bluuebunny/crossref_metadata_2025 huggingface dataset:
Xylazine in Drug Seizure Reports and Overdose Deaths in the US, 2018-2022
Authors: Cano Manuel , Daniulaitye Raminta , Marsiglia Flavio
Published: August 2023

Xylazine is increasingly reported in street drugs and fatal overdoses in the United States (US), often in combination with synthetic opioids, yet state-level xylazine data are limited, hampering local public health responses. The present study analyzed 2018-2022 state-level data from the National Forensic Laboratory Information System (xylazine-positive reports of seized drugs analyzed by forensic laboratories), the Centers for Disease Control and Prevention (population estimates, synthetic opioid overdose mortality rates), and individual states’ medical examiner/public health agency reports (numbers of xylazine-involved overdose deaths). An ordinary least squares regression model predicted state-level synthetic opioid overdose mortality rates by xylazine seizure report rates, adjusting for US Census Region. In 2018, relatively low rates of xylazine seizure reports were observed, with 21 states reporting zero xylazine seizures. In 2022, only three states reported zero xylazine seizures, and the highest xylazine seizure report rates (per 100,000 residents) were observed in New Jersey (30.4), Rhode Island (22.7), Maryland (18.9), Virginia (15.5), New Hampshire (13.0), and Ohio (10.9). Data on 2019-2022 xylazine-involved overdose deaths were available for 21 states/DC (60 state-years), with the highest 2022 xylazine-involved overdose death rates (per 100,000 residents) in Vermont (10.5) and Connecticut (9.8). Finally, in 2021, at the state level, each additional reported xylazine seizure per 100,000 residents was associated with a 2% higher synthetic opioid overdose mortality rate (b=0.02, robust standard error=0.01;p=0.049). Overall, study results emphasize xylazine’s increasing involvement in US law enforcement drug seizure reports and overdose deaths, primarily in the East, yet also extending across the country.
Rates of SARS-CoV-2 transmission between and into California state prisons
Authors: Dubey Preeti , Hoover Christopher M. , Lu Phoebe , Blumberg Seth , Porco Travis C. , Parsons Todd L. , Worden Lee
Published: August 2023

Correctional institutions are a crucial hotspot amplifying SARS-CoV-2 spread and disease disparity in the U.S. In the California state prison system, multiple massive outbreaks have been caused by transmission between prisons. Correctional staff are a likely vector for transmission into the prison system from surrounding communities. We used publicly available data to estimate the magnitude of flows to and between California state prisons, estimating rates of transmission from communities to prison staff and residents, among and between residents and staff within facilities, and between staff and residents of distinct facilities in the state’s 34 prisons through March 22, 2021. We use a mechanistic model, the Hawkes process, reflecting the dynamics of SARS-CoV-2 transmission, for joint estimation of transmission rates. Using nested models for hypothesis testing, we compared the results to simplified models (i) without transmission between prisons, and (ii) with no distinction between prison staff and residents. We estimated that transmission between different facilities’ staff is a significant cause of disease spread, and that staff are a vector of transmission between resident populations and outside communities. While increased screening and vaccination of correctional staff may help reduce introductions, large-scale decarceration remains crucially needed as more limited measures are not likely to prevent large-scale disease spread.
Epidemiology of pediatric astrovirus gastroenteritis in a Nicaraguan birth cohort
Authors: Rubinstein Rebecca J , Reyes Yaoska , González Fredman , Gutiérrez Lester , Toval-Ruíz Christian , Hammond Kelli , Bode Lars , Vinjé Jan , Vilchez Samuel , Becker-Dreps Sylvia , Bucardo Filemón , Vielot Nadja A.
Published: August 2023

Background

Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low-and-middle-income countries.

Methods

We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections and seasonality of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017-2018, followed for 36 months. Children were recruited from maternity hospitals and birth records in an economically-diverse neighborhood of León, the second-largest city in Nicaragua. Astrovirus-positive episodes and genotypes were identified from diarrheal specimens with reverse transcription quantitative polymerase chain reaction and Sanger sequencing.

Results

Of 1708 total specimens tested, eighty children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). The incidence of astrovirus episodes was 7.8/100 child-years (95% CI: 6.2, 9.8). Genotype-specific incidence of astrovirus also exhibited seasonality. Median age of astrovirus episode onset was 16 months (IQR 9, 23). Initial astrovirus episodes were not associated with protection against future episodes during the age span studied. Astrovirus cases were exclusively breastfed for a shorter period than uninfected children, and the human milk oligosaccharide lacto-N-fucopentaose-I was more concentrated in mothers of these children. Home toilets appeared to protect against future astrovirus episodes (HR=0.19, 95% CI 0.04-0.91). Human astrovirus-5 episodes, comprising 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus co-infections.

