bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting Nurse Manager Professional Well-being
Authors: Mericle Jane , Haut Catherine , Jones Pam
Published: December 2022

Healthcare delivery is increasingly complex, with frontline leader roles, especially the nurse manager (NM), pivotal for success. This role is highly stressful, often leading to burnout influencing job satisfaction and leadership effectiveness. A quality improvement project, including preintervention and postintervention assessment with a focused improvement event for NMs, in a large children's hospital was completed. Organization strategies to support professional well-being and enhance support for the NMs were identified and implemented.
Vitamin A-treated natural killer cells reduce interferon-gamma production and support regulatory T cell differentiation
Authors: Jeong Mingeum , See Jia-Xiang , De La Torre Carolina , Cerwenka Adelheid , Stojanovic Ana
Published: December 2022

Natural killer (NK) cells are innate cytotoxic lymphocytes that contribute to immune responses against stressed, transformed or infected cells. NK cell effector functions are regulated by microenvironmental factors, including cytokines, metabolites and nutrients. Vitamin A is an essential micronutrient that plays an indispensable role in embryogenesis and development, but was also reported to regulate immune responses. However, the role of vitamin A in regulating NK cell functions remains poorly understood. Here, we show that the most prevalent vitamin A metabolite, all-transretinoic acid (atRA), induces transcriptional and functional changes in NK cells leading to altered metabolism and reduced IFN-γ production in response to a wide range of stimuli. atRA-exposed NK cells display a reduced ability to support dendritic cell (DC) maturation and to eliminate immature DCs. Moreover, they support the polarization and proliferation of regulatory T cells. These results imply that in vitamin A-enriched environments, NK cells can acquire regulatory-like functions and might promote tolerogenic immunity and/or immunosuppression.
PADAPT 1.0 – the Pannonian Database of Plant Traits
Authors: Sonkoly Judit , Tóth Edina , Balogh Nóra , Balogh Lajos , Bartha Dénes , Bata Kinga , Bátori Zoltán , Békefi Nóra , Botta-Dukát Zoltán , Bölöni János , Csecserits Anikó , Csiky János , Csontos Péter , Dancza István , Deák Balázs , Dobolyi Zoltán Konstantin , E-Vojtkó Anna , Gyulai Ferenc , Hábenczyus Alida Anna , Henn Tamás , Horváth Ferenc , Höhn Mária , Jakab Gusztáv , Kelemen András , Király Gergely , Kis Szabolcs , Kovacsics-Vári Gergely , Kun András , Lehoczky Éva , Lengyel Attila , Lhotsky Barbara , Löki Viktor , Lukács Balázs András , Matus Gábor , McIntosh-Buday Andrea , Mesterházy Attila , Miglécz Tamás , Molnár V. Attila , Molnár Zsolt , Morschhauser Tamás , Papp László , Pósa Patrícia , Rédei Tamás , Schmidt Dávid , Szmorad Ferenc , Takács Attila , Tamás Júlia , Tiborcz Viktor , Tölgyesi Csaba , Tóth Katalin , Tóthmérész Béla , Valkó Orsolya , Virók Viktor , Wirth Tamás , Török Péter
Published: December 2022

We present PADAPT 1.0, the Pannonian Database of Plant Traits which relies on regional data sources and integrates existing data and new measurements on a wide range of traits and attributes of the plant species of the Pannonian Biogeographical Region and makes it freely accessible atwww.padapt.eu. The current version covers the species of the region occurring in Hungary (cc. 90% of the region’s flora) and consists of 126,337 records on 2745 taxa. There are 53 plant attributes in PADAPT 1.0 organised in six major groups: (i) Habitus and strategy, (ii) Reproduction, (iii) Kariology, (iv) Distribution and conservation, (v) Ecological indicator values, and (vi) Leaf traits. By including species of the eastern part of Europe not covered by other databases, PADAPT can facilitate studying the flora and vegetation of the eastern part of the continent. Data collection will continue in the future and the PADAPT team welcomes researchers interested in contributing with data. The main task before an updated version of the database is to include species of the Pannonian region not covered by the current version. In conclusion, although data coverage is far from complete, PADAPT meets the longstanding need for a regional database of the Pannonian flora.
IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling
Authors: Bachus Holly , McLaughlin Erin , Lewis Crystal , Papillion Amber M. , Benveniste Etty N. , Hill Dave Durrell , Rosenberg Alexander F. , Ballesteros-Tato André , León Beatriz
Published: December 2022

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house-dust-mite (HDM)-induced Th2 differentiation and allergic airway inflammation, we show that IL-6 signaling in allergen-specific T cells was required to prevent Th2 development and subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. Importantly, we found that IL-6 turned off IL-2 signaling during early T cell activation and thus inhibited Th2 priming. Mechanistically, we found that IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.
“Sharing my story has been part of my healing process”: how Native women survivors heal from IPV
Authors: Park Susanna Y
Published: December 2022

Four out of five Native women experience intimate partner violence (IPV) in their lifetime. Culture, Native identity, and other socioeconomic factors influence how survivors experience seeking support and healing. High rates of IPV among Native women indicate an urgent public health need to address the long-term implications of being a survivor. This study explores how Native women in California seek healing as survivors of violence through stories shared in Community Circles and Oral Histories supported by collaborations with local Indigenous community organizations in Southern California. Seeking support and healing for Native women survivors of IPV are layered with their identities as Indigenous women, historical oppression, and its resulting intergenerational traumas. Healing from the violence has cultural implications, amplifying the need for community-based systems of support that are Indigenous-centered. For AIAN women survivors of IPV, healing transcends beyond their selves, extending to their families, tribal communities, and future generations. Culturally-rooted systems of support that cultivate Indigenous values of connection and healing are needed.
Identifying B-cell epitopes using AlphaFold2 predicted structures and pretrained language model
Authors: Zeng Yuansong , Wei Zhuoyi , Yuan Qianmu , Chen Sheng , Yu Weijiang , Lu Yutong , Gao Jianzhao , Yang Yuedong
Published: December 2022

Motivation

Identifying the B-cell epitopes is an essential step for guiding rational vaccine development and immunotherapies. Due to experimental approaches being expensive and time-consuming, many computational methods have been designed to assist B-cell epitope prediction. However, existing sequence-based methods have limited performance since they only use contextual features of the sequential neighbors while neglecting structural information.

Results

Based on the recent breakthrough of AlphaFold2 in protein structure prediction, we propose GraphBepi, a novel graph-based model for accurate B-cell epitope prediction. GraphBepi first generates the effective information sequence representations and protein structures from antigen sequences through the pretrained language model and AlphaFold2, respectively. GraphBepi then applies the edge-enhanced deep graph neural network (EGNN) to capture the spatial information from predicted protein structures and leverages the bidirectional long short-term memory neural networks (BiLSTM) to capture long-range dependencies from sequences. The low-dimensional representation learned by EGNN and BiLSTM is then combined to predict B-cell epitopes through a multilayer perceptron. Through comprehensive tests on the curated epitope dataset, GraphBepi was shown to outperform the state-of-the-art methods by more than 5.5% and 44.0% in terms of AUC and AUPR, respectively. We also provide the GraphBepi web server that is freely available athttps://biomed.nscc-gz.cn/apps/GraphBepi.

Availability

The datasets, pre-computed features, source codes, and the pretrained model of GraphBepi are available athttps://github.com/biomed-AI/GraphBepi.

Contact

yangyd25@mail.sysu.edu.cnorgaojz@nankai.edu.cn
Using light for energy: examining the evolution of phototrophic metabolism through synthetic construction
Authors: Peterson Autumn , Baskett Carina , Ratcliff William C. , Burnetti Anthony
Published: December 2022

The origin of phototrophy was pivotal in increasing the size and scale of the biosphere, as it allowed organisms to utilize light-driven energy transport to drive biological processes. Retinalophototrophy, one of two independently evolved phototrophic pathways, consists of a simple system of microbial rhodopsins which have spread broadly through the tree of life via horizontal gene transfer. Here, we sought to determine whetherSaccharomyces cerevisiae, a heterotrophic fungus with no known evolutionary history of phototrophy, can function as a facultative artificial phototroph after acquiring a single rhodopsin gene. We transformedS. cerevisiaeinto a facultative phototroph by inserting a rhodopsin protein fromUstilago maydisinto the yeast vacuole, allowing light to pump protons into the vacuolar compartment, a function typically driven by consuming ATP. We show that yeast with rhodopsins gain a selective advantage when grown under green light, growing more rapidly than their non-phototrophic ancestor or rhodopsin-bearing yeast cultured in the dark. These results underscore the remarkable ease with which rhodopsins may be horizontally transferred even in eukaryotes, providing novel biological function without first requiring evolutionary optimization.
Low-pass Whole Genome Imputation Enables the Characterization of Polygenic Breast Cancer Risk in the Indigenous Arab Population
Authors: Al-Jumaan Mohammed , Chu Hoyin , Al-Sulaiman Abdullah , Camp Sabrina Y. , Han Seunghun , Gillani Riaz , Al Marzooq Yousef , Almulhim Fatmah , Vatte Chittibabu , Al Nemer Areej , Almuhanna Afnan , Van Allen Eliezer M , Al-Ali Amein , AlDubayan Saud H
Published: December 2022

The indigenous Arab population has traditionally been underrepresented in cancer genomics studies, and as a result the polygenic risk landscape of breast cancer in the population remains elusive. Here we show by utilizing low-pass whole genome sequencing (lpWGS), we can accurately impute population-specific variants with high exome concordance (median dosage correlation: 0.9459, Interquartile range: 0.9410-0.9490) and construct breast cancer burden-sensitive polygenic risk scores (PRS) using publicly available resources. After adjusting the PRS to the Arab population, we found significant associations between PRS performance in risk prediction and first-degree relative breast cancer history prediction (Spearman rho=0.43, p = 0.03), where breast cancer patients in the top PRS decile are 5.53 (95% CI: 1.76-17.97, p = 0.003) times more likely to also have a first degree relative diagnosed with breast cancer compared to those in the middle deciles. In addition, we found evidence for the genetic liability threshold model of breast cancer where among patients with a family history of breast cancer, pathogenic rare variant carriers had significantly lower PRS than non-carriers (p = 0.0205, M.W.U.) while for non-carriers every standard deviation increase in PRS corresponded to 4.52 years (95% CI: 8.88-0.17, p = 0.042) earlier age of presentation. Overall, our study provides a viable strategy utilizing lpWGS to assess polygenic risk in an understudied population and took steps in addressing existing global health disparities.
Identification of fibroinflammatory and fibrotic transcriptomic subsets of human sclerotic cutaneous chronic graft-versus-host disease
Authors: Rosenstein Rachel K. , Rose Jeremy J. , Brooks Stephen R. , Tsai Wanxia L. , Gadina Massimo , Pavletic Steven Z. , Nagao Keisuke , Cowen Edward W.
Published: December 2022

Cutaneous sclerotic chronic graft-versus-host disease (cGVHD) is a common and highly morbid complication of allogeneic hematopoietic stem cell transplantation (HSCT). We identified genes that are significantly upregulated in the skin of sclerotic cGVHD patients (n = 17) compared to HSCT patients without sclerotic cGVHD (n = 9) by bulk RNA sequencing. This revealed two transcriptomic groups of affected patients: those with fibrotic and inflammatory/Th1 gene expression, the fibroinflammatory group, and those with predominantly fibrotic/TGFβ-associated expression, the fibrotic group. This transcriptomic heterogeneity was also associated with histopathologic heterogeneity, with the fibroinflammatory sub-cluster showing more histopathologic features of epidermal cGVHD and inflammation. Further study will help elucidate if these gene expression and histopathologic findings can be used to tailor treatment decisions. Multiple highly induced genes in the skin (SFRP4, SERPINE2, COMP) were also found to be significantly induced in sclerotic cGVHD patient plasma (n = 16) compared to control HSCT patients without sclerotic cGVHD (n = 17), suggesting these TGFβ and Wnt pathway mediators as candidate blood biomarkers of disease.
Investigating shared genetic architecture between obesity and multiple sclerosis
Authors: Zeng Ruijie , Jiang Rui , Huang Wentao , Wang Jiaxuan , Zhang Lijun , Ma Yuying , Wu Yanjun , Meng Meijun , Leung Felix W , Lian Qizhou , Sha Weihong , Chen Hao
Published: December 2022

Background and aims

Observational studies have suggested a complex relationship between obesity and multiple sclerosis (MS). However, the role of genetic factors in the comorbidity and whether obesity exist consistent shared genetic relationships with MS, remains unclear. Our study aims to investigate the extent of shared genetic architecture underlying obesity and MS.

Methods

Based on genome-wide association studies (GWAS) summary statistics, we investigate the genetic correlation by the linkage disequilibrium score regression (LDSC) and genetic covariance analyzer (GNOVA). The casualty was identified by using bidirectional Mendelian randomization. Linkage disequilibrium score regression in specifically expressed genes (LDSC-SEG) and multi-marker analysis of GenoMic annotation (MAGMA) were utilized to investigate single-nucleotide polymorphisms (SNP) enrichment in the tissue and cell-type levels. We then identified shared risk SNPs using cross-trait meta-analyses and Heritability Estimation from Summary Statistics (ρ-HESS). We further explore the potential functional genes for BMI and MS using summary-data-based Mendelian randomization (SMR).

Result

We found significantly positive genetic correlation and 18 novel shared genetic SNPs were identified in cross-trait meta-analyses. We found the causality of BMI on MS using Mendelian randomization, but slight inconsistent evidence for the causality of MS on BMI. We observed tissue-specific level SNP heritability enrichment for BMI in 9 tissues and MS in 4 tissues, and in cell-type-specific level SNP heritability enrichment 12 consistent cell types were identified for BMI and MS in brain, spleen, lung and whole blood.

Conclusion

Our study identifies the genetical correlation and shared risk SNPs between BMI and MS. These findings could provide new insights into the etiology of comorbidity and have implications for future therapeutic trials.
Sample average treatment effect on the treated analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma
Authors: Mitra Amit Kumar , Mukherjee Ujjal Kumar , Mazumder Suman , Madhira Vithal , Bergquist Timothy , Shao Yu Raymond , Liu Feifan , Song Qianqian , Su Jing , Kumar Shaji , Bates Benjamin A. , Sharafeldin Noha , Topaloglu Umit
Published: December 2022

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS’ National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date).

Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the propensity score matching (PSM) method.

As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma.

To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.
Female ticks (Ixodes scapularis) infected withBorrelia burgdorferihave increased overwintering survival, with implications for tick population growth
Authors: El Nabbout Amal , Ferguson Laura V. , Miyashita Atsushi , Adamo Shelley A.
Published: December 2022

The tick,Ixodes scapularis, vectors pathogens such asBorrelia burgdorferi, the bacterium that causes Lyme Disease. Over the last few decadesI. scapularishas expanded its range, introducing a novel health threat into these areas. Warming temperatures appear to be one cause of its range expansion to the north. However, other factors are also involved. We show that unfed adult female ticks infected withB. burgdorferihave greater overwintering survival than uninfected female ticks. Locally collected adult female ticks were placed in individual microcosms and allowed to overwinter in both forest and dune grass environments. In the spring we collected the ticks and tested both dead and living ticks forB. burgdorferiDNA. Infected ticks had greater overwintering survival compared with uninfected ticks every winter for three consecutive winters in both forest and dune grass environments. We discuss the most plausible explanations for this result. The increased winter survival of adult female ticks could enhance tick population growth. Our results suggest that, in addition to climate change,B. burgdorferiinfection itself may be promoting the northern range expansion ofI. scapularis. Our study highlights how pathogens could work synergistically with climate change to promote host range expansion.
Genetic modification of inflammation and clonal hematopoiesis-associated cardiovascular risk
Authors: Yu Zhi , Fidler Trevor P. , Ruan Yunfeng , Vlasschaert Caitlyn , Nakao Tetsushi , Uddin Md Mesbah , Mack Taralynn , Niroula Abhishek , Heimlich J. Brett , Zekavat Seyedeh M. , Gibson Christopher J. , Griffin Gabriel K. , Wang Yuxuan , Peloso Gina M. , Heard-Costa Nancy , Levy Daniel , Vasan Ramachandran S. , Aguet François , Ardlie Kristin , Taylor Kent D. , Rich Stephen S. , Rotter Jerome I. , Libby Peter , Jaiswal Siddhartha , Ebert Benjamin L. , Bick Alexander G. , Tall Alan R. , Natarajan Pradeep
Published: December 2022

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data of blood DNA and modeled both as a composite and for common drivers (DNMT3A,TET2,ASXL1,andJAK2) separately. We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identifyIL1RAPas a potential key molecule for CHIP-associated CVD risk across genes and increasedAIM2gene expression leading to heightenedJAK2- andASXL1-associated CVD risks. We show that CRISPR- inducedAsxl1mutated murine macrophages have a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVD protective effect ofIL10expression inASXL1CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides new evidence to support gene-specific strategies to address CHIP-associated CVD risk.
A multi-parameter optimization in middle-down analysis of monoclonal antibodies by LC-MS/MS
Authors: Dhenin Jonathan , Dupré Mathieu , Druart Karen , Krick Alain , Mauriac Christine , Chamot-Rooke Julia
Published: December 2022

In antibody-based drug research, regulatory agencies request a complete characterization of antibody proteoforms covering both the amino acid sequence and all post-translational modifications. The usual mass spectrometry-based approach to achieve this goal is bottom-up proteomics, which relies on the digestion of antibodies, but does not allow the diversity of proteoforms to be assessed. Middle-down and top-down approaches have recently emerged as attractive alternatives but are not yet mastered and thus used in routine by many analytical chemistry laboratories. The work described here aims at providing guidelines to achieve the best sequence coverage for the fragmentation of intact light and heavy chains generated from a simple reduction of intact antibodies using Orbitrap mass spectrometry. Three parameters were found crucial to this aim: the use of an electron-based activation technique, the multiplex selection of precursor ions of different charge states and the combination of replicates.
Cell type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behaviour in fragile X syndrome model mice
Authors: Longo Francesco , Aryal Sameer , Anastasiades Paul , Maltese Marta , Baimel Corey , Albanese Federica , Tabor Joanna , Zhu Jeffrey D , Oliveira Mauricio M , Gastaldo Denise , Bagni Claudia , Santini Emanuela , Tritsch Nicolas X , Carter Adam G , Klann Eric
Published: December 2022

Individuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviours (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent with dysfunctional cortico-striatal circuits, an area relatively unexplored in FXS. Using a multidisciplinary approach, we dissected the contribution of two populations of striatal medium spiny neurons (SPNs) in the expression of RRBs in FXS model mice. We found that dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice. Cell-type-specific translational profiling of the FXS mouse striatum revealed differentially translated mRNAs, providing critical information concerning potential therapeutic targets. Our findings represent the first evidence of a cell-type specific impact of the loss of FMRP on translation and the sequence of neuronal events in the striatum that drive RRBs in FXS.

Highlights

Dysregulated striatal protein synthesis underlies altered synaptic plasticity and RRBs displayed by FXS model mice

FXS model mice exhibit cell type-specific molecular, morphological, and synaptic changes in the dorsolateral striatum

Selective deletion ofFmr1from dSNPs in mice alters translation and causes repetitive behavior

TRAP-Seq indicates that there is altered binding of >120 mRNAs to ribosomes in dSNPs ofFmr1KO mice

G-protein signaling (RGS) 4 translation is significantly reduced in dSPNs in FXS model mice

Treatment of FXS model mice with VU0152100, a positive allosteric modulator of the M4 muscarinic receptor that is upstream of RGS4, can reverse RRBs
Microbiome, resistome and mobilome of chlorine-free drinking water treatment systems
Authors: Calderón-Franco David , Corbera-Rubio Francesc , Cuesta-Sanz Marcos , Pieterse Brent , de Ridder David , van Loosdrecht Mark C. M. , van Halem Doris , Laureni Michele , Weissbrodt David G.
Published: December 2022

Drinking water treatment plants (DWTPs) are designed to remove physical, chemical, and biological contaminants. However, until recently, the role of DWTPs in minimizing the cycling of antibiotic resistance determinants has got limited attention. In particular, the risk of selecting antibiotic-resistant bacteria (ARB) is largely overlooked in chlorine-free DWTPs where biological processes are applied. Here, we combined high-throughput quantitative PCR and metagenomics to analyze the abundance and dynamics of microbial communities, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) across the treatment trains of two chlorine-free DWTPs involving dune-based and reservoir-based systems. The microbial diversity of the water being treated increased after all biological unit operations, namely rapid and slow sand filtration (SSF), and granular activated carbon filtration. Both DWTPs reduced the concentration of ARGs and MGEs in the water by about 2.5 log gene copies mL-1, despite their relative increase in the disinfection sub-units (SSF in dune-based and UV treatment in reservoir-based DWTPs). The total microbial concentration was also reduced (2.5 log units), and none of the DWTPs were enriched for antibiotic resistant bacteria. Our findings highlight the effectiveness of chlorine-free DWTPs in supplying safe drinking water while reducing the concentration of antibiotic resistance determinants. To the best of our knowledge, this is the first study that monitors the presence and dynamics of antibiotic resistance determinants in chlorine-free DWTPs.
Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants
Authors: Vaid Roshan , Mendez Akram , Thombare Ketan , Burgos-Panadero Rebeca , Robinot Rémy , Fonseca Barbara F , Gandasi Nikhil R , Ringlander Johan , Baig Mohammad Hassan , Dong Jae-June , Cho Jae Yong , Reinius Björn , Chakrabarti Lisa A , Nystrom Kristina , Mondal Tanmoy
Published: December 2022

Host-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics.N6-methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during a stress response. Gene expression profiles observed post-infection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers and erasers. We found that infection with SARS-CoV-2 variants caused a loss of m6A in cellular RNAs, whereas m6A was detected abundantly in viral RNA. METTL3, the m6A methyltransferase, showed an unusual cytoplasmic localization post-infection. The B.1.351 variant had a less pronounced effect on METTL3 localization and loss of m6A than the B.1 and B.1.1.7 variants. We also observed a loss of m6A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m6A loss is characteristic of SARS-CoV-2 infected cells. Further, transcripts with m6A modification were preferentially down-regulated post-infection. Inhibition of the export protein XPO1 resulted in the restoration of METTL3 localization, recovery of m6A on cellular RNA, and increased mRNA expression. Stress granule formation, which was compromised by SARS-CoV-2 infection, was restored by XPO1 inhibition and accompanied by a reduced viral infectionin vitro. Together, our study elucidates how SARS-CoV-2 inhibits the stress response and perturbs cellular gene expression in an m6A-dependent manner.
Quantifying Drift-Fitness Balance Using an Agent-Based Biofilm Model of Identical Heterotrophs Under Low Nutrient Conditions
Authors: Weaver Joseph Earl
Published: December 2022

Both deterministic and stochastic forces shape biofilm communities, but the balance between those forces is variable. Quantifying the balance is both desirable and challenging. For example, negative drift selection, a stochastic force, can be thought of as an organism experiencing ‘bad luck’ and manipulating ‘luck’ as a factor in real world systems is difficult. We used an agent-based model to manipulate luck by controlling seed values governing random number generation. We determined which organism among identical competitors experienced the greatest negative drift selection, gave it a deterministic growth advantage, and re-ran the simulation with the same seed. This enabled quantifying the growth advantage required to overcome drift,e.g., a 50% chance to thrive may require a 10-20% improved growth rate. Further, we found that crowding intensity affected that balance. At moderate spacings, there were wide ranges where neither drift nor growth dominated. Those ranges shrank at extreme spacings; close and loose crowding respectively favoured drift and growth. We explain how these results may partially illuminate two conundrums: the difference between taxa and functional stability in wastewater treatment plans and the difference between equivalent and total community size in neutral community assembly models.
Proposed three-phenylalanine motif involved in magnetoreception signaling of an Actinopterygii protein expressed in mammalian cells
Authors: Ricker Brianna , Mitra Sunayana , Castellanos E. Alejandro , Grady Connor J. , Pelled Galit , Gilad Assaf A.
Published: December 2022

Studies at the cellular and molecular level of magnetoreception – sensing and responding to magnetic fields – is a relatively new research area. As it appears that different mechanisms of magnetoreception in animals evolved from different origins, many questions about the mechanisms remain left open. Here we present new information regarding the Electromagnetic Perceptive Gene (EPG) fromKryptopterus vitreolusthat may serve as part of the foundation to understanding and applying magnetoreception. Using HaloTag coupled with fluorescent ligands and phosphatidylinositol specific phospholipase C (PI-PLC) we show that EPG is associated to the membrane via glycosylphosphatidylinositol (GPI) anchor. EPG’s function of increasing intracellular calcium was also used to generate an assay using GCaMP6m to observe the function of EPG and to compare its function with homologous proteins. It was also revealed that EPG relies on a motif of three phenylalanine residues in order to function – stably swapping these residues using site directed mutagenesis resulted in a loss of function in EPG. This information not only expands upon our current understanding of magnetoreception but may provide a foundation and template to continue characterizing and discovering more within the field.

Graphical Abstract

In Brief

EPG is a magnetoreceptive GPI anchored protein. Critical to its function is a three-phenylalanine motif which allows EPG to sense and respond to EMF. When expressed in mammalian cell, an increase in intracellular calcium is observed using GCaMP6m. This work represents progress towards understanding magnetoreception for use in future technologies.

Highlights

EPG is associated to the cell membrane via glycosylphosphatidylinositol anchoring

In mammalian cells, EPG increases intracellular calcium upon EMF stimulation

Homologs of EPG from the uPAR/Ly6 family show different responses to EMF

A three-phenylalanine motif in EPG is critical to its magnetoreceptive ability
Biochemistry-informed design selects potent siRNAs against SARS-CoV-2
Authors: Houbron Élisabeth , Mockly Sophie , Rafasse Sophia , Gros Nathalie , Muriaux Delphine , Seitz Hervé
Published: December 2022

RNA interference (RNAi) offers an efficient way to repress genes of interest, and it is widely used in research settings. Clinical applications emerged more recently, with 5 approved siRNAs (the RNA guides of the RNAi effector complex) against human diseases. The development of siRNAs against the SARS-CoV-2 virus could therefore provide the basis of novel COVID-19 treatments, while being easily adaptable to future variants or to other, unrelated viruses. Because the biochemistry of RNAi is very precisely described, it is now possible to design siRNAs with high predicted activity and specificity using only computational tools. While previous siRNA design algorithms tended to rely on simplistic strategies (raising fully complementary siRNAs against targets of interest), our approach uses the most up-to-date mechanistic description of RNAi to allow mismatches at tolerable positions and to force them at beneficial positions, while optimizing siRNA duplex asymmetry. Our pipeline proposes 8 siRNAs against SARS-CoV-2, andex vivoassessment confirms the high antiviral activity of 6 out of 8 siRNAs, also achieving excellent variant coverage (with several 3-siRNA combinations recognizing each correctly-sequenced variant as of September 2022). Our approach is easily generalizable to other viruses as long as a variant genome database is available. With siRNA delivery procedures being currently improved, RNAi could therefore become an efficient and versatile antiviral therapeutic strategy.
Direct LiF imaging diagnostics on refractive X-ray focusing at the EuXFEL High Energy Density instrument
Authors: Makarov Sergey , Makita Mikako , Nakatsutsumi Motoaki , Pikuz Tatiana , Ozaki Norimasa , Preston Thomas R. , Appel Karen , Konopkova Zuzana , Cerantola Valerio , Brambrink Erik , Schwinkendorf Jan-Patrick , Mohacsi Istvan , Burian Tomas , Chalupsky Jaromir , Hajkova Vera , Juha Libor , Vozda Vojtech , Nagler Bob , Zastrau Ulf , Pikuz Sergey
Published: December 2022

The application of fluorescent crystal media in wide-range X-ray detectors provides an opportunity to directly image the spatial distribution of ultra-intense X-ray beams including investigation of the focal spot of free-electron lasers. Here the capabilities of the micro- and nano-focusing X-ray refractive optics available at the High Energy Density instrument of the European XFEL are reported, as measured in situ by means of a LiF fluorescent detector placed into and around the beam caustic. The intensity distribution of the beam focused down to several hundred nanometers was imaged at 9 keV photon energy. A deviation from the parabolic surface in a stack of nanofocusing Be compound refractive lenses (CRLs) was found to affect the resulting intensity distribution within the beam. Comparison of experimental patterns in the far field with patterns calculated for different CRL lens imperfections allowed the overall inhomogeneity in the CRL stack to be estimated. The precise determination of the focal spot size and shape on a sub-micrometer level is essential for a number of high energy density studies requiring either a pin-size backlighting spot or extreme intensities for X-ray heating.
Better understanding of technology effects in adoption of predictive supply chain business analytics among SMEs: fresh insights from developing countries
Authors: AL-Shboul Moh'd Anwer
Published: December 2022

Purpose

This study contributes to the supply chain management (SCM) literature differently. It offers insightful information about the use and adoption of technologies for small and medium-sized enterprises (SMEs) in developing countries. Some challenges regarding the predictive supply chain business analytics (SCBA) tools and their prediction remain unexplored and require addressing and examination in developing economies. Therefore, this study examines the substantial roles of relative advantage (RA) and compatibility (Comp.) in using technology in predictive SCBA adoption among SMEs in developing countries.

Design/methodology/approach

This paper performed a quantitative survey-based study to analyze the substantial role of RA and Comp. with the aim of using predictive SCBA adoption. To this end, the author conducted an online survey through which 262 SMEs from developing countries (i.e. Jordan, Kingdom of Saudi Arabia (KSA), the United Arab Emirates (UAE), Egypt, Turkey and Qatar) only responded by email.

Findings

The partial least squares structural equation modeling (PLS-SEM) clearly shows a significant relationship between RA and predictive SCBA adoption. Still, Comp. does not significantly affect the use of predictive SCBA adoption.

Originality/value

Such findings of this study can provide insightful implications for stakeholders and policymakers regarding the importance of using predictive SCBA adoption in SMEs in developing countries.
Travel behaviour differences among Indonesian youth in Generations Y and Z: pre-, during and post-travel
Authors: Damanik Janianton , Priyambodo Tri Kuntoro , Wibowo Moh Edi , Pitanatri Putu Diah Sastri , Wachyuni Suci Sandi
Published: December 2022

Purpose

This study aims to explore the differences in the travel behaviour of Indonesian youth of Generations Y and Z in the pre-, during and post-travel stages and their associated use of information and communication technology.

Design/methodology/approach

Data were gathered through a questionnaire that was distributed via the internet for six weeks; 569 people provided their full responses. Chi-square tests and linear regression were used for data analysis.

Findings

These generations use digital media and word of mouth differently when searching for travel information. The differences are also apparent in the pre-, during and post-travel stages. Generation Z tends to use digital media and share travel experiences through a certain social media platform more frequently than Generation Y.

Research limitations/implications

This study covers the travel history prior to and during the COVID-19 pandemic and equalises the situation in these two periods. The number of samples was relatively small to capture the current population of both generations.

Practical implications

This study promotes a new understanding of the travel behaviours of the two generations based on the stages of the travel examined. The findings suggest that the travel industry can distinguish between promotional media and types of services to serve each of the generational cohorts more effectively.

Originality/value

To the best of the authors’ knowledge, this is the first study to reveal differences in travel behaviour between Generations Y and Z in Indonesia.
Digitization of supply chain: a case of Haryana (India) public distribution system
Authors: Tapar Archit Vinod , Jain Deepika , Patro Archana
Published: December 2022

Learning outcomes

The learning outcomes are as follows: to decipher the role of technology in the supply chain management (SCM); to understand the importance of supply chain integration with various stakeholders in the supply chain in increasing efficiency and effectiveness; and to comprehend the challenges in the implementation of technology in SCM.

Case overview/synopsis

This case study presents Haryana’s challenges in implementing the digitization of the supply of food grains to the public. Mr Srinivas, a consultant to the Department of Food and Public Distribution, is required to suggest the future roadmap while accounting for the challenges faced in the digitization of the distribution of grains to the public in the state of Haryana. The students are expected to use the information given in the case and exhibits to discuss and critically think about the various stakeholders involved when change initiatives are implemented on an organizational level and recommend solutions based on the voices of various internal stakeholders.

Complexity academic level

Postgraduate/Masters in Business Administration/Masters in Management.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 9: Operations and Logistics.
An artificial intelligent manufacturing process for high-quality low-cost production
Authors: Hassan Noha M. , Hamdan Ameera , Shahin Farah , Abdelmaksoud Rowaida , Bitar Thurya
Published: December 2022

Purpose

To avoid the high cost of poor quality (COPQ), there is a constant need for minimizing the formation of defects during manufacturing through defect detection and process parameters optimization. This research aims to develop, design and test a smart system that detects defects, categorizes them and uses this knowledge to enhance the quality of subsequent parts.

Design/methodology/approach

The proposed system integrates data collected from the deep learning module with the machine learning module to develop and improve two regression models. One determines if set process parameters would yield a defective product while the second model optimizes them. The deep learning model utilizes final product images to categorize the part as defective or not and determines the type of defect based on image analysis. The developed framework of the system was applied to the forging process to determine its feasibility during actual manufacturing.

Findings

Results reveal that implementation of such a smart process would lead to significant contributions in enhancing manufacturing processes through higher production rates of acceptable products and lower scrap rates or rework. The role of machine learning is evident due to numerous benefits which include improving the accuracy of the regression model prediction. This artificial intelligent system enhances itself by learning which process parameters could lead to a defective product and uses this knowledge to adjust the process parameters accordingly overriding any manual setting.

Research limitations/implications

The proposed system was applied only to the forging process but could be extended to other manufacturing processes.

Originality/value

This paper studies how an artificial intelligent (AI) system can be developed and used to enhance the yield of good products.
Quality improvement of long oil alkyd (LOA) resin requirements in the formulation of Hi-gloss paints
Authors: James Joseph Myoka , Taifa Ismail W. R.
Published: December 2022

Purpose

This research aimed at lowering the non-volatile matter (NVM) of long oil alkyd (LOA) resin to meet the resin requirements in producing Hi-gloss paints. The research also aimed to assist Hi-gloss paint manufacturers who require solid resin content below 70%.

Design/methodology/approach

The research utilised both the document review and experimental methods. The experimental method, which involved the blending process, was used in lowering the NVM of LOA resin, whereby eight experiments were conducted as reputations to obtain accurate data and results. A factorial design was used in the design of the experiment (DOE), where three factors were required to be evaluated: specific gravity, viscosity and NVM and two levels were required: weight of LOA and white spirit.

Findings

The NVM of LOA resin was successfully lowered, and different shades of paint were produced for reliability testing. The quality parameters of Hi-gloss paints that used the modified LOA were all found within the company's specifications compared to those with unmodified LOA, where some parameters were either above or below the specifications. However, all samples with the NVM of LOA used below 50% were found to be poor in terms of quality during the reliability testing. So, if the company had used the modified LOA resin in the production of Hi-gloss paints, it would have potentially saved 18,925.2 kg and 9,446.4 kg, respectively, of LOA just in producing Hi-gloss black and white paints only. Moreover, the cost of 1 kg of LOA is $2.3, which is equal to Tanzanian Shillings (Tshs) 5,290. The company would have potentially saved Tshs 100.114 million Tshs and Tshs 49.97 million Tshs in producing Hi-gloss black and white paints, respectively, making a total of Tshs 150.08 million per year. This was counted as a loss during that year because they did not use LOA resin with 50% NVM in production.

Research limitations/implications

This study focused on LOA resin used in producing Hi-gloss paints. The study also did not consider other categories of alkyd resins used in producing paints and varnishes e.g. epoxy resin and short and medium oil alkyd resins.

Originality/value

This is probably the first alkyd resin improvement study conducted using white spirit as Tanzania's main agent or material. The study utilised vegetable oils such as coconut, sunflower and tobacco seeds.
CEO general work experience and FDI-based internationalization
Authors: Xu Le
Published: December 2022

Purpose

The purpose of this study is to study the impact of the chief executive officer (CEO) general work experience on the level of firm internationalization in the form of foreign direct investment.

Design/methodology/approach

The author collects and analyzes data on publicly traded US firms in the manufacturing sector from 1993 to 2012.

Findings

The author finds that CEOs with more general work experience tend to engage in a higher degree of foreign direct investment (FDI)-based internationalization. This relationship will be weakened by CEO stock ownership and enhanced by CEO Ivy League education.

Originality/value

This study enriches the understanding of the important role top managers play in internationalization decisions. The study also contributes to the literature on managerial risk-taking by exploring the outcomes of managerial risk-taking, which have been less studied than the antecedents.