limits of this marker for some groups of species within the subgeneraCulexandMelanoconion.
Plant-Pollinator Interactions along the Altitudinal Gradient inBerberis lyciumRoyle: An Endangered Medicinal Plant Species of the Himalayan Region
Authors: Anjum Nahila , Khan Sajid , Verma Susheel , Gaira Kailash S. , Rawat Balwant , Hanief Mohd , Chettri Nakul
Published: September 2024

Mountain ecosystems influence species distribution by offering climatic variables intertwined with rising altitude. These climatic factors determine species phenology and niche width. Although the distributional patterns of some prominent insect groups in relation to altitude have been determined, the environmental preferences along the altitudinal range that differentially influence the pollination of specific plant species are unknown. Here we assess how the composition and abundance of pollinator fauna of the important medicinal plantBerberis lyciumRoyle (Berberidaceae) differ across five distinct altitudinal gradients (800-2200 m) in the Pir-Panjal mountain range in the northwestern part of the Indian Himalayas. We monitored insect pollinators of major groups (bees, butterflies, wasps, flies) over two consecutive flowering seasons during 2022-2023. In total, 39 insect species belonging to five orders and 17 families were observed visiting the plant species during the flowering period across the altitudinal gradient. The results of the linear regression model depict that all four pollination indices show a negative correlation with increasing altitude in foraging activities when all the data are pooled together. However, only foraging speed (FS) and index of visiting rate (IVR) were statistically significant. In the case of individual orders, only Lepidoptera exhibited a notable relation to altitude. However, asynchrony in foraging activities among other pollinator groups has been reported along altitudinal gradients. The reproductive output (fruit and seed production) shows a significant negative correlation with increasing altitude. We concluded that while altitude influences species distribution, it also differentially shapes plant-pollinator interactions, pollinator activities, and reproductive output. This work is of great significance in order to monitor plant-pollinator interactions, which are essential component of biodiversity rich but fragile mountain ecosystem.
Are specific, measurable, action-oriented, realistic, and time-bound (SMART) goals associated with improved walking outcomes for stroke survivors undergoing outpatient stroke rehabilitation? An observational cross-sectional retrospective cohort study
Authors: Mohammadi-Ghayeghchi Helia , Bhagat Nidhi , Campbell Mackenzie , Mayhew Madi , Dufresne Rheall , Ewald Levi , Devasahayam Augustine J. , Mansfield Avril
Published: September 2024

Background

Goal-setting is a core principle used in clinical practice to guide treatment. Setting goals improves adherence to rehabilitation treatments and may lead to better outcomes in people with neurological disorders. However, there is a lack of research into the prevalence of goals using a Specific, Measurable, Action-Oriented, Realistic, and Time-Bound (SMART) framework. Additionally, it is currently unclear if the SMART framework improves ambulatory outcomes in outpatient stroke rehabilitation.

Methods

This observational, cross-sectional, retrospective cohort study reviewed charts of all patients admitted to outpatient stroke rehabilitation at three hospitals over a 1-year period. Patients were included in the analysis if they had documented ambulatory goals. Goals were classified as either SMART or non-SMART. Analysis of covariance was used to compare Functional Ambulation Category scores at discharge between the SMART and non-SMART groups, controlling for admission scores, length of stay, and time post-stroke.

Results

300 patients were included in the analysis. Of these, 61 (20.3%) had at least one SMART ambulatory goal. Analysis of covariance revealed a statistically significantly greater Functional Ambulation Category scores at discharge for the SMART goal group compared to the non-SMART group (mean Functional Ambulation Category scores at discharge [95% confidence interval], SMART group: 4.2 [4.0, 4.5], non-SMART group: 3.8 [3.6, 4.1]; F1,60= 4.40, p = 0.043).

Conclusion

The use of SMART goals in outpatient stroke rehabilitation is associated with better ambulatory outcomes compared to non-SMART goals. These findings suggest that incorporating the SMART framework in clinical practice can enhance the effectiveness of rehabilitation interventions for stroke patients. Further studies are recommended to explore the long-term effects and broader applications of SMART goal-setting.
Integrating Heart Rate Variability and Psychometric Assessments to Evaluate Stress and Burnout in ICU Nursing Staff: A Pilot Study
Authors: Rubio-López Alberto , Sierra-Puerta Teresa , Navas Alejandro Rubio
Published: September 2024

Background

Intensive Care Units (ICUs) are recognized as highly demanding environments that significantly contribute to stress and burnout among nursing staff. Despite increasing concern over burnout in healthcare, the relationship between physiological stress indicators, such as heart rate variability (HRV), and psychometric assessments has not been thoroughly explored in this setting.

