bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV
Authors: Albalawi Yasmeen A. , Shull Tanner , Virdi Amber K. , Subra Caroline , Mitchell Julie , Slike Bonnie M. , Jian Ningbo , Krebs Shelly J. , Sacdalan Carlo , Ratnaratorn Nisakorn , Hsu Denise C. , Phanuphak Nittaya , Spudich Serena , Trautmann Lydie , Al-Harthi Lena
Published: October 2023

Objective:

HIV-associated neuroinflammation persists in the brain despite suppressive combination antiretroviral therapy (cART). We evaluated associations between a subset of CD8+ T cells, termed CD4dimCD8bright T cells, and soluble markers of immune activation and/or neuroinflammation in the cerebrospinal fluid (CSF) and plasma of people with HIV (PWH).

Design:

Fifteen cART-naive PWH were enrolled and underwent blood draw, lumbar puncture for CSF collection, and neuropsychological tests at week 0 (pre-cART) and 24 weeks after cART initiation.

Methods:

CSF and peripheral blood T cells were evaluated with flow cytometry and soluble markers of immune activation were measured by multiplex and singleplex assays. Spearman bootstrap correlation coefficients with 10 000 resamples were computed and reported with corresponding 95% confidence intervals (CIs) for each marker of interest and T-cell type.

Results:

The frequency of CSF CD4dimCD8bright T cells at week 0 was inversely related with CSF neopterin. In contrast, at week 24, CSF CD4−CD8+ T cells were positively correlated with CSF s100β, a marker of brain injury. In the blood, at week 0, CD4dimCD8bright T cells were inversely correlated with MCP-1, IP-10, IL-8, IL-6, G-CSF, and APRIL and positively correlated with plasma RANTES and MMP1. At week 0, the frequency of blood CD4−CD8+ were positively correlated with CRP and BAFF.

Conclusion:

CD4dimCD8bright T cells are associated with some anti-inflammatory properties, whereas CD4−CD8+ T cells may contribute to inflammation and injury. Assessing the contrast between these two cell populations in neuroHIV may inform targeted therapeutic intervention to reduce neuroinflammation and associated neurocognitive impairment.
Perception and Emotional Experiences of Infant Feeding Among Women Living With HIV in a High-Income Setting: A Longitudinal Mixed Methods Study
Authors: Moseholm Ellen , Fetters Michael D. , Aho Inka , Mellgren Åsa , Johansen Isik S. , Katzenstein Terese L. , Pedersen Gitte , Storgaard Merete , Weis Nina
Published: October 2023

Background:

The recommendation of breastfeeding avoidance for women living with HIV in high-income settings may be influenced by cultural beliefs and come at an emotional cost. This multicenter, longitudinal, convergent mixed methods study aimed to compare differences in attitudes, concerns, and experiences surrounding breastfeeding in women living with HIV of Nordic and non-Nordic origin.

Setting:

High-income setting.

Methods:

Pregnant women living with HIV in the Nordic countries Denmark, Finland, and Sweden were recruited in 2019–2020. Quantitative data on attitudes surrounding infant feeding were assessed using the Positive Attitudes Concerning Infant Feeding questionnaire completed in the third trimester (T1), and 3 (T2) and 6 (T3) months postpartum. Women who completed the survey were also invited to participate in semistructured interviews at T1 and T3. The findings from the quantitative survey and qualitative interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the data sets and to draw metainferences.

Results:

In total, 44 women completed the survey, of whom 31 also participated in qualitative interviews. The merged analyses identified three overarching domains representing commonalities across the quantitative and qualitative data: emotional impact, justifying not breastfeeding, and coping strategies. Not being able to breastfeed was emotionally challenging. Cultural expectations influenced the women's experiences and the strategies they used to justify their infant feeding choice.

Conclusions:

For women living with HIV in Nordic countries not breastfeeding was a complex, multilayered process substantially influenced by social and cultural expectations.
Brief Report: Ryan White Participation Increased the Prevalence of COVID-19 Vaccination Among People Living with HIV in Michigan
Authors: Convery Christine , Diesel Jill , Brantley Antoine , Miller Jennifer , Karram Sarah
Published: October 2023

Introduction:

People living with HIV (PLWH) have higher prevalence of adverse COVID-19 outcomes, and many reside in socially vulnerable communities. Our aim was to evaluate how engagement in HIV care may increase vaccination likelihood.

Methods:

Michigan HIV surveillance data were extracted from the Enhanced HIV/AIDS Reporting System and matched at the person-level to COVID-19 vaccination records from the Michigan Care Improvement Registry (through December 31, 2021 [n = 15,537]). Based on residential census tract, we classified PLWH into quartiles (<25th percentile [least vulnerable], 25th to <50th, 50th to <75th, ≥75th [most vulnerable]) of the 2018 CDC Social Vulnerability Index. Using log binomial regression, we estimated the relative prevalence of COVID-19 vaccine series initiation among PLWH by quartile of social vulnerability and Ryan White participation; models were adjusted for covariates.