Conclusion

Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity.
Improved dual-color GRAB sensors for monitoring dopaminergic activityin vivo
Authors: Zhuo Yizhou , Luo Bin , Yi Xinyang , Dong Hui , Wan Jinxia , Cai Ruyi , Williams John T. , Qian Tongrui , Campbell Malcolm G. , Miao Xiaolei , Li Bozhi , Wei Yu , Li Guochuan , Wang Huan , Zheng Yu , Watabe-Uchida Mitsuko , Li Yulong
Published: August 2023

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a vast network of dopaminergic projections. To fully dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent GPCR activation‒based DA (GRABDA) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity, and signal-to-noise properties with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in freely moving mice to measure both optogenetically evoked and behaviorally relevant DA release while measuring neurochemical signaling in the nucleus accumbens, amygdala, and cortex. Using these sensors, we also detected spatially resolved heterogeneous cortical DA release in mice performing various behaviors. These next-generation GRABDAsensors provide a robust set of tools for imaging dopaminergic activity under a variety of physiological and pathological conditions.
Rationally designed multimeric nanovaccines using icosahedral DNA origami for molecularly controlled display of SARS-CoV-2 receptor binding domain
Authors: Feng Qingqing , Cheng Keman , Zhang Lizhuo , Gao Xiaoyu , Liang Jie , Liu Guangna , Ma Nana , Xu Chen , Tang Ming , Chen Liting , Wang Xinwei , Ma Xuehui , Zou Jiajia , Shi Quanwei , Du Pei , Wang Qihui , Nie Guangjun , Zhao Xiao
Published: August 2023

Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employed an icosahedral DNA origami (ICO) as a display particle for SARS-CoV-2 RBD nanovaccines. The morphology and diameter of the particles were close to those of the virus (91 ± 11 nm). The surface addressability of the DNA origami permitted facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using anin vitroscreening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoked stronger and more enduring humoral and T cell immune responses in mouse models compared to soluble RBD antigens. Our vaccines activated similar humoral immunity and slightly stronger cellular immunity compared to mRNA vaccines. These results provide reference principles for the rational design of nanovaccines and exemplify the utility of DNA origami as a display platform for vaccines against infectious disease.
Genome replication in asynchronously growing microbial populations
Authors: Pflug Florian , Bhat Deepak , Pigolotti Simone
Published: August 2023

Biological cells replicate their genomes in a well-planned manner. The DNA replication program of an organism determines the timing at which different genomic regions are replicated, with fundamental consequences for cell homeostasis and genome stability. Qualitatively, in a growing cell culture, one expects that genomic regions that are replicated early should be more abundant than regions that are replicated late. This abundance pattern can be experimentally measured using deep sequencing. However, a general quantitative theory to explain these data is still lacking. In this paper, we predict the abundance of DNA fragments in asynchronously growing cultures from any given stochastic model of the DNA replication program. As key examples, we present stochastic models of the DNA replication programs inEscherichia coliand in budding yeast. In both cases, our approach leads to analytical predictions that are in excellent agreement with experimental data and permit to infer key information about the replication program. In particular, our method is able to infer the locations of known replication origins in budding yeast with high accuracy. These examples demonstrate that our method can provide insight into a broad range of organisms, from bacteria to eukaryotes.
Isoform-resolved genome annotation enables mapping of tissue-specific betalain regulation in amaranth
Authors: Winkler Tom S. , Vollmer Susanne K. , Dyballa-Rukes Nadine , Metzger Sabine , Stetter Markus G
Published: August 2023

• Betalains are coloring pigments produced in some families of the order Caryophyllales, where they replace anthocyanins as coloring pigments. While the betalain pathway itself is well studied, the tissue-specific regulation of the pathway remains mostly unknown.

• We enhance the high-qualityAmaranthus hypochondriacusreference genome and produce a substantially more complete genome annotation, incorporating isoform details. We annotate betalain and anthocyanin pathway genes along with their regulators in amaranth and map the genetic control and tissue-specific regulation of the betalain pathway.

• Our improved genome annotation allowed us to identify causal mutations that lead to a knock-out of red betacyanins in natural accessions of amaranth. We reveal the tissue-specific regulation of flower color via a previously uncharacterized MYB transcription factor,AhMYB2. Downregulation ofAhMYB2in the flower leads to reduced expression of key betalain enzyme genes and loss of red flower color.

