bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a novel botybirnavirus with a unique dsRNA infectingDidymella theifoliafrom tea plants
Authors: Ye Liangchao , Shi Xinyu , He Yunqiang , Chen Jiao , Xu Qingeng , Shafik Karim , Xu Wenxing
Published: December 2022

Didymella theifoliaspecifically infects some local varieties ofCamellia sinensisin China, representing a unique fungal species, and characterization of the mycoviruses related to this fungal species is attractive. Three double-stranded RNAs (dsRNAs; dsRNAs 1, 2 and 3 with sizes of 6338, 5910 and 727 bp, respectively) were identified in an avirulent strain CJP4-1 ofD. theifoliaexhibiting normal growth and morphologies. Characterization of the dsRNAs 1 and 2 revealed that they are genomic components of a novel botybirnavirus, tentatively named Didymella theifolia botybirnavirus 1 (DtBRV1), and encapsidated in isometric virions with a size of ∼39.8 nm in diameter. It is worth noting that dsRNA3 shares no detectable identity with those sequences deposited in NCBI database, while a high identity (36.58% and 40.93%) with the left regions of dsRNAs 1 and 2, but is not encapsidated in DtBRV1 particles, suggesting it is a unique dsRNA unit that is not a DtBRV1 component or a satellite and its taxonomic classification remains unclear. SDS-polyacrylamide gel electrophoresis in combination with peptide mass fingerprint analysis revealed that DtBRV1 capsid protein consisting of polypeptides encoded by the left regions of both genomic components. DtBRV1 is efficiently vertically transmitted through conidia while difficult in horizontal transmission from strain CJP4-1 to other strains. DtBRV1 has no effects on fungal growth and virulence as accessed with the transfectants of virulent strain JYC1-6 ofD. theifoliainfected by DtBRV1. DtBRV1 with specific molecular traits contributes useful information for a better understanding of the mycoviral community.

Importance

Tea plants represent an ancient and unique plant species community cultured in China, while the mycoviruses related to the phytopathogenetic fungi infecting tea remain limited. Here, we characterized a novel botybirnavirus (tentatively named Didymella theifolia botybirnavirus1 (DtBRV1), and a specific dsRNA infectingDidymella theifoliaresponsible for a noticeable disease of tea plants. DtBRV1 contains two dsRNAs (1 and 2) encapsidated in isometric virions in size of ∼39.8 nm, while dsRNA3 is not encapsidated in the viral particles although it has a high identity with the mycoviral genomic components. Additionally, DtBRV1 coat proteins are composed of fused proteins encoded by both dsRNA-coding open reading frames most likely after cleave and fuse processing progress, which is striking unlike most mycoviruses. With some specific molecular traits, DtBRV1 and the related specific dsRNA unit expand our understanding of virus diversity, taxonomy, and evolution.
Continence problems and mental health in adolescents from a UK cohort
Authors: Gordon Katie , Warne Naomi , Heron Jon , Gontard Alexander von , Joinson Carol
Published: December 2022

Background

Adolescents with continence problems experience a unique range of threats to their psychological wellbeing including perceived stigma, social isolation, and poor self-image. Despite this, the long-term mental health sequelae of adolescent continence problems are unknown.

Methods

We used data from the Avon Longitudinal Study of Parents and Children (n=7,332: 3,639 males, 3,693 females) to examine prospective relationships between self-reported incontinence/lower urinary tract symptoms (LUTS) at 14 years (daytime wetting, bedwetting, soiling, urgency, frequent urination, low voided volume, voiding postponement, and nocturia) and common mental health problems at 18 years (any common mental disorder, depression, anxiety, self-harm, and disordered eating). We estimated multivariable regression models adjusted for sex, socioeconomic position, developmental level, IQ, stressful life events, maternal psychopathology, body mass index, and earlier emotional/behavioural problems.

Findings

Daytime wetting and voiding postponement showed the greatest number of associations with mental health problems. All incontinence subtypes/LUTS were associated with increased odds of generalised anxiety disorder symptoms [e.g., odds ratio for daytime wetting= 3.01, 95% confidence interval (1.78, 5.09), p<0.001] and/or higher anxiety scores. There was also evidence of associations with common mental disorder [e.g., voiding postponement: 1.88 (1.46, 2.41), p<0.001], depression [e.g., urgency: 1.94 (1.19, 3.14), p=0.008], depressive symptoms [e.g., daytime wetting: 1.70 (1.13, 2.56), p=0.011], self-harm thoughts [e.g., voiding postponement: 1.52 (1.16, 1.99), p=0.003], and disordered eating [e.g., nocturia 1.72 (1.27, 2.34), p=0.001].