Results:

By December 31, 2021, 67% of PLWH in Michigan had initiated a COVID-19 vaccine series; 47% resided in an area deemed most vulnerable and 54% had participated in Ryan White services. Compared with PLWH in the most vulnerable quartile, those who resided in least vulnerable quartiles had higher prevalence of vaccine initiation (Prevalence Ratio [95% Confidence Interval]: 1.67 [1.50 to 1.86]). Participants in Ryan White had greater prevalence of initiation (1.52 [1.42 to 1.62]) compared with those who were not participants; initiation remained higher when adjusted for covariates including social vulnerability quartile.

Conclusions:

Ryan White participation was associated with increased COVID-19 vaccine initiation regardless of community-level vulnerability. Wraparound services may be key in vaccine promotion interventions in this vulnerable population.
Bone SPECT/CT in Advanced Diffuse Tenosynovial Giant Cell Tumor of the Wrist
Authors: Lampe Nina A. , Strobel Klaus , Pallaver Armin , Hany Thomas F. , Grünig Hannes
Published: October 2023

Tenosynovial giant cell tumor, previously known as pigmented villonodular synovitis, is a benign low-grade fibrohistiocytic proliferation with hemosiderin deposits in synovial joints. Mostly affecting the knee, it can also manifest in other synovial joints, infrequently also in the wrist. Tenosynovial giant cell tumor typically causes intense radionuclide uptake in all phases in planar bone scintigraphy, making a differentiation from other bone tumors or osteomyelitis difficult, especially in cases associated with extensive bone destruction. We present a case of an unusually advanced and extended tenosynovial giant cell tumor of the wrist in bone scintigraphy, SPECT/CT, radiograph, and MRI.
The genome of a steinernematid-associated Pseudomonas piscis bacterium encodes the biosynthesis of insect toxins
Authors: Awori Ryan Musumba , Hendre Prasad , Amugune Nelson O.
Published: October 2023

Several species of soil-dwelling Steinernema nematodes are used in the biocontrol of crop pests, due to their natural capacity to kill diverse lepidopteran species. Although this insect-killing trait is known to be augmented by the nematodes’

Xenorhabdus

endosymbionts, the role of other steinernematid-associated bacterial genera in the nematode lifecycle remains unclear. This genomic study aimed to determine the potential of

Pseudomonas piscis

to contribute to the entomopathogenicity of its Steinernema host. Insect larvae were infected with three separate Steinernema cultures. From each of the three treatments, the prevalent bacteria in the haemocoel of cadavers, four days post-infection, were isolated. These three bacterial isolates were morphologically characterised. DNA was extracted from each of the three bacterial isolates and used for long-read genome sequencing and assembly. Assemblies were used to delineate species and identify genes that encode insect toxins, antimicrobials, and confer antibiotic resistance. We assembled three complete genomes. Through digital DNA–DNA hybridisation analyses, we ascertained that the haemocoels of insect cadavers previously infected with Steinernema sp. Kalro, Steinernema sp. 75, and Steinernema sp. 97 were dominated by

Xenorhabdus griffiniae

Kalro,

Pseudomonas piscis

75, and

X. griffiniae

97, respectively.

X. griffiniae

Kalro and

X. griffiniae

97 formed a subspecies with other

X. griffiniae

symbionts of steinernematids from Kenya.

P. piscis

75 phylogenetically clustered with pseudomonads that are characterised by high insecticidal activity. The

P. piscis

75 genome encoded the production pathway of insect toxins such as orfamides and rhizoxins, antifungals such as pyrrolnitrin and pyoluteorin, and the broad-spectrum antimicrobial 2,4-diacetylphloroglucinol. The

P. piscis

75 genome encoded resistance to over ten classes of antibiotics, including cationic lipopeptides. Steinernematid-associated

P. piscis

bacteria hence have the biosynthetic potential to contribute to nematode entomopathogenicity.
Development of Recombinant Proteins for Vaccine Candidates Against Serotype O and A of Foot and Mouth Disease Virus in Bangladesh
Authors: Akter Salma , Rahman M. Shaminur , Islam M. Rafiul , Akther Masuda , Anjume Humaira , Marjia Mafruha , Rahaman Md Mizanur , Hossain M Anwar , Sultana Munawar
Published: October 2023

Frequent vaccine failure leading to recurrent outbreaks of Foot-and-Mouth Disease (FMD) in livestock populations necessitates the development of a customizable vaccine platform comprising potential antigenic determinants of circulating lineages of FMD viruses. Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse FMD Virus (FMDV) strains. Among seven recognized serotypes, only serotypes O and A are dominantly circulating in Bangladesh and neighboring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages of FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse genotypes of FMDV serotypes O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for existing serotypes O and A of FMDV in Bangladesh and surrounding territories.
Comparative genomic analysis of Chryseobacterium species: deep insights into plant-growth-promoting and halotolerant capacities
Authors: Jung Hyejung , Lee Duyoung , Lee Seungchul , Kong Hee Jeong , Park Jungwook , Seo Young-Su
Published: October 2023