Objective

This pilot study aimed to evaluate the relationship between HRV metrics and psychometric assessments of stress and anxiety in ICU nursing staff. Additionally, it explored the influence of shift type, shift duration, demographic factors, and lifestyle habits on these stress indicators.

Methods

An observational cross-sectional pilot study was conducted with 24 ICU healthcare professionals at a University Hospital in Madrid, Spain. HRV data were collected under controlled conditions, with measurements taken at the beginning and end of shifts. Psychometric assessments were conducted using the State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS-14), Nursing Stress Scale (NSS), and a Visual Analogue Scale for Stress (VASS). Non-parametric statistical tests were used to analyze correlations between HRV metrics, psychometric scores, and demographic/lifestyle variables.

Results

Significant negative correlations were observed between HRV metrics and perceived stress levels, particularly between the LF/HF ratio and stress measures. Night and extended shifts were associated with elevated stress, as indicated by lower HRV and higher psychometric stress scores. These findings suggest that shift type and duration significantly influence stress levels in ICU nursing staff.

Conclusion

This pilot study highlights the potential of HRV as an objective measure of stress in ICU nursing staff, with significant correlations observed between HRV metrics and psychometric assessments. The findings suggest that HRV could be a valuable tool for monitoring stress in real-time and identifying individuals at risk of burnout. However, further research with larger samples and a longitudinal approach is needed to validate these results and explore their implications for occupational health practices in ICU settings.
Digital risk score sensitively identifies presence of α-synuclein aggregation or dopaminergic deficit
Authors: Schalkamp Ann-Kathrin , Peall Kathryn J , Harrison Neil A , Escott-Price Valentina , Barnaghi Payam , Sandor Cynthia
Published: September 2024

Background

Use of digital sensors to passively collect long-term offers a step change in our ability to screen for early signs of disease in the general population. Smartwatch data has been shown to identify Parkinson’s disease (PD) several years before the clinical diagnosis, however, has not been evaluated in comparison to biological and pathological markers such as dopaminergic imaging (DaTscan) or cerebrospinal fluid (CSF) alpha-synuclein seed amplification assay (SAA) in an at-risk cohort.

Methods

To address this, we performed a cohort study using longitudinal clinical assessment data from the Parkinson’s Progression Marker Initiative (PPMI) cohort collected between 2010 and 2020 with additional long-term (mean: 485 days) at-home digital monitoring data (collected 2018-2020) from the Verily Study Watch. We derived a digital risk score and evaluated it in an at-risk cohort (N = 109) consisting of people with genetic markers (LRRK2, GBA) or prodromal symptoms (hyposmia, polysomnography-proven Rapid-Eye-Movement behavioral sleep disorder) without a diagnosis of PD for whom all modalities were available (digital, DaTscan, SAA). The digital risk score was compared to the Movement Disorder Society (MDS) research criteria for prodromal PD, alpha-synuclein SAA and DaTscan.

Findings

In the at-risk cohort (N=109, mean age = 64.62±6.86, 37% male), the digital risk correlated with the MDS research criteria for prodromal PD (r = 0.36, p-value = 1.46x10-4) and was increased in individuals with subthreshold Parkinsonism (UPDRS III > 6) (p-value = 4.99x10-6) and hyposmia (p-value = 3.77x10-2). Notably, the digital risk was correlated with DaTscan putamen binding ratio (r = -0.32, p-value = 6.64x10-4) and CSF SAA (r = 0.2, p-value = 3.9x10-2). The digital risk achieved higher sensitivity in identifying people with SAA positivity (0.71 vs 0.43) or DaTscan positivity (0.43 vs 0.14) than the MDS prodromal score but performed on-par or worse than hyposmia (SAA+: 0.71 vs 0.71, DaT+: 0.48 vs 0.57).