• Our improved amaranth reference genome represents the most complete genome of amaranth to date and a valuable resource for betalain and amaranth research. High similarity of the flower betalain regulatorAhMYB2to anthocyanin regulators and a partially conserved interaction motif support the co-option of anthocyanin regulators for the betalain pathway as possible reason for mutual exclusiveness of the two pigments.
Differential regulation of the proteome and phosphosproteome along the dorso-ventral axis of the earlyDrosophilaembryo
Authors: Gomez Juan Manuel , Nolte Hendrik , Vogelsang Elisabeth , Dey Bipasha , Takeda Michiko , Giudice Girolamo , Faxel Miriam , Cepraga Alina , Zinzen Robert Patrick , Krüger Marcus , Petsalaki Evangelia , Wang Yu-Chiun , Leptin Maria
Published: August 2023

The initially homogeneous epithelium of the earlyDrosophilaembryo differentiates into regional subpopulations with different behaviours and physical properties that are needed for morphogenesis. The factors at top of the genetic hierarchy that control these behaviours are known, but many of their targets are not. To understand how proteins work together to mediate differential cellular activities, we studied in an unbiased manner the proteomes and phosphoproteomes of the three main cell populations along the dorso-ventral axis during gastrulation using mutant embryos that represent the different populations. We detected 6111 protein groups and 6259 phosphosites of which 3399 and 3433 respectively, were differentially regulated. The changes in phosphosite abundance did not correlate with changes in host protein abundance, showing phosphorylation to be a regulatory step during gastrulation. Hierarchical clustering of protein groups and phosphosites identified clusters that contain known fate determinants such as Doc1, Sog, Snail and Twist. The recovery of the appropriate known marker proteins in each of the different mutants we used validated the approach, but also revealed that two mutations that both interfere with the dorsal fate pathway,Toll10Bandserpin27aexdo this in very different manners. Diffused network analyses within each cluster point to microtubule components as one of the main groups of regulated proteins. Functional studies on the role of microtubules provide the proof of principle that microtubules have different functions in different domains along the DV axis of the embryo.
Elephants develop wrinkles through both form and function
Authors: Schulz Andrew K. , Reveyaz Noemie , Kaufmann Lena , Ritter Cindy , Hildebrandt Thomas , Brecht Michael
Published: August 2023

The trunks of elephants have prominent wrinkles from their base to the very tip. But neither the obvious differences in wrinkles between elephant species nor their development have been studied before. Asian elephants have more dorsal major, meaning deep and wide, trunk wrinkles (~126 ± 25 SD) than African elephants (~83 ± 13 SD). Both species have more dorsal than ventral major trunk wrinkles and a closer wrinkle spacing distally than proximally. In Asian elephants wrinkle density is high in the ‘trunk wrapping zone’. Wrinkle numbers on the left and right sides of the distal trunk differed as a function of trunk lateralization, with frequent bending in one direction causing wrinkle formation. MicroCT-imaging and microscopy of newborn elephants’ trunks revealed a constant thickness of the putative epidermis, whereas the putative dermis shrinks in the wrinkle troughs. During fetal development wrinkle numbers double every 20 days in an early exponential phase. Later wrinkles are added slowly, but at a faster rate in Asian than African elephants. We characterize the lifelong development of trunk wrinkles in Asian and African elephants and discuss the relation of species differences in trunk wrinkle distribution and number with behavioral, environmental, genetic, and biomechanical factors.
KLP-7/Kinesin-13 orchestrates axon-dendrite checkpoints for polarized trafficking in neurons
Authors: Dey Swagata , Kumar Nitish , Feldman Jessica , Ghosh-Roy Anindya
Published: August 2023

Neurons are compartmentalized cells with spatiotemporal distinction of anatomy and molecular repertoire. Microtubule organization in the neuron is crucial for its polarized structure and composition. Microtubule dynamics are differentially optimized in the axons and dendrites by the interplay between the microtubule-stabilizing and destabilizing factors. It is unclear how the destabilizing factors are important for developing and maintaining neuronal polarity.

We investigated the function of KLP-7, a microtubule depolymerizing motor from the Kinesin-13 family, in the compartmentalization of axons and dendrites using the PVD neurons inCaenorhabditis elegans. In the absence of KLP-7, axonal proteins such as RAB-3 and SAD-1 were mislocalized to dendrites, suggesting a disruption in axon-dendrite compartmentalization. Notably, this phenomenon was independent of other depolymerizing factors like EFA-6, highlighting the specific role of KLP-7 in this process. We observed a reduced rate of microtubule polymerization and an altered polarity of microtubules in the PVD major dendrite due to the loss ofklp-7. Additionally, the deletion ofklp-7led to the formation of ectopic neurites from the cell body and the ectopic localization of UNC-44/Ankyrin-G, a protein associated with the axon initial segment (AIS), to the dendrites. Additionally, live imaging of GFP::KLP-7 revealed that KLP-7 is more dynamic in the dendrites as compared to the axon. These observations indicate that the precise dynamics of KLP-7 in neurites are crucial for maintaining distinct microtubule polymerization in the axons and dendrites, thereby influencing neuronal polarity.