Members of the genus

Chryseobacterium

have attracted great interest as beneficial bacteria that can promote plant growth and biocontrol. Given the recent risks of climate change, it is important to develop tolerance strategies for efficient applications of plant-beneficial bacteria in saline environments. However, the genetic determinants of plant-growth-promoting and halotolerance effects in

Chryseobacterium

have not yet been investigated at the genomic level. Here, a comparative genomic analysis was conducted with seven

Chryseobacterium

species. Phylogenetic and phylogenomic analyses revealed niche-specific evolutionary distances between soil and freshwater

Chryseobacterium

species, consistent with differences in genomic statistics, indicating that the freshwater bacteria have smaller genome sizes and fewer genes than the soil bacteria. Phosphorus- and zinc-cycling genes (required for nutrient acquisition in plants) were universally present in all species, whereas nitrification and sulphite reduction genes (required for nitrogen- and sulphur-cycling, respectively) were distributed only in soil bacteria. A pan-genome containing 6842 gene clusters was constructed, which reflected the general features of the core, accessory and unique genomes. Halotolerant species with an accessory genome shared a Kdp potassium transporter and biosynthetic pathways for branched-chain amino acids and the carotenoid lycopene, which are associated with countermeasures against salt stress. Protein–protein interaction network analysis was used to define the genetic determinants of

Chryseobacterium salivictor

NBC122 that reduce salt damage in bacteria and plants. Sixteen hub genes comprised the aromatic compound degradation and Por secretion systems, which are required to cope with complex stresses associated with saline environments. Horizontal gene transfer and CRISPR–Cas analyses indicated that

C. salivictor

NBC122 underwent more evolutionary events when interacting with different environments. These findings provide deep insights into genomic adaptation to dynamic interactions between plant-growth-promoting

Chryseobacterium

and salt stress.
EEG Based Oculographic Analysis of Epileptic Nystagmus
Authors: Acar Aybuke , Zampino Anthony , Fotedar Neel
Published: October 2023

Epileptic nystagmus (EN) is a subtle seizure semiology, most commonly seen in seizures originating in the posterior cortical regions. EN is broadly categorized into type I and type II. Type I EN consists of contralateral repetitive saccadic eye movements alternating with post-saccadic slow drifts with an overall contralateral deviation. Type II EN is characterized by ipsilateral slow drift alternating with contralateral corrective saccades. In this article, we report a method to perform oculographic analysis of eye movements using EEG only. We used this method to classify the type of EN in three patients with parieto-occipital seizures.

In all three patients, the ictal EEG demonstrated repetitive saccadic eye movements, directed contralateral to the seizure onset zone. With prolonged time constant, we were able to identify this eye movement pattern as EN with distinct slow and fast phases. We were able to further characterize the type of EN as type I and type II. In all three patients, the direction of EN (direction of fast phase or saccades) was contralateral to the seizure onset zone.

EN can be easily missed on video-electroencephalography (vEEG) recordings because of various reasons. Our study demonstrates a systematic method of eye movement analysis on EEG, which can be used to not only identify EN as seizure semiology but also classify it, without requiring additional electrodes.
Investigating Racial Disparities in Drug Prescriptions for Patients with Endometriosis
Authors: Kashyap Aparajita , Aziz Maryam , Sun Tony Y. , Lipsky-Gorman Sharon , Opoku-Anane Jessica , Elhadad Noémie
Published: October 2023

Background

Endometriosis is a chronic disease with a long time to diagnosis and several known comorbidities that requires a range of treatments including of pain management and hormone-based medications. Racial disparities specific to endometriosis treatments are unknown.

Objective

We aim to investigate differences in patterns of drug prescriptions specific to endometriosis management in Black and White patients prior to diagnosis and after diagnosis of endometriosis and compare these differences to racial disparities established in the general population.

Study Design

We conduct a retrospective cohort study using observational health data from the IBM MarketScan® Multi-state Medicaid dataset. We identify a cohort of endometriosis patients consisting of women between the ages of 15 and 49 with an endometriosis-related surgical procedure and a diagnosis code for endometriosis within 30 days of this procedure. Cohort is further restricted to patients with at least 3 years of continuous observation prior to diagnosis.

We identify a non-endometriosis cohort of women between the ages of 15 and 49 with no endometriosis diagnosis and at least 1 year of continuous observation. We compare prevalence of prescriptions across selected drug classes for Black vs. White endometriosis patients. We further examine prevalence differences in the non-endometriosis cohort and prevalence differences pre- and post-diagnosis in the endometriosis cohort.

Results

The endometriosis cohort comprised 16,372 endometriosis patients (23.3% Black, 66.0% White). Of the 28 drug classes examined, 17 were prescribed significantly less in Black patients compared to 21 in non-endometriosis cohort (n=3,663,904), and 4 were prescribed significantly more in Black patients compared to 6 in the non-endometriosis cohort. Of the 17 drugs prescribed more often in White patients, 16 have larger disparities pre-diagnosis than post-diagnosis.

Conclusions

Our analysis identified significant differences in medication prescriptions between White and Black patients with endometriosis, notably in hormonal treatments, pain management, and treatments for common endometriosis co-morbidities. Racial disparities in drug prescriptions are well established in healthcare, and better understanding these disparities in the specific context of chronic reproductive conditions and chronic pain is important for increasing equity in drug prescription practices.
Integration of Expression QTLs with fine mapping via SuSiE
Authors: Zhang Xiangyu , Jiang Wei , Zhao Hongyu
Published: October 2023

Genome-wide association studies (GWASs) have achieved remarkable success in associating thousands of genetic variants with complex traits. However, the presence of linkage disequilibrium (LD) makes it challenging to identify the causal variants. To address this critical gap from association to causation, many fine mapping methods have been proposed to assign well-calibrated probabilities of causality to candidate variants, taking into account the underlying LD pattern. In this manuscript, we introduce a statistical framework that incorporates expression quantitative trait locus (eQTL) information to fine mapping, built on the sum of single-effects (SuSiE) regression model. Our new method, SuSiE2, connects two SuSiE models, one for eQTL analysis and one for genetic fine mapping. This is achieved by first computing the posterior inclusion probabilities (PIPs) from an eQTL-based SuSiE model with the expression level of the candidate gene as the phenotype. These calculated PIPs are then utilized as prior inclusion probabilities for risk variants in another SuSiE model for the trait of interest. By leveraging eQTL information, SuSiE2enhances the power of detecting causal SNPs while reducing false positives and the average size of credible sets by prioritizing functional variants within the candidate region. The advantages of SuSiE2over SuSiE are demonstrated by simulations and an application to a single-cell epigenomic study for Alzheimer’s disease. We also demonstrate that eQTL information can be used by SuSiE2to compensate for the power loss because of an inaccurate LD matrix.

Author summary

Genome-wide association studies (GWASs) have proven powerful in detecting genetic variants associated with complex traits. However, there are challenges in distinguishing the causal variants from other variants strongly correlated with them. To better identify causal SNPs, many fine mapping methods have been proposed to assign well-calibrated probabilities of causality to candidate variants. We introduce a statistical framework that incorporates expression quantitative trait locus (eQTL) information to fine mapping, which can improve the accuracy and efficiency of association studies by prioritizing functional variants within the risk genes before evaluating the causation. Our new fine mapping framework, SuSiE2, connects two sum of single-effects (SuSiE) models, one for eQTL analysis and one for genetic fine mapping. The posterior inclusion probabilities from an eQTL-based SuSiE model are utilized as prior inclusion probabilities for risk variants in another SuSiE model for the trait of interest. Through simulations and a real data analysis focused on Alzheimer’s disease, we demonstrate that SuSiE2improves fine mapping results by simultaneously increasing statistical power, controlling the type I error rate, and reducing the average size of credible sets.
Excitatory and Inhibitory neurochemical markers of anxiety in young females
Authors: Johnstone Nicola , Kadosh Kathrin Cohen
Published: October 2023

Between the ages of 10-25 years the maturing brain is sensitive to a multitude of changes, including neurochemical variations in metabolites. Of the different metabolites, gamma-aminobutyric acid (GABA) has long been linked neurobiologically to anxiety symptomology, which begins to manifest in adolescence. To prevent persistent anxiety difficulties into adulthood, we need to understand the maturational trajectories of neurochemicals and how these relate to anxiety levels during this sensitive period. We used magnetic resonance spectroscopy in a sample of younger (aged 10-11) and older (aged 18-25) females to estimate GABA and glutamate levels in brain regions linked to emotion regulation processing, as well as a conceptually distinct control region. Within the Bayesian framework, we found that GABA increased, and glutamate decreased with age, negative associations between anxiety and glutamate and GABA ratios in the dorsolateral prefrontal cortex, and a positive relationship of GABA with anxiety levels. The results support the neural over-inhibition hypothesis of anxiety based on GABAergic activity.
Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing
Authors: Sritong Navaporn , Ngo Winston Wei , Ejendal Karin F. K. , Linnes Jacqueline C.
Published: October 2023

Background

The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive analytical sensitivity in the lab, the assessment of clinical accuracy with IACs is often overlooked. In some cases, the IACs were run spatially, complicating assay workflow. Therefore, the multiplex assay for pathogen and IAC is needed.

Results

We developed a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for saliva samples, a non-invasive and simple collected specimen for POC NAATs. The ORF1ab gene of SARS-CoV-2 was used as a target and a human 18S ribosomal RNA in human saliva was employed as an IAC to ensure clinical reliability of the RT-LAMP assay. The optimized assay could detect SARS-CoV-2 viral particles down to 100 copies/μL of saliva within 30 minutes without RNA extraction. The duplex RT-LAMP for SARS-CoV-2 and IAC is successfully amplified in the same reaction without cross-reactivity. The valid results were easily visualized in triple-line lateral flow immunoassay, in which two lines (flow control and IAC lines) represent valid negative results and three lines (flow control, IAC, and test line) represent valid positive results. This duplex assay demonstrated a clinical sensitivity of 95%, specificity of 100%, and accuracy of 96% in 30 clinical saliva samples.

Significance

IACs play a crucial role in ensuring user confidence with respect to the accuracy and reliability of at-home and POC molecular diagnostics. We demonstrated the multiplex capability of SARS-COV-2 and human18S ribosomal RNA RT-LAMP without complicating assay design. This generic platform can be extended in a similar manner to include human18S ribosomal RNA IACs into different clinical sample matrices.
Cooperativity, information gain, and energy cost during early LTP in dendritic spines
Authors: Karbowski Jan , Urban Paulina
Published: October 2023

We investigate a mutual relationship between information and energy during early phase of LTP induction and maintenance in a large-scale system of mutually coupled dendritic spines with discrete internal states and probabilistic dynamics within the framework of nonequilibrium stochastic thermodynamics. In order to analyze this computationally intractable stochastic multidimensional system, we introduce a pair approximation, which allows us to reduce the spine dynamics into a lower dimensional manageable system of closed equations. It is found that the rates of information gain and energy attain their maximal values during an initial period of LTP (i.e. during stimulation), and after that they recover to their baseline low values, as opposed to a memory trace that lasts much longer. This suggests that learning phase is much more energy demanding than the memory phase. We show that positive correlations between neighboring spines increase both a duration of memory trace and energy cost during LTP, but the memory time per invested energy increases dramatically for very strong positive synaptic cooperativity, suggesting a beneficial role of synaptic clustering on memory duration. In contrast, information gain after LTP is the largest for negative correlations, and energy efficiency of that information generally declines with increasing synaptic cooperativity. We also find that dendritic spines can use sparse representations for encoding of long-term information, as both energetic and structural efficiencies of retained information and its lifetime exhibit maxima for low fractions of stimulated synapses during LTP. Moreover, we find that such efficiencies drop significantly with increasing the number of spines. In general, our stochastic thermodynamics approach provides a unifying framework for studying, from first principles, information encoding and its energy cost during learning and memory in stochastic systems of interacting synapses.
Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors
Authors: Nigam AkshatKumar , Hurley Matthew F. D. , Li Fengling , Konkoľová Eva , Klíma Martin , Trylčová Jana , Pollice Robert , Çinaroğlu Süleyman Selim , Levin-Konigsberg Roni , Handjaya Jasemine , Schapira Matthieu , Chau Irene , Perveen Sumera , Ng Ho-Leung , Ümit Kaniskan H. , Han Yulin , Singh Sukrit , Gorgulla Christoph , Kundaje Anshul , Jin Jian , Voelz Vincent A. , Weber Jan , Nencka Radim , Boura Evzen , Vedadi Masoud , Aspuru-Guzik Alán
Published: October 2023

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. A crucial viral protein, the non-structural protein 14 (nsp14), catalyzes the methylation of viral RNA and plays a critical role in viral genome replication and transcription. Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of potential nsp14 inhibitors by leveraging virtual screening and the NCI open compound collection, which contains 250,000 freely available molecules for researchers worldwide. The introduced pipeline provides a cost-effective and efficient approach for early-stage drug discovery by allowing researchers to evaluate promising molecules without incurring synthesis expenses. Our pipeline successfully identified seven promising candidates after experimentally validating only 40 compounds. Notably, we discovered NSC620333, a compound that exhibits a strong binding affinity to nsp14 with a dissociation constant of 427 ± 84 nM. In addition, we gained new insights into the structure and function of this protein through molecular dynamics simulations. We identified new conformational states of the protein and determined that residues Phe367, Tyr368, and Gln354 within the binding pocket serve as stabilizing residues for novel ligand interactions. We also found that metal coordination complexes are crucial for the overall function of the binding pocket. Lastly, we present the solved crystal structure of the nsp14-MTase complexed with SS148 (PDB:8BWU), a potent inhibitor of methyltransferase activity at the nanomolar level (IC50value of 70 ± 6 nM). Our computational pipeline accurately predicted the binding pose of SS148, demonstrating its effectiveness and potential in accelerating drug discovery efforts against SARS-CoV-2 and other emerging viruses.
Specificity and promiscuity of JAK recruitment regulates pleiotropy of cytokine-receptor signaling
Authors: Zoler Eyal , Meyer Thomas , Bellón Junel Sotolongo , Sun Boyue , Piehler Jacob , Schreiber Gideon
Published: October 2023

Promiscuous binding of different Janus kinases (JAKs) to class I/II cytokine receptors has been reported, yet its role in signaling is unclear. To systematically explore JAK pairing in type I interferon (IFN-I) signaling, we generated an artificial IFN-I receptor (AIR) by replacing the extracellular domains of IFNAR1 and IFNAR2 with anti mEGFP and mCherry nanobodies. The heterodimeric AIR restored near-native IFN-I activity, while the homomeric variant of IFNAR2 (AIR-dR2) initiated much weaker signaling despite harboring docking sites for signal transducer and activator of transcription (STAT) proteins. AIR-dR1 was signaling inactive, yet, pulldown uncovered its ICD to bind both TYK2 and JAK1. To further investigate the roles of JAKs on the receptors, knockout (KO) JAK1, JAK2, TYK2, and JAK2/TYK2 were generated. JAK1 KO led to complete loss of IFN-I signaling, which was partially restored by TYK2 overexpression. TYK2 KO cells retained partial activity, which was elevated by JAK1 overexpression, suggesting both JAKs to partially substitute each other. Conversely, JAK2 KO only moderately impacted the biological activity of IFN-Is, even in JAK2/TYK2 KO cells. Live cell micropatterning confirmed promiscuous binding of JAK1, JAK2 and TYK2 to IFNAR1 and IFNAR2, in line with an AlphaFold model that shows JAKs interchangeability on IFNAR ICDs. Similar promiscuity of JAK binding was observed for TPOR and GHR but not EPOR, accompanied by different downstream signaling activity. The competitive binding of JAKs to cytokine receptors together with the highly diverse absolute and relative JAK expression levels can account for cell type-dependent signaling pleiotropy observed for cytokine receptors.

One Sentence Summary

Promiscuous and interchangeable binding of JAKs to cytokine receptors enables cell type-specific pleiotropic signaling.
Comprehensive isoform-level analysis reveals the contribution of alternative isoforms to venom evolution and repertoire diversity
Authors: Ye Xinhai , He Chun , Yang Yi , Sun Yu H. , Xiong Shijiao , Chan Kevin C. , Si Yuxuan , Xiao Shan , Zhao Xianxin , Lin Haiwei , Mei Yang , Yao Yufeng , Ye Gongyin , Wu Fei , Fang Qi
Published: October 2023

Animal venom systems have emerged as valuable models for investigating how novel polygenic phenotypes may arise from gene evolution by varying molecular mechanisms. However, a significant portion of venom genes produce alternative mRNA isoforms that have not been extensively characterized, hindering a comprehensive understanding of venom biology. In this study, we present a full-length isoform-level profiling workflow integrating multiple RNA sequencing technologies, allowing us to reconstruct a high-resolution transcriptome landscape of venom genes in the parasitoid waspPteromalus puparum. Our findings demonstrate that more than half of the venom genes generate multiple isoforms within the venom gland. Through mass spectrometry analysis, we confirm that alternative splicing contributes to the diversity of venom proteins, acting as a mechanism for expanding the venom repertoire. Notably, we identified seven venom genes that exhibit distinct isoform usages between the venom gland and other tissues. Furthermore, evolutionary analyses of venomserpin3andorcokininfurther reveal that the co-option of an ancient isoform and a newly evolved isoform, respectively, contributes to venom recruitment, providing valuable insights into the genetic mechanisms driving venom evolution in parasitoid wasps. Overall, our study presents a comprehensive investigation of venom genes at the isoform level, significantly advancing our understanding of alternative isoforms in venom diversity and evolution and setting the stage for further in-depth research on venoms.
The high of higher education: interactivity its influence and effectiveness on virtual communities
Authors: Srivastava Kajal , Siddiqui Masood H. , Kaurav Rahul Pratap Singh , Narula Sumit , Baber Ruturaj
Published: October 2023

Purpose

Amidst the COVID-19 pandemic, education has shifted to online teaching and learning. Interactivity is a crucial tool used to make online education effective. This study empirically examines the role of interactivity in higher education and its influence on students' behavioral outcomes, specifically focusing on soft skills and personality upgradation.

Design/methodology/approach

A quasi-experimental research design was carried out for post-graduate students undergoing a business communication course from four major institutions. For analysis, t-test, confirmatory factor analysis (CFA) and partial least squares structural equation modeling (PLS-SEM) have been employed. Experimental research has established the causal relationship between interactivity, personality and soft skill upgradation (SSU).

Findings

It was found that the theoretical structural model has a rational model-fit validity. Resultantly, practitioners may use prior knowledge of virtual community (VC) members to enhance web interactivity, thereby increasing social identity and social bonds in a group for more meaningful and effective delivery of online courses.

Research limitations/implications

The major limitations lie in its context-dependent nature, predominantly influenced by the pandemic-induced mandatory online learning. The study's cross-sectional design also inhibits its ability to assess goal-directed behaviors over time, necessitating further longitudinal research.

Originality/value

The study is one of the pioneering pieces of research that examines the role of pre-defined grouping and enhanced web interactivity in VCs in the context of online learning, especially during the COVID-19 pandemic. Integrating theories of web interactivity, social bond theory (SBT) and social identity theory (SIT) provides a novel understanding of cognitive and social influences that drive meaningful online discussions and their impacts on knowledge enhancement and personality development. Its findings have implications for the design of effective online learning environments and e-learning pedagogy, contributing to the growing domain of information and communication technology (ICT)-enabled education.
A subgrid model with multiple relaxation time for lattice Boltzmann method based on the Cartesian grid
Authors: Qiu Aoxiang , Sang Weimin , Zhou Feng , Li Dong
Published: October 2023

Purpose

The paper aims to expand the scope of application of the lattice Boltzmann method (LBM), especially in the field of aircraft engineering. The traditional LBM is usually applied to incompressible flows at a low Reynolds number, which is not sufficient to satisfy the needs of aircraft engineering. Devoted to tackling the defect, the paper proposes a developed LBM combining the subgrid model and the multiple relaxation time (MRT) approach. A multilayer adaptive Cartesian grid method to improve the computing efficiency of the traditional LBM is also employed.

Design/methodology/approach

The subgrid model and the multilayer adaptive Cartesian grid are introduced into MRT-LBM for simulations of incompressible flows at a high Reynolds number. Validated by several typical flow simulations, the numerical methods in this paper can efficiently study the flows under high Reynolds numbers.

Findings

Some numerical simulations for the lid-driven flow of cavity, flow around iced GLC305, LB606b and ONERA-M6 are completed. The paper presents the investigation results, indicating that the methods are accurate and effective for the separated flow after icing.

Originality/value

LBM is developed with the addition of the subgrid model and the MRT method. A numerical strategy is proposed using a multilayer adaptive Cartesian grid method and its treatment of boundary conditions. The paper refers to innovative algorithm developments and applications to the aircraft engineering, especially for iced wing simulations with flow separations.
Aligning company's business goals, social responsibility and employee happiness in the banking industry
Authors: Wulandari Nuri , Gantara Audyan Tri , Wijayanti Retno Wahyuni
Published: October 2023

Purpose

This study aims to investigate the role of corporate social responsibility (CSR) to increase the happiness of employees and in the same time contributing to the goals of organization. It is argued that a type of CSR, namely cause-related marketing (CrM) can drive employee happiness at work (HaW) through employee's cause involvement (CI). CrM is activity form of collaboration between companies and nonprofit organizations to sell products or services and donate some portion of the sales to support a cause. The study is needed to understand this CSR action and its effects, in particular on employees as company stakeholders.

Design/methodology/approach

The study was conducted by survey questionnaire with sample of 216 respondents employed by a state-owned bank in Indonesia which active in CSR actions. Analysis conducted using PLS SEM method and SMART PLS software.

Findings

The finding confirms that CrM does indeed have an effect on employee happiness, especially if employee's cause involvement in the CrM is evident. The result suggested that CrM initiatives should be promoted together with employee's cause involvement with the program because this will increase the general level of HaW in the organization.

Originality/value

The study is unique because of its effort in aligning three aspects; employee happiness, social responsibility while still takes account for company's business goals. It also addresses a rarely explored yet crucial area in a highly stressed environment: the financial industry in a pandemic situation.
Exploring belonging through photovoice: examining the impact of space design on diverse student populations in an academic library
Authors: Poljak Leslie , Webster Berenika M. , Kiner Renee
Published: October 2023

Purpose

This paper aims to uncover characteristics of physical spaces that evoke feelings of welcome and belonging in a diverse student population in an academic library.

Design/methodology/approach

The photovoice method was used to allow research participants an active role in shaping research questions and collecting and analyzing data.

Findings

The research reveals that space design significantly influences students' feelings of physical safety, emotional well-being and safety and ownership (or sense of belonging) in academic library spaces, thereby emphasizing the importance of considering space design in promoting student well-being and inclusiveness.

Originality/value

This research used photovoice methodology to engage underrepresented student communities in providing input into the design of library spaces.
Hotel employees’ intention to stay through psychological contract fulfillment and positive emotions in post-lockdown era
Authors: Mehta (Karani) Anushree , Mall Sunita , Kothari Tanvi , Deshpande Revati
Published: October 2023

Purpose

The study aims to investigate hotel employees’ intentions to stay in industry with the mediating role of psychological contract fulfilment (PCF) and moderating role of positive emotions and position held (frontline employees vs managers) in post-lockdown era.

Design/methodology/approach

The study has followed quantitative approach following the cross-sectional design. 414 respondents of hotel industry were contacted via online and offline method. The data was analysed using partial least square method using SmartPLS 3.0.

Findings

The findings suggest that perceived organizational support and supervisor trust had a good impact on psychological contract fulfilment and contributed positively to psychological empowerment. Additionally, psychological empowerment positively impacted psychological well-being and psychological well-being positively impacted intention to stay in hotel industry. PCF positively mediated the relationship between organizational support, trust in supervisor and psychological empowerment. Positive emotions positively moderated the relationship between PCF and psychological empowerment. Multi-group analysis revealed that the managers and frontline employees perceived the PCF and psychological well-being differently.

Originality/value

To the best of the authors’ knowledge, this study is one of the few to explore the intention to stay in hotel industry by integrating social exchange theory, organization support theory and broaden-and-build theory post lockdown circumstances.
Seismic hazard assessment studies based on developed deterministic and probabilistic approaches for the central-east of Iran region
Authors: Foyouzati Amin , Rahimzadeh Rofooei Fayaz
Published: October 2023

Purpose

This Study aims to present the seismic hazard assessment of the earthquake-prone eastern of Iran that has become more important due to its growing economic importance. Many cities in this region have experienced life and financial losses due to major earthquakes in recent years. Thus, in this study the seismic hazard maps and curves, and site-specific spectrums were obtained by using probabilistic approaches for the region.

Design/methodology/approach

The seismotectonic information, seismicity data and earthquake catalogues were gathered, main active seismic sources were identified and seismic zones were considered to cover the potential active seismic regions. The seismic model based on logic tree method used two seismic source models, two declustered catalogues, three choices for earthquake recurrence parameters and maximum considered earthquakes and four ground motion predicting (attenuation) models (GMPE).

Findings

The results showed a wide range of seismic hazards levels in the study region. The peak ground acceleration (PGAs) for 475 years returns period ranges between 0.1 g in the north-west part of the region with low seismic activity, to 0.52 g in the south-west part with high levels of seismicity. The PGAs for a 2,475-year period, also ranged from 0.12 to 0.80 g for the same regions. The computed hazard results were compared to the acceptable level of seismic hazard in the region based on Iran seismic code.

Originality/value

A new probabilistic approach has been developed for obtaining seismic hazard maps and curves; these results would help engineers in design of earthquake-resistant structures.
Evaluating the purchasing behavior of organic food among Chinese consumers
Authors: Huo Haiyan , Sh. Ahmad Fauziah , Teoh Bryan
Published: October 2023

Purpose

This study aims to identify the key factors that influence the intention and behavior of Chinese consumers toward purchasing organic food. The extended theory of planned behavior (TPB) model is adopted as the underlying theory to explore the relationship between attitudes (ATT), subjective norms (SN) and perceived behavioral control (PBC) on consumers’ intention and behavior to buy organic food. Trust (TR) and the moderating role of short food supply chain preferences (SFSCPs) were integrated to address the research gap.

Design/methodology/approach

Three hundred three questionnaire responses were received from organic food buyers in China using a convenience sampling method. Structural equation modeling was used to analyze the data and to examine the relationship between the various constructs.

Findings

The results demonstrated that the purchase intention (PI) of Chinese consumers correlates positively with ATT, SN, PBC and TR. Additionally, the results show that consumers’ SFSCPs positively moderate the relationship between PI and purchase behavior (PB).

Practical implications

The findings of this study provide valuable insights for marketers to develop compelling messages that evoke positive ATT, establish consumer TR and integrate short food supply chains to drive PB. The study can also be useful to policymakers and other supply chain participants.

Social implications

An increased understanding of the factors influencing Chinese organic food consumption can contribute to promoting healthier food choices, supporting sustainable agriculture and fostering environmentally friendly consumption habits.

Originality/value

This research contributes to the existing pool of knowledge by incorporating TR into the conventional TPB. The study also introduces SFSCP as a moderating variable on the relationship between PI and PB.
Distribution, drivers and restoration priorities of plant invasions in India
Authors: Mungi Ninad Avinash , Qureshi Qamar , Jhala Yadvendradev V.
Published: October 2023

Biological invasions threaten biodiversity and human wellbeing, with developing tropical countries being more vulnerable. Despite the urgency to reduce impacts of invasions, management interventions are constrained by unavailability of timely information on invasive species occurrence, potential drivers and restoration priorities. Generating this information at biogeographic scales can be costly, unless integrated with multi‐objective biodiversity monitoring.

Invasive plant monitoring is integrated with India's national‐scale tiger population assessment, wherein natural areas are sampled at 25 km2 scale to inventory plants. In 2018, a total of 158,979 plots were sampled covering ~358,550 km2. We used 206,393 locations of high concern invasive plants to model their distribution using socio‐ecological covariates and identify potential drivers of invasions. Considering the invasion magnitude and financial constraints in management, we further identified priority restorations sites at national‐scale to maximise biodiversity outcomes.

High‐concern invasive plants were recorded from ~254,880 km2 (72% sampled area) and modelled to invade in total ~750,905 km2 (66%) Indian natural systems. While open and deciduous ecosystems were the highest invaded by woody plants, areas with extreme climate and less anthropic pressure were least invaded. Since managing invasions across their range seemed futile due to costly (~13.5 billion USD for one‐time management) and ineffective strategies, restoration priority was assigned to least invaded areas (11% protected areas, 23% multi‐use) to maximise biodiversity returns.

Synthesis and applications: India implemented national‐scale invasive plant monitoring by integrating it with the umbrella project on tiger assessment. Embarking on this big data, we show that two‐thirds of India's natural areas are under multiple plant invasions, owing to the legacy of anthropogenic modifications. Our study offers a restoration priority model, empowering policymakers to devise adaptive strategies for restoring invaded biomes and maximizing biodiversity returns.