Interpretation

A digital risk score from smartwatch data could be used as a sensitive screening tool for early detection of PD followed by more specific tests.
Nonlinear dendritic integration supports Up-Down states in single neurons
Authors: Quaresima Alessio , Duarte Renato , Fitz Hartmut , Hagoort Peter , Petersson Karl Magnus
Published: September 2024

Changes in the activity profile of cortical neurons are due to phenomena at the scale of local and long-range networks. Accordingly, the states of cortical neurons and their, often abrupt, transitions – a phenomenon known as Up/Down states – are attributed to variations in the afferent neurons’ activity. However, cellular physiology and morphology may also play a role. This study examines the impact of dendritic nonlinearities, in the form of voltage-gated NMDA receptors, on the response of cortical neurons to balanced excitatory/inhibitory synaptic inputs. Using a neuron model with two segregated dendritic compartments, we compare cells with and without dendritic nonlinearities. Our analysis shows that NMDA receptors boost somatic firing in the balanced condition and increase the correlation of membrane potentials across the three compartments of the neuron model. Then we introduce controlled fluctuations in excitatory inputs and quantify the ensuing bimodality of the somatic membrane potential. We show that dendritic nonlinearities are crucial for detecting these fluctuations and initiating Up-Down states whose shape and statistics closely resemble electrophysiological data. Our results provide new insights into the mechanisms underlying cortical bistability and highlight the complex interplay between dendritic integration and network dynamics in shaping neuronal behavior.

Significance statement

In several physiological states, such as sleep or quiet wakefulness, the membrane of cortical cells shows a stereotypical bistability. The cell is either fully depolarized and ready to spike or in a silent, hyperpolarized state. This dynamics, known as Up-Down states, has often been attributed to changes in the network activity. However, whether cell-specific properties, such as dendritic nonlinearity, have a role in driving the neuron’s bistability remains unclear. This study examines the issue using a model of a pyramidal cell and reveals that the presence of dendritic NMDA receptors, drives the up-down states in response to small fluctuations in the network activity.
Cryo-EM structure and polar assembly of the PS2 S-layer ofCorynebacterium glutamicum
Authors: Sogues Adrià , Sleutel Mike , Petit Julienne , Megrian Daniela , Bayan Nicolas , Wehenkel Anne Marie , Remaut Han
Published: September 2024

The polar-growing Corynebacteriales have a complex cell envelope architecture characterized by the presence of a specialized outer membrane composed of mycolic acids. In some Corynebacteriales, this mycomembrane is further supported by a proteinaceous surface layer or ‘S-layer’, whose function, structure and mode of assembly remain largely enigmatic. Here, we isolatedex vivoPS2 S-layers from the industrially importantCorynebacterium glutamicumand determined its atomic structure by 3D cryoEM reconstruction. PS2 monomers consist of a six-helix bundle ‘core’, a three-helix bundle ‘arm’, and a C-terminal transmembrane (TM) helix. The PS2 core oligomerizes into hexameric units anchored in the mycomembrane by a channel-like coiled-coil of the TM helices. The PS2 arms mediate trimeric lattice contacts, crystallizing the hexameric units into an intricate semipermeable lattice. Using pulse-chase live cell imaging, we show that the PS2 lattice is incorporated at the poles, coincident with the actinobacterial elongasome. Finally, phylogenetic analysis shows a paraphyletic distribution and dispersed chromosomal location of PS2 in Corynebacteriales as a result of multiple recombination events and losses. These findings expand our understanding of S-layer biology and enable applications of membrane-supported self-assembling bioengineered materials.
Interhemispheric CA1 projections support spatial cognition and are affected in a mouse model of the 22q11.2 deletion syndrome
Authors: de León Reyes Noelia S. , Bortolozzo-Gleich Maria Helena , Nomura Yuki , García Fregola Cristina , Nieto Marta , Gogos Joseph A. , Leroy Félix
Published: September 2024