Interpretation

Incontinence/LUTS at age 14 are associated with increased vulnerability to mental health problems in late adolescence. Treatment of incontinence/LUTS should be integrated with psychological support to mitigate long-term sequelae.
Effective tree-based classification for automated flow cytometry data analysis on samples with suspected haematological malignancy
Authors: Rothwell Alex , Carter Anthony , Green Peter , Jones Andrew R
Published: December 2022

Flow cytometry is a commonly used diagnostic technique for haematological malignancies. The gold standard method for analysis of flow cytometry data is manual gating, which is time consuming and requires a highly skilled operator, generating a bottleneck in the workflow and potentially increasing time to diagnose malignancy. For nearly 20 years attempts have been made at replacing manual analysis with automated algorithms, however these are not deemed accurate enough for clinical practice. Clustering methods have been the focus of previous automated attempts, though supervised methods have been shown to be more accurate and require less manual intervention. Tree-based classification algorithms make decisions using an analogous process to manual gating. One hundred and fifty-two flow cytometry files were generated from peripheral blood samples of patients with suspected haematological malignancies. A trained operator labelled events in these files as one of nine cell types. CART, Random Forest and XGBoost were trained on the labelled dataset and the performance was evaluated against previously published clustering methods. Classification algorithms showed higher mean F1 scores than clustering methods. There was no significant difference between CART, Random Forest and XGBoost mean F1 scores, and all three algorithms showed mean prediction times per sample of less than 25 seconds. Tree-based methods struggled to differentiate B cell subtypes, which show similar phenotypic signatures and present an area for future improvement. This work demonstrates the effectiveness of tree-based classification algorithms for flow cytometry analysis. Overall, CART may offer a solution to automated flow cytometry analysis for the purpose of haematological malignancies due to showing high agreement with manual analysis, and short prediction and training times.
Selection for insecticide resistance can promotePlasmodium falciparuminfection inAnopheles
Authors: Adams Kelsey L. , Selland Emily K. , Willett Bailey C. , Carew John W. , Vidoudez Charles , Singh Naresh , Catteruccia Flaminia
Published: December 2022

Insecticide resistance is under strong selective pressure inAnophelesmosquitoes due to widespread usage of insecticides in vector control strategies. Resistance mechanisms likely cause changes that profoundly affect mosquito physiology, yet it remains poorly understood how selective pressures imposed by insecticides may alter the ability of the mosquito to host and transmit aPlasmodiuminfection. From pyrethroid-resistant field-derivedAnopheles gambiae s.l. mosquitoes, we performed selection experiments to establish resistant (RES) and susceptible (SUS) colonies by either selection for, or loss of, insecticide resistance. We show increased prevalence, intensity, and oocyst growth rate ofPlasmodium falciparuminfection in RES females compared to SUS. The increase in infection intensity in RES females was not associated with the presence of thekdrL1014F mutation, and was not impacted by inhibition of Cytochrome P450s. The lipid transporter lipophorin (Lp), which was upregulated in RES compared to SUS, was at least partly implicated in the increased intensity ofP. falciparumbut not directly in the insecticide resistance phenotype. Interestingly, we observed that althoughP. falciparuminfections were not affected when RES females were exposed to permethrin, these females had decreased lipid abundance in the fat body following exposure, pointing to a possible role for lipid mobilization in response to damage caused by insecticide challenge. The finding that selection for insecticide resistance can increaseP. falciparuminfection intensities and growth rate reinforces the need to assess the overall impact on malaria transmission dynamics of selective pressures mosquitoes experience during repeated insecticide challenge.

Significance Statement

Insecticide resistance poses a severe threat for malaria control. Resistance to pyrethroid insecticides, the active component of most insecticide-treated nets, is now widespread in sub-Saharan Africa, reducing the efficacy of these crucial tools. Despite significant research characterizing insecticide resistance mechanisms, it remains unknown how these traits influencePlasmodium falciparuminfections in malaria-transmittingAnophelesmosquitoes. We established a pyrethroid-resistant and pyrethroid-susceptible population ofAnopheles gambiaederived from the same genetic background and performed experimental infections withP. falciparum. We found that the pyrethroid-resistant population was more supportive of malaria parasites compared to the susceptible population. This was not caused by well-known insecticide resistance mechanisms, but linked with a lipid transporter, lipophorin, which may play an indirect role in resistance.
Engineered retrovirus-like nanocarriers for messenger RNA delivery into neurons
Authors: Gu Wenchao , Luozhong Sijin , Cai Simian , Londhe Ketaki , Elkasri Nadine , Hawkins Robert , Yuan Zhefan , Su-Greene Kai , Cruz Margaret , Chang Yu-Wei , McMullen Patrick , Wu Chunyan , Seo Changwoo , Guru Akash , Gao Wenting , Sarmiento Tara , Schaffer Chris , Nishimura Nozomi , Cerione Richard , Warden Melissa , Langer Robert , Jiang Shaoyi
Published: December 2022

Systemic delivery of mRNAs into disease neurons is first limited by the blood-brain-barrier (BBB). Leukocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, emerging as promising carriers to target the disease brain. However, efficient mRNA loading into EVs and their uptake by neurons remain challenges. Here we incorporated inside EVs the endogenous retrovirus-like Arc protein capsids, stabilized by Arc 5’UTR RNA elements, to effectively load and deliver mRNAs. Produced from self-derived leukocytes, engineered retrotransposon Arc EVs (eraEVs) are immunologically inert with minimal clearance. Equipped with endothelial adhesion molecules from donor leukocytes, circulating eraEVs enter the brain enriching at neuro-inflammatory sites. During self-assembly, Arc recruits enveloping proteins onto eraEVs further promoting neuronal uptake. Possessing high effectiveness like viral vectors and biocompatibility as natural vesicles, eraEV-nanocarriers can be produced from virtually all donor cell types, potentially leading to the development of future clinical therapies for a range of diseases.