Our findings shed light on the pivotal role of KLP-7/Kinesin-13 in the establishment of axon-dendrite checkpoints, which in turn impact the polarized trafficking of cellular components within neurons.
Dysregulation of chromatin via H3K27 methylation underpins differentiation arrest in Isocitrate dehydrogenase-mutant Acute Myeloid Leukaemia
Authors: Silveira Douglas RA , Chatzikyriakou Prodromos , Casares Aláez Pilar , Mackie Sarah , Hulks Roan , Yavorska Olena , Siejka-Zielińska Paulina , Smith Alastair , Metzner Marlen , Usukhbayar Batchimeg , Penard-Lacronique Virginie , Song Chun-Xiao , Gandhi Anita K. , Vyas Paresh , Milne Thomas A. , Kriaucionis Skirmantas , Hasan Maroof , Quek Lynn
Published: August 2023

Dysregulation of cellular differentiation is a hallmark of cancer. Isocitrate dehydrogenase (IDH) is commonly mutated multiple cancers including glioma, cholangiocarcinoma, lymphoma and Acute Myeloid Leukaemia (AML). Mutant IDH generates d-2-hydroxyglutarate that inhibits enzymes including Jumonji histone demethylases and TET2. Using primary human IDH2-mutant AML cells as a model, single cell RNA-seq and ATAC-seq, we demonstrated the continuum of cell states during restoration of neutrophilic differentiation to leukaemic progenitors by Enasidenib, a mutant IDH2 inhibitor. In cells which ultimately differentiate, there is co-expression of competing GATA2/RUNX3/SOX4-driven stem-progenitor and pro-differentiation EGR1/JUN/FOS programmes, followed by expression of cell cycle and terminal neutrophil programmes involving CEBP family and SPI1/PU.1. Genes upregulated during differentiation display loss of H3K27me3 in bivalent chromatin but not of H3K4me3, while downregulated genes are enriched for PRC2/EZH2 targets. In contrast to previous reports of a TET2-dependent mechanism for IDH-mutations, we observed only a modest link between promoter DNA CpG methylation and gene expression. For the first time in primary AML, we describe the lifting of differentiation block by de-repression of pro-differentiation genes through modulation of H3K27 demethylation in bivalent chromatin, and thus highlight a novel and important mechanism in how IDH mutations disrupt cell fates in cancer.
Disruption of Aldehyde Dehydrogenase 2 protects against bacterial infection
Authors: Berry Samuel B. , Espich Scott , Thuong Nguyen T.T. , Chang Xuling , Dorajoo Rajkumar , Khor Chiea-Chuen , Heng Chew-Kiat , Yuan Jian-Min , Fox Douglas , Anaya-Sanchez Andrea , Tenney Logan , Chang Christopher J. , Kotov Dmitri I. , Vance Russell E. , Dunstan Sarah J. , Darwin K. Heran , Stanley Sarah A.
Published: August 2023

TheALDH2*2(rs671) allele is one of the most common genetic mutations in humans, yet the positive evolutionary selective pressure to maintain this mutation is unknown, despite its association with adverse health outcomes. ALDH2 is responsible for the detoxification of metabolically produced aldehydes, including lipid-peroxidation end products derived from inflammation. Here, we demonstrate that host-derived aldehydes 4-hydroxynonenal (4HNE), malondialdehyde (MDA), and formaldehyde (FA), all of which are metabolized by ALDH2, are directly toxic to the bacterial pathogensMycobacterium tuberculosisandFrancisella tularensisat physiological levels. We find thatAldh2expression in macrophages is decreased upon immune stimulation, and that bone marrow-derived macrophages fromAldh2–/–mice contain elevated aldehydes relative to wild-type mice. Macrophages deficient forAldh2exhibited enhanced control ofFrancisellainfection.Finally, mice lackingAldh2demonstrated increased resistance to pulmonary infection byM. tuberculosis, including in a hypersusceptible model of tuberculosis, and were also resistant toFrancisellainfection. We hypothesize that the absence of ALDH2 contributes to the host’s ability to control infection by pathogens such asM. tuberculosisandF. tularensis, and that host-derived aldehydes act as antimicrobial factors during intracellular bacterial infections.

One sentence summary

Aldehydes produced by host cells contribute to the control of bacterial infections.
Two functionally distinct HEATR5 protein complexes are defined by fast-evolving co-factors in yeast
Authors: Marmorale Lucas J. , Jin Huan , Reidy Thomas G. , Palomino-Alonso Brandon , Zysnarski Christopher , Jordan-Javed Fatima , Lahiri Sagar , Duncan Mara C
Published: August 2023

The highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving co-factors to bind to AP1. However, how HEATR5 proteins interact with these co-factors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their co-factors and indicate that Laa1 performs functions besides recruiting AP1.
WITHDRAWN: Mapping miRNA regulation of MGAT3 reveals upregulation as the dominant mode of action
Authors: Zohora Fatema Tuz , Batu Tigist Tesfaye , Mahal Lara K.
Published: August 2023

Withdrawal Statement

The authors have withdrawn their manuscript owing to issues of cloning in the original pFmiR-MGAT3 sensor which make the data profiling miRNA regulation of this gene inaccurate. As a result, any miRNA identified should be disregarded and the data is invalid. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma
Authors: Augustin Ryan C. , Newman Sarah , Li Aofei , Joy Marion , Lyons Maureen , Pham Mary , Lucas Peter C. , Smith Kate , Sander Cindy , Isett Brian , Davar Diwakar , Najjar Yana G. , Zarour Hassane M. , Kirkwood John M. , Luke Jason J. , Bao Riyue
Published: August 2023

Background

Acral melanoma (AM) has distinct characteristics as compared to cutaneous melanoma and exhibits poor response to immune checkpoint inhibitors (ICI). Tumor-intrinsic mechanisms of immune exclusion have been identified in many cancers but less studied in AM.