Untangling the hippocampus connectivity is critical for understanding the mechanisms supporting learning and memory. However, the function of interhemispheric connections between hippocampal formations is still poorly understood. So far, two major hippocampal commissural projections have been characterized in rodents. Mossy cells from the hilus of the dentate gyrus project to the inner molecular layer of the contralateral dentate gyrus and CA3 and CA2 pyramidal neuron axonal collaterals to contralateral CA3, CA2 and CA1. In contrary, little is known about commissural projection from the CA1 region. Here, we show that CA1 pyramidal neurons from the dorsal hippocampus project to contralateral dorsal CA1 as well as dorsal subiculum. We further demonstrate that the interhemispheric projection from CA1 to dorsal subiculum supports spatial memory and spatial working memory in WT mice, two cognitive functions impaired in male mice from theDf16(A)+/-model of 22q11.2 deletion syndrome (22q11.2DS) associated with schizophrenia. Investigation of the CA1 interhemispheric projections inDf16(A)+/-mice revealed that these projections are disrupted with male mutants showing stronger anatomical defects compared to females. Overall, our results characterize a novel interhemispheric projection from dCA1 to dorsal subiculum and suggest that dysregulation of this projection may contribute to the cognitive deficits associated with the 22q11.2DS.
Characterization of tumor heterogeneity through segmentation-free representation learning
Authors: Tan Jimin , Le Hortense , Deng Jiehui , Liu Yingzhuo , Hao Yuan , Hollenberg Michelle , Liu Wenke , Wang Joshua M. , Xia Bo , Ramaswami Sitharam , Mezzano Valeria , Loomis Cynthia , Murrell Nina , Moreira Andre L. , Cho Kyunghyun , Pass Harvey , Wong Kwok-Kin , Ban Yi , Neel Benjamin G. , Tsirigos Aristotelis , Fenyö David
Published: September 2024

The interaction between tumors and their microenvironment is complex and heterogeneous. Recent developments in high-dimensional multiplexed imaging have revealed the spatial organization of tumor tissues at the molecular level. However, the discovery and thorough characterization of the tumor microenvironment (TME) remains challenging due to the scale and complexity of the images. Here, we propose a self-supervised representation learning framework, CANVAS, that enables discovery of novel types of TMEs. CANVAS is a vision transformer that directly takes high-dimensional multiplexed images and is trained using self-supervised masked image modeling. In contrast to traditional spatial analysis approaches which rely on cell segmentations, CANVAS is segmentation-free, utilizes pixel-level information, and retains local morphology and biomarker distribution information. This approach allows the model to distinguish subtle morphological differences, leading to precise separation and characterization of distinct TME signatures. We applied CANVAS to a lung tumor dataset and identified and validated a monocytic signature that is associated with poor prognosis.
PIP2 promotes the incorporation of CD43, PSGL-1 and CD44 into nascent HIV-1 particles
Authors: Cardoso Ricardo de Souza , Murakami Tomoyuki , Jacobovitz Binyamin , Veatch Sarah L. , Ono Akira
Published: September 2024

Abstract

Determinants regulating sorting of host transmembrane proteins at sites of enveloped virus assembly on the plasma membrane (PM) remain poorly understood. Here, we demonstrate for the first time that PM acidic phospholipid PIP2 regulates such sorting into an enveloped virus, HIV-1. Incorporation of CD43, PSGL-1, and CD44 into HIV-1 particles is known to have profound effects on viral spread; however, the mechanisms promoting their incorporation were unknown. We found that depletion of cellular PIP2 blocks the incorporation of CD43, PSGL-1, and CD44 into HIV-1 particles. Expansion microscopy revealed that PIP2 depletion diminishes nanoscale co-clustering between viral structural protein Gag and the three transmembrane proteins at PM and that Gag induces PIP2 enrichment around itself. CD43, PSGL-1, and CD44 also increased local PIP2 density, revealing their PIP2 affinity. Altogether, these results support a new mechanism where local enrichment of an acidic phospholipid drives co-clustering between viral structural and cellular transmembrane proteins, thereby modulating the content, and hence the fate, of progeny virus particles.
SARS-CoV-2 Nsp15 antagonizes the cGAS-STING-mediated antiviral innate immune responses
Authors: Chiu Hsin-Ping , Yeo Yao Yu , Lai Tsoi Ying , Hung Chuan-Tien , Kowdle Shreyas , Haas Griffin D , Jiang Sizun , Sun Weina , Lee Benhur
Published: September 2024