Abstract Figure
Interchromosomal segmental duplication drives translocation and loss ofP. falciparumhistidine-rich protein 3
Authors: Hathaway Nicholas J. , Kim Isaac E. , Young Neeva Wernsman , Hui Sin Ting , Crudale Rebecca , Liang Emily Y. , Nixon Christian P. , Giesbrecht David , Juliano Jonathan J. , Parr Jonathan B. , Bailey Jeffrey A.
Published: December 2022

Most malaria rapid diagnostic tests (RDTs) detectPlasmodium falciparumhistidine-rich protein 2 (PfHRP2) and PfHRP3, but deletions ofpfhrp2andphfrp3genes make parasites undetectable by RDTs. We analyzed 19,313 public whole-genome-sequenced P. falciparum field samples to understand these deletions better.Pfhrp2deletion only occurred by chromosomal breakage with subsequent telomere healing.Pfhrp3deletions involved loss frompfhrp3to the telomere and showed 3 patterns: no other associated rearrangement with evidence of telomere healing at breakpoint (Asia; Pattern 13-TARE1); associated with duplication of a chromosome 5 segment containing multidrug-resistant-1 gene (Asia; Pattern 13-5++); and most commonly, associated with duplication of a chromosome 11 segment (Americas/Africa; Pattern 13-11++). We confirmed a 13-11 hybrid chromosome with long-read sequencing, consistent with a translocation product arising from recombination between large interchromosomal ribosome-containing segmental duplications. Within most 13-11++parasites, the duplicated chromosome 11 segments were identical. Across parasites, multiple distinct haplotype groupings were consistent with emergence due to clonal expansion of progeny from intrastrain meiotic recombination. Together, these observations suggest negative selection normally removes 13-11++pfhrp3 deletions, and specific conditions are needed for their emergence and spread including low transmission, findings that can help refine surveillance strategies.
Pleiotropy of autism-associated chromatin regulators
Authors: Lasser Micaela , Sun Nawei , Xu Yuxiao , Law Karen , Gonzalez Silvano , Wang Belinda , Drury Vanessa , Drake Sam , Zaltsman Yefim , Dea Jeanselle , Bader Ethel , McCluskey Kate E. , State Matthew W. , Willsey A. Jeremy , Willsey Helen Rankin
Published: December 2022

Gene ontology analyses of high confidence autism spectrum disorder (hcASD) risk genes have historically highlighted chromatin regulation and synaptic function as major contributors to pathobiology. Our recent functional workin vivohas additionally implicated microtubule biology and identified disrupted cellular proliferation as a convergent ASD phenotype. As many chromatin regulators, including ASD risk genesADNPandCHD3, are known to directly regulate both tubulins and histones, we studied the five chromatin regulators most strongly associated with ASD (ADNP, CHD8, CHD2, POGZ, andSUV420H1/KMT5B) specifically with respect to microtubule biology. We observe that all five localize to microtubules of the mitotic spindlein vitroandin vivo. Further in-depth investigation ofCHD2provides evidence that patient-derived mutations lead to a range of microtubule-related phenotypes, including disrupted localization of the protein at the mitotic spindle, spindle defects, cell cycle stalling, DNA damage, and cell death. Lastly, we observe that ASD genetic risk is significantly enriched among microtubule-associated proteins, suggesting broader relevance. Together, these results provide further evidence that the role of tubulin biology and cellular proliferation in ASD warrant further investigation and highlight the pitfalls of relying solely on annotated gene functions in the search for pathological mechanisms.
Structure of a reversible amyloid fibril formed by the CPEB3 prion-like domain reveals a core sequence involved in translational regulation
Authors: Flores Maria D. , Sawaya Michael R. , Boyer David R. , Zink Samantha , Tovmasyan Susanna , Saucedo Adrian , Zee Chih-Te , Cardenas Jorge , Fioriti Luana , Rodriguez Jose A.
Published: December 2022

The cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a prion-like RNA-binding polypeptide. As a functional prion, CPEB3 is thought to modulate protein synthesis at synapses and enable consolidation of long-term memory in neurons. Here, we report that the prion-like domain 1 of CPEB3 self-assembles into labile amyloid fibrilsin vitro. A cryoEM structure of these fibrils reveals an ordered 48-residue core, spanning L103 to F151. CPEB3 constructs lacking this amyloidogenic segment form abnormal puncta in cells when compared to wild type CPEB3, with reduced localization in dormant p-bodies and increased localization in stress granules. Removal of the amyloid core segment in CPEB3 also abolishes its ability to regulate protein synthesis in neurons. Collectively, this evidence suggests that the newly identified amyloidogenic segment within the CPEB3 prion domain is important for its regulated aggregation in cells and suggest its involvement in regulating translational activity and potentially long-term memory formation.
Associations of Socioeconomic Disparities With Buccal DNA-Methylation Measures Of Biological Aging
Authors: Raffington L. , Schwaba T. , Aikins M. , Richter D. , Wagner G.G. , Harden K.P. , Belsky D.W. , Tucker-Drob E.M.
Published: December 2022

Background

Individuals who are socioeconomically disadvantaged are at increased risk for aging-related diseases and perform less well on tests of cognitive function. The Weathering Hypothesis proposes that these disparities in physical and cognitive health arise from an acceleration of biological processes of aging. Theories of how life adversity is biologically embedded identify epigenetic alterations, including DNA methylation (DNAm), as a mechanistic interface between the environment and health. Consistent with the Weathering hypothesis and theories of biological embedding, recently developed DNAm algorithms have revealed profiles reflective of more advanced aging and lower cognitive function among socioeconomically-at-risk groups. These DNAm algorithms were developed using blood-DNA, but social and behavioral science research commonly collect saliva or cheek-swab DNA. This discrepancy is a potential barrier to research to elucidate mechanisms through which socioeconomic disadvantage affects aging and cognition. We therefore tested if social gradients observed in blood-DNAm measures could be reproduced using buccal-cell DNA obtained from cheek swabs.

Results

We analyzed three DNAm measures of biological aging and one DNAm measure of cognitive performance, all of which showed socioeconomic gradients in previous studies: the PhenoAge and GrimAge DNAm clocks, DunedinPACE, and Epigenetic-g. We first computed blood-buccal cross-tissue correlations in n=21 adults (GEO111165). Cross-tissue correlations were low-to-moderate across (r=.25 tor=.48). We next conducted analyses of socioeconomic gradients using buccal DNAm data from SOEP-G (n=1128, 57% female; age mean=42 yrs, SD=21.56, range 0-72). Associations of socioeconomic status with DNAm measures of aging were in the expected direction, but were smaller as compared to reports from blood DNAm datasets (r=-.08 tor=-.13).

Conclusions

Our findings are consistent with the hypothesis that socioeconomic disadvantage is associated with DNAm indicators of worse physical and cognitive health. However, relatively low cross-tissue correlations and attenuated effect-sizes for socioeconomic gradients in buccal DNAm compared with reports from analysis of blood DNAm suggest that, in order to take full advantage of buccal-DNA samples, DNAm algorithms customized to buccal DNAm are needed.
Trans-cellular control of synapse properties by a cell type-specific splicing regulator
Authors: Traunmüller Lisa , Schulz Jan , Ortiz Raul , Feng Huijuan , Furlanis Elisabetta , Gomez Andrea , Schreiner Dietmar , Bischofberger Josef , Zhang Chaolin , Scheiffele Peter
Published: December 2022

The recognition of synaptic partners and specification of synaptic properties are fundamental for the function of neuronal circuits. ‘Terminal selector’ transcription factors coordinate the expression of terminal gene batteries that specify cell type-specific properties. Moreover, pan-neuronal alternative splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell type-specific loss-of-function studies to uncover the contribution of the nuclear RNA binding protein SLM2 to hippocampal synapse specification. Focusing on hippocampal pyramidal cells and SST-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins, thereby generating cell type-specific isoforms. In the absence of SLM2, cell type-specification, differentiation, and viability are unaltered and neuronal populations exhibit normal intrinsic properties. By contrast, cell type-specific loss of SLM2 results in highly selective, non-cell autonomous synaptic phenotypes, altered synaptic transmission, and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner.
The Prioritization of Eleven-Nineteen-Leukemia Inhibitors as Potential Drug Candidates to Treat Acute Myeloid Leukemia
Authors: Guo Xuejiao Shirley , Chen Peng-Hsun Chase , Xu Shiqing , Liu Wenshe Ray
Published: December 2022

Acute myeloid leukemia (AML) is the second most diagnosed and the deadliest subtype of leukemia. Recently genetic loss-of-function studies have demonstrated that a human YEATS domain-containing protein named eleven-nineteen-leukaemia (ENL) functions as a transcriptional coactivator and is essential for the proliferation of AML that harbours oncogenic multiple lineage leukemia (MLL) rearrangements. We previously synthesized a series of small molecule inhibitors (1,7-9,11-15and24) that displayed significant and specific inhibitory effects against the ENL YEAST domain. In the current work, we report the development of a novel NanoBRET system that allows the analysis of cellular permeability, potency, selectivity, and stability of synthesized ENL inhibitors for their prioritization for further characterizations. Followed byin vitrometabolic stability and cell growth inhibition studies, we narrowed down to a potent and specific ENL YEATS domain inhibitor13with both highin vitrometabolic stability and strong anti-proliferation ability on MLL-fusion leukemia cell lines. A mouse pharmacokinetic (PK) analysis showed that at an oral dose of 20 mg/kg compound13had 60.9% bioavailability and 2.6 h mean residence time. With these favorable PK characteristics, compound13is ready for efficacy studies in an animal model. Cumulatively, the current study has prioritized compound13as a promising drug candidate to disrupt the pathogenic functions of ENL for the AML treatment.
Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice
Authors: Deshpande Rajashree A. , Marin-Gonzalez Alberto , Ha Taekjip , Paull Tanya T.
Published: December 2022

The Mre11-Rad50-Nbs1 (MRN) complex recognizes and processes DNA double-strand breaks for homologous recombination by performing short-range removal of 5ʹ strands. Endonucleolytic processing by MRN requires a stably bound protein at the break site—a role we postulate is played by DNA-dependent protein kinase (DNA-PK) in mammals. Here we interrogate the sites of MRN-dependent processing by isolating and sequencing DNA-PK-bound DNA fragments that are products of MRN cleavage. These intermediates are generated with highest efficiency when DNA-PK is catalytically blocked, yielding products within 200 bp of the break site, whereas DNA-PK products in the absence of kinase inhibition show much greater dispersal. Use of light-activated Cas9 to induce breaks facilitates temporal resolution of DNA-PK and Mre11 binding, showing that Mre11 and DNA-PK both bind to DNA ends before release of DNA-PK-bound products. These results support a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.
Discrete Ricci curvatures capture age-related changes in human brain functional connectivity networks
Authors: Yadav Yasharth , Elumalai Pavithra , Williams Nitin , Jost Jürgen , Samal Areejit
Published: December 2022

Geometry-inspired notions of discrete Ricci curvature have been successfully used as markers of disrupted brain connectivity in neuropsychiatric disorders, but their ability to characterize age-related changes in functional connectivity is unexplored. Here, we apply Forman-Ricci curvature and Ollivier-Ricci curvature to compare functional connectivity networks of healthy young and older subjects from the Max Planck Institute Leipzig Study for Mind-Body-Emotion Interactions (MPI-LEMON) dataset (N= 225). We found that both Forman-Ricci curvature and Ollivier-Ricci curvature can capture whole-brain and region-level age-related differences in functional connectivity. Meta-analysis decoding demonstrated that those brain regions with age-related curvature differences were associated with cognitive domains known to manifest age-related changes – movement, affective processing and somatosensory processing. Moreover, the curvature values of some brain regions showing age-related differences exhibited correlations with behavioral scores of affective processing. Finally, we found an overlap between brain regions showing age-related curvature differences and those brain regions whose non-invasive stimulation resulted in improved movement performance in older adults. These results suggest that both Forman-Ricci curvature and Ollivier-Ricci curvature correctly identify brain regions that are known to be functionally or clinically relevant. Our results add to a growing body of evidence demonstrating the sensitivity of discrete Ricci curvature measures to changes in the organisation of functional connectivity networks, both in health and disease.
Inductive biases of neural specialization in spatial navigation
Authors: Zhang Ruiyi , Pitkow Xaq , Angelaki Dora E
Published: December 2022

The brain may have evolved a modular architecture for reward-based learning in daily tasks, with circuits featuring functionally specialized modules that match the task structure. We propose that this architecture enables better learning and generalization than architectures with less specialized modules. To test this hypothesis, we trained reinforcement learning agents with various neural architectures on a naturalistic navigation task. We found that the architecture that largely segregates computations of state representation, value, and action into specialized modules enables more efficient learning and better generalization. Behaviors of agents with this architecture also resemble macaque behaviors more closely. Investigating the latent state computations in these agents, we discovered that the learned state representation combines prediction and observation, weighted by their relative uncertainty, akin to a Kalman filter. These results shed light on the possible rationale for the brain’s modular specializations and suggest that artificial systems can use this insight from neuroscience to improve learning and generalization in natural tasks.
Controlling the bioelectrical properties of neurons with ferritin-based Magnetogenetics
Authors: Hernández-Morales Miriam , Morales-Weil Koyam , Han Sang Min , Han Victor , Pegram Kelly , Benner Eric J. , Miller Evan W. , Kramer Richard H , Liu Chunlei
Published: December 2022

Magnetogenetics promises remote control of neurons, but its validity is questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Recent studies discovered that ferritin, used in Magnetogenetics, transduces radiofrequency (RF) magnetic fields into biochemical signals (reactive oxygen species and oxidized lipids). Magnetic stimulation of ferritin-tethered TRPV channels induces Ca2+responses and modulates behavior but electrophysiological studies indicate that a particular channel, Magneto2.0, is ineffective in affecting the neuronal bioelectrical properties. We investigated this problem using the Magnetogenetic technique FeRIC. We resolved the electromagnetic interference caused by RF in patch-clamp recordings and supported the data with voltage imaging experiments. In neurons expressing TRPV4FeRIC, RF depolarizes the membrane potential and increases the spiking frequency. In neurons expressing the chloride-permeable TMEM16AFeRIC, RF hyperpolarizes the membrane potential and decreases the spiking frequency. Our study reveals the control of neuronal bioelectrical properties with Magnetogenetics that is non-instantaneous, long-lasting, and moderate, but effective and comparable to that induced by endogenous signaling molecules.
Structure of an endogenous mycobacterial MCE lipid transporter
Authors: Chen James , Fruhauf Alice , Fan Catherine , Ponce Jackeline , Ueberheide Beatrix , Bhabha Gira , Ekiert Damian C.
Published: December 2022

To replicate inside human macrophages and cause the disease tuberculosis,Mycobacterium tuberculosis(Mtb) must scavenge a variety of nutrients from the host1,2. The Mammalian Cell Entry (MCE) proteins are important virulence factors inMtb1,3, where they are encoded in large gene clusters and have been implicated in the transport of fatty acids4–7and cholesterol1,4,8across the impermeable mycobacterial cell envelope. Very little is known about how cargos are transported across this barrier, and how the ~10 proteins encoded in a mycobacterialmcegene cluster might assemble to transport cargo across the cell envelope remains unknown. Here we report the cryo-EM structure of the endogenous Mce1 fatty acid import machine fromMycobacterium smegmatis, a non-pathogenic relative ofMtb. The structure reveals how the proteins of the Mce1 system assemble to form an elongated ABC transporter complex, long enough to span the cell envelope. The Mce1 complex is dominated by a curved, needle-like domain that appears to be unrelated to previously described protein structures, and creates a protected hydrophobic pathway for lipid transport across the periplasm. Unexpectedly, our structural data revealed the presence of a previously unknown subunit of the Mce1 complex, which we identified using a combination of cryo-EM and AlphaFold2, and name LucB. Our data lead to a structural model for Mce1-mediated fatty acid import across the mycobacterial cell envelope.
xrd_simulator: 3D X-ray diffraction simulation software supporting 3D polycrystalline microstructure morphology descriptions
Authors: Henningsson Axel , Hall Stephen A.
Published: December 2022

An open source Python package named xrd_simulator, capable of simulating geometrical interactions between a monochromatic X-ray beam and a polycrystalline microstructure, is described and demonstrated. The software can simulate arbitrary intragranular lattice variations of single crystals embedded within a multiphase 3D aggregate by making use of a tetrahedral mesh representation where each element holds an independent lattice. By approximating the X-ray beam as an arbitrary convex polyhedral region in space and letting the sample be moved continuously through arbitrary rigid motions, data from standard and non-standard measurement sequences can be simulated. This implementation is made possible through analytical solutions to a modified, time-dependent version of the Laue equations. The software, which primarily targets three-dimensional X-ray diffraction microscopy (high-energy X-ray diffraction microscopy) type experiments, enables the numerical exploration of which sample quantities can and cannot be reconstructed for a given acquisition scheme. Similarly, xrd_simulator targets investigations of different measurement sequences in relation to optimizing both experimental run times and sampling.
COVID-19 information seeking behavior versus value perception among U.S. ethnic/racial minorities: differences and vaccination implications
Authors: Kim Hyehyun , Chan-Olmsted Sylvia , Chen Huan
Published: December 2022

Purpose

This study explores information behavior and perception and vaccination among America's three largest ethnic minorities, Hispanic, Black/African American and Asian, in COVID-19 context. Information behavior and perception are investigated from cultural and demographic characteristics, while vaccination is explored from COVID-19 related information behavior and utility/value of COVID-19 vaccine information.

Design/methodology/approach

Using Qualtrics survey panel, a national survey of America's Hispanic, Black/African American and Asian population was conducted to better understand the impact of cultural and demographic factors on COVID-19 related information. Data were collected in Fall 2021. Multiple and logistic regression were conducted to analyze data.

Findings

Results show that cultural factors (i.e. cultural identity, social identity, social capital and religiousness) exert significant impact on information value and seeking across all three minority groups, while some demographic factors, Republicanism and age, also significantly predict COVID-19 related information seeking and value for Black/African Americans and Hispanics, but less for Asian Americans. Lastly, information value was found to significantly predict vaccine status, willingness and eagerness, the three facets of vaccination as conceptualized in this study, for top three racial/ethic minorities.

Originality/value

The finding of this study reveal that there are variations in terms of the level and type of attachment to one's culture/social group in COVID-19 informational context. Between the three groups, granular differences were observed regarding the relationship between cultural factors and perceived COVID-19 information value. While cultural identity is most associated with African Americans, social capital is most evident for the Asian Americans, but social identity was the strongest predictor among Hispanics. Thus, this study offers important strategic insights into a unique population sample to better understand the impact of COVID-19 related information perception and vaccination implication.
Teachers' perceived usefulness of assistive technology in Ontario classrooms
Authors: Lamond Bronwyn , Mo Shimin , Cunningham Todd
Published: December 2022

Purpose

Despite the positive impact that assistive technology (AT) can have on the academic success of students with learning disabilities, it is often inconsistently implemented or abandoned. It has been established that teachers' perceived usefulness of AT can act as a barrier to classroom AT implementation. The purpose of this study is to expand the current understanding of the challenges with implementation of AT within the classroom environment to inform teacher training on AT tools, improve professional development around AT and address the systemic and practical barriers that impact AT implementation within Ontario classrooms.

Design/methodology/approach

This research examined Grade 6–10 Ontario-certified teachers' (N = 111) perceptions of AT and the variables that predict perceived usefulness of AT. The study used a mixed methods design including a survey consisting of open- and closed-ended items that elicited information about teachers' AT knowledge and training, their access to AT resources, their perception of administrative support for access to and implementation of AT, the usefulness of AT and the barriers to AT use in the classroom.

Findings

An exploratory linear regression was conducted to predict perceived usefulness of AT from AT training, AT resources and AT knowledge and revealed that AT resources and AT knowledge added statistically significantly to the prediction, whereas AT training did not. A thematic analysis of open-ended survey responses and interview data further identified that access, training, Internet and student motivation may influence AT use.

Originality/value

Implications for teachers’ AT training and provision of AT resources are discussed.
Impetuses and constraints in the policy formation process of the International Science and Business Belt in Korea
Authors: Lee Seunghyun
Published: December 2022

Purpose

Korea’s Institute for Basic Science (IBS), the first research institute dedicated to basic science in Korea, started ten years ago as part of a science policy called the Science Belt. It is noteworthy that Korea, with a short history of basic science, established such a research institute exclusively for basic science within a short period of time and made it one of the representative institutions of basic science in Korea. This paper aims to uncover the impetuses and constraints surrounding the policy of Science Belt, centering on the IBS.

Design/methodology/approach

Kingdon’s stream theory is used to clarify the factors that acted as impetuses or constraints for the Science Belt. For the analysis, in-depth interviews with the active policy participants were conducted in addition to the thorough literature review. The interviews enabled an in-depth understanding of the underlying factors for the Science Belt and the actual procedures of the policy decision.

Findings

This study found that the most powerful impetus in the Science Belt policymaking process was the President and a small group composed of a few scientists who played a leading role in the political stream. The constraint of the Science Belt was that the participation of scientist experts and governmental officials, the so-called invisible participants of Kingdon, was insignificant. In particular, there was no system in place to select policy alternatives for basic science through discussion between scientists and governmental officials.

Research limitations/implications

The temporal scope of this study was limited to policy formation, that is, until the establishment of IBS. Therefore, future studies shall conduct a research on the implementation of the actual policy, IBS’s achievements and IBS’s impact of Korea’s basic science community.

Originality/value

This study applied both a theoretical framework and in-depth interviews along with the literature overview to understand a policymaking process from various angles.
Social media aesthetics as part of academic library merchandising
Authors: Wójcik Magdalena
Published: December 2022

Purpose

The subject of this paper is the phenomenon of social media aesthetics, which can be perceived as a tool for promoting and building the image of libraries, especially in terms of merchandising. The aim of this paper is to analyse the potential of the dark academia social media trend in the promotion of academic libraries.

Design/methodology/approach

The article is based on a review of the social networking sites YouTube and Instagram and an analysis of network resources using the Brand24 tool.

Findings

Resources that are described by Internet users as “dark academia” are popular in social media. Dark academia as an aesthetic concept creates potential for the promotion of academic libraries, especially those that are more traditional in terms of their architecture, décor or how they offer their services.

Research limitations/implications

The paper concerns a phenomenon which, although popular socially, has not yet been scientifically analysed in the literature on the subject. Since the topic is new and there is no scientific literature on it, the author had to base the paper on less standard sources of information (e.g. analysis of the content of social media). The article is a review, an introduction, as well as an invitation to further discussion. The author's aim is not to comprehensively cover this topic but only to draw attention to an interesting and rarely discussed issue that has great potential for practical activities.

Practical implications

The topic has great potential for the practical improvement of the promotional activities of libraries, especially older, more traditional libraries, to create a strong and positive image on the basis of characteristics often perceived as weaknesses.

Social implications

Social media services are powerful social impact tools. Showing the potential role of social media aesthetics for cultural institutions could serve to make the public more aware of the role of the proper use of social media for promotion and image building.

Originality/value

The use of social media aesthetics is very rarely discussed in the subject literature.
Analyzing walkability in the vicinity of three metro stations in Doha, Qatar
Authors: Salaheldin Hadeel T. , Major Mark David , Ahmad Ahmad Mohammed , Tannous Heba O.
Published: December 2022

Purpose

Many factors contribute to public rail transit use in an urban network. However, a dysfunctional relationship between the built environment and the transport system significantly deters such use. Architects, urban designers, town planners and policymakers must understand the factors that promote or deter pedestrian use of the urban environment.

Design/methodology/approach

The paper investigates four connectivity and walkability factors for three different metro stations in Doha, Qatar: Al Aziziyah, Hamad Hospital and West Bay. The analysis includes pedestrian sheds, block sizes, ground-level land uses and connectedness in the urban spatial network based on catchment contour maps using space syntax.

Findings

The results indicate the three metro stations and neighborhoods are representative of diverse type of neighborhoods in Doha: relatively compact but expansive for the Hamad Hospital Station area, metrically and topologically restrictive due to the poor planning and the peninsular location of the reclaimed land in the West Bay area, and expansive, shallow and reliant on attraction for the Al Waab transportation corridor associated with Al Aziziyah Station.

Research limitations/implications

Time factors and temporary closure/capacity reductions due to the global pandemic restricted planned efforts to collect more pedestrian use data based on passive observations and preference choices using surveys during the study. Nonetheless, adapting the investigation to the circumstances produced significant findings.

Social implications

The analysis can help us develop better guidelines and diagnostic tools to calibrate design and planning strategies promoting more walkable, healthy and sustainable neighborhoods.

Originality/value

The study is original due to examining stations of the new Doha Metro for the first time. However, it relies on well-established representational techniques in urban morphology and space syntax research.
The path from customer experience to customer citizenship: new adventure is a touristic railway journey
Authors: Samsa Çağlar
Published: December 2022

Purpose

In this study, the author aimed to measure the effect of customer loyalty on customer citizenship behavior as well as the effect of experience value perceptions of tourist railway journey customers on customer loyalty within the scope of social exchange theory.

Design/methodology/approach

The author obtained data from 126 participants who had experienced the tourist railway adventure through random sampling. In the next stage, the author extracted the data obtained with the bootstrapping sample technique to 5,000 samples. The author analyzed these obtained data with the PLS-SEM model with the Smart PLS 3 software.

Findings

The results of the research show that the most important experience value dimension that creates loyalty in the touristic railway journey is the emotional value dimension; the second important dimension is the hedonic value dimension and other experience value dimensions did not have any effect on customer loyalty intention levels. In addition, an important result of the study is that loyal customers mostly intend to advise other customers, and relatively less of them intend to give feedback to the firm.

Research limitations/implications

The fact that the concepts of touristic railway journeys are different due to the nature of tourism is an important limitation of the study, which is only for individuals who have experienced the Touristic Eastern Express. The fact that the Touristic Eastern Express is a long journey and stops at many destinations on its arrival and departure route can affect customers' perceptions of the experience value.

Practical implications

The values that create customer loyalty in the touristic railway journey are mostly emotional and hedonic values. In addition, customers who are loyal as a result of this journey are more intent on advising other customers than giving feedback to the firm.

Originality/value

The study was carried out on the customers of the touristic eastern express, which started its activities in 2019. Ensuring customer loyalty for the sustainability of this trend has significant tourism potential; Afterwards, the transformation of customer loyalty into customer citizenship has a very important place. In addition, as far as we have examined the literature, the absence of similar studies in the tourism sector is an indicator of the study's originality. Considering these data, it is expected that the study will fill an important gap in terms of both sectoral and academic.
Modelling pollinator and nonpollinator selection on flower colour variation
Authors: Tenhumberg Brigitte , Dellinger Agnes S. , Smith Stacey D.
Published: December 2022

Flower colour variation is ubiquitous within and between populations, which is why it has long been a focal point for studies of natural selection. This body of work has uncovered a wide range of selective agents, including pollinators, herbivores and various abiotic factors. Nevertheless, we lack an integrative framework for predicting the phenotypic outcome in terms of floral pigmentation when these forces act collectively and often in opposition.

We here present such a framework through a model that incorporates selection on pigmentation at the vegetative phase (i.e. through survival to reproduction) and at the flowering phase (i.e. on pollinator attraction). We focus on anthocyanins as common class of pigments although the model is equally applicable to any compounds that can be jointly expressed in vegetative tissue and in flowers. We explore the dynamics of our model in a theoretical context and in four scenarios based on classic systems for studying selection on flower colour.

Our model predicts that pollinators are the main driver for flower colour evolution, but selection on seedling survival plays a major role in the absence of pollen limitation, that is, if pollinator abundance is sufficiently high, or if pollinator preference is absent or weak (high variance in colour preference). In each of the case studies, our model recovered the predicted patterns of fitness for each floral morph given the strength and nature of selection.

This work suggests that selection at the vegetative phase must act alone or be exceptionally strong to negate pollinator preference for particular colours. Nevertheless, the influence of differential survival associated with anthocyanin production leaves a clear signature on the fitness curves, suggesting that nonpollinator agents of selection can often be detected from empirical data.

Synthesis: Overall, the application of this model to empirical systems will be key for understanding how flower colour diversity evolves and for predicting how changes in climate and pollinator communities may jointly alter evolutionary trajectories.