Methods

We characterized clinically annotated tumors from patients diagnosed with AM at our institution in correlation with ICI response using whole transcriptome RNAseq, whole exome sequencing, CD8 immunohistochemistry, and multispectral immunofluorescence imaging. A defined interferon-γ-associated T cell-inflamed gene signature was used to categorize tumors into non-T cell-inflamed and T cell-inflamed phenotypes. In combination with AM tumors from two published studies, we systematically assessed the immune landscape of AM and detected differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME). Two single-cell(sc) RNAseq AM cohorts and 11 bulk RNAseq cohorts of various tumor types were used for independent validation on pathways associated with lack of ICI response. In total, 892 specimens were included in this study.

Results

72.5% of AM tumors showed low expression of the T cell-inflamed gene signature, with 23.9% of total tumors categorized as the non-T cell-inflamed phenotype. Patients of low CD3+CD8+PD1+intratumoral T cell density showed poor prognosis. We identified 11 oncogenic pathways significantly upregulated in non-T cell-inflamed relative to T cell-inflamed TME shared across all three acral cohorts (MYC, HGF, MITF, VEGF, EGFR, SP1, ERBB2, TFEB, SREBF1, SOX2, and CCND1). scRNAseq analysis revealed that tumor cell-expressing pathway scores were significantly higher in low vs high T cell-infiltrated AM tumors. We further demonstrated that the 11 pathways were enriched in ICI non-responders compared to responders across cancers, including acral melanoma, cutaneous melanoma, triple-negative breast cancer, and non-small cell lung cancer. Pathway activation was associated with low expression of interferon stimulated genes, suggesting suppression of antigen presentation. Across the 11 pathways, fatty acid synthase and CXCL8 were unifying downstream target molecules suggesting potential nodes for therapeutic intervention.

Conclusions

A unique set of pathways is associated with immune exclusion and ICI resistance in AM. These data may inform immunotherapy combinations for immediate clinical translation.
GENESIS CGDYN: large-scale coarse-grained MD simulation with dynamic load balancing for heterogeneous biomolecular systems
Authors: Jung Jaewoon , Tan Cheng , Sugita Yuji
Published: August 2023

Residue-level coarse-grained (CG) molecular dynamics (MD) simulation is widely used to investigate slow biological processes that involve multiple proteins, nucleic acids, and their complexes. Biomolecules in a large simulation system are distributed non-uniformly, limiting computational efficiency with conventional methods. Here, we develop a hierarchical domain decomposition scheme with dynamic load balancing for heterogeneous biomolecular systems to keep computational efficiency even after drastic changes in particle distribution. The new schemes are applied to intrinsically disordered protein (IDP) droplet fusions. The droplet shape changes correlate with mixing IDP chains from two droplets. We also simulate formations of large IDP droplets, whose sizes are almost equivalent to those observed in microscopy. The methods have been implemented in CGDYN of the GENESIS software, which provides a new tool for investigating mesoscopic biological phenomena using the residue-level CG models.
Exposure to titanium dioxide nanoparticles accelerates abnormal fat deposition through the mediation of the ROS via the AGE-RAGE signaling pathway in mice
Authors: Liu Jingyi , Zhong Liang , Yuan Tiantian , Sun Jingchun , Wang Yaxin , Chen Jiahao , Yang Gongshe , Yu Taiyong
Published: August 2023

Titanium dioxide nanoparticles (TiO2NPs) are widely added to various types of foods as food additives. Previous studies have shown that TiO2NPs exposure can cause abnormal deposition of adipose tissue in organisms, resulting in lipid metabolism disorder. However, the potential molecular mechanisms underlying TiO2NPs’ effects have yet to be elucidated. In this study, our data indicated that TiO2NPs (100 mg/Kg BW, 20 nm) accelerated abnormal fat deposition in the epididymal adipose tissues and disturbed the level of blood glucose subsequently in normal-fat diet mice. Further studies showed that TiO2NPs at a concentration of 100 µg/mL significantly induced the proliferation and differentiation of 3T3-L1 preadipocytes. Mechanistic studies we revealed that TiO2NPs induced the overproduction of reactive oxygen species (ROS) in the cytoplasm, which subsequently upregulated the expression of receptors for advanced glycation end products (AGEs) leading to lipid accumulation in the adipocytes with a higher level of ROS. However, the antioxidant N-acetylcysteine (NAC) was a therapeutic potential for lipid overaccumulation in the adipocytes. This study provides insight into the mechanism underlying fat deposition induced by TiO2NPs and highlighted the need for reevaluation of food-grade TiO2NPs exposure in daily life.
Determinants of health-related quality of life in healthy children and adolescents during the COVID-19 pandemic: results from a prospective longitudinal cohort study
Authors: Haile Sarah R , Peralta Gabriela P , Raineri Alessia , Rueegg Sonja , Ulyte Agne , Puhan Milo A , Radtke Thomas , Kriemler Susi
Published: August 2023

Purpose

Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological and social factors in a large longitudinal population-based sample.

Methods

Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort studyCiao Coronain Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc), psychological (sadness, anxiousness, stress) and social (nationality, parents’ education, etc) factors, were assessed in 2020 and 2021, and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level.

Results

Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions or nationality, were determinants only in individual subscales.

Conclusion

Recent mental health, more than biological, physical or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group.

What is known

Assessing health-related quality of life (HRQOL) in children and adolescents aids in under- standing how life circumstances impact their well-being.

HRQOL is a complex construct, involving biological, psychological and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples.

What is new

Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors.

Public health strategies to improve mental health may be effective in improving HRQOL in children.
Differential Regulation of Excitatory vs Inhibitory Synaptic Release by Complexin/CPX-1 and CAPS/UNC-31 at theC. elegansNeuromuscular Junctions
Authors: Wang Ya , Chow Chun Hin , Huang Mengjia , Higazy Randa , Ramakrishnan Neeraja , Zhang Cuntai , Sugita Shuzo , Gao Shangbang
Published: August 2023

The excitation and inhibition (E/I) balance at neuromuscular junctions plays a crucial role in coordinating animal motor behavior. Prominent synaptic vesicle secretory regulatory proteins, specifically complexin and CAPS (Calcium-dependent Activator Protein for Secretion), have not garnered sufficient attention for E/I balance regulation. Here, we investigate the roles of complexin/CPX-1 and CAPS/UNC-31 in excitatory vs inhibitory synapses ofC. elegansneuromuscular junctions. In our study,cpx-1null mutants displayed remarkable reduction evoked release in both excitatory and inhibitory synapses. Intriguingly, these mutants exhibited an enhanced level of spontaneous release, particularly within the context of excitatory synapse. This enhancement aligns with its “clamp” role that preventing SV from fusing with the presynaptic membrane. Additionally, a clamping-specific knockin mutantcpx-1(Δ12), which displayed no alterations in evoked release at either type of synapse, also revealed a biased substantial increase in excitatory spontaneous release. In contrast,unc-31null mutation, with normal spontaneous release, led to a more pronounced decreased evoked release in the excitatory synapse independent of dense-core vesicle regulation. Intriguingly, we found that the enhanced excitatory spontaneous release observed incpx-1mutants was abolished byunc-31in a Ca2+-dependent manner, implying that UNC-31 is essential for maintaining a high level of spontaneous fusion events. Collectively, our findings unveil a distinct regulatory pattern governing excitatory and inhibitory synaptic release, orchestrated by the interplay of CPX-1 and UNC-31. Notably, we uncover an unforeseen role of UNC-31 in influencing CPX-1’s “clamp” function, further adding complexity to the neural dynamics, which may underlie complex behavioral phenotypes observed inC. elegans.
Phylogenetic modeling of enhancer shifts in African mole-rats reveals regulatory changes associated with tissue-specific traits
Authors: Parey Elise , Fernandez-Aroca Diego , Frost Stephanie , Uribarren Ainhoa , Park Thomas J. , Zöttl Markus , St. John Smith Ewan , Berthelot Camille , Villar Diego
Published: August 2023

Changes in gene regulation are thought to underlie most phenotypic differences between species. For subterranean rodents such as the naked mole-rat, proposed phenotypic adaptations include hypoxia tolerance, metabolic changes, and cancer resistance. However, it is largely unknown what regulatory changes may associate with these phenotypic traits, and whether these are unique to the naked mole-rat, the mole-rat clade, or are also present in other mammals. Here, we investigate regulatory evolution in the heart and liver from two African mole-rat species and two rodent outgroups using genome-wide epigenomic profiling. First, we adapted and applied a phylogenetic modeling approach to quantitatively compare epigenomic signals at orthologous regulatory elements and identified thousands of promoter and enhancer regions with differential epigenomic activity in mole-rats. These elements associate with known mole-rat adaptations in metabolic and functional pathways and suggest candidate genetic loci that may underlie mole-rat innovations. Second, we evaluated ancestral and species-specific regulatory changes in the study phylogeny and report several candidate pathways experiencing stepwise remodeling during the evolution of mole-rats, such as the insulin and hypoxia response pathways. Third, we report nonorthologous regulatory elements overlap with lineage-specific repetitive elements and appear to modify metabolic pathways by rewiring of HNF4 and RAR/RXR transcription factor binding sites in mole-rats. These comparative analyses reveal how mole-rat regulatory evolution informs previously reported phenotypic adaptations. Moreover, the phylogenetic modeling framework we propose here improves upon the state of the art by addressing known limitations of inter-species comparisons of epigenomic profiles and has broad implications in the field of comparative functional genomics.
Microstructure and texture analysis of 304 austenitic stainless steel using Bragg edge transmission imaging
Authors: Bakhtiari Mahdi , Sadeghi Fazlollah , Sato Hirotaka , Um Wooyong , Yim Chang Hee , Lee Hee-Seock
Published: August 2023

Bragg edge imaging using pulsed neutrons is a non-destructive technique for studying microstructure and texture of materials. It provides two-dimensional visualization of crystallographic information using a pixelated gas electron multiplier detector and a time-of-flight method. In this work, the properties of type 304 austenitic stainless steel samples were studied via Bragg edge imaging. The samples included hot-rolled, cold-rolled and heat-treated specimens, which were characterized to investigate texture, phase fraction and grain growth. The results showed that the crystallite size increased with increasing annealing temperature. The cold-rolled and annealed samples exhibited strong textures, while the hot-rolled sample showed no preferred orientation. The phase volume fraction of induced martensite in the cold-rolled sample was also obtained. Two-dimensional maps of microstructures and textures were obtained without destructive processes. The results were validated by electron backscatter diffraction and found to be consistent. This work provides valuable information for non-destructive characterization of bulk materials by performing Bragg edge imaging using the Hokkaido University compact accelerator neutron source.
Consumer responses to sustainable product branding strategies: a literature review and future research agenda
Authors: Fatemi Hajar , Leijerholt Ulrika , Rezvani Zeinab , Schnittka Oliver
Published: August 2023

Purpose

This literature review aims to synthesise the research on various sustainable product branding activities and their impact on consumer responses to sustainable products and brands.

Design/methodology/approach

This literature review is semi-systematic and can be classified as a domain-based review. The search strategy was systematic and well-defined.

Findings

The authors identified four themes: building brand equity, brand communication, product development and third-party labels and ratings, within the sustainable product branding activities that influence consumers' responses to sustainable products and brands. The study's findings revealed diverse, and not always favourable, types of behavioural and attitudinal responses from consumers. As for the positive consumer responses, the authors found positive attitudes towards brands, willingness to pay a premium price and positive word-of-mouth intentions. As for the negative consumer responses, the authors found perceived greenwashing, negative brand evaluations and resistance to sustainable products with unfamiliar third-party labels. Several future research propositions and implications for research and practice are discussed.

Originality/value

Despite the large number of studies that look at sustainable branding strategies, there is a gap in terms of synthesising the knowledge on consumer responses to sustainable product branding strategies. This paper intends to fill this gap.
Performance-oriented HR and career development of women managers: the mediation of self-leadership and the moderated mediation of supervisor’s gender equality
Authors: Joo Jaehong , Kim Hee Sun , Song Sae Gyoung , Ro Yun Jeong , Song Ji Hoon
Published: August 2023

Purpose

The purpose of this study is to emphasize the important role of performance-oriented human resource (HR) practices and gender equality perceptions in supervisors and chief executive officers (CEOs) for career development among women in management.

Design/methodology/approach

This study used a quantitative methodology to examine relationships among variables. The authors conducted a survey to investigate factors influencing the career development of women managers in professional settings, with a sample of 1,502 female managers in South Korea.

Findings

The relationship between performance-oriented HR practices and career development for women managers was supported. In addition, self-leadership significantly mediated the relationship between performance-oriented HR practices and career development. Finally, double moderator effects of gender equality perceptions of CEOs and supervisors on the relationship between performance-oriented HR practices and self-leadership were significant.

Originality/value

This study emphasizes that career development for women in South Korea depends on gender equality awareness and institutional reorganization for best practices at top management levels. Specifically, this study identified the essential role of performance-based HR practices to support self-leadership and career development in women managers. Furthermore, this study recognized gender equality perceptions of CEOs and supervisors as a critical factor in the successful career development of women managers.
Exploring Indian working mothers' transition to involuntary telecommuting
Authors: Javad Shahina , Nema Priyanka , Chowdhary Nimit
Published: August 2023

Purpose

During the COVID-19 pandemic, many working mothers in India adopted involuntary telecommuting work option for the first time. However, no research explored their adjustments and experiences in the new work setting. This paper aims to gain an in-depth understanding of Indian working mothers' lived experience of involuntary telecommuting.

Design/methodology/approach

A phenomenological research design was adopted. The authors conducted 14 in-depth, semi-structured telephonic and online interviews. Data were analyzed using Interpretative Phenomenological Analysis framework.

Findings

The data analysis yielded two interconnected superordinate themes in this research: (1) characteristics of involuntary telecommuting and (2) the impact of involuntary telecommuting. Under the first theme, four sub-themes emerged: long working hours, increased family demands, reduced interaction with coworkers and technology-enabled communication with supervisors. The second theme comprised five sub-themes: time-based work interference with family, time-based family interference with work, strain-based family interference with work, absence of emotional and professional support and performance management concerns. Involuntary telecommuting mothers faced challenges due to lack of control over their daily work schedule and demands, along with an increased burden of unpaid household work, leading to difficulties in managing their work schedule and negotiating their professional role identity within the family. These findings emphasize that working mothers who participated in involuntary telecommuting encountered bidirectional time-based conflicts and unidirectional strain-based conflict.

Research limitations/implications

The study examines a particular subset of women telecommuters who were working mothers with young children. These potential limitations are to be addressed in future research.

Practical implications

The findings suggest that managers should develop HR policies and telecommuting ecosystems in order to enhance effectiveness of telecommuting. Specifically, organizations offering telecommuting work options should create opportunities for informal interaction among peers and formal one-to-one interaction with managers. Moreover, HR managers should develop and implement employee-friendly telecommuting policies.

Social implications

The research contributes to HRM and gender literature.

Originality/value

The paper contributes to the discourses of work-life balance, workplace relationships and work policies within telecommuting literature.
Ghana's textile and apparel sector: a strategic assessment of skills needs and development through the STED framework
Authors: Anyigba Hod , Preko Alexander , Senayah William Kwesi
Published: August 2023

Purpose

This study is to examine and develop sector skills strategies and action plans for the textile and apparel (T&A) sector.

Design/methodology/approach

The paper used a participatory action qualitative method anchored on the Skills for Trade and Economic Diversification (STED) framework, utilising the workshop-based approach with 24 key stakeholders of the sector. Content analysis was used with the help of Nvivo software.

Findings

The findings revealed that there are skills shortages, skills gaps, skills mismatches and skills diversification programmes available through higher education and work-based learning. Further, there are labour supply challenges such as national skills policy and strategy, government and stakeholder coordination, funding, relevance of curriculum and qualifications, access to practicals and the absence of a clear national vision for the sector.

Research limitations/implications

This study possesses an inherent limitation in terms of generalising the findings derived from qualitative research.

Originality/value

This research is among the first of its kind to assess skills needs and gaps through the lens of STED framework, which has been overlooked in previous literature. Importantly, this study provides vocational insights into skill needs in the sector.
I'll be there for you: coopetition and competitor-oriented activities among South Asian restaurants in two UK regional clusters
Authors: Chaudhry Shiv , Crick Dave , Crick James M.
Published: August 2023

Purpose

This study investigates how a competitor orientation (knowledge of and acting on competitors' strengths and weaknesses) facilitates coopetition activities (collaboration with competitors), within networks of competing micro-sized, independent, family restaurants, owned by entrepreneurs from ethnic minority backgrounds.

Design/methodology/approach

An instrumental case study features data collected from interviews with 30 owners (as key informants) of micro-sized, independent, family-owned restaurants, in two urban clusters within the Midlands (UK). Specifically, the context involves restaurants offering South Asian cuisine and where the owner originated from the Indian sub-continent (Bangladesh, India or Pakistan). Secondary data were collected wherever possible. These two clusters (not named for ethics reasons) are highly populated by members of these respective ethnic communities; also, they contain a relatively large number of restaurants offering South Asian cuisine.

Findings

A competitor orientation facilitated strong coopetition-oriented partnerships comprised of extended family and intra-community members that helped enhance individual firms' performance, maintained family employment and sustained their cluster. It also helped owners develop subtle counter strategies where weak ties existed, such as via inter-community networks. For example, strategies attracted customers that were not loyal to a particular restaurant, or indeed, sub-ethnic cuisine (within Bangladesh, India or Pakistan, like the Punjab region). Subtle as opposed to outright counter strategies minimised retaliation, since restaurant owners wanted to avoid price wars, or spreading misinformation where the reputation of a cluster may suffer alongside the likely survival of individual businesses within that regional cluster.

Originality/value

Mixed evidence exists in earlier studies regarding the competitive rivalry in certain sectors where ethnic minority ownership is prominent; not least, restaurants located in regional clusters. However, this investigation considers the notion – what if some of these earlier studies are wrong? More specifically, does certain prior research under-represent the extent that rival entrepreneurs of an ethnic minority origin collaborate rather than compete for mutually beneficial purposes? New evidence emerges regarding ways in which a competitor orientation can influence the performance-enhancing nature of coopetition activities among business owners originating from both intra and inter-ethnic communities.