Coronavirus (CoV) Nsp15 is a viral endoribonuclease (EndoU) with a preference for uridine residues. CoV Nsp15 is an innate immune antagonist which prevents dsRNA sensor recognition and stress granule formation by targeting viral and host RNAs. SARS-CoV-2 restricts and delays the host antiviral innate immune responses through multiple viral proteins, but the role of SARS-CoV-2 Nsp15 in innate immune evasion is not completely understood. Here, we generate an EndoU activity knockout rSARS-CoV-2Nsp15-H234Ato elucidate the biological functions of Nsp15. Relative to wild-type rSARS-CoV-2, replication of rSARS-CoV-2Nsp15-H234Awas significantly decreased in IFN-responsive A549-ACE2 cells but not in its STAT1 knockout counterpart. Transcriptomic analysis revealed upregulation of innate immune response genes in cells infected with rSARS-CoV-2Nsp15-H234Arelative to wild-type virus, including cGAS-STING, cytosolic DNA sensors activated by both DNA and RNA viruses. Treatment with STING inhibitors H-151 and SN-011 rescued the attenuated phenotype of rSARS-CoV-2Nsp15-H234A. SARS-CoV-2 Nsp15 inhibited cGAS-STING-mediated IFN-β promoter and NF-κB reporter activity, as well as facilitated the replication of EV-D68 and NDV by diminishing cGAS and STING expression and downstream innate immune responses. Notably, the decline in cGAS and STING was also apparent during SARS-CoV-2 infection. The EndoU activity was essential for SARS-CoV-2 Nsp15-mediated cGAS and STING downregulation, but not all HCoV Nsp15 share the consistent substrate selectivity. In the hamster model, rSARS-CoV-2Nsp15-H234Areplicated to lower titers in the nasal turbinates and lungs and induced higher innate immune responses. Collectively, our findings exhibit that SARS-CoV-2 Nsp15 serves as a host innate immune antagonist by targeting host cGAS and STING.

Significance statement

Host innate immune system serves as the primary defense against pathogens, including SARS-CoV-2. Co-evolving with the hosts, viruses develop multiple approaches to escape the host surveillance. SARS-CoV-2 silences and dysregulates innate immune responses, and the chaos of antiviral IFN responses highly correlates to COVID-19 disease severity. Nsp15 is a conventional innate immune antagonist across coronaviruses, but the biological impact about SARS-CoV-2 Nsp15 is still unclear. Here, we provide a novel insight that SARS-CoV-2 Nsp15 hampers the expression of innate immune regulator – cGAS and STING via its endoribonuclease activity, then further ameliorates virus replication.
A genome assembly and annotation for the Australian alpine skinkBassiana duperreyiusing long-read technologies
Authors: Hanrahan Benjamin J. , Alreja Kirat , Reis Andre L. M. , Chang J King , Dissanayake Duminda S.B. , Edwards Richard J. , Bertozzi Terry , Hammond Jillian M. , O’Meally Denis , Deveson Ira W. , Georges Arthur , Waters Paul , Patel Hardip R.
Published: September 2024

The eastern three-lined skink (Bassiana duperreyi) inhabits the Australian high country in the southwest of the continent including Tasmania. It is an oviparous species that is distinctive because it undergoes sex reversal (from XX genotypic females to phenotypic males) at low incubation temperatures. We present a chromosome-scale genome assembly of aBassiana duperreyiXY male individual, constructed using a combination of PacBio HiFi and ONT long reads scaffolded using Illumina HiC data. The genome assembly length is 1.57 Gb with a scaffold N50 of 222 Mbp, N90 of 26 Mbp, 200 gaps and 43.10% GC content. Most (95%) of the assembly is scaffolded into 6 macrochromosomes, 8 microchromosomes and the X chromosome, corresponding to the karyotype. Fragmented Y chromosome scaffolds (n=11>1 Mbp) were identified using Y-specific contigs generated by genome subtraction. We identified two novel alpha-satellite repeats of 187 bp and 199 bp in the putative centromeres that did not form higher order repeats. The genome assembly exceeds the standard recommended by the Earth Biogenome Project; 0.02% false expansions, 99.63% kmer completeness, 94.66% complete single copy BUSCO genes and an average 98.42% of transcriptome data mappable to the genome assembly. The mitochondrial genome (17,506 bp) and the model rDNA repeat unit (15,154 bp) were assembled. TheB. duperreyigenome assembly has one of the highest completeness levels for a skink and will provide a resource for research focused on sex determination and thermolabile sex reversal, as an oviparous foundation species for studies of the evolution of viviparity, and for other comparative genomics studies of the Scincidae.

Species Taxonomy

Eukaryota; Animalia; Chordata; Reptilia; Squamata; Scincidae; Lygosominae; Eugongylini;Bassiana(=Acritoscincus);Bassiana duperreyi(Gray, 1838) (NCBI: txid316450).
Nanomotion technology for testing azithromycin susceptibility ofSalmonella enterica
Authors: Hinnu Mariliis , Mets Toomas , Kerkez Ivana , Putrinš Marta , Kaldalu Niilo , Cathomen Gino , Verge Marta Pla , Cichocka Danuta , Sturm Alexander , Tenson Tanel ,   ERADIAMR consortium
Published: September 2024

Azithromycin is used to treat invasive salmonellosis, despite conflicting effective concentrationsin vitroandin vivo. Resistance ofSalmonella entericato azithromycin is increasing. We demonstrate that nanomotion technology can be used for rapid phenotypic testing ofSalmonella’s susceptibility to azithromycin. Nanomotion changes under various culture conditions correlated with susceptibility measured by MIC determination, CFU counting, and fluorescent reporter-based estimates of intrabacterial azithromycin accumulation.
Motor learning is regulated by GDNF levels in postnatal cerebellar Purkinje cells
Authors: Nagaeva Elina , Turconi Giorgio , Mätlik Kärt , Segerstråle Mikael , Olfat Soophie , Iivanainen Vilma , Taira Tomi , Andressoo Jaan-Olle
Published: September 2024

Purkinje cells, the sole output neurons of the cerebellar cortex, are crucial for cerebellum-dependent motor learning. Previously we demonstrated that a ubiquitous 2-3-fold increase of endogenous glial cell line-derived neurotrophic factor (GDNF) improves motor learning. However, GDNF impacts many organ systems and cell types throughout the body leaving the underlying mechanism elusive. Here, we utilize an innovative conditional GDNF Hypermorphic mouse model to show that a 2-fold increase in endogenous GDNF specifically in postnatal Purkinje cells (PCs) is sufficient to enhance motor learning in adult animals. We demonstrate that improved motor learning is associated with increased glutamatergic input to PCs and elevated spontaneous firing rate of these cells, opposite to cerebellar ataxia where reduction in motor function and learning associates with decreased spontaneous activity of PCs. Notably, the GDNF expression levels variation range studied in our mouse model’s cerebellum falls within the normal range of variation observed in healthy human cerebellums. Our findings uncover a molecular pathway and a specific cell type that regulate motor learning, potentially explaining some individual differences in human motor skill acquisition.
HOXB6 and HOXB8 control immune-cancer cell interactions in pancreatic cancer
Authors: Bertonnier-Brouty Ludivine , Achanta Kavya , Andersson Jonas , Bsharat Sara , Singh Tania , Kaprio Tuomas , Hagström Jaana , Haglund Caj , Seppänen Hanna , Prasad Rashmi B , Artner Isabella
Published: September 2024

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer lacking effective drugs and therefore new treatment targets are needed. Transcriptomic analysis comparing human embryonic and PDAC tissue identified a large overlap of expression profiles suggesting a re-initiation of developmental programs in pancreatic cancer. Specifically, we identified the transcription factors HOXB6 and HOXB8 as potential key regulators in PDAC. Loss of HOXB6 and HOXB8 in pancreatic cancer cells inhibited cell proliferation, induced apoptosis and senescence and enhanced gemcitabine sensitivity. Moreover, reduced HOXB6 and HOXB8 expression in pancreatic and lung adenocarcinoma cell lines affected transcription of immune response pathways which resulted in an increased sensitivity of cancer cells to anti-tumorigenic activities of macrophages suggesting that the HOXB6 and HOXB8 immune regulatory pattern is conserved in different cancer types. Additionally, naïve M0 macrophages exposed to HOXB8 deficient PDAC cells were unable to differentiate into tumor associated macrophages, suggesting that HOXB8 promotes the transition of initial anti-tumor macrophage to a tumor-promoting macrophage phenotype in pancreatic cancer. Our findings indicate that HOXB6 and HOXB8 play important roles in regulating cell proliferation, immune response and treatment resistance to promote pancreatic cancer tumorigenesis and could be useful therapeutic targets.
Femtoscopy analysis of ultrasoft pion trap at energies available at the CERN Large Hadron Collider
Authors: Rzesa W. , Kornakov G. , Kisiel A. R. , Sinyukov Yu. M. , Shapoval V. M.
Published: September 2024

Femtoscopy studies of pion radiation in heavy-ion collisions have been conducted extensively at all available collider energies, both theoretically and experimentally. In all these studies special attention is given to mT dependency of pion femtoscopy radii, usually approximated by a power-law function at transverse momenta above 200MeV/c. However, the radii behavior has been much less explored for the ultrasoft pions, possessing transverse momentum comparable to or lower than the pion mass. For many experimental setups this region is difficult to measure. In this work we present theoretical calculations of pion emission in the ultrasoft region in the two hybrid models iHKM and LHYQUID+thERMINATOR2. Along with the particle transverse momentum spectra, we present the calculated femtoscopy radii, in both one-dimensional and three-dimensional representations. We investigate the radii dependence on pair mT and observe, in particular, a departure from the power-law behavior at ultrasoft momenta, potentially reflecting a decoupling of such slow pions from the rest of collectively expanding system. We provide the theoretical interpretation of this result and discuss its significance, in particular, for the ongoing nonidentical particle femtoscopy analysis for pairs consisting of a pion and a baryon (or of a pion and a charmed meson).

Published by the American Physical Society
2024
Identifying barriers in constructing green buildings in Oman: a study on project contractors’ experience
Authors: Zainul Abidin Nazirah , Powmya Ayishathul
Published: September 2024

Purpose

Oman commitment for Sustainable Development Goals 2030 pushes green building at the forefront of construction industry. However, its green building progress is slower than other Gulf Cooperation Council countries, and only a handful of local contractors have been involved in green project development. Understanding the barriers to green project delivery will open avenues for better project planning and preparation. This research aims to identify the barriers experienced by the contractors when constructing green buildings in Oman.

Design/methodology/approach

Qualitative research, via a semi-structured interview process, explores the barriers experienced by 14 contractors when constructing Leadership in Energy and Environmental Design (LEED) green building projects in Oman. Using NVivo 12 software, thematic analysis was conducted through the generation of coding and themes which enable the identification of the relevant barriers.

Findings

The research uncovered 10 barriers and grouped them into five categories. The five categories are as follows: (1) insufficient skills development, (2) lack of government support and regulatory adjustment, (3) limitation in materials procurement, (4) documentation and coordination limitation and (5) difficulty in green rating compliance.

Originality/value

The research identified 10 barriers of constructing green buildings in Oman. These barriers gravitated on 4 issues: knowledge and competency, green rating requirements, government involvement and materials procurement. It streamlined clusters of the potential research area for more effective green building action plans in the future. Two barriers are deemed uniquely applied to Oman, namely “lack of needed regulatory adjustment” and “absence of local rating tools”. This insight can serve as a valuable steppingstone to push more green buildings for the country.
Unveiling the inhibitors to CPS adoption in freight logistics: a TOE-based perspective
Authors: Rawat Umabharati , Anbanandam Ramesh
Published: September 2024

Purpose

The digital evolution of production and logistics systems requires seamless integration of various functions. Cyber-physical systems (CPS) can streamline operations, reduce costs and optimise freight transport dynamics. Therefore, CPS adoption is essential to transform existing logistics infrastructure by connecting logistical equipment to cyberspace. This research addresses the critical issue of low CPS adoption in logistics. By analysing the barriers, the study proposes effective strategies to increase CPS integration significantly.

Design/methodology/approach

This study used the technology-organisation-environment (TOE) framework and identified 18 barriers to CPS adoption in freight logistics. The barriers were then analysed using the fuzzy data-driven multi-criteria decision-making (MCDM) method, i.e. fuzzy-based decision-making trial and evaluation laboratory (Fuzzy-DEMATEL).

Findings

The computational analysis of the proposed framework shows that “the complexity of CPS and lagged data-driven logistics infrastructure” (T1) is a major technological inhibitor to CPS adoption. The “high cost of CPS technology” (O8) and a “lack of top management support” (O3) are the top causal inhibitors at the organisational level. “Lack of data governance and regulatory framework” (E2) is the main environmental inhibitor.

Practical implications

The causal mapping of the TOE-based barriers helps policymakers and logisticians to develop strategies or follow recommended adoption strategies to improve CPS adoption in logistics.

Originality/value

This study is a pioneering effort to unveil the adoption barriers of CPS in the freight logistics industry and suggest strategies for fostering adoption. This research could provide valuable insights for logistics organisations to support CPS-driven logistics modernisation.
A comprehensive review on survivor syndrome in the workplace
Authors: George Tijo , Maheshwari Bhawana
Published: September 2024

Purpose

This study explores the concept of “workplace survivor syndrome” (WSS) using bibliometric analysis and literature review, thereby identifying the avenues for future research in business management.

Design/methodology/approach

The study adopted a methodological combination of bibliometric analysis and literature review. The methodological order is as follows: using the Scopus database and identifying 118 articles from ABDC listed journals, performance analysis by VOS viewer (citation analysis), science mapping analysis by Biblioshiny (visualisation and graphical presentation), and finally, the content analysis of the best 40 articles with a minimum of 50 citations and without any year restriction.

Findings

The bibliometric analysis reveals the most influential authors, articles, journals, countries, publication trends, impactful articles, and impactful authors of workplace survivor syndrome research, along with popular keywords used in this area. The content analysis identified three themes: emotional, cognitive, and behavioural syndrome. The content analysis reported the central mechanism adopted in 40 articles, including theories, methodologies, variables, sample size, etc. Additionally, the study explored the positive reviews on WSS.

Research limitations/implications

The study considered only the articles from the ABDC journal quality list for the review.

Originality/value

The article is persuasively the first research to provide the intellectual structure and comprehensive bibliometric analysis of workplace survivor syndrome.
Construction and application of a novel grey relational analysis model considering factor coupling relationship
Authors: Hu Aqin , Xie Naiming
Published: September 2024

Purpose

The purpose of this paper is to explore a new grey relational analysis model to measure the coupling relationship between the indicators for the water environment status assessment. Meanwhile, the model deals with the problem that the changing of indicator order may result in the changing of the degree of grey relation.

Design/methodology/approach

The binary index submatrix of the sample matrix is given first. Then the product of the matrix and its own transpose is used to measure the characteristics of the index and the coupling relationship between the indicators. Thirdly, the grey relational coefficient is defined based on the matrix norm, and a grey coupling relational analysis model is proposed.

Findings

The paper provides a novel grey relational analysis model based on the norm of matrix. The properties, normalization, symmetry, relational order invariance to the multiplicative, are studied. The paper also shows that the model performs very well on the water environment status assessment in the eight cities along the Yangtze River.

Originality/value

The model in this paper has supplemented and improved the grey relational analysis theory for panel data.
Investigating supply chain resilience in digital car sharing enterprises: a case study from Turkey
Authors: Karadayi-Usta Saliha , Kadaifci Cigdem
Published: September 2024

Purpose

The purpose of this study is to extract factors enabling the digital car sharing enterprises' supply chain resilience (SCR), to interpret different factor prioritizations in terms of industry representatives’ assessments and specialties, and to discuss the results by applying and comparing different ranking techniques.

Design/methodology/approach

To achieve the purpose, the factors were identified via an in-depth systematic literature review, and next, these factors were examined by industry representatives to gather the decision matrices, then analytic hierarchy process (AHP) and measuring attractiveness by a categorical based evaluation technique (MACBETH) were applied separately to model the decision problem, and finally the findings were interpreted with different participants’ perspectives.

Findings

The findings revealed that the AHP and MACBETH provide nearly identical rankings in terms of main factors by implying the significance of the triple bottom line of sustainability. Therefore, the economic, social, and environmental dimensions of sustainability should be accomplished to obtain a resilient digital car sharing enterprise supply chain. In addition, readiness and agility are the other important factors affecting the enterprises’ resilience, and finally, although digitalization seemed to be the least important one, its sub-factor emerged at the top of the ranking list.

Originality/value

Up to the authors’ knowledge, this is the first study in the literature that focuses on the SCR of car sharing companies, a particular type of digital enterprise, and uses AHP and MACBETH to examine the important factors that might affect the SCR of these companies. Practitioners should take the findings of both methods into account when evaluating the results and determine the short- and long-term strategies accordingly.
The influence of foreignness on CEO pay
Authors: Rivas Jose Luis , Lopez-Iturriaga Felix , Semadeni Mathew
Published: September 2024

Purpose

This study aims to explore the relationship between foreignness and CEO pay.

Design/methodology/approach

This study combines cross-sectional and time series observations analyzed with panel data methodology in a sample of 59 firms listed in the Spanish IBEX-35 index between 2006 and 2020.

Findings

International ownership influences CEO underpayment and foreign sales influence CEO overpayment.

Practical implications

CEO pay is susceptible to being influenced by foreign non-American variables. An appropriate understanding of these factors can contribute to discussing policies that balance the level of CEO payment in large public firms.

Originality/value

Research on internationalization and CEO pay is scarce. A handful of studies confirm the link between Americanization and executive compensation in Europe. However, the authors still do not know if the level of CEO pay is influenced by non-American exposure. To do this, the authors test the effect of firm – ownership, sales, board – and individual – CEO – exposure to international, non-US environments on the level of over/underpayment of CEOs in a sample of Spanish